WorldWideScience

Sample records for mri-evaluated neoadjuvant chemotherapy

  1. Early prediction of the response of breast tumors to neoadjuvant chemotherapy using quantitative MRI and machine learning.

    Science.gov (United States)

    Mani, Subramani; Chen, Yukun; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Bhave, Sandeep R; Welch, E Brian; Levy, Mia A; Yankeelov, Thomas E

    2011-01-01

    The ability to predict early in the course of treatment the response of breast tumors to neoadjuvant chemotherapy can stratify patients based on response for patient-specific treatment strategies. Currently response to neoadjuvant chemotherapy is evaluated based on physical exam or breast imaging (mammogram, ultrasound or conventional breast MRI). There is a poor correlation among these measurements and with the actual tumor size when measured by the pathologist during definitive surgery. We tested the feasibility of using quantitative MRI as a tool for early prediction of tumor response. Between 2007 and 2010 twenty consecutive patients diagnosed with Stage II/III breast cancer and receiving neoadjuvant chemotherapy were enrolled on a prospective imaging study. Our study showed that quantitative MRI parameters along with routine clinical measures can predict responders from non-responders to neoadjuvant chemotherapy. The best predictive model had an accuracy of 0.9, a positive predictive value of 0.91 and an AUC of 0.96.

  2. Evaluation of response to neoadjuvant chemotherapy in breast cancer

    International Nuclear Information System (INIS)

    Jia Li; Deng Zhiyong

    2013-01-01

    Preoperative neoadjuvant chemotherapy has become the standardized treatment for patients with locally advanced breast cancer. With the wide application of neoadjuvant chemotherapy in clinic, evaluation of response to neoadjuvant chemotherapy seems increasingly important. How to evaluate the curative effect of chemotherapy timely, accurately, effectively and noninvasively has become the focus of clinical research. At present, clinical palpation,radiographic measurement and pathological examination are usually used in clinic, and the study of breast cancer biology factor is also rapidly spread. The application status of different evaluation methods of neoadjuvant chemotherapy were reviewed in this article. (authors)

  3. Pretreatment Diffusion-Weighted MRI Can Predict the Response to Neoadjuvant Chemotherapy in Patients with Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Guo-Yi Zhang

    2015-01-01

    Full Text Available Purpose. To explore the potential of diffusion-weighted (DW magnetic resonance imaging (MRI using apparent diffusion coefficient (ADC for predicting the response to neoadjuvant chemotherapy in nasopharyngeal carcinoma (NPC. Methods and Materials. Ninety-two consecutive patients with NPC who underwent three cycles of neoadjuvant chemotherapy were retrospectively analyzed. DW and anatomical MRI were performed before and after neoadjuvant chemotherapy prior to radiotherapy. Pretreatment ADCs and percentage increases in ADC after chemotherapy were calculated for the primary lesions and metastatic adenopathies. Receiver operating characteristic curve analysis was used to select optimal pretreatment ADCs. Results. Pretreatment mean ADCs were significantly lower for responders than for nonresponders (primary lesions, P=0.012; metastatic adenopathies, P=0.013. Mean percentage increases in ADC were higher for responders than for nonresponders (primary lesions, P=0.008; metastatic adenopathies, P<0.001. The optimal pretreatment primary lesion and metastatic adenopathy ADCs for differentiating responders from nonresponders were 0.897 × 10−3 mm2/sec and 1.031 × 10−3 mm2/sec, respectively. Conclusions. NPC patients with low pretreatment ADCs tend to respond better to neoadjuvant chemotherapy. Pretreatment ADCs could be used as a new pretreatment imaging biomarker of response to neoadjuvant chemotherapy.

  4. Neoadjuvant chemotherapy evaluation by MRI volumetry in rectal cancer followed by chemoradiation and total mesorectal excision: Initial experience.

    Science.gov (United States)

    Nougaret, Stephanie; Fujii, Shinya; Addley, Helen C; Bibeau, Frederic; Pandey, Himanshu; Mikhael, Hisham; Reinhold, Caroline; Azria, David; Rouanet, Philippe; Gallix, Benoit

    2013-09-01

    To evaluate rectal cancer volumetry in predicting initial neoadjuvant chemotherapy response. Sixteen consecutive patients who underwent neoadjuvant chemotherapy (CX) before chemoradiotherapy (CRT) and surgery were enrolled in this retrospective study. Tumor volume was evaluated at the first magnetic resonance imaging (MRI), after CX and after CRT. Tumor volume regression (TVR) and downstaging were compared with histological results according to Tumor Regression Grade (TRG) to assess CX and CRT response, respectively. The mean tumor volume was 132 cm(3) ± 166 before and 56 cm(3) ± 71 after CX. TVR after CX was significantly different between patients with poor histologic response (TRG1/2) and those with good histologic response (TRG3/4) (P = 0.001). An optimal cutoff of TVR >68% (area under the curve [AUC]: 0.9, 95% confidence interval [CI]: 0.65-0.98, P = 0.0001) to predict good histology response after CX was assessed by receiver operating characteristic curve. According to previous data and this study, we defined 70% as the best cutoff values according to sensitivity (86%), specificity (100%) of TVR for predicting good histology response. In contradistinction, MRI downstaging was associated with TRG only after CRT (P = 0.04). Our pilot study showed that MRI volumetry can predict early histological response after CX and before CRT. MRI volumetry could help the clinician to distinguish early responders in order to aid appropriate individually tailored therapies. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

  5. Locally advanced breast cancer: comparison of mammography, sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Londero, Viviana; Bazzocchi, Massimo; Del Frate, Chiara; Francescutti, Giuliana; Zuiani, Chiara; Puglisi, Fabio; Di Loreto, Carla

    2004-01-01

    The accuracy of mammography, sonography and magnetic resonance imaging (MRI) in identifying residual disease after neoadjuvant chemotherapy is evaluated and imaging findings are correlated with pathologic findings. Fifteen patients enrolled in an experimental protocol of preoperative neoadjuvant chemotherapy underwent clinical examination, mammography, sonography and dynamic MRI, performed in this order, before and respectively after 2 and 4 cycles of neoadjuvant chemotherapy. Four radiologists, two for mammography, one for sonography and one for MR, examined the images, blinded to the results of the other examinations. All patients underwent radical or conservative surgery, and imaging findings were compared with pathologic findings. MRI identified 2/15 (13.3.%) clinically complete response (CR), 9/15 (60%) partial response (PR), 3/15 (20%) stable disease (SD) and 1/15 (6.7%) progressive disease. Mammography identified 1/15 (6.7%) clinically CR, 8/15 (53.3%) PR and 4/15 (27%) SD, and was not able to evaluate the disease in 2/15 (13%) cases. Sonography presented the same results as MRI. Therefore, MRI and sonography compared to mammography correctly identified residual disease in 100 vs. 86%. MRI resulted in two false-negative results because of the presence of microfoci of in situ ductal carcinoma (DCIS) and invasive lobular carcinoma (LCI). MRI was superior to mammography in cases of multifocal or multicentric disease (83 vs. 33%). Sonography performed after MRI improves the accuracy in evaluation of uncertain foci of multifocal disease seen on MR images with an increase of diagnostic accuracy from 73 to 84.5%. MRI assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination and mammography. (orig.)

  6. Locally advanced breast cancer: comparison of mammography, sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Londero, Viviana; Bazzocchi, Massimo; Del Frate, Chiara; Francescutti, Giuliana; Zuiani, Chiara [Institute of Radiology, University of Udine, via Colugna 50, 33100, Udine (Italy); Puglisi, Fabio [Department of Oncology, University of Udine, via Colugna 50, 33100, Udine (Italy); Di Loreto, Carla [Institute of Pathology, University of Udine, via Colugna 50, 33100, Udine (Italy)

    2004-08-01

    The accuracy of mammography, sonography and magnetic resonance imaging (MRI) in identifying residual disease after neoadjuvant chemotherapy is evaluated and imaging findings are correlated with pathologic findings. Fifteen patients enrolled in an experimental protocol of preoperative neoadjuvant chemotherapy underwent clinical examination, mammography, sonography and dynamic MRI, performed in this order, before and respectively after 2 and 4 cycles of neoadjuvant chemotherapy. Four radiologists, two for mammography, one for sonography and one for MR, examined the images, blinded to the results of the other examinations. All patients underwent radical or conservative surgery, and imaging findings were compared with pathologic findings. MRI identified 2/15 (13.3.%) clinically complete response (CR), 9/15 (60%) partial response (PR), 3/15 (20%) stable disease (SD) and 1/15 (6.7%) progressive disease. Mammography identified 1/15 (6.7%) clinically CR, 8/15 (53.3%) PR and 4/15 (27%) SD, and was not able to evaluate the disease in 2/15 (13%) cases. Sonography presented the same results as MRI. Therefore, MRI and sonography compared to mammography correctly identified residual disease in 100 vs. 86%. MRI resulted in two false-negative results because of the presence of microfoci of in situ ductal carcinoma (DCIS) and invasive lobular carcinoma (LCI). MRI was superior to mammography in cases of multifocal or multicentric disease (83 vs. 33%). Sonography performed after MRI improves the accuracy in evaluation of uncertain foci of multifocal disease seen on MR images with an increase of diagnostic accuracy from 73 to 84.5%. MRI assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination and mammography. (orig.)

  7. MRI evaluation of residual breast cancer after neoadjuvant chemotherapy: influence of patient, tumor and chemotherapy characteristics on the correlation with pathological response.

    Science.gov (United States)

    Diguisto, Caroline; Ouldamer, Lobna; Arbion, Flavie; Vildé, Anne; Body, Gilles

    2015-01-01

    The aim of this study was to evaluate the correlation between the residual tumor measured on magnetic resonance imaging and pathological results and to assess whether this correlation varies according to patient, tumor or chemotherapy characteristics. The study population included women treated for breast cancer with indication of neoadjuvant chemotherapy in our tertiary breast cancer Unit between January 2008 and December 2011. Factors related to patients, tumor and chemotherapy were studied. Pearson's correlation coefficient between the size of the tumor on MRI and pathological response was calculated for the entire population. It was also calculated according to patient, tumor and chemotherapy characteristics. During the study period, 107 consecutive women were included. The size of residual tumor on the MRI significantly correlated with the size on pathological result with a Pearson correlation coefficient of 0.52 (pcorrelation was stronger for women aged 50 years and older (r=0.64, pcorrelation was stronger for those with triple-negative tumors (r=0.69, p=0.002) but weaker for those with tumors with a ductal carcinoma in situ component (r =0.18, p=0.42). The size of breast cancer obtained by MRI is significantly correlated to the pathological size of the tumor. This correlation was stronger among women aged 50 years and more, among post-menopausal women, and among women who had triple-negative tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. Early Prediction and Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy Using Quantitative DCE-MRI

    Directory of Open Access Journals (Sweden)

    Alina Tudorica

    2016-02-01

    Full Text Available The purpose is to compare quantitative dynamic contrast-enhanced (DCE magnetic resonance imaging (MRI metrics with imaging tumor size for early prediction of breast cancer response to neoadjuvant chemotherapy (NACT and evaluation of residual cancer burden (RCB. Twenty-eight patients with 29 primary breast tumors underwent DCE-MRI exams before, after one cycle of, at midpoint of, and after NACT. MRI tumor size in the longest diameter (LD was measured according to the RECIST (Response Evaluation Criteria In Solid Tumors guidelines. Pharmacokinetic analyses of DCE-MRI data were performed with the standard Tofts and Shutter-Speed models (TM and SSM. After one NACT cycle the percent changes of DCE-MRI parameters Ktrans (contrast agent plasma/interstitium transfer rate constant, ve (extravascular and extracellular volume fraction, kep (intravasation rate constant, and SSM-unique τi (mean intracellular water lifetime are good to excellent early predictors of pathologic complete response (pCR vs. non-pCR, with univariate logistic regression C statistics value in the range of 0.804 to 0.967. ve values after one cycle and at NACT midpoint are also good predictors of response, with C ranging 0.845 to 0.897. However, RECIST LD changes are poor predictors with C = 0.609 and 0.673, respectively. Post-NACT Ktrans, τi, and RECIST LD show statistically significant (P < .05 correlations with RCB. The performances of TM and SSM analyses for early prediction of response and RCB evaluation are comparable. In conclusion, quantitative DCE-MRI parameters are superior to imaging tumor size for early prediction of therapy response. Both TM and SSM analyses are effective for therapy response evaluation. However, the τi parameter derived only with SSM analysis allows the unique opportunity to potentially quantify therapy-induced changes in tumor energetic metabolism.

  9. Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

    NARCIS (Netherlands)

    Schmitz, Alexander M Th; Teixeira, Suzana C; Pengel, Kenneth E; Loo, Claudette E; Vogel, Wouter V; Wesseling, Jelle; Rutgers, Emiel J Th; Valdés Olmos, Renato A; Sonke, Gabe S; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T F D; Gilhuijs, Kenneth G A

    2017-01-01

    PURPOSE: To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. MATERIALS AND METHODS: In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and

  10. Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Bajpai, Jyoti; Bakhshi, Sameer [Dr. B. R. A. Institute Rotary Cancer Hospital, Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi (India); Gamnagatti, Shivanand [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India); Kumar, Rakesh; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Sreenivas, Vishnubhatla [All India Institute of Medical Sciences, Department of Biostatistics, New Delhi (India); Sharma, Mehar Chand; Safaya, Rajni [All India Institute of Medical Sciences, Department of Pathology, New Delhi (India); Khan, Shah Alam; Rastogi, Shishir [All India Institute of Medical Sciences, Department of Orthopedics, New Delhi (India)

    2011-04-15

    Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naive osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response {>=}90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma. (orig.)

  11. Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

    International Nuclear Information System (INIS)

    Bajpai, Jyoti; Bakhshi, Sameer; Gamnagatti, Shivanand; Kumar, Rakesh; Malhotra, Arun; Sreenivas, Vishnubhatla; Sharma, Mehar Chand; Safaya, Rajni; Khan, Shah Alam; Rastogi, Shishir

    2011-01-01

    Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naive osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma. (orig.)

  12. Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

    NARCIS (Netherlands)

    Schmitz, Alexander M. Th; Teixeira, Suzana C.; Pengel, Kenneth E.; Loo, Claudette E.; Vogel, Wouter V.; Wesseling, Jelle; Rutgers, Emiel J. Th; Valdés Olmos, Renato A.; Sonke, Gabe S.; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T. F. D.; Gilhuijs, Kenneth G. A.

    2017-01-01

    To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and 18F-FDG-PET/CT were acquired

  13. Evidence-based guideline recommendations on treatment strategies for localized Ewing's sarcoma of bone following neo-adjuvant chemotherapy.

    Science.gov (United States)

    Werier, Joel; Yao, Xiaomei; Caudrelier, Jean-Michel; di Primio, Gina; Ghert, Michelle; Gupta, Abha A; Kandel, Rita; Verma, Shailendra

    2016-06-01

    (1) To provide recommendations regarding the choice of surgery, radiation therapy (RT), or the combination of surgery plus RT in patients with localized Ewing's sarcoma of bone following neoadjuvant chemotherapy. (2) To determine the appropriate surgical planning imaging (pre-chemotherapy magnetic resonance imaging [MRI] or post-chemotherapy MRI) to identify optimal resection margins in patients with localized Ewing's sarcoma who undergo surgery following neoadjuvant chemotherapy. MEDLINE, EMBASE, the Cochrane Library (1999 to February 2015), main guideline websites, and relevant annual meeting abstracts (2012 to January 2015) were searched. Internal and external reviews were conducted. 1. Recommendation (1) - In patients with localized Ewing's sarcoma of bone following neoadjuvant chemotherapy: (a) Surgery alone or RT alone are two reasonable treatment options; the combination of surgery plus RT is not recommended as an initial treatment option. (b) The local treatment for an individual patient should be decided by a multidisciplinary tumour board together with the patient after consideration of the following: (1) patient characteristics (e.g., age, tumour location, tumour size, response to neoadjuvant chemotherapy, and existing comorbidities), (2) the potential benefit weighed against the potential complications from surgery and/or toxicities associated with RT, and (3) patient preferences. 2. Recommendation (2) - In patients with localized Ewing's sarcoma who will undergo surgery: (a) Both pre-chemotherapy and post-chemotherapy MRI scans should be taken into consideration for surgical planning. In certain anatomic locations with good chemotherapy response, the post-chemotherapy MRI may be the appropriate imaging modality to plan surgical resection margins. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Effect of Imaging Parameter Thresholds on MRI Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes.

    Directory of Open Access Journals (Sweden)

    Wei-Ching Lo

    Full Text Available The purpose of this study is to evaluate the predictive performance of magnetic resonance imaging (MRI markers in breast cancer patients by subtype. Sixty-four patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy were enrolled in this study. Each patient received a dynamic contrast-enhanced (DCE-MRI at baseline, after 1 cycle of chemotherapy and before surgery. Functional tumor volume (FTV, the imaging marker measured by DCE-MRI, was computed at various thresholds of percent enhancement (PEt and signal-enhancement ratio (SERt. Final FTV before surgery and percent changes of FTVs at the early and final treatment time points were used to predict patients' recurrence-free survival. The full cohort and each subtype defined by the status of hormone receptor and human epidermal growth factor receptor 2 (HR+/HER2-, HER2+, triple negative were analyzed. Predictions were evaluated using the Cox proportional hazard model when PEt changed from 30% to 200% in steps of 10% and SERt changed from 0 to 2 in steps of 0.2. Predictions with high hazard ratios and low p-values were considered as strong. Different profiles of FTV as predictors for recurrence-free survival were observed in each breast cancer subtype and strong associations with survival were observed at different PEt/SERt combinations that resulted in different FTVs. Findings from this retrospective study suggest that the predictive performance of imaging markers based on FTV may be improved with enhancement thresholds being optimized separately for clinically-relevant subtypes defined by HR and HER2 receptor expression.

  15. The assessment of breast cancer response to neoadjuvant chemotherapy: comparison of magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Park, Jeong Seon; Moon, Woo Kyung; Lyou, Chae Yeon; Cho, Nariya; Kang, Keon Wook; Chung, June-Key

    2011-01-01

    Background: Neoadjuvant chemotherapy for locally advanced breast cancer is a widely accepted treatment. For assessment of the tumor response after chemotherapy, both magnetic resonance imaging (MRI) and 18 F-fluorodeoxyglucose positron emission tomography (PET) are promising methods. Purpose: To retrospectively compare MRI and PET in the assessment of tumor response to neoadjuvant chemotherapy for primary breast cancer with the pathologic response as the reference standard. Material and Methods: Between August 2006 and May 2008, 32 women with breast cancer underwent concurrent MRI and PET before and after neoadjuvant chemotherapy. For response assessment, we calculated the changes in the maximum diameters of the tumor (ΔDmax) on MRI, and the changes in the standard uptake values (ΔSUV) on PET. The correlation between the ΔDmax and ΔSUV was analyzed using Pearson's correlation coefficient. The correspondence rates between each imaging modality and pathologic assessment were calculated. For prediction of the pathologic complete response (pCR), the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analyzed using the McNemar test. Results: The pathologic assessment of tumor response to neoadjuvant chemotherapy identified eight complete responses (25.0%), 10 partial responses (31.2%), and 14 non-responses (43.8%). The change in size on MRI was moderately correlated with the change in SUV on PET (r = 0.574, p = 0.001). The correspondence rate of response assessment was 75.0% (24/32) between MRI and pathologic response and 53.1% (17/32) between PET and pathologic response. For the pCR, specificity (95.8% vs. 62.5%) and PPV (83.3% vs. 47.1%) were statistically higher on MRI than PET (p < 0.05), while sensitivity (100.0% vs. 62.5%) and NPV (100.0% vs. 88.5%) on PET tended to be higher than MRI. Conclusion: Before and after neoadjuvant chemotherapy for breast cancer, the ΔDmax of MRI correlated moderately with the

  16. Soft Tissue Sarcoma Response to Two Cycles of Neoadjuvant Chemotherapy: A Multireader Analysis of MRI Findings and Agreement with RECIST Criteria and Change in SUVmax.

    Science.gov (United States)

    Favinger, Jennifer L; Hippe, Daniel S; Davidson, Darin J; Elojeimy, Saeed; Roth, Eira S; Lindberg, Antoinette W; Ha, Alice S

    2018-04-01

    When soft tissue sarcomas are treated with neoadjuvant chemotherapy, the number of cycles of chemotherapy is usually dependent on the tumor's initial response. Popular methods to assess tumor response include Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which rely solely on tumor size, and maximum standardized uptake value (SUVmax) reduction in positron emission tomography (PET), which requires an expensive and high radiation test. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI) may offer a good alternative by providing additional information beyond tumor size. Following IRB approval, a retrospective review identified patients with soft tissue sarcomas who underwent both PET and MRI before and after two cycles of neoadjuvant chemotherapy. Five readers independently examined the MRI exams for: changes in size, T2 or T1 signal, necrosis and degree of enhancement. Readers then made a subjective binary assessment of tumor response to therapy. Each reader repeated the anonymized randomized reading at least 2 weeks apart. 18 F-FDG PET exams were interpreted by a nuclear medicine specialist. The maximum standardized uptake values (SUVmax) for pre and post-chemotherapy exams were compared. Intra- and inter-reader agreement was assessed using Cohen's kappa and Light's kappa, respectively. . Twenty cases were selected for this multireader study, of which 9 (45%) were responders and 11 were nonresponders by SUVmax. Using all MRI criteria, 43% were classified as responders based on MRI and 1.5% were classified as responders by RECIST criteria. Using PET as the reference, the sensitivity and the specificity of the MRI diagnosis for response using all findings were 50% and 63%, respectively. There was fair to moderate intrareader (kappa = 0.37) and inter-reader (kappa = 0.48) agreement for the MRI diagnosis of response. None of the individual MRI signal characteristics were significantly different between the PET responders and

  17. Evaluation of static and dynamic MRI for assessing response of bone sarcomas to preoperative chemotherapy: Correlation with histological necrosis

    International Nuclear Information System (INIS)

    Amit, Priyadarshi; Malhotra, Atul; Kumar, Rahul; Kumar, Lokesh; Patro, Dilip Kumar; Elangovan, Sundar

    2015-01-01

    Preoperative chemotherapy plays a key role in management of bone sarcomas. Postoperative evaluation of histological necrosis has been the gold standard method of assessing response to preoperative chemotherapy. This study was done to evaluate the efficacy of static and dynamic magnetic resonance imaging (MRI) for assessing response preoperatively. Our study included 14 patients (12 osteosarcomas and 2 malignant fibrous histiocytomas) with mean age of 21.8 years, treated with preoperative chemotherapy followed by surgery. They were evaluated with static and dynamic MRI twice, before starting chemotherapy and again prior to surgery. Change in tumor volume and slope of signal intensity - time curve were calculated and correlated with percentage of histological necrosis using Pearson correlation test. The change in dynamic MRI slope was significant (P = 0.001). Also, ≥60% reduction in slope of the curve proved to be an indicator of good histological response [positive predictive value (PPV) =80%]. Change in tumor volume failed to show significant correlation (P = 0.071). Although it showed high negative predictive value (NPV = 85.7%), PPV was too low (PPV = 57.14%). Dynamic MRI correctly predicts histological necrosis after administration of preoperative chemotherapy to bone sarcomas. Hence, it can be used as a preoperative indicator of response to neoadjuvant chemotherapy. On the other hand, volumetric assessment by static MRI is not an effective predictor of histological necrosis. This study proves the superiority of dynamic contrast-enhanced study over volumetric study by MRI

  18. Race is associated with completion of neoadjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Knisely, Anne T; Michaels, Alex D; Mehaffey, J Hunter; Hassinger, Taryn E; Krebs, Elizabeth D; Brenin, David R; Schroen, Anneke T; Showalter, Shayna L

    2018-05-03

    Completion of prescribed neoadjuvant chemotherapy for breast cancer is paramount to patients obtaining full benefit from the treatment; however, factors affecting neoadjuvant chemotherapy completion are not known. We hypothesized that race is a predictor of completion of neoadjuvant chemotherapy in patients with breast cancer. All patients with breast cancer treated with neoadjuvant chemotherapy 2009-2016 at a single institution were stratified by completion of neoadjuvant chemotherapy and by race. Univariate analysis and multivariable logistic regression were used to identify patient and tumor characteristics that affected the rate of neoadjuvant chemotherapy completion. A total of 92 (74%) of 124 patients completed their prescribed neoadjuvant chemotherapy. On univariate analysis, white patients were more likely to complete neoadjuvant chemotherapy than non-white patients (76% vs 50%, P = .006). Non-white patients were more likely to have government insurance and larger prechemotherapy tumors (both, P < .05), but these factors were not associated with rates of neoadjuvant chemotherapy completion. After controlling for age, insurance status, tumor size, and estrogen receptor status, whites remained associated with completion of neoadjuvant chemotherapy (OR 3.65, P = .014). At our institution, white patients with breast cancer were more likely than non-white patients to complete neoadjuvant chemotherapy. Further investigation into the underlying factors impacting this disparity is needed. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI.

    Science.gov (United States)

    Panzeri, M M; Losio, C; Della Corte, A; Venturini, E; Ambrosi, A; Panizza, P; De Cobelli, F

    2018-01-01

    To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (BC). 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC), T2 signal intensity, and the following dynamic parameters: k -trans, peak enhancement, area under curve (AUC), time to maximal enhancement (TME), wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis). Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria) were assessed. Out of 69 tumors, 33 (47.8%) achieved complete pathological response, 26 (37.7%) partial response, and 10 (14.5%) no response. Higher levels of AUCmax ( p value = 0.0338), AUCrange ( p value = 0.0311), and TME 75 ( p value = 0.0452) and lower levels of washout 10 ( p value = 0.0417), washout 20 ( p value = 0.0138), washout 25 ( p value = 0.0114), and washout 30 ( p value = 0.05) were predictive of noncomplete response. Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC.

  20. Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy.

    Science.gov (United States)

    Sun, Zhipeng; Zhang, Nengwei

    2014-12-29

    In the clinical practice of neoadjuvant chemotherapy, response markers are very important. We aimed o investigate whether tumor markers CEA(carcino-embryonic antigen), CA19-9(carbohydrate antigen 19-9), CA72-4(carbohydrate antigen 72-4), and CA125(carbohydrate antigen 125) can be used to evaluate the response to neoadjuvant chemotherapy, and to evaluate the diagnosis and prognosis value of four tumor markers in the patients of gastric cancer. A retrospective review was performed of 184 gastric cancer patients who underwent a 5-Fu, leucovorin, and oxaliplatin (FOLFOX) neoadjuvant chemotherapy regimen, followed by surgical treatment. Blood samples for CEA, CA19-9, CA72-4, and CA125 levels were taken from patients upon admission to the hospital and after neoadjuvant chemotherapy. Statistical analysis was performed to identify the clinical value of these tumor markers in predicting the survival and the response to neoadjuvant chemotherapy. Median overall survival times of pretreatment CA19-9-positive and CA72-4-positive patients (14.0 +/-2.8 months and 14.8 +/-4.0 months, respectively) were significantly less than negative patients (32.5 +/-8.9 months and 34.0 +/-10.1 months, respectively) (P = 0.000 and P = 0.002, respectively). Pretreatment status of CA19-9 and CA72-4 were independent prognostic factors in gastric cancer patients (P = 0.029 and P = 0.008, respectively). Pretreatment CEA >50 ng/ml had a positive prediction value for clinical disease progression after neoadjuvant chemotherapy according to the ROC curve (AUC: 0.694, 95% CI: 0.517 to 0.871, P = 0.017). The decrease of tumor markers CEA, CA72-4, and CA125 was significant after neoadjuvant chemotherapy (P = 0.030, P = 0.010, and P = 0.009, respectively), especially in patients with disease control (including complete, partial clinical response, and stable disease) (P = 0.012, P = 0.020, and P = 0.025, respectively). A decrease in CA72-4 by more than 70% had

  1. Noninvasive assessment of response to neoadjuvant chemotherapy in osteosarcoma of long bones with diffusion-weighted imaging: an initial in vivo study.

    Directory of Open Access Journals (Sweden)

    Cheng-Sheng Wang

    Full Text Available OBJECTIVES: The purpose of our study is to investigate whether diffusion-weighted imaging (DWI is useful for monitoring the therapeutic response after neoadjuvant chemotherapy in osteosarcoma of long bones. MATERIALS AND METHODS: Conventional magnetic resonance imaging (MRI and DWI were obtained from 35 patients with histologically proven osteosarcomas. MR examinations were performed in all patients before and after 4 courses of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC were measured. The degree of tumor necrosis was assessed macroscopically and histologically by two experienced pathologists after operation. Student's t test was performed for testing changes in ADC value. Pearson's correlation coefficient was used to estimate the correlation between necrosis rate and post- neoadjuvant chemotherapy ADC values. P<0.05 was considered to denote a significant difference. RESULTS: The difference of the whole osteosarcoma between pre- neoadjuvant chemotherapy ADC value (1.24±0.17×10(-3 mm(2/s and post- (1.93±0.39×10(-3 mm(2/s was significant difference (P<0.01. Regarding in patients with good response, the post- neoadjuvant chemotherapy values were significantly higher than the pre- neoadjuvant chemotherapy values (P<0.01. The post- neoadjuvant chemotherapy ADC value in patients with good response was higher than that of poor response (t = 8.995, P<0.01. The differences in post- neoadjuvant chemotherapy ADC between viable (1.03±0.17×10(-3 mm(2/s and necrotic (2.38±0.25×10(-3 mm(2/s tumor was highly significant (t = 23.905, P<0.01. A positive correlation between necrosis rates and the whole tumor ADC values (r = 0.769, P<0.01 was noted, but necrosis rates were not correlated with the ADC values of necrotic (r = -0.191, P = 0.272 and viable tumor areas (r = 0.292, P = 0.089. CONCLUSIONS: DWI can identify residual viable tumor tissues and tumor necrosis induced by neoadjuvant

  2. Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Pickles, Martin D.; Manton, David J.; Lowry, Martin; Turnbull, Lindsay W.

    2009-01-01

    The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

  3. Prognostic value of pre-treatment DCE-MRI parameters in predicting disease free and overall survival for breast cancer patients undergoing neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Pickles, Martin D. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.pickles@hull.ac.uk; Manton, David J. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: d.j.manton@hull.ac.uk; Lowry, Martin [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: m.lowry@hull.ac.uk; Turnbull, Lindsay W. [Centre for Magnetic Resonance Investigations, Division of Cancer, Postgraduate Medical School, University of Hull, Hull Royal Infirmary, Anlaby Road, Hull, HU3 2JZ (United Kingdom)], E-mail: l.w.turnbull@hull.ac.uk

    2009-09-15

    The purpose of this study was to investigate whether dynamic contrast enhanced MRI (DCE-MRI) data, both pharmacokinetic and empirical, can predict, prior to neoadjuvant chemotherapy, which patients are likely to have a shorter disease free survival (DFS) and overall survival (OS) interval following surgery. Traditional prognostic parameters were also included in the survival analysis. Consequently, a comparison of the prognostic value could be made between all the parameters studied. MR examinations were conducted on a 1.5 T system in 68 patients prior to the initiation of neoadjuvant chemotherapy. DCE-MRI consisted of a fast spoiled gradient echo sequence acquired over 35 phases with a mean temporal resolution of 11.3 s. Both pharmacokinetic and empirical parameters were derived from the DCE-MRI data. Kaplan-Meier survival plots were generated for each parameter and group comparisons were made utilising logrank tests. The results from the 54 patients entered into the univariate survival analysis demonstrated that traditional prognostic parameters (tumour grade, hormonal status and size), empirical parameters (maximum enhancement index, enhancement index at 30 s, area under the curve and initial slope) and adjuvant therapies demonstrated significant differences in survival intervals. Further multivariate Cox regression survival analysis revealed that empirical enhancement parameters contributed the greatest prediction of both DFS and OS in the resulting models. In conclusion, this study has demonstrated that in patients who exhibit high levels of perfusion and vessel permeability pre-treatment, evidenced by elevated empirical DCE-MRI parameters, a significantly lower disease free survival and overall survival can be expected.

  4. Hybrid 18F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Goorts, Briete; Nijnatten, Thiemo J.A. van; Voeoe, Stefan; Wildberger, Joachim E.; Lobbes, Marc B.I.; Kooreman, Loes F.S.; Boer, Maaike de; Keymeulen, Kristien B.M.I.; Aarnoutse, Romy; Smidt, Marjolein L.; Mottaghy, Felix M.

    2017-01-01

    Our purpose in this study was to assess the added clinical value of hybrid 18 F-FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed. A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed. Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients. (orig.)

  5. Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    Avendano Juan; Buitrago, Giancarlo; Ramos, Pedro; Suescun Oscar

    2010-01-01

    Objective: To describe the experience at the National Cancer Institute (NCI) on the use of neoadjuvant chemotherapy as primary treatment for epithelial ovarian cancer among patients in stages IIIC and IV. Methods: We conducted a descriptive retrospective study (case series type) of patients diagnosed with epithelial ovarian cancer in stages IIIC and IV, treated at the NCI from January 1, 2003 to December 31,2006, who underwent neoadjuvant chemotherapy as primary treatment. Demographic characteristics and clinical outcomes are described. Results: Seventeen patients who fulfilled the above mentioned criteria were selected. Once neoadjuvant chemotherapy ended, 5 patients (29.4%) achieved complete or partial clinical response; 4 (23.8%) remained in stable condition, and 8 (47.6%) showed signs of progressive illness. Interval debulking surgery was performed on objective response patients. Maximum cytoreduction was achieved in 5 patients (100%); first relapse was reported at month 18 of follow-up; 2 disease-free survivors were identified in December, 2007; 8 (49%) reported some degree of non-severe chemotherapy-related toxicity. No mortality was related to chemotherapy, no post surgical complications were observed and no patient required advanced support management. Conclusions: Neoadjuvant chemotherapy, followed by optimal interval debulking surgery among selected patients, can be an alternative treatment for advanced epithelial ovarian cancer among women with irresecability or the critically ill. Further studies with improved design are required to confirm these findings.

  6. Assessment of the responses to neoadjuvant chemotherapy of osteosarcoma by diffusion-weighted MR image: initial results

    International Nuclear Information System (INIS)

    Shu Min; Du Lianjun; Ding Xiaoyi; Lu Yong; Yan Ling; Jiang Hao; Chen Kemin

    2009-01-01

    Objective: To determine the utility of diffusion-weighted magnetic resonance imaging (MR DWI) in detecting tumor necrosis with histological correlation after neoadjuvant chemotherapy. Methods: Conventional MRI and DWI were obtained from 36 patients with histological proven osteosarcoma. Magnetic resonance examinations were performed in all patients before and after 4 cycles of preoperative neoadjuvant chemotherapy. Apparent diffusion coefficients (ADC) were calculated. The degree of tumor necrosis was assessed using the histological Huvos classification after chemotherapy. t-test was performed for testing changes in ADC value between the 2 groups. P value less than 0.05 were considered as a statistically significant difference. Results: The differences in ADC between viable [(1.06 ± 0.30)x10 -3 mm 2 /s] and necrotic [(2.39 ± 0.44)x10 -3 mm 2 /s] tumor were significant (t = 3.515, P -3 mm 2 /s to (2.27 ± 0.20)x10 -3 mm 2 s, the corresponding value in poor responses was increased from (1.45 ± 0.11)x10 -3 mm 2 /s to (1.83 ± 0.16)x10 -3 mm 2 /s. There was significant difference in changes of ADC values between good responses and poor responses (t = 4.981, P < 0.01). Conclusion: Diffusion-weighted MRI permits recognition of tumor necrosis induced by chemotherapy in osteosarcoma. DWI is correlated directly with tumor necrosis. They have potential utility in evaluating the preoperative chemotherapy response in patients with primary osteosarcoma. (authors)

  7. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

  8. Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI

    Directory of Open Access Journals (Sweden)

    M. M. Panzeri

    2018-01-01

    Full Text Available Purpose. To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC for locally advanced breast cancer (BC. Materials and Methods. 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC, T2 signal intensity, and the following dynamic parameters: k-trans, peak enhancement, area under curve (AUC, time to maximal enhancement (TME, wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis. Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria were assessed. Results. Out of 69 tumors, 33 (47.8% achieved complete pathological response, 26 (37.7% partial response, and 10 (14.5% no response. Higher levels of AUCmax (p value = 0.0338, AUCrange (p value = 0.0311, and TME75 (p value = 0.0452 and lower levels of washout10 (p value = 0.0417, washout20 (p value = 0.0138, washout25 (p value = 0.0114, and washout30 (p value = 0.05 were predictive of noncomplete response. Conclusion. Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC.

  9. Neoadjuvant chemotherapy in locally advanced colon cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

    2015-01-01

    BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...... 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005). CONCLUSION: Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted....

  10. Hybrid {sup 18}F-FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Goorts, Briete; Nijnatten, Thiemo J.A. van [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); Voeoe, Stefan; Wildberger, Joachim E.; Lobbes, Marc B.I. [Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); Kooreman, Loes F.S. [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Pathology, Maastricht (Netherlands); Boer, Maaike de [Maastricht University Medical Center, Department of Medical Oncology, Maastricht (Netherlands); Keymeulen, Kristien B.M.I. [Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Aarnoutse, Romy; Smidt, Marjolein L. [Maastricht University Medical Center, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Maastricht University Medical Center, Department of Surgery, P.O. Box 5800, Maastricht (Netherlands); Mottaghy, Felix M. [Maastricht University Medical Center, Department of Radiology and Nuclear Medicine, Maastricht (Netherlands); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany)

    2017-10-15

    Our purpose in this study was to assess the added clinical value of hybrid {sup 18}F-FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed. A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed. Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients. (orig.)

  11. Pathological response for neoadjuvant chemotherapy in locally ...

    African Journals Online (AJOL)

    Background: Breast cancer is the leading cancer in Sudanese females. Objectives: This study was done to evaluate the clinical response to neoadjuvant chemotherapy for patients treated at National Cancer Institute (NCI) and to compare it with the published literature. Methods: This is a retrospective study conducted in ...

  12. Exploring patient experiences of neo-adjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Beaver, Kinta; Williamson, Susan; Briggs, Jean

    2016-02-01

    Neo-adjuvant chemotherapy is recommended for 'inoperable' locally advanced and inflammatory breast cancers. For operable breast cancers, trials indicate no survival differences between chemotherapy given pre or post-surgery. Communicating evidence based information to patients is complex and studies examining patient experiences of neo-adjuvant chemotherapy are lacking. This study aims to explore the experiences of women who received neo-adjuvant chemotherapy for breast cancer. A qualitative approach using in-depth interviews with 20 women who had completed neo-adjuvant chemotherapy for breast cancer. Interview data were analysed using thematic analysis. The sample included a relatively young group of women, with caring responsibilities. Five main themes emerged: coping with the rapid transition from 'well' to 'ill', information needs and decision making, needing support and empathy, impact on family, and creating a new 'normal'. More support was needed towards the end of chemotherapy, when side effects were at their most toxic, and decisions about forthcoming surgery were being made. Some women were referred to psychological services, but usually when a crisis point had been reached. Information and support would have been beneficial at key time points. This information is vital in developing services and interventions to meet the complex needs of these patients and potentially prevent late referral to psychological services. Specialist oncology nurses are able to develop empathetic relationships with patients and have the experience, knowledge and skills to inform and support women experiencing neo-adjuvant chemotherapy. Targeting key time points and maintaining relationship throughout neo-adjuvant chemotherapy would be highly beneficial. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Evaluation of Sentinel Node Biopsy in Locally Advanced Breast Cancer Patients Who Become Clinically Node-Negative after Neoadjuvant Chemotherapy: A Preliminary Study

    International Nuclear Information System (INIS)

    Thomas, Sh.; Prakash, A.; Goyal, V.; Agarwal, Sh.; Choudhury, M.; Popli, M.B.

    2011-01-01

    Introduction. Controversy continues over the appropriate timing of sentinel lymph node (SLN) biopsy in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy. We evaluated the feasibility and accuracy of SLN biopsy in LABC patients with cytology-proven axillary nodal metastasis who become clinically node-negative after neoadjuvant chemotherapy. Materials. 30 consecutive patients with LABC, who had become clinically node-negative after 3 cycles of neoadjuvant chemotherapy, were included in the study. They were then subjected to SLN biopsy, axillary lymph node dissection, and breast surgery. Results. Sentinel nodes were successfully identified in 26 of the 30 patients, resulting in an identification rate of 86.67%, sensitivity of 83.33%, false negative rate of 20%, negative predictive value of 72.73%, and an overall accuracy of 88.46%. No complications were observed as a result of dye injection. Conclusions. SLN biopsy is feasible and safe in LABC patients with cytology-positive nodes who become clinically node-negative after neoadjuvant chemotherapy. Our accuracy rate, identification rate, and false negative rate are comparable to those in node-negative LABC patients. SLN biopsy as a therapeutic option in LABC after neoadjuvant chemotherapy is a promising option which should be further investigated

  14. Neoadjuvant chemotherapy and radiotherapy in locally advanced hypopharyngeal cancer

    International Nuclear Information System (INIS)

    Kim, Su Zy; Wu, Hong Gyun; Heo, Dae Seog; Park, Cham II

    2000-01-01

    To see the relationship between the response to chemotherapy and the final outcome of neoadjuvant chemotherapy and radiotherapy in patients with locally advanced hypopharyngeal cancer. A retrospective analysis was done for thirty-two patients with locally advanced hypopharyngeal cancer treated in the Seoul National University Hospital with neoadjuvant chemotherapy and radiotherapy from August 1979 to July 1997. The patients were treated with Co-60 teletherapy unit or 4MV or 6MV photon beam produced by linear accelerator. Daily fractionation was 1.75 to 2 Gy, delivered five times a week. Total dose ranged from 60.8 Gy to 73.8 Gy. Twenty-nine patients received continuous infusion of cisplatin and 5-FU. Other patients were treated with cisplatin combined with bleomycin or vinblastin. Twenty-four (75%) patients received all three prescribed cycles of chemotherapy delivered three weeks apart. Six patients received two cycles, and two patients received only one cycle. The overall 2-year and 5-year survival rates are 65.6% and 43.0, respectively. 5-year local control rate is 34%. Organ preservation for more than five years is achieved in 12 patients (38%). After neoadjuvant chemotherapy, 24 patients achieved more than partial remission (PR); the response rate was 75% (24/32). Five patients had complete remission (CR), 19 patients PR, and 8 patients no response (NR). Among the 19 patients who had PR to chemotherapy, 8 patients achieved CR after radiotherapy. Among the 8 non-responders to chemotherapy, 2 patients achieved CR, and 6 patients achieved PR after radiotherapy, There was no non-responder after radiotherapy. The overall survival rates were 60% for CR to chemotherapy group, 35.1 % for PR to chemotherapy group, and 50% for NR to chemotherapy group. respectively (p=0.93). There were significant difference in five-year overall survival rates between the patients with CR and PR after neoadjuvant chemotherapy and radiotherapy (73.3% vs. 14.7%, p< 0.01). The prognostic

  15. Combined use of 18F-FDG PET/CT and MRI for response monitoring of breast cancer during neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Pengel, Kenneth E.; Loo, Claudette E.; Koolen, Bas B.; Vogel, Wouter V.; Valdes Olmos, Renato A.; Wesseling, Jelle; Lips, Esther H.; Rutgers, Emiel J.T.; Vrancken Peeters, Marie Jeanne T.F.D.; Rodenhuis, Sjoerd; Gilhuijs, Kenneth G.A.

    2014-01-01

    To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype. We performed 18 F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in 18 F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses. Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p = 0.033), breast cancer subtype (p < 0.001), relative change in SUVmax on PET/CT (p < 0.001) and relative change in largest tumour diameter on MRI (p < 0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95 % CI 0.68-0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95 % CI 0.70-0.89). The AUC increased to 0.90 (95 % CI 0.83-0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p = 0.012). PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype. (orig.)

  16. Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis.

    Science.gov (United States)

    Passot, Guillaume; Vaudoyer, Delphine; Cotte, Eddy; You, Benoit; Isaac, Sylvie; Noël Gilly, François; Mohamed, Faheez; Glehen, Olivier

    2012-07-01

    The objective of this retrospective study was to evaluate the influence of neoadjuvant systemic chemotherapy on patients with colorectal carcinomatosis before a curative procedure. Peritoneal carcinomatosis (PC) from colorectal cancer may be treated with a curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The role of perioperative systemic chemotherapy for this particular metastatic disease remains unclear. One hundred twenty patients with PC from colorectal cancer were consecutively treated by 131 procedures combining CRS with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on data from previous explorative surgery and/or radiological imaging. Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom 32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19 (21%) developed diseases progression. Response could not be evaluated in 20 patients (22%). On univariate analysis, the use of neoadjuvant systemic chemotherapy had a significant positive prognostic influence (P = 0.042). On multivariate analysis, the completeness of CRS and the use of adjuvant systemic chemotherapy were the only significant prognostic factors (P systemic chemotherapy had no significant prognostic impact with median survival of 31.4 months in patients showing disease progression. In patients with PC from colorectal cancer without extraperitoneal metastases, failure of neoadjuvant systemic chemotherapy should not constitute an absolute contraindication to a curative procedure combining CRS and HIPEC.

  17. The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery.

    Science.gov (United States)

    Saunders, John H; Bowman, Christopher R; Reece-Smith, Alex M; Pang, Vincent; Dorrington, Matthew S; Mumtaz, Errum; Soomro, Irshad; Kaye, Philip; Madhusudan, Srinivasan; Parsons, Simon L

    2017-06-01

    For patients with operable esophagogastric cancer, peri-operative chemotherapy confers a significant overall survival benefit compared to surgery alone, however only 30-40% of patients demonstrate histopathological response. It is unclear whether those with no neoadjuvant chemotherapy response should go onto receive adjuvant chemotherapy, as no further benefit may be conferred. Esophagogastric cancers were prospectively captured with associated histopathological tumor regression grades following neoadjuvant chemotherapy. This cohort was then interrogated for clinico-pathological and survival outcomes. Following neoadjuvant chemotherapy and surgery, patients with chemotherapy responsive cancers, who were administered adjuvant chemotherapy gained a significant overall survival benefit. Multivariate Cox analysis, demonstrated a final adjusted hazard ratio for adjuvant therapy of 0.509; (95%CI 0.28-0.93); P = 0.028. In contrast, patients with non-responsive tumors, who underwent adjuvant chemotherapy, did not show any survival benefit. Chemotherapy toxicity was prevalent and contributed to only half of patients receiving adjuvant chemotherapy. These results suggest the benefit of the adjuvant portion of chemotherapy is limited to those who demonstrate a histopathological response to neoadjuvant chemotherapy. The administration of the adjuvant portion of chemotherapy to patients without a response to neoadjuvant chemotherapy may not provide any survival benefit, while potentially causing increased morbidity. © 2017 Wiley Periodicals, Inc.

  18. Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

    Science.gov (United States)

    van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

    2006-04-01

    Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

  19. MR-guided simultaneous integrated boost in preoperative radiotherapy of locally advanced rectal cancer following neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Seierstad, Therese; Hole, Knut Hakon; Saelen, Erik; Ree, Anne Hansen; Flatmark, Kjersti; Malinen, Eirik

    2009-01-01

    Purpose: To evaluate a simultaneous integrated boost (SIB) strategy in preoperative radiotherapy of rectal cancer patients following neoadjuvant chemotherapy using pre- and post-chemotherapy tumor volumes assessed by MRI. Materials and methods: Ten patients with locally advanced rectal cancer, receiving chemotherapy prior to radiotherapy, were included in this study. Pre- and post-chemotherapy MR tumor images were co-registered with CT images for IMRT planning. Three planning target volumes were defined: PTV risk , PTV pre c hemo and PTV post c hemo . For SIB, prescribed mean doses to the PTVs were 46, 50 and 58 Gy, respectively, given in 25 fractions. Organs at risk (OARs) were bladder and intestine. The novel three-volume SIB strategy was compared to a conventional two-volume SIB plan, in which PTV post c hemo was ignored, using dose-volume histograms (DVHs) and the generalized equivalent uniform dose (gEUD). Results: All patients showed tumor shrinkage following chemotherapy. For the novel SIB, population-based mean doses given to PTV risk , PTV pre c hemo and PTV post c hemo were 46.8 ± 0.3, 50.6 ± 0.4 and 58.1 ± 0.4 Gy, respectively. DVHs and gEUDs for PTV risk , PTV pre c hemo , bladder and intestine revealed minimal differences between the two SIB strategies. Conclusions: Tumor volume reduction for rectal cancer patients following neoadjuvant chemotherapy allows for increased tumor dose using a SIB strategy without increased OAR toxicity.

  20. Clinical Application of Magnetic Resonance Imaging in Management of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jeon-Hor Chen

    2013-01-01

    Full Text Available Neoadjuvant chemotherapy (NAC, also termed primary, induction, or preoperative chemotherapy, is traditionally used to downstage inoperable breast cancer. In recent years it has been increasingly used for patients who have operable cancers in order to facilitate breast-conserving surgery, achieve better cosmetic outcome, and improve prognosis by reaching pathologic complete response (pCR. Many studies have demonstrated that magnetic resonance imaging (MRI can assess residual tumor size after NAC, and that provides critical information for planning of the optimal surgery. NAC also allows for timely adjustment of administered drugs based on response, so ineffective regimens could be terminated early to spare patients from unnecessary toxicity while allowing other effective regimens to work sooner. This review article summarizes the clinical application of MRI during NAC. The use of different MR imaging methods, including dynamic contrast-enhanced MRI, proton MR spectroscopy, and diffusion-weighted MRI, to monitor and evaluate the NAC response, as well as how changes of parameters measured at an early time after initiation of a drug regimen can predict final treatment outcome, are reviewed. MRI has been proven a valuable tool and will continue to provide important information facilitating individualized image-guided treatment and personalized management for breast cancer patients undergoing NAC.

  1. Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

    Science.gov (United States)

    Cruz Ciria, S; Jiménez Aragón, F; García Mur, C; Esteban Cuesta, H; Gros Bañeres, B

    2014-01-01

    To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  2. Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gollub, M.J.; Gultekin, D.H.; Akin, O.; Do, R.K.; Fuqua, J.L. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States); Gonen, M.; Kuk, D. [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Weiser, M.; Paty, P.; Guillem, J.; Nash, G.M.; Temple, L. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, New York, NY (United States); Saltz, L. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, New York, NY (United States); Schrag, D. [Dana Farber Cancer Institute, Boston, MA (United States); Goodman, K. [Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States); Shia, J. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Schwartz, L.H. [Columbia University Medical Center/New York Presbyterian Hospital, Department of Radiology, New York, NY (United States)

    2012-04-15

    To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K{sup trans}, k{sub ep}, v{sub e}, AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P {<=} 0.05 was considered significant. Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K{sup trans} (mean 0.5 min{sup -1} vs. 0.2 min{sup -1}, P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. (orig.)

  3. Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Gollub, M.J.; Gultekin, D.H.; Akin, O.; Do, R.K.; Fuqua, J.L.; Gonen, M.; Kuk, D.; Weiser, M.; Paty, P.; Guillem, J.; Nash, G.M.; Temple, L.; Saltz, L.; Schrag, D.; Goodman, K.; Shia, J.; Schwartz, L.H.

    2012-01-01

    To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K trans , k ep , v e , AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P ≤ 0.05 was considered significant. Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K trans (mean 0.5 min -1 vs. 0.2 min -1 , P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. (orig.)

  4. Background parenchymal enhancement in breast MRI before and after neoadjuvant chemotherapy: correlation with tumour response

    Energy Technology Data Exchange (ETDEWEB)

    Preibsch, H.; Wanner, L.; Bahrs, S.D.; Wietek, B.M.; Nikolaou, K.; Wiesinger, B. [University Hospital Tuebingen, Diagnostic and Interventional Radiology, Tuebingen (Germany); Siegmann-Luz, K.C. [Diagnostic Center for Breast Cancer and Screening Mammography Brandenburg Ost, Koenigs Wusterhausen (Germany); Oberlecher, E.; Hahn, M. [University Hospital Tuebingen, Department of Gynecology and Obstetrics, Tuebingen (Germany); Staebler, A. [University Hospital Tuebingen, Institute of Pathology and Neuropathology, Tuebingen (Germany)

    2016-06-15

    To correlate the decrease in background parenchymal enhancement (BPE) and tumour response measured with MRI in breast cancer patients treated with neoadjuvant chemotherapy (NAC). One hundred and forty-six MRI examinations of 73 patients with 80 biopsy-proven breast cancers who underwent breast MRI before and after NAC were retrospectively analysed. All images were reviewed by two blinded readers, who classified BPE into categories (BEC; 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) before and after NAC. Histopathological and morphological tumour responses were analysed and compared. The distribution of BEC 1/2/3/4 was 25/46/18/11 % before and 78/20/2/0 % after NAC. On average, BPE decreased by 0.87 BEC. Cohen's kappa showed substantial agreement (k = 0.73-0.77) before and moderate agreement (k = 0.43-0.60) after NAC and moderate agreement (k = 0.62-0.60) concerning the change in BEC. Correlating the change in BPE with tumour response, the average decrease in BEC was 1.3 in cases of complete remission, 0.83 in cases with partial response, 0.85 in cases with stable disease and 0.40 in cases with progressive disease. Correlation analysis showed a significant correlation between the decrease in BEC and tumour response (r = -0.24, p = 0.03). BPE decreased by, on average, 0.87 BEC following NAC for breast cancer. The degree of BPE reduction seemed to correlate with tumour response. (orig.)

  5. Prediction of response to neoadjuvant chemotherapy in breast cancer: a radiomic study

    Science.gov (United States)

    Wu, Guolin; Fan, Ming; Zhang, Juan; Zheng, Bin; Li, Lihua

    2017-03-01

    Breast cancer is one of the most malignancies among women in worldwide. Neoadjuvant Chemotherapy (NACT) has gained interest and is increasingly used in treatment of breast cancer in recent years. Therefore, it is necessary to find a reliable non-invasive assessment and prediction method which can evaluate and predict the response of NACT. Recent studies have highlighted the use of MRI for predicting response to NACT. In addition, molecular subtype could also effectively identify patients who are likely have better prognosis in breast cancer. In this study, a radiomic analysis were performed, by extracting features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and immunohistochemistry (IHC) to determine subtypes. A dataset with fifty-seven breast cancer patients were included, all of them received preoperative MRI examination. Among them, 47 patients had complete response (CR) or partial response (PR) and 10 had stable disease (SD) to chemotherapy based on the RECIST criterion. A total of 216 imaging features including statistical characteristics, morphology, texture and dynamic enhancement were extracted from DCE-MRI. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.923 (P = 0.0002) in leave-one-out crossvalidation. The performance of the classifier increased to 0.960, 0.950 and 0.936 when status of HER2, Luminal A and Luminal B subtypes were added into the statistic model, respectively. The results of this study demonstrated that IHC determined molecular status combined with radiomic features from DCE-MRI could be used as clinical marker that is associated with response to NACT.

  6. Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive Intracranial Immature Teratoma.

    Science.gov (United States)

    Kitahara, Takahiro; Tsuji, Yoshihito; Shirase, Tomoyuki; Yukawa, Hiroyuki; Takeichi, Yasuhiro; Yamazoe, Naohiro

    2016-04-01

    Immature teratoma (IMT) is the most frequent histological subtype of infantile intracranial teratoma, the most common congenital brain tumor. IMT contains incompletely differentiated components resembling fetal tissues. Infantile intracranial IMT has a dismal prognosis, because it is often inoperable due to its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to be effective in decreasing tumor volume and vascularity to facilitate surgical resection in other types of infantile brain tumors. However, only one recent case report described the effectiveness of neoadjuvant chemotherapy for infantile intracranial IMT in the literature, even though it is common entity with a poor prognosis in infants. Here, we describe the case of a 2-month-old male infant with a very large intracranial IMT. Maximal surgical resection was first attempted but was unsuccessful because of severe intraoperative hemorrhage. Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered with the aim of shrinking and devascularizing the tumor. After neoadjuvant chemotherapy, tumor size did not decrease, but intraoperative blood loss significantly decreased and near-total resection was achieved by the second and third surgery. The patient underwent adjuvant CARE chemotherapy and has been alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant chemotherapy does not decrease tumor volume of infantile intracranial IMT, surgical resection should be tried because chemotherapy can facilitate surgical resection and improve clinical outcome by reducing tumor vascularity.

  7. Neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs

    International Nuclear Information System (INIS)

    Ramos, Pedro; Gonzalez, Manuel; Perry, Fernando; Cardona, Andres Felipe

    2005-01-01

    Background: the use of neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs continues to be an area of controversy; however, the number of clinical studies favoring the use of an anthracycline and iphosphamide-based regimen is increasing steadily. This approach may provide some advantages for facilitating the surgical resection of the tumor and for local disease control. The historical 5-year survival rate of approximately 50% in this high-risk group treated with local therapy alone represents a poor standard of care; thus, there is a need to incorporate systemic therapy early in the management of these patients. Objective: to describe the role of neoadjuvant chemotherapy in the treatment of soft-tissue sarcomas. Materials and methods: the records of 42 patients who attended the national cancer institute of Colombia in search for management of primary soft-tissue sarcomas were retrospectively reviewed. Ten patients with high-grade tumors larger than 8 cm, treated from June 2000 to February 2002 with neoadjuvant chemotherapy based on an anthracycline and iphosphamide regimen, plus vincristin and cisplatinum in selected cases, followed by surgery and adjuvant therapy with chemotherapy combined with local radiotherapy, were included. Evaluations of objective tumor response, survival, and toxicity were carried out. Results: after neoadjuvant therapy, s ix patients underwent conservative and limb-salvage surgery, three required radical interventions, and one refused surgical treatment. Seven experienced an objective response: it was complete in four and partial in three; the disease kept stable in two patients, and the tumor progressed in one case. After an average 46-month follow-up, four patients were permanently free of disease. Hematological and gastrointestinal toxicity was remarkable, and no patient had a long-term morbidity related to the treatment. Conclusions: this limited retrospective review suggests an advantage for the use of

  8. Investigating the prediction value of multiparametric magnetic resonance imaging at 3 T in response to neoadjuvant chemotherapy in breast cancer

    International Nuclear Information System (INIS)

    Minarikova, Lenka; Bogner, Wolfgang; Zaric, Olgica; Trattnig, Siegfried; Gruber, Stephan; Pinker, Katja; Valkovic, Ladislav; Bago-Horvath, Zsuzsanna; Bartsch, Rupert; Helbich, Thomas H.

    2017-01-01

    To explore the predictive value of parameters derived from diffusion-weighted imaging (DWI) and contrast-enhanced (CE)-MRI at different time-points during neoadjuvant chemotherapy (NACT) in breast cancer. Institutional review board approval and written, informed consent from 42 breast cancer patients were obtained. The patients were investigated before and at three different time-points during neoadjuvant chemotherapy (NACT) using tumour diameter and volume from CE-MRI and ADC values obtained from drawn 2D and segmented 3D regions of interest. Prediction of pathologic complete response (pCR) was evaluated using the area under the curve (AUC) of receiver operating characteristic analysis. There was no significant difference between pathologic complete response and non-pCR in baseline size measures (p > 0.39). Diameter change was significantly different in pCR (p < 0.02) before the mid-therapy point. The best predictor was lesion diameter change observed before mid-therapy (AUC = 0.93). Segmented volume was not able to differentiate between pCR and non-pCR at any time-point. The ADC values from 3D-ROI were not significantly different from 2D data (p = 0.06). The best AUC (0.79) for pCR prediction using DWI was median ADC measured before mid-therapy of NACT. The results of this study should be considered in NACT monitoring planning, especially in MRI protocol designing and time point selection. (orig.)

  9. Investigating the prediction value of multiparametric magnetic resonance imaging at 3 T in response to neoadjuvant chemotherapy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Minarikova, Lenka; Bogner, Wolfgang; Zaric, Olgica; Trattnig, Siegfried; Gruber, Stephan [Medical University of Vienna, High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna (Austria); Pinker, Katja [Medical University of Vienna, Division of Molecular and Gender Imaging, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Memorial Sloan-Kettering Cancer Center, Molecular Imaging and Therapy Service, New York, NY (United States); Valkovic, Ladislav [Medical University of Vienna, High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); University of Oxford, John Radcliffe Hospital, Oxford Centre for Clinical Magnetic Resonance Research, Oxford (United Kingdom); Bago-Horvath, Zsuzsanna [Medical University of Vienna, Department of Pathology, Comprehensive Cancer Center, Vienna (Austria); Bartsch, Rupert [Medical University of Vienna, Clinical Division of Oncology, Department of Medicine I, Vienna (Austria); Helbich, Thomas H. [Medical University of Vienna, Division of Molecular and Gender Imaging, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria)

    2017-05-15

    To explore the predictive value of parameters derived from diffusion-weighted imaging (DWI) and contrast-enhanced (CE)-MRI at different time-points during neoadjuvant chemotherapy (NACT) in breast cancer. Institutional review board approval and written, informed consent from 42 breast cancer patients were obtained. The patients were investigated before and at three different time-points during neoadjuvant chemotherapy (NACT) using tumour diameter and volume from CE-MRI and ADC values obtained from drawn 2D and segmented 3D regions of interest. Prediction of pathologic complete response (pCR) was evaluated using the area under the curve (AUC) of receiver operating characteristic analysis. There was no significant difference between pathologic complete response and non-pCR in baseline size measures (p > 0.39). Diameter change was significantly different in pCR (p < 0.02) before the mid-therapy point. The best predictor was lesion diameter change observed before mid-therapy (AUC = 0.93). Segmented volume was not able to differentiate between pCR and non-pCR at any time-point. The ADC values from 3D-ROI were not significantly different from 2D data (p = 0.06). The best AUC (0.79) for pCR prediction using DWI was median ADC measured before mid-therapy of NACT. The results of this study should be considered in NACT monitoring planning, especially in MRI protocol designing and time point selection. (orig.)

  10. Efficacy of neoadjuvant chemotherapy and radiotherapy for the histology-confirmed intracranial germinoma-preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Young Ju; Kim, Hak Jae; Heo, Dae Seog; Shin, Hee Yung; Kim, Il Han [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2002-06-15

    We intended to decrease late CNS reaction after radical radiotherapy for an intracranial germinoma by using combined neoadjuvant chemotherapy and involved-field radiotherapy. The efficacy in terms of its acute toxicity and short-term relapse patterns was analyzed. Eighteen patients were treated with combined neoadjuvant chemotherapy and radiotherapy between 1995 and 2001. The chemotherapy regimen used was the Children's Cancer Group (CCG) 9921A (cisplatin, cyclophosphamide, VP-16, vincristine) for 5 patients younger than 16 years, BEP(bleomycin, VP-16, cisplatin) for 12 patients, and EP (VP-16, cisplatin) for 1 patient. The radiotherapy covered the whole craniospinal axis for 5 patients, the whole brain for 1, and the partial brain (involved field) for 12. the primary lesion received tumour doses between 3,960 and 5,400 cGy. The male to female ratio was 16:2 and the median age was 16 years old. The tumors were located in the pineal gland in 12 patients, in the suprasellar region in 1, in the basal ganglia in 1, in the thalamus in 1. Three patients had multiple lesions and ventricular seedings were shown at MRI. In 3 patients, tumor cells were detected in the cerebrospinal fluid and MRI detected a spinal seeding in 2 patients. The response to neoadjuvant chemotherapy was complete remission in 5 patients, partial remission in 12, and no response in 1. However, after radiotherapy, all except 1 patient experienced complete remission. The toxicity during or after chemotherapy greater than or equal to grade III was remarkable; hematologic toxicity was observed in 11 patients, liver toxicity in none, kidney toxicity in none, and gastrointestinal toxicity in one. One patient suffered from bleomycin-induced pneumonitis. Radiotherapy was therefore stopped and the patient eventually died of respiratory failure. The other 17 are alive without any evidence of disease or relapse during an average of 20 months follow-up. A high response rate and disease control was

  11. Efficacy of neoadjuvant chemotherapy and radiotherapy for the histology-confirmed intracranial germinoma-preliminary report

    International Nuclear Information System (INIS)

    Noh, Young Ju; Kim, Hak Jae; Heo, Dae Seog; Shin, Hee Yung; Kim, Il Han

    2002-01-01

    We intended to decrease late CNS reaction after radical radiotherapy for an intracranial germinoma by using combined neoadjuvant chemotherapy and involved-field radiotherapy. The efficacy in terms of its acute toxicity and short-term relapse patterns was analyzed. Eighteen patients were treated with combined neoadjuvant chemotherapy and radiotherapy between 1995 and 2001. The chemotherapy regimen used was the Children's Cancer Group (CCG) 9921A (cisplatin, cyclophosphamide, VP-16, vincristine) for 5 patients younger than 16 years, BEP(bleomycin, VP-16, cisplatin) for 12 patients, and EP (VP-16, cisplatin) for 1 patient. The radiotherapy covered the whole craniospinal axis for 5 patients, the whole brain for 1, and the partial brain (involved field) for 12. the primary lesion received tumour doses between 3,960 and 5,400 cGy. The male to female ratio was 16:2 and the median age was 16 years old. The tumors were located in the pineal gland in 12 patients, in the suprasellar region in 1, in the basal ganglia in 1, in the thalamus in 1. Three patients had multiple lesions and ventricular seedings were shown at MRI. In 3 patients, tumor cells were detected in the cerebrospinal fluid and MRI detected a spinal seeding in 2 patients. The response to neoadjuvant chemotherapy was complete remission in 5 patients, partial remission in 12, and no response in 1. However, after radiotherapy, all except 1 patient experienced complete remission. The toxicity during or after chemotherapy greater than or equal to grade III was remarkable; hematologic toxicity was observed in 11 patients, liver toxicity in none, kidney toxicity in none, and gastrointestinal toxicity in one. One patient suffered from bleomycin-induced pneumonitis. Radiotherapy was therefore stopped and the patient eventually died of respiratory failure. The other 17 are alive without any evidence of disease or relapse during an average of 20 months follow-up. A high response rate and disease control was experienced

  12. Gadoxetic acid-enhanced MRI and diffusion-weighted imaging for the detection of colorectal liver metastases after neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Yu, Mi Hye; Lee, Jeong Min; Han, Joon Koo; Choi, Byung-Ihn; Hur, Bo Yun; Kim, Tae-You; Jeong, Seung-Yong; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    To investigate the diagnostic performance of gadoxetic acid-enhanced MRI including diffusion-weighted imaging (DWI) for the detection of colorectal liver metastases (CRLMs) after neoadjuvant chemotherapy (NAC). Our study population comprised 77 patients with 140 CRLMs who underwent gadoxetic acid-enhanced MRI within 1 month prior to surgery: group A (without NAC, n = 38) and group B (with NAC, n = 39). Two radiologists independently assessed all MR images and graded their diagnostic confidence for CRLM on a 5-point scale. Diagnostic accuracy, sensitivity and positive predictive values (PPV) were calculated and compared between the two groups. Diagnostic accuracy of gadoxetic acid-enhanced MRI in group B was slightly lower than in group A, but a statistically significant difference was not observed (observer 1: A z , 0.926 in group A, 0.905 in group B; observer 2: A z , 0.944 in group A, 0.885 in group B; p > 0.05). Sensitivity and PPV of group B were comparable to those of group A (observer 1: sensitivity = 93.5 % vs. 93.6 %, PPV = 95.1 % vs. 86.9 %; observer 2: sensitivity = 96.8 % vs. 91.0 %; PPV = 90.0 % vs. 89.7 %; all p > 0.05). Gadoxetic acid-enhanced MRI including DWI provided good diagnostic performance with high sensitivity (>90 %) for the detection of CRLMs, regardless of the influence of NAC. (orig.)

  13. Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Keam, Bhumsuk; Moon, Woo Kyung; Kim, Tae-You; Park, In Ae; Noh, Dong-Young; Chung, June-Key; Bang, Yung-Jue; Im, Seock-Ah; Koh, Youngil; Han, Sae-Won; Oh, Do-Youn; Cho, Nariya; Kim, Jee Hyun; Han, Wonshik; Kang, Keon Wook

    2011-01-01

    This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype. ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/NCT01396655

  14. Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

    Science.gov (United States)

    Moureau-Zabotto, L; Viret, F; Giovaninni, M; Lelong, B; Bories, E; Delpero, J R; Pesenti, C; Caillol, F; de Chaisemartin, C; Minsat, M; Monges, G; Sarran, A; Resbeut, M

    2011-07-01

    This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy. Copyright © 2011 Wiley-Liss, Inc.

  15. Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection

    NARCIS (Netherlands)

    van Rijk, Maartje C.; Nieweg, Omgo E.; Rutgers, Emiel J. T.; Oldenburg, Hester S. A.; Valdés Olmos, Renato; Hoefnagel, Cornelis A.; Kroon, Bin B. R.

    2006-01-01

    BACKGROUND: Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy,

  16. Incidence and Timing of Thromboembolic Events in Patients With Ovarian Cancer Undergoing Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Greco, Patricia S; Bazzi, Ali A; McLean, Karen; Reynolds, R Kevin; Spencer, Ryan J; Johnston, Carolyn M; Liu, J Rebecca; Uppal, Shitanshu

    2017-06-01

    To identify the incidence and timing of venous thromboembolism as well as any associated risk factors in patients with ovarian, fallopian tube, or primary peritoneal cancer undergoing neoadjuvant chemotherapy. We conducted a retrospective cohort study of patients diagnosed with ovarian, fallopian tube, and primary peritoneal cancer and receiving neoadjuvant chemotherapy from January 2009 to May 2014 at a single academic institution. The timing and number of venous thromboembolic events for the entire cohort were categorized as follows: presenting symptom, during neoadjuvant chemotherapy treatment, after debulking surgery, and during adjuvant chemotherapy. Of the 125 total patients with ovarian cancer undergoing neoadjuvant chemotherapy, 13 of 125 patients (10.4%, 95% confidence interval [CI] 6.1-17.2%) had a venous thromboembolism as a presenting symptom and were excluded from further analysis. Of the 112 total patients at risk, 30 (26.8%, 95% CI 19.3-35.9%) experienced a venous thromboembolism. Based on the phase of care, 13 (11.6%, 95% CI 6.8-19.1%) experienced a venous thromboembolism during neoadjuvant chemotherapy, six (5.4%, 95% CI 2.4-11.5%) developed a postoperative venous thromboembolism, and 11 (9.9%, 95% CI 5.5-17%) developed a venous thromboembolism during adjuvant chemotherapy. Two of the four patients with clear cell histology developed a venous thromboembolism in this cohort. Overall new diagnosis of venous thromboembolism was associated with one fourth of the patients undergoing neoadjuvant chemotherapy for ovarian cancer with nearly half of these diagnosed during chemotherapy cycles before interval debulking surgery. Efforts to reduce venous thromboembolism so far have largely focused on the postoperative period. Additional attention to venous thromboembolic prophylaxis during chemotherapy (neoadjuvant and adjuvant) in this patient population is warranted in an effort to decrease the rates of venous thromboembolism.

  17. Changes in sonoelastography indices of stiffness as a criterion of evaluation of efficiency of neoadjuvant chemotherapy for breast cancer

    Directory of Open Access Journals (Sweden)

    E. A. Bus'ko

    2014-01-01

    Full Text Available The purpose of this study was to evaluate the capabilities of sonoelastography to monitor neoadjuvant chemotherapy of breast cancer and to determine correlation between reduction of stiffness of the tumor and the grade of pathology response.

  18. Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Diocésio Alves Pinto de [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Zucca-Matthes, Gustavo; Vieira, René Aloísio da Costa [Hospital de Câncer de Barretos, Barretos, SP (Brazil); Andrade, Cristiane Thomaz de Aquino Exel de [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Costa, Allini Mafra da [Hospital de Câncer de Barretos, Barretos, SP (Brazil); Monteiro, Aurélio Julião de Castro [Instituto Oncológico de Ribeirão Preto, Ribeirão Preto, SP (Brazil); Lago, Lissandra Dal [Institut Jules Bordet, Brussels (Belgium); Nunes, João Soares [Hospital de Câncer de Barretos, Barretos, SP (Brazil)

    2013-07-01

    To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/ cyclophosphamide regimen followed by paclitaxel. A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m{sup 2} and cyclophosphamide 600mg/m{sup 2} every 21 days; 4 cycles of paclitaxel 175mg/m{sup 2} every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose – duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. Neoadjuvant chemotherapy with doxorubicin/ cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.

  19. Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

    Science.gov (United States)

    Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

    2018-03-01

    To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

  20. Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Lindebjerg, Jan

    2017-01-01

    BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy....... MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors...... was 55%, compared to 94% in the group of patients with a high TSR. CONCLUSIONS: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting...

  1. Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations

    Energy Technology Data Exchange (ETDEWEB)

    Bedair, Reem; Manavaki, Roido; Gill, Andrew B.; Abeyakoon, Oshaani; Gilbert, Fiona J. [University of Cambridge, Department of Radiology, School of Clinical Medicine, Cambridge (United Kingdom); Priest, Andrew N.; Patterson, Andrew J. [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); McLean, Mary A. [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); University of Cambridge, Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Graves, Martin J. [University of Cambridge, Department of Radiology, School of Clinical Medicine, Cambridge (United Kingdom); Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); Griffiths, John R. [University of Cambridge, Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Cambridge (United Kingdom)

    2017-07-15

    To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm{sup 2}). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D{sub t}), vascular fraction (Florin), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. (orig.)

  2. Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations

    International Nuclear Information System (INIS)

    Bedair, Reem; Manavaki, Roido; Gill, Andrew B.; Abeyakoon, Oshaani; Gilbert, Fiona J.; Priest, Andrew N.; Patterson, Andrew J.; McLean, Mary A.; Graves, Martin J.; Griffiths, John R.

    2017-01-01

    To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm"2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D_t), vascular fraction (Florin), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. (orig.)

  3. Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

    Science.gov (United States)

    Vetterlein, Malte W; Wankowicz, Stephanie A M; Seisen, Thomas; Lander, Richard; Löppenberg, Björn; Chun, Felix K-H; Menon, Mani; Sun, Maxine; Barletta, Justine A; Choueiri, Toni K; Bellmunt, Joaquim; Trinh, Quoc-Dien; Preston, Mark A

    2017-11-15

    Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [Pchemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell carcinoma of the bladder can distinguish between residual tumour and post-chemotherapy effect

    International Nuclear Information System (INIS)

    Donaldson, Stephanie B.; Bonington, Suzanne C.; Kershaw, Lucy E.; Cowan, Richard; Lyons, Jeanette; Elliott, Tony; Carrington, Bernadette M.

    2013-01-01

    Introduction: Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff). Methods and materials: Twenty-one patients underwent DCE-MRI scans with 2.5 s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T 2 -weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI 80s ) and plasma perfusion (F p ) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Student's t-test. Results: Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI 80s and F p were significantly higher in areas of residual tumour than Tr-Eff (rSI 80s = 2.9 vs 1.7, p < 0.001; F p = 20.7 vs 9.1 ml/100 ml/min, p = 0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI 80s ), 60% and 86% (F p ), and 75% and 100% when combined. Conclusion: DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy

  5. Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment.

    Science.gov (United States)

    Chen, Jianghao; Yao, Qing; Wang, Hui; Wang, Bo; Zhang, Juliang; Wang, Ting; Lv, Yonggang; Han, Zenghui; Wang, Ling

    2015-07-01

    Neoadjuvant chemotherapy has been increasingly used to downstage breast cancer prior to surgery recently. However, in some cases, it was observed that despite sufficient regression of primary tumors, the metastatic lymph nodes remained nonresponsive. In this study, we applied lymphatic-targeted strategy to evaluate its efficacy and safety for patients presenting refractory nodes following systemic chemotherapy. A total of 318 breast cancer patients were demonstrated with lymph node metastasis by needle biopsy and given neoadjuvant chemotherapy. Two cycles later, 72 patients were observed with responsive tumors but stable nodes, 42 of which received a subcutaneous injection of lymphatic-targeted pegylated liposomal doxorubicin during the third cycle, while the remaining 30 patients were continued with former neoadjuvant therapeutic pattern and regarded as the control. Lymphatic-targeted treatment substantially increased both clinical and pathological node response rate [62 % (26/42) vs. 13 % (4/30) and 12 % (5/42) vs. 0 (0/30), respectively], and induced a higher apoptosis level of metastatic cells (median, 41 vs. 6 %), compared with the control. Moreover, a higher disease-free survival was observed after a median follow-up of 4 years (69 vs. 56 %). Inflammatory reaction surrounding injection sites was the most common side effect. Lymphatic chemotherapy has reliable efficacy and well-tolerated toxicity for breast cancer patients presenting refractory lymph nodes following neoadjuvant chemotherapy.

  6. MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer

    Science.gov (United States)

    Seierstad, T; Hole, K H; Grøholt, K K; Dueland, S; Ree, A H; Flatmark, K

    2015-01-01

    Objective: To investigate if MRI-assessed tumour volumetry correlates with histological tumour response to neoadjuvant chemotherapy (NACT) and subsequent chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods: Data from 69 prospectively enrolled patients with LARC receiving NACT followed by CRT and radical surgery were analysed. Whole-tumour volumes were contoured in T2 weighted MR images obtained pre-treatment (VPRE), after NACT (VNACT) and after the full course of NACT followed by CRT (VCRT). VPRE, VNACT and tumour volume changes relative to VPRE, ΔVNACT and ΔVCRT were calculated and correlated to histological tumour regression grade (TRG). Results: 61% of good histological responders (TRG 1–2) to NACT followed by CRT were correctly predicted by combining VPRE  −78.2% and VNACT volumetry may be a tool for early identification of good and poor responders to NACT followed by CRT and surgery in LARC in order to aid more individualized, multimodal treatment. PMID:25899892

  7. Neoadjuvant chemotherapy in patients with stages III/IV breast ...

    African Journals Online (AJOL)

    The aim of this study was to determine disease response, recurrence and development of distant metastasis with the use of chemotherapy in the form of neoadjuvant chemotherapy. Patients and methods: This was a prospective study that had enrolled a total of 57 patients with locally advanced breast cancer disease ...

  8. Reevaluation of Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma

    OpenAIRE

    Zheng, Yan; Li, Yin; Liu, Xianben; Sun, Haibo; Wang, Zongfei; Zhang, Ruixiang

    2015-01-01

    Abstract The effect of neoadjuvant chemotherapy on the survival of patients with thoracic esophageal squamous cell carcinomas (ESCCs) remains controversial. The optimal management strategy for resectable ESCCs varies regionally based on local randomized controlled trials. A systematic review and meta-analysis was conducted to re-evaluate this controversial issue. A systematic review of the Medline, Embase, and PubMed databases was carried out on data collected between August 1994 and August 2...

  9. Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of neoadjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Letourneau, Joseph M; Sinha, Nikita; Wald, Kaitlyn; Harris, Eve; Quinn, Molly; Imbar, Tal; Mok-Lin, Evelyn; Chien, A Jo; Rosen, Mitchell

    2017-10-01

    Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast cancer? Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely to delay time to initiation of neoadjuvant chemotherapy start. Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not well-understood. Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consultation prior to starting neoadjuvant chemotherapy for breast cancer. A chart-review was performed. Study inclusion criteria were female sex; age 18-45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evaluation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those who did not using T-tests and linear modeling. A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for those

  10. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.

    Science.gov (United States)

    Ladoire, Sylvain; Mignot, Grégoire; Dabakuyo, Sandrine; Arnould, Laurent; Apetoh, Lionel; Rébé, Cedric; Coudert, Bruno; Martin, Francois; Bizollon, Marie Hélène; Vanoli, André; Coutant, Charles; Fumoleau, Pierre; Bonnetain, Franck; Ghiringhelli, François

    2011-07-01

    Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report.

    Science.gov (United States)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-10-07

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer.Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes.The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%.Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

  12. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

    International Nuclear Information System (INIS)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-01-01

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer.Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes.The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%.Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making. (paper)

  13. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

    Science.gov (United States)

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-10-01

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer. Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes. The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%. Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

  14. Evaluation with 3.0-T MR imaging: predicting the pathological response of triple-negative breast cancer treated with anthracycline and taxane neoadjuvant chemotherapy.

    Science.gov (United States)

    Kim, Min Jung; Kim, Eun-Kyung; Park, Seho; Moon, Hee Jung; Kim, Seung Il; Park, Byeong-Woo

    2015-09-01

    Triple-negative breast cancer (TNBC) which expresses neither hormonal receptors nor HER-2 is associated with poor prognosis and shorter survival. Several studies have suggested that TNBC patients attaining pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) show a longer survival than those without pCR. To assess the accuracy of 3.0-T breast magnetic resonance imaging (MRI) in predicting pCR and to evaluate the clinicoradiologic factors affecting the diagnostic accuracy of 3.0-T breast MRI in TNBC patients treated with anthracycline and taxane (ACD). This retrospective study was approved by the institutional review board; patient consent was not required. Between 2009 and 2012, 35 TNBC patients with 3.0-T breast MRI prior to (n = 26) or after (n = 35) NAC were included. MRI findings were reviewed according to pCR to chemotherapy. The diagnostic accuracy of 3.0-T breast MRI for predicting pCR and the clinicoradiological factors affecting MRI accuracy and response to NAC were analyzed. 3.0-T MRI following NAC with ACD accurately predicted pCR in 91.4% of TNBC patients. The residual tumor size between pathology and 3.0-T MRI in non-pCR cases showed a higher correlation in the Ki-67-positive TNBC group (r = 0.947) than in the Ki-67 negative group (r = 0.375) with statistical trends (P = 0.069). Pre-treatment MRI in the non-pCR group compared to the pCR group showed a larger tumor size (P = 0.030) and non-mass presentation (P = 0.015). 3.0-T MRI in TNBC patients following NAC with ACD showed a high accuracy for predicting pCR to NAC. Ki-67 can affect the diagnostic accuracy of 3.0-T MRI for pCR to NAC with ACD in TNBC patients. © The Foundation Acta Radiologica 2014.

  15. [Effect of neoadjuvant chemotherapy on nutritional status of locally advanced gastric cancer].

    Science.gov (United States)

    Deng, Guopeng; Qu, Jianjun; Zhai, Shengyong; Shi, Yiran; Wang, Xinbo

    2018-03-25

    To study the effect of neoadjuvant chemotherapy on nutritional status in patients with locally advanced gastric cancer. Cases inclusion criteria: (1)18-65 years old; (2) Gastric cancer confirmed by gastroscopic biopsy; (3) Preoperative TNM stage III( according to the AJCC stage 2000 standard; (4) Kamosfsky functional status score> 60 points; (5)Receiving neoadjuvant chemotherapy voluntarily and signing the informed consent form. Case exclusion criteria: (1)Having contraindications of chemotherapy and surgery; (2) Suffering from heart, liver and kidney and other underlying diseases; (3) Concurrent with malignant diseases, wasting disease or other digestive diseases. According to the above criteria, clinical data of 73 patients of stage III( gastric cancer receiving neoadjuvant chemotherapy at Weifang People's Hospital from May 2015 to March 2017 were prospectively collected. The cohort study was adopted. After removing 3 patients who did not complete the chemotherapy, a total of 70 patients who completed the chemotherapy were included in the study. All the patients received SOX chemotherapy without nutritional support during chemotherapy. Changes of body composition and nutritional indicators were analyzed before and after chemotherapy, and according to the tumor regression after chemotherapy, patients were divided into response group (complete or sub-total tumor regression) and non-response group (tumor part, with or without a small amount of retreat) for stratified analysis. Of 70 gastric cancer patients, 40 were male and 30 were female with a age of (53.8±6.4) (28 to 64) years. There were 26 cases (37.1%) of stage III(a, 35 cases (50.0%) of stage III(b and 9 cases (12.9%) of stage III(c. There were 41 cases in response group and 29 cases in non-response group. Three patients (4.3%) were complete remission (CR) and 38 patients (54.3%) were partial remission (PR) in response group, while 23 cases (32.9%) were stable disease (SD) and 6 cases (8.6%) were progressive

  16. Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies

    International Nuclear Information System (INIS)

    Kumar, L.; Grover, R.; Pokharel, Y.H.; Chander, S.; Kumar, S.; Singh, R.; Rath, G.K.; Kochupillai, V.

    1998-01-01

    The results of two studies looking at the place of neo-adjuvant chemotherapy in the treatment of locally advanced cervical cancer being treated with radiotherapy are presented. Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IVA were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT). Three patients died of CT toxicity - two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. The neo-adjuvant chemotherapy prior to radiotherapy demonstrated a high response rate, but this did not translate into improved overall survival compared to those patients receiving radiotherapy alone

  17. Predicting response before initiation of neoadjuvant chemotherapy in breast cancer using new methods for the analysis of dynamic contrast enhanced MRI (DCE MRI) data

    Science.gov (United States)

    DeGrandchamp, Joseph B.; Whisenant, Jennifer G.; Arlinghaus, Lori R.; Abramson, V. G.; Yankeelov, Thomas E.; Cárdenas-Rodríguez, Julio

    2016-03-01

    The pharmacokinetic parameters derived from dynamic contrast enhanced (DCE) MRI have shown promise as biomarkers for tumor response to therapy. However, standard methods of analyzing DCE MRI data (Tofts model) require high temporal resolution, high signal-to-noise ratio (SNR), and the Arterial Input Function (AIF). Such models produce reliable biomarkers of response only when a therapy has a large effect on the parameters. We recently reported a method that solves the limitations, the Linear Reference Region Model (LRRM). Similar to other reference region models, the LRRM needs no AIF. Additionally, the LRRM is more accurate and precise than standard methods at low SNR and slow temporal resolution, suggesting LRRM-derived biomarkers could be better predictors. Here, the LRRM, Non-linear Reference Region Model (NRRM), Linear Tofts model (LTM), and Non-linear Tofts Model (NLTM) were used to estimate the RKtrans between muscle and tumor (or the Ktrans for Tofts) and the tumor kep,TOI for 39 breast cancer patients who received neoadjuvant chemotherapy (NAC). These parameters and the receptor statuses of each patient were used to construct cross-validated predictive models to classify patients as complete pathological responders (pCR) or non-complete pathological responders (non-pCR) to NAC. Model performance was evaluated using area under the ROC curve (AUC). The AUC for receptor status alone was 0.62, while the best performance using predictors from the LRRM, NRRM, LTM, and NLTM were AUCs of 0.79, 0.55, 0.60, and 0.59 respectively. This suggests that the LRRM can be used to predict response to NAC in breast cancer.

  18. Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy.

    Science.gov (United States)

    Bouzón, Alberto; Acea, Benigno; García, Alejandra; Iglesias, Ángela; Mosquera, Joaquín; Santiago, Paz; Seoane, Teresa

    2016-01-01

    Breast conservative surgery after neoadjuvant chemotherapy intends to remove any residual tumor with negative margins. The purpose of this study was to analyze the preoperative clinical-pathological factors influencing the margin status after conservative surgery in breast cancer patients receiving neoadjuvant chemotherapy. A retrospective study of 91 breast cancer patients undergoing neoadjuvant chemotherapy (92 breast lesions) during the period 2006 to 2013. A Cox regression analysis to identify baseline tumor characteristics associated with positive margins after breast conservative surgery was performed. Of all cases, 71 tumors were initially treated with conservative surgery after neoadjuvant chemotherapy. Pathologic exam revealed positive margins in 16 of the 71 cases (22.5%). The incidence of positive margins was significantly higher in cancers with initial size >5cm (P=.021), in cancers with low tumor grade (P=.031), and in patients with hormone receptor-positive cancer (P=.006). After a median follow-up of 45.2 months, 7 patients of the 71 treated with conservative surgery had disease recurrence (9.8%). There was no significant difference in terms of disease-free survival according to the margin status (P=.596). A baseline tumor size >5cm, low tumor grade and hormone receptor-positive status increase the risk for surgical margin involvement in breast conservative surgery after neoadjuvant chemotherapy. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment: Series report and literature review.

    Science.gov (United States)

    Bartel, Ricardo; Gonzalez-Compta, Xavier; Cisa, Enric; Cruellas, Francesc; Torres, Alberto; Rovira, Aleix; Manos, Manel

    2017-10-20

    Olfactory neuroblastoma (ONB) is a rare entity that constitutes less than 5% of nasosinusal malignancies. Mainstream treatment consists in surgical resection+/-adjuvant radiotherapy. By exposing results observed with apparition of new therapeutic options as neoadjuvant chemotherapy, the objective is to evaluate a series and a review of the current literature. A retrospective review was conducted including patients diagnosed and followed-up for ONB from 2008 to 2015 in our institution. 9 patients were included. Mean follow-up of 52.5 months (range 10-107). Kadish stage: A, 1 patient (11.1%) treated with endoscopic surgery; B, 2 patients (22.2%) treated with endoscopic surgery (one of them received adjuvant radiotherapy); C, 6 patients (66.7%), 4 patients presented intracranial extension and were treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. The other 2 patients presented isolated orbital extension, treated with radical surgery (endoscopic or craniofacial resection) plus radiotherapy. The 5-year disease free and overall survival observed was 88.9%. Neoadjuvant chemotherapy could be an effective treatment for tumor reduction, improving surgical resection and reducing its complications. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  20. Evaluation of lymph node status after neoadjuvant chemotherapy in breast cancer patients: comparison of diagnostic performance of ultrasound, MRI and ¹⁸F-FDG PET/CT.

    Science.gov (United States)

    You, S; Kang, D K; Jung, Y S; An, Y-S; Jeon, G S; Kim, T H

    2015-08-01

    To evaluate the diagnostic performance of ultrasound, MRI and fluorine-18 fludeoxyglucose positron emission tomography (¹⁸F-FDG PET)/CT for the diagnosis of metastatic axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC) and to find out histopathological factors affecting the diagnostic performance of these imaging modalities. From January 2012 to November 2014, 191 consecutive patients with breast cancer who underwent NAC before surgery were retrospectively reviewed. We included 139 patients with ALN metastasis that was confirmed on fine needle aspiration or core needle biopsy at initial diagnosis. After NAC, 39 (28%) patients showed negative conversion of ALN on surgical specimens of sentinel lymph node (LN) or ALN. The sensitivity of ultrasound, MRI and PET/CT was 50% (48/96), 72% (70/97) and 22% (16/73), respectively. The specificity of ultrasound, MRI and PET/CT was 77% (30/39), 54% (21/39) and 85% (22/26), respectively. The Az value of combination of ultrasound and PET/CT was the highest (0.634) followed by ultrasound (0.626) and combination of ultrasound, MRI and PET/CT (0.617). The size of tumour deposit in LN and oestrogen receptor was significantly associated with the diagnostic performance of ultrasound (p performance of PET/CT (p = 0.023, p = 0.002, p = 0.036, p = 0.044 and p = 0.008, respectively). On multivariate logistic regression analysis, size of tumour deposit within LN was identified as being independently associated with diagnostic performance of ultrasound [odds ratio, 13.07; 95% confidence interval (CI), 2.95-57.96] and PET/CT (odds ratio, 6.47; 95% CI, 1.407-29.737). Combination of three imaging modalities showed the highest sensitivity, and PET/CT showed the highest specificity for the evaluation of ALN metastasis after NAC. Ultrasound alone or combination of ultrasound and PET/CT showed the highest positive-predictive value. The size of tumour deposit within ALN was significantly associated with

  1. Neoadjuvant chemotherapy for primary adenocarcinomas of the urinary bladder: a single-site experience.

    Science.gov (United States)

    Yu, Bin; Zhou, Jin; Cai, Hongzhou; Xu, Ting; Xu, Zicheng; Zou, Qing; Gu, Min

    2015-01-28

    Adenocarcinoma of the urinary bladder is a rare malignancy. Radical surgery is suggested as the best available treatment for early-stage disease, but there is currently no consensus on standard chemotherapy regimen for advanced stage. We assessed the feasibility and effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) plus S-1 for patients with locally advanced primary adenocarcinomas of the urinary bladder. Six patients with locally advanced urachal or non-urachal (n = 3, each) primary adenocarcinoma of the bladder were treated from October 2010 to October 2013 at a single center. All the patients were treated with 3 cycles (21d, each) of GC plus S-1 (gemcitabine, 1000 mg/m2, days 1 and 8; cisplatin, 70 mg/m2, day 2; and S-1, 50 mg bid, day 1-14). After neoadjuvant chemotherapy, patients with urachal cancer were treated with en bloc radical cystectomy and umbilectomy; the remaining 3 patients were treated with cystectomy. All patients successfully completed the neoadjuvant chemotherapy without serious side effects. Two patients were assessed as complete response, 2 as partial response, 1 as stable disease and 1 as progressive disease. Despite the limitations of a small study population, the GC plus S-1 regimen for locally advanced primary adenocarcinoma of the urinary bladder was effective, and facilitated the success of surgery to a certain extent. Short follow-up time was also a limitation of our study. More studies are needed to evaluate the results.

  2. Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

    Science.gov (United States)

    Wang, Jifei; Sun, Meili; Liu, Dawei; Hu, Xiaoshu; Pui, Margaret H; Meng, Quanfei; Gao, Zhenhua

    2017-08-01

    Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10 -3  mm 2 /s) was significantly ( P  0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.

  3. Prevalence of Clostridium Difficile Infection in Patients After Radical Cystectomy and Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Cotter, Katherine J; Fan, Yunhua; Sieger, Gretchen K; Weight, Christopher J; Konety, Badrinath R

    2017-10-27

    Clostridium Difficile is the most common cause of nosocomial infectious diarrhea. This study evaluates the prevalence and predictors of Clostridium Difficile infections in patients undergoing radical cystectomy with or without neoadjuvant chemotherapy. Retrospective chart review was performed of all patients undergoing cystectomy and urinary diversion at a single institution from 2011-2017. Infection was documented in all cases with testing for Clostridium Difficile polymerase chain reaction toxin B. Patient and disease related factors were compared for those who received neoadjuvant chemotherapy vs. those who did not in order to identify potential risk factors associated with C. Difficile infections. Chi squared test and logistic regression analysis were used to determine statistical significance. Of 350 patients who underwent cystectomy, 41 (11.7%) developed Clostridium Difficile in the 30 day post-operative period. The prevalence of C. Difficile infection was higher amongst the patients undergoing cystectomy compared to the non-cystectomy admissions at our hospital (11.7 vs. 2.9%). Incidence was not significantly different among those who underwent cystectomy for bladder cancer versus those who underwent the procedure for other reasons. Median time to diagnosis was 6 days (range 3-28 days). The prevalence of C. Diff infections was not significantly different among those who received neoadjuvant chemotherapy vs. those who did not (11% vs. 10.4% p  = 0.72). A significant association between C. Difficile infection was not seen with proton pump inhibitor use ( p  = 0.48), patient BMI ( p  = 0.67), chemotherapeutic regimen ( p  = 0.94), individual surgeon ( p  = 0.54), type of urinary diversion (0.41), or peri-operative antibiotic redosing ( p  = 0.26). Clostridium Difficile infection has a higher prevalence in patients undergoing cystectomy. No significant association between prevalence and exposure to neoadjuvant chemotherapy was seen.

  4. TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

    International Nuclear Information System (INIS)

    Wu, J; Gong, G; Cui, Y; Li, R

    2016-01-01

    Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

  5. TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wu, J; Gong, G; Cui, Y; Li, R [Stanford University, Palo Alto, CA (United States)

    2016-06-15

    Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

  6. Integrated 18F-FDG PET/MRI in breast cancer. Early prediction of response to neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Cho, Nariya; Im, Seock-Ah; Lee, Kyung-Hun; Kim, Tae-Yong; Cheon, Gi Jeong; Park, In-Ae; Kim, Young Seon; Kwon, Bo Ra; Lee, Jung Min; Suh, Hoon Young; Suh, Koung Jin

    2018-01-01

    To explore whether integrated 18 F-FDG PET/MRI can be used to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Between November 2014 and April 2016, 26 patients with breast cancer who had received NAC and subsequent surgery were prospectively enrolled. Each patient underwent 18 F-FDG PET/MRI examination before and after the first cycle of NAC. Qualitative MRI parameters, including morphological descriptors and the presence of peritumoral oedema were assessed. Quantitatively, PET parameters, including maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis (TLG), and MRI parameters, including washout proportion and signal enhancement ratio (SER), were measured. The performance of the imaging parameters singly and in combination in predicting a pathological incomplete response (non-pCR) was assessed. Of the 26 patients, 7 (26.9%) exhibited a pathological complete response (pCR), and 19 (73.1%) exhibited a non-pCR. No significant differences were found between the pCR and non-pCR groups in the qualitative MRI parameters. The mean percentage reductions in TLG 30% on PET and SER on MRI were significantly greater in the pCR group than in the non-pCR group (TLG 30% -64.8 ± 15.5% vs. -25.4 ± 48.7%, P = 0.005; SER -34.6 ± 19.7% vs. -8.7 ± 29.0%, P = 0.040). The area under the receiver operating characteristic curve for the percentage change in TLG 30% (0.789, 95% CI 0.614 to 0.965) was similar to that for the percentage change in SER (0.789, 95% CI 0.552 to 1.000; P = 1.000). The specificity of TLG 30% in predicting pCR was 100% (7/7) and that of SER was 71.4% (5/7). The sensitivity of TLG 30% in predicting non-pCR was 63.2% (12/19) and that of SER was 84.2% (16/19). When the combined TLG 30% and SER criterion was applied, sensitivity was 100% (19/19), and specificity was 71.4% (5/7). 18 F-FDG PET/MRI can be used to predict non-pCR after the first cycle of NAC in patients with breast cancer

  7. CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and locally advanced pancreatic adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, Mathilde; Lucidarme, Oliver [Sorbonne Universites, UPMC, Department of Radiology, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France); Antunes, Celia [Coimbra University Hospital, Department of Radiology, Coimbra (Portugal); Pietrasz, Daniel [Sorbonne Universites, UPMC, Department of Digestive and Hepatobiliary Surgery, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France); Cassinotto, Christophe [Centre Hospitalier Universitaire de Bordeaux, Department of Diagnostic and Interventional Imaging, Hopital Haut Leveque, Bordeaux (France); Zappa, Magaly [Hopitaux Universitaires Paris Nord Val de Seine, Department of Radiology, Hopital Beaujon, Assistance Publique-Hopitaux de Paris, Clichy (France); Sa Cunha, Antonio [Hopitaux Universitaires Paris Sud, Department of Hepatobiliary Surgery, Liver Transplant Center, Hopital Paul Brousse, Villejuif (France); Bachet, Jean-Baptiste [Sorbonnes Universites, UPMC, Department of Gastroenterology and Digestive Oncology, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris (France)

    2017-07-15

    To assess anatomic changes on computed tomography (CT) after neoadjuvant FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) chemotherapy for secondary resected borderline resectable (BR) and locally advanced (LA) pancreatic adenocarcinoma and their accuracy to predict resectability and pathological response. Thirty-six patients with secondary resected BR/LA pancreatic adenocarcinoma after neoadjuvant FOLFIRINOX chemotherapy (± chemoradiotherapy) were retrospectively included. Two radiologists reviewed baseline and pre-surgical CTs in consensus. NCCN (National Comprehensive Cancer Network) classification, largest axis, product of the three axes (P3A), and arterial/venous involvement were studied and compared to pathological response and resection status and to disease-free survival (DFS). Thirty-one patients had R0 resection, including only six exhibiting a downstaging according to the NCCN classification. After treatment, the largest axis and P3A decreased (P < 0.0001). The pre-surgical largest axis and P3A were smaller in case of R0 resection (P = 0.019/P = 0.021). The largest axis/P3A variations were higher in case of complete pathological response (P = 0.011/P = 0.016). A decrease of the arterial/venous involvement was not able to predict R0 or ypT0N0 (P > 0.05). Progression of the vascular involvement was seen in two (5 %) patients and led to a shorter DFS. In BR/LA pancreatic adenocarcinoma after the neoadjuvant FOLFIRINOX regimen (± chemoradiotherapy), significant tumour size decreases were observed on CT. However, CT staging was not predictive of resectability and pathological response. (orig.)

  8. Survival is associated with complete response on MRI after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer

    NARCIS (Netherlands)

    Loo, Claudette E; Rigter, Lisanne S; Pengel, Kenneth E; Wesseling, Jelle; Rodenhuis, Sjoerd; Peeters, Marie-Jeanne T F D Vrancken; Sikorska, Karolina; Gilhuijs, Kenneth G A

    2016-01-01

    BACKGROUND: Pathological complete remission (pCR) of estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the prognostic value of pCR for this breast cancer subtype is limited. We

  9. A deep learning classifier for prediction of pathological complete response to neoadjuvant chemotherapy from baseline breast DCE-MRI

    Science.gov (United States)

    Ravichandran, Kavya; Braman, Nathaniel; Janowczyk, Andrew; Madabhushi, Anant

    2018-02-01

    Neoadjuvant chemotherapy (NAC) is routinely used to treat breast tumors before surgery to reduce tumor size and improve outcome. However, no current clinical or imaging metrics can effectively predict before treatment which NAC recipients will achieve pathological complete response (pCR), the absence of residual invasive disease in the breast or lymph nodes following surgical resection. In this work, we developed and applied a convolu- tional neural network (CNN) to predict pCR from pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans on a per-voxel basis. In this study, DCE-MRI data for a total of 166 breast cancer pa- tients from the ISPY1 Clinical Trial were split into a training set of 133 patients and a testing set of 33 patients. A CNN consisting of 6 convolutional blocks was trained over 30 epochs. The pre-contrast and post-contrast DCE-MRI phases were considered in isolation and conjunction. A CNN utilizing a combination of both pre- and post-contrast images best distinguished responders, with an AUC of 0.77; 82% of the patients in the testing set were correctly classified based on their treatment response. Within the testing set, the CNN was able to produce probability heatmaps that visualized tumor regions that most strongly predicted therapeutic response. Multi- variate analysis with prognostic clinical variables (age, largest diameter, hormone receptor and HER2 status), revealed that the network was an independent predictor of response (p=0.05), and that the inclusion of HER2 status could further improve capability to predict response (AUC = 0.85, accuracy = 85%).

  10. Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

    Science.gov (United States)

    Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

    2013-01-01

    Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

  11. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review...

  12. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection.

    Directory of Open Access Journals (Sweden)

    Brian D Lehmann

    Full Text Available Triple-negative breast cancer (TNBC is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype, with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM and mesenchymal stem-like (MSL subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype into four (TNBCtype-4 tumor-specific subtypes (BL1, BL2, M and LAR and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50 or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively. Collectively, we provide pre-clinical data that could inform

  13. Integrated {sup 18}F-FDG PET/MRI in breast cancer. Early prediction of response to neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Im, Seock-Ah; Lee, Kyung-Hun; Kim, Tae-Yong [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Cheon, Gi Jeong [Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of); Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Park, In-Ae [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Kim, Young Seon [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Yeungnam University, Department of Radiology, College of Medicine, Daegu (Korea, Republic of); Kwon, Bo Ra [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Lee, Jung Min; Suh, Hoon Young [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Suh, Koung Jin [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of)

    2018-03-15

    To explore whether integrated {sup 18}F-FDG PET/MRI can be used to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Between November 2014 and April 2016, 26 patients with breast cancer who had received NAC and subsequent surgery were prospectively enrolled. Each patient underwent {sup 18}F-FDG PET/MRI examination before and after the first cycle of NAC. Qualitative MRI parameters, including morphological descriptors and the presence of peritumoral oedema were assessed. Quantitatively, PET parameters, including maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis (TLG), and MRI parameters, including washout proportion and signal enhancement ratio (SER), were measured. The performance of the imaging parameters singly and in combination in predicting a pathological incomplete response (non-pCR) was assessed. Of the 26 patients, 7 (26.9%) exhibited a pathological complete response (pCR), and 19 (73.1%) exhibited a non-pCR. No significant differences were found between the pCR and non-pCR groups in the qualitative MRI parameters. The mean percentage reductions in TLG{sub 30%} on PET and SER on MRI were significantly greater in the pCR group than in the non-pCR group (TLG{sub 30%} -64.8 ± 15.5% vs. -25.4 ± 48.7%, P = 0.005; SER -34.6 ± 19.7% vs. -8.7 ± 29.0%, P = 0.040). The area under the receiver operating characteristic curve for the percentage change in TLG{sub 30%} (0.789, 95% CI 0.614 to 0.965) was similar to that for the percentage change in SER (0.789, 95% CI 0.552 to 1.000; P = 1.000). The specificity of TLG{sub 30%} in predicting pCR was 100% (7/7) and that of SER was 71.4% (5/7). The sensitivity of TLG{sub 30%} in predicting non-pCR was 63.2% (12/19) and that of SER was 84.2% (16/19). When the combined TLG{sub 30%} and SER criterion was applied, sensitivity was 100% (19/19), and specificity was 71.4% (5/7). {sup 18}F-FDG PET/MRI can be used to predict non-pCR after the first

  14. [Neoadjuvant therapy for esophageal cancer - indication and efficacy].

    Science.gov (United States)

    Kato, Ken; Hamaguchi, Tetsuya; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro

    2007-10-01

    Some approaches such as adjuvant chemotherapy, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been tried to improve the efficacy of treatment for resectable esophageal cancer patients. The usefullness of neoadjuvant chemotherapy, has remained a matter of controversy. However, there is a report from JCOG9907 in Japan that two courses of neoadjuvant 5-FU/CDDP improved the survival of esophageal squamous cell cancer patients. Neoadjuvant chemoradiotherapy has not had a consistent evaluation because of the varying results of each trial. But from the results of meta-analysis and CALGB9781, the neoadjuvant chemoradiotherapy called "trimodality therapy" has been a standard treatment in the United States. We should evaluate whether there would be similar effectiveness in Japan, where the histology and operative approach are different. Some approaches such as DNA microarray and proteomics, which can predict the treatment effect, are being tried.

  15. Phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2-negative breast cancer: NSABP Foundation Study FB-9.

    Science.gov (United States)

    Abraham, Jame; Robidoux, André; Tan, Antoinette R; Limentani, Steven; Sturtz, Keren; Shalaby, Ibrahim; Alcorn, Hope; Buyse, Marc E; Wolmark, Norman; Jacobs, Samuel A

    2015-07-01

    Locally advanced breast cancer (LABC) is a good setting in which to monitor response to neoadjuvant chemotherapy, to downsize the tumor (which facilitates breast-conserving surgery), and to test newer agents in untreated patients. Eribulin (E) has shown activity in patients who have undergone previous taxane, anthracycline, and capecitabine treatment. We aimed to evaluate the neoadjuvant use of E followed by doxorubicin and cyclophosphamide (AC) in patients with HER2-negative LABC, using as a control a randomized group of women who received weekly paclitaxel (WP). Fifty women with LABC were accrued January-August 2013. Patients were randomized (1:2) to receive either WP (N = 19) for 12 treatments or E (N = 31) every 3 weeks for 4 cycles followed by AC every 3 weeks for 4 cycles before surgery. 17/19 patients who took WP and 25/30 who took E completed all cycles. Patients were evaluated by clinical examination and breast MRI at baseline and after completion of E or WP. Surgical pCR in breast and lymph nodes was determined by a local pathologist following chemotherapy. Forty-nine patients received ≥1 dose of neoadjuvant chemotherapy and are included in this analysis. Forty-eight underwent surgery; one had disease that was inoperable (on E) and is included as no-pCR patient. 17/19 of these patients who took WP completed 12 doses; 28/30 on E completed 4 cycles. Six discontinued treatment on WP, E, or AC. Both treatments were well tolerated. pCR on WP = 5/19(26 %) and on E = 5/30(17 %). Both regimens were equally well tolerated with no unexpected toxicities. pCR did not suggest higher activity with E than with other standard regimens in these LABC patients.

  16. Bevacizumab and Combination Chemotherapy in rectal cancer Until Surgery (BACCHUS): a phase II, multicentre, open-label, randomised study of neoadjuvant chemotherapy alone in patients with high-risk cancer of the rectum

    International Nuclear Information System (INIS)

    Glynne-Jones, R.; Hava, N.; Goh, V.; Bosompem, S.; Bridgewater, J.

    2015-01-01

    In locally advanced rectal cancer (LARC) preoperative chemoradiation (CRT) is the standard of care, but the risk of local recurrence is low with good quality total mesorectal excision (TME), although many still develop metastatic disease. Current challenges in treating rectal cancer include the development of effective organ-preserving approaches and the prevention of subsequent metastatic disease. Neoadjuvant systemic chemotherapy (NACT) alone may reduce local and systemic recurrences, and may be more effective than postoperative treatments which often have poor compliance. Investigation of intensified NACT is warranted to improve outcomes for patients with LARC. The objective is to evaluate feasibility and efficacy of a four-drug regimen containing bevacizumab prior to surgical resection. This is a multi-centre, randomized phase II trial. Eligible patients must have histologically confirmed LARC with distal part of the tumour 4–12 cm from anal verge, no metastases, and poor prognostic features on pelvic MRI. Sixty patients will be randomly assigned in a 1:1 ratio to receive folinic acid + flurourcil + oxaliplatin (FOLFOX) + bevacizumab (BVZ) or FOLFOX + irinotecan (FOLFOXIRI) + BVZ, given in 2 weekly cycles for up to 6 cycles prior to TME. Patients stop treatment if they fail to respond after 3 cycles (defined as ≥ 30 % decrease in Standardised Uptake Value (SUV) compared to baseline PET/CT). The primary endpoint is pathological complete response rate. Secondary endpoints include objective response rate, MRI tumour regression grade, involved circumferential resection margin rate, T and N stage downstaging, progression-free survival, disease-free survival, overall survival, local control, 1-year colostomy rate, acute toxicity, compliance to chemotherapy. In LARC, a neoadjuvant chemotherapy regimen - if feasible, effective and tolerable would be suitable for testing as the novel arm against the current standards of short course preoperative radiotherapy (SCPRT

  17. Topoisomerase II alpha and TLE3 as predictive markers of response to anthracycline and taxane-containing regimens for neoadjuvant chemotherapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Susini T

    2014-11-01

    Full Text Available Tommaso Susini,1 Barbara Berti,1 Carlo Carriero,1 Ketty Tavella,2 Jacopo Nori,3 Ermanno Vanzi,3 Cecilia Molino,1 Mariarosaria Di Tommaso,1 Marco Santini,1 Valeria Saladino,4 Simonetta Bianchi4 1Department of Health Science, Gynecology Section, 2Department of Health Science, Chemotherapy Section, University of Florence, Italy; 3Diagnostic Senology Unit, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy; 4Department of Surgery and Translational Medicine, Pathology Unit, University of Florence, Italy Purpose: Anthracyclines and taxanes are considered the standard for neoadjuvant chemotherapy of breast cancer, although they are often associated with serious side effects and wide variability of individual response. In this study, we analyzed the value of topoisomerase II alpha (TOP2A and transducin-like enhancer of split 3 (TLE3 as predictive markers of response to therapy with anthracyclines and taxanes. Materials and methods: TOP2A and TLE3 protein expressions were evaluated using immunohistochemistry on 28 samples, obtained by core needle biopsy in patients with locally advanced breast carcinoma, subsequently subjected to epirubicin- and paclitaxel-based neoadjuvant chemotherapy. The immunohistochemical staining was correlated with the clinical response measured by the tumor size reduction evaluated by breast magnetic resonance imaging, prior and after chemotherapy, and by pathologic evaluation of the surgical specimen. Results: Neoadjuvant chemotherapy achieved a size reduction in 26/28 tumors (92.9%, with an average percentage decrease of 45.6%. A downstaging was achieved in 71.4% of the cases of locally advanced carcinoma. TOP2A positivity was correlated with a greater reduction in tumor diameter (P=0.06; negative staining for TLE3 was predictive of a better response to neoadjuvant chemotherapy (P=0.07. A higher reduction in tumor diameter (P=0.03 was also found for tumors that were concurrently TLE3-negative and TOP2A

  18. Neoadjuvant radiation in primary extremity liposarcoma: correlation of MRI features with histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Wortman, Jeremy R. [Harvard Medical School, Department of Radiology, Brigham and Women' s Hospital, Boston, MA (United States); Tirumani, Sree Harsha; Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H. [Harvard Medical School, Department of Radiology, Brigham and Women' s Hospital, Boston, MA (United States); Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Boston, MA (United States); Tirumani, Harika [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Boston, MA (United States); University of Arkansas Medical Sciences, Department of Radiology, Little Rock, AR (United States); Hornick, Jason L. [Harvard Medical School, Department of Pathology, Brigham and Women' s Hospital, Boston, MA (United States)

    2016-05-15

    To evaluate MRI features of response of primary extremity liposarcoma (LPS) to neoadjuvant radiation therapy (RT) with histopathologic correlation. In this IRB-approved study including 125 patients with extremity LPS treated with neoadjuvant RT from 2000 to 2013, MRI of the primary tumour in 18 patients (5 pleomorphic LPS, 13 myxoid LPS) before and after RT were reviewed by two radiologists by consensus. Histopathology of the surgical specimens was reviewed by a pathologist with expertise in sarcomas. In the pleomorphic LPS cohort, 3/5 tumours increased in size; 3/5 decreased in enhancing component; and 3/5 increased in peritumoral oedema, intratumoral haemorrhage, and necrosis. In the myxoid LPS cohort, 12/13 tumours decreased in size, 8/13 decreased in enhancing component, and 5/13 increased in internal fat following RT. Histopathology showed ≥50 % residual tumour in 1/5 pleomorphic LPS and 2/13 myxoid LPS. Hyalinization/necrosis of ≥75 % was noted in 4/5 pleomorphic LPS and 11/13 myxoid LPS. Cytodifferentiation was noted in 1/5 pleomorphic and 9/13 myxoid LPS. While pleomorphic LPS showed an increase in size, peritumoral oedema, intratumoral haemorrhage, and necrosis on MRI following neoadjuvant RT, myxoid LPS showed a decrease in size and enhancement with an increase in internal fat. (orig.)

  19. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma.

    Science.gov (United States)

    Schmitt, Thomas; Lehner, Burkhard; Kasper, Bernd; Bischof, Marc; Roeder, Falk; Dietrich, Sascha; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G; Mechtersheimer, Gunhild; Wuchter, Patrick; Ho, Anthony D; Egerer, Gerlinde

    2011-12-07

    The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m(2) iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m(2) day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published

  20. A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Schmitt Thomas

    2011-12-01

    Full Text Available Abstract Background The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS. Method Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC] were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m2 iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m2 day 1, pegfilgrastim 6 mg sc day 5, definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA. Result Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%, 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3, 24% PR (n = 12, 62% SD (n = 31 and 8% PD (n = 4. Local recurrence occurred in 3 subjects (6%. Distant metastasis was observed in 12 patients (24%. Overall survival (OS and disease-free survival (DFS at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50, cardiac toxicity (2/50, and CNS toxicity (4/50 leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far. Conclusion The current protocol is feasible for achieving local control rates, as well as OS

  1. Neoadjuvant therapy for esophageal cancer. Indication and efficacy

    International Nuclear Information System (INIS)

    Kato, Ken; Hamaguchi, Tetsuya; Yamada, Yasuhide; Shirao, Kuniaki; Shimada, Yasuhiro

    2007-01-01

    Some approaches such as adjuvant chemotherapy, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been tried to improve the efficacy of treatment for resectable esophageal cancer patients. The usefullness of neoadjuvant chemotherapy, has remained a matter of controversy. However, there is a report from JCOG9907 in Japan that two courses of neoadjuvant 5-fluorouracil/cisplatin (5-FU/CDDP) improved the survival of esophageal squamous cell cancer patients. Neoadjuvant chemoradiotherapy has not had a consistent evaluation because of the varying results of each trial. But from the results of meta-analysis and CALGB9781, the neoadjuvant chemoradiotherapy called ''trimodality therapy'' has been a standard treatment in the United States. We should evaluate whether there would be similar effectiveness in Japan, where the histology and operative approach are different. Some approaches such as DNA microarray and proteomics, which can predict the treatment effect, are being tried. (author)

  2. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer

    OpenAIRE

    Chen, Victor E.; Gillespie, Erin F.; Zakeri, Kaveh; Murphy, James D.; Yashar, Catheryn M.; Lu, Sharon; Einck, John P.

    2017-01-01

    Purpose: Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy. Methods and materials: This was an institutional review board–approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservat...

  3. Effect of neoadjuvant chemotherapy in hepatic steatosis.

    Science.gov (United States)

    Jiménez, Raúl; Hijona, Elizabeth; Emparanza, José; Alústiza, Jose M; Hijona, Lander; Macarulla, Maria T; Portillo, Maria P; Herreros-Villanueva, Marta; Beguiristain, Adolfo; Arenas, Juan; Bujanda, Luis

    2012-01-01

    Chemotherapy drugs often produce side effects in the liver. In recent years, there has been speculation about the ability to produce hepatic steatosis in patients treated with 5-fluorouracil and oxaliplatin. This prospective study examines whether these drugs can produce steatosis in patients with neoadjuvant treatment who were operated on for liver tumors. Our objective was to assess the effect of neoadjuvant chemotherapy (NAC) on the development of hepatic steatosis in the healthy liver. This was a prospective study based on 32 patients divided into two groups. The presence of steatosis was assessed using a histological score (Kleiner classification) and a biochemical method (Folch method) for patients from both groups. A total of 14 patients (44%) had hepatic steatosis and half of these were in each group. The steatosis was moderate to severe (grades 2-3) in 4 patients (13%), 2 in each group. The mean levels of triglycerides in the liver were 33.38 and 29.94 mg/g in group I and group II, respectively, with the difference not being statistically significant. Almost half of the patients treated with NAC for liver neoplasia developed steatosis. Nevertheless, NAC does not seem to increase the risk of hepatic steatosis. Copyright © 2012 S. Karger AG, Basel.

  4. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG): The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    International Nuclear Information System (INIS)

    Lorenzen, Sylvie; Debus, Jürgen; Jäger, Dirk; Münter, Marc W; Gall, Carl von; Stange, Annika; Haag, Georg M; Weitz, Jürgen; Haberkorn, Uwe; Lordick, Florian; Weichert, Wilko; Abel, Ulrich

    2011-01-01

    18-Fluorodeoxyglucose-PET ( 18 F-FDG-PET) can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG) undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy. The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a < 35% decrease of SUV two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (chemoradiotherapy (45 Gy) before surgery. 18 FDG-PET scans will be performed before (= Baseline) and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1) and at the end of radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference ΔSUV = 100 (SUV Baseline - SUV PET1 )/SUV Baseline

  5. Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

    Science.gov (United States)

    Leone, B; Vallejo, C; Perez, J; Cuevas, M A; Machiavelli, M; Lacava, J; Focaccia, G; Ferreyra, R; Suttora, G; Romero, A; Castaldi, J; Arroyo, A; Rabinovich, M

    1996-04-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

  6. Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major regional differences

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik

    2012-01-01

    The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval debulking...

  7. Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.

    Science.gov (United States)

    McCaffrey, Rebecca; Bahtiyar, Mert; Kohorn, Ernest I; Chambers, Joseph T; Schwartz, Peter E; Chambers, Setsuko K

    2011-04-01

    The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented. Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied. The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation. Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant

  8. Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

    2016-12-01

    Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  9. Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Chen L

    2017-05-01

    Full Text Available Li Chen,1 Yanjiao Zuo,1 Lihua Zhu,2 Yuxin Zhang,3 Sen Li,1 Fei Ma,4 Yu Han,5 Hongjiang Song,1 Yingwei Xue11Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, 3Department of General Surgery, Mudanjiang First People’s Hospital, Mudanjiang, 4Department of Breast Surgery, 5Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of ChinaBackground: Accurate and useful predictors of gastric carcinoma treated with neoadjuvant chemotherapy are lacking at present. We aim to explore the potential prognostic significance of the neutrophil-to-lymphocyte ratio (NLR in advanced gastric cancer receiving S-1 plus oxaliplatin (SOX or oxaliplatin and capecitabine (XELOX regimen.Methods: We enrolled 91 patients with advanced gastric cancer treated with neoadjuvant chemotherapy from August 2008 to September 2015. The peripheral venous blood samples were collected before neoadjuvant chemotherapy. The NLR was divided into two groups: low NLR <2.17 group and high NLR ≥2.17 group. Univariate analysis on disease-free survival (DFS and overall survival (OS were generated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were assessed by univariate analyses, and the independent prognostic factors were evaluated using multivariate analysis (Cox’s proportional-hazards regression model.Results: The univariate analysis showed that median DFS and median OS were worse for high NLR values than low NLR values before neoadjuvant chemotherapy (median DFS: 19.97 and 26.87 months, respectively, P=0.299; median OS: 25.83 and 29.73 months, respectively, P=0.405. Multivariate analysis showed that the NLR before neoadjuvant

  10. Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

    Science.gov (United States)

    Iotti, Valentina; Ravaioli, Sara; Vacondio, Rita; Coriani, Chiara; Caffarri, Sabrina; Sghedoni, Roberto; Nitrosi, Andrea; Ragazzi, Moira; Gasparini, Elisa; Masini, Cristina; Bisagni, Giancarlo; Falco, Giuseppe; Ferrari, Guglielmo; Braglia, Luca; Del Prato, Alberto; Malavolti, Ivana; Ginocchi, Vladimiro; Pattacini, Pierpaolo

    2017-09-11

    Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and

  11. Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours

    DEFF Research Database (Denmark)

    Sengeløv, Lisa; von der Maase, Hans; Lundbeck, Finn

    2002-01-01

    This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma...... was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were...... independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19...

  12. Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

    2015-01-01

    Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

  13. Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

    Science.gov (United States)

    Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

    2015-05-09

    Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

  14. Using Flow Characteristics in Three-Dimensional Power Doppler Ultrasound Imaging to Predict Complete Responses in Patients Undergoing Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Shia, Wei-Chung; Huang, Yu-Len; Wu, Hwa-Koon; Chen, Dar-Ren

    2017-05-01

    Strategies are needed for the identification of a poor response to treatment and determination of appropriate chemotherapy strategies for patients in the early stages of neoadjuvant chemotherapy for breast cancer. We hypothesize that power Doppler ultrasound imaging can provide useful information on predicting response to neoadjuvant chemotherapy. The solid directional flow of vessels in breast tumors was used as a marker of pathologic complete responses (pCR) in patients undergoing neoadjuvant chemotherapy. Thirty-one breast cancer patients who received neoadjuvant chemotherapy and had tumors of 2 to 5 cm were recruited. Three-dimensional power Doppler ultrasound with high-definition flow imaging technology was used to acquire the indices of tumor blood flow/volume, and the chemotherapy response prediction was established, followed by support vector machine classification. The accuracy of pCR prediction before the first chemotherapy treatment was 83.87% (area under the ROC curve [AUC] = 0.6957). After the second chemotherapy treatment, the accuracy of was 87.9% (AUC = 0.756). Trend analysis showed that good and poor responders exhibited different trends in vascular flow during chemotherapy. This preliminary study demonstrates the feasibility of using the vascular flow in breast tumors to predict chemotherapeutic efficacy. © 2017 by the American Institute of Ultrasound in Medicine.

  15. Impact of age on efficacy of postoperative oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy.

    Science.gov (United States)

    Huang, Xuan-Zhang; Gao, Peng; Song, Yong-Xi; Sun, Jing-Xu; Chen, Xiao-Wan; Zhao, Jun-Hua; Ma, Bin; Wang, Jun; Wang, Zhen-Ning

    2016-04-12

    Clinical practice guidelines focusing on age-related adjuvant chemotherapy for rectal cancer are currently limited. The present study aimed to explore the impact of age on the efficacy of adjuvant oxaliplatin-based chemotherapy in patients with rectal cancer after neoadjuvant chemoradiotherapy. We performed a retrospective cohort analysis using data from the Surveillance, Epidemiology, and End Results-Medicare-linked database from 1992-2009. We enrolled patients with yp stages I-III rectal cancer who received neoadjuvant chemoradiotherapy and underwent curative resection. The age-related survival benefit of adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy was evaluated using Kaplan-Meier survival analysis with propensity score-matching and Cox proportional hazards models. Comparing the oxaliplatin group with the 5-FU group, there were significant interactions between age and chemotherapy efficacy in terms of overall survival (OS) (p for interaction = 0.017) among patients with positive lymph nodes (ypN+). Adding oxaliplatin to 5-FU could prolong survival in patients aged rectal cancer who have already received neoadjuvant chemoradiotherapy and undergone curative resection, adding oxaliplatin to 5-FU could prolong OS in patients aged < 73 years and ypN+ category. However, adding oxaliplatin did not translate into survival benefits in patients age ≥ 73 years and ypN+ category, or in ypN- patients.

  16. Assessing Prediction Performance of Neoadjuvant Chemotherapy Response in Bladder Cancer

    OpenAIRE

    Cremer, Chris

    2016-01-01

    Neoadjuvant chemotherapy is a treatment routinely prescribed to patients diagnosed with muscle-invasive bladder cancer. Unfortunately, not all patients are responsive to this treatment and would greatly benefit from an accurate prediction of their expected response to chemotherapy. In this project, I attempt to develop a model that will predict response using tumour microarray data. I show that using my dataset, every method is insufficient at accurately classifying responders and non-respond...

  17. Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

    Science.gov (United States)

    Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

    2017-07-01

    Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

  18. Local staging of sigmoid colon cancer using MRI

    DEFF Research Database (Denmark)

    Dam, Claus; Lindebjerg, Jan; Jakobsen, Anders

    2017-01-01

    BACKGROUND: An accurate radiological staging of colon cancer is crucial to select patients who may benefit from neoadjuvant chemotherapy. PURPOSE: To evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) in identifying locally advanced sigmoid colon cancer, poor...... prognostic factors, and the inter-observer variation of the tumor apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). MATERIAL AND METHODS: Using 1.5 T MRI with high resolution T2-weighted (T2W) imaging, DWI, and no contrast enhancement, 35 patients with sigmoid colon cancer were...... the measured mean ADC values were below 1.0 × 10(-3) mm(2)/s with an intra-class correlation coefficient in T3cd-T4 tumors of 0.85. CONCLUSION: Preoperative MRI can identify locally advanced sigmoid colon cancer and has potential as the imaging of choice to select patients for neoadjuvant chemotherapy. Initial...

  19. Effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Yu-Lin Zhao

    2017-07-01

    Full Text Available Objective: To study the effect of cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy on esophageal cancer cell proliferation and invasion. Methods: A total of 62 patients with esophageal cancer who were treated in the hospital between January 2015 and December 2016 were collected and divided into control group and observation group according to random number table, with 31 cases in each group. Control group of patients received paclitaxel + cisplatin neoadjuvant chemotherapy + surgery, and observation group of patients accepted cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy + surgery. The differences in proliferation and invasion gene expression in the tumor tissue were compared between two groups of patients before and after chemotherapy. Results: Before chemotherapy, differences in proliferation and invasion gene expression in tumor tissue were not statistically significant between two groups of patients. After chemotherapy, proproliferation genes FOXA1, ABCE1, USP39 and Nestin mRNA expression in tumor tissue of observation group were significantly lower than those of control group; anti-proliferation genes PETN, KLF4, TSLC1 and AnnexinA2 mRNA expression were significantly higher than those of control group; pro-invasion genes γ-synuclein, CXCR4 and Snail mRNA expression were significantly lower than those of control group; anti-invasion genes CIAPIN1, Fez and Lrig1 mRNA expression were significantly higher than that of control group. Conclusions: Cetuximab combined with paclitaxel + cisplatin neoadjuvant chemotherapy can effectively inhibit the malignant degree of esophageal cancer cells and inhibit its proliferation and invasion.

  20. Smoking may modify the association between neoadjuvant chemotherapy and survival from ovarian cancer.

    Science.gov (United States)

    Kelemen, Linda E; Warren, Graham W; Koziak, Jennifer M; Köbel, Martin; Steed, Helen

    2016-01-01

    Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer. Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease. Among patients receiving adjuvant chemotherapy (N=432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50-48.7) and progression-free (PFS; HR, 5.74; 95% CI, 1.05-31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However, among patients receiving neoadjuvant chemotherapy (N=44), current smokers had shorter PFS (HR, 4.32; 95% CI, 1.36-13.8; N=32 progressed/9 censored events) compared to never smokers, but the HRs were not statistically different across smoking categories (P interaction=0.87). Adverse associations were observed between smoking status and OS or PFS among patients with mucinous ovarian cancer receiving adjuvant chemotherapy. No significant effect was found from neoadjuvant chemotherapy on PFS overall; however, smoking may modify this association. Although needing replication, these findings suggest that patients may benefit from smoking cessation interventions prior to treatment with chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Sequential FDG-PET and induction chemotherapy in locally advanced adenocarcinoma of the Oesophago-gastric junction (AEG: The Heidelberg Imaging program in Cancer of the oesophago-gastric junction during Neoadjuvant treatment: HICON trial

    Directory of Open Access Journals (Sweden)

    Weichert Wilko

    2011-06-01

    Full Text Available Abstract Background 18-Fluorodeoxyglucose-PET (18F-FDG-PET can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy. Methods/Design The HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a 18FDG-PET scans will be performed before ( = Baseline and after 14 days of standard neoadjuvant therapy as well as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1 and at the end of radiochemotherapy (PET2. Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV. The percentage difference ΔSUV = 100 (SUVBaseline - SUV PET1/SUVBaseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference

  2. [Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement].

    Science.gov (United States)

    Jiménez-Ballvé, A; Serrano-Palacio, A; García-Sáenz, J A; Ortega Candil, A; Salsidua-Arroyo, O; Román-Santamaría, J M; Pelayo Alarcón, A; Fuentes Ferrer, M E; Carreras-Delgado, J L

    2015-01-01

    To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  3. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

    Science.gov (United States)

    Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

    2017-04-01

    The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

  4. Treatment of muscle invasive bladder cancer. Is there a role for neoadjuvant chemotherapy?

    International Nuclear Information System (INIS)

    Kuten, A.; Baz, M.; Rubinov, R.; Dale, J.; Haim, N.; Robinson, E.; Cohen, Y.

    1994-01-01

    We compared the outcome of 3 different but widely accepted treatment protocols for bladder cancer in ordet to find which, if any, was superior, with particular emphasis upon the performance of the newest treatment, neoadjuvant chemotherapy. Data on 224 bladder patients treated at our institution (1975 to 1991) with 1 of the 3 protocols was analyzed. Those protocols were: 1. Radiotherapy >60 Gy (143 patients); 2. low dose radiotherapy followed by cystectomy (25 patients); 3. chemotherapy followed by either definitive radiotherapy or surgery (56 patients). Because the latter group was also a chronologically newer group with a shorter possible follow-up, we compared all treatments on the basis of 2-year survival, using Kaplan-Meier life tables. We briefly reviewed those modalities which are bladder-sparing because of the significance to quality of life of this factor. Two-year survival figures for the patients were: 63% for those wo received only radiotherapy; 72% for those undergoing cystectomy: 68% for the group to whom neoadjuvant chemotherapy was administered. The differences were not statistically significant. However, 23% of those patients treated neoadjuvantly were alive with intact bladders at 2 years. (orig./MG) [de

  5. Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Qiuyun Li

    Full Text Available BACKGROUND: Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. METHODS: The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. RESULTS: Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87-1.40, p = 0.43, pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83-1.18, p = 0.90, overall response rate (ORR; RR = 1.00, 95% CI 0.94-1.07, p = 0.93, or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93-1.04, p = 0.49. CONCLUSIONS: Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.

  6. Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Shelley; Lerski, Richard [Ninewells Hospital and Medical School, Department of Medical Physics, Dundee (United Kingdom); Purdie, Colin [Ninewells Hospital and Medical School, Department of Pathology, Dundee (United Kingdom); Michie, Caroline [Ninewells Hospital and Medical School, Department of Oncology, Dundee (United Kingdom); Evans, Andrew; Vinnicombe, Sarah [University of Dundee, Division of Imaging and Technology, Ninewells Hospital and Medical School, Dundee (United Kingdom); Johnston, Marilyn [Ninewells Hospital and Medical School, Department of Clinical Radiology, Dundee (United Kingdom); Thompson, Alastair M. [University of Texas MD Anderson Cancer Centre, Department of Breast Surgical Oncology, Houston, TX (United States)

    2017-11-15

    To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. (orig.)

  7. Neoadjuvant conformal chemoradiation with induction chemotherapy for rectal adenocarcinoma. A prospective observational study.

    Science.gov (United States)

    Fekete, Zsolt; Muntean, Alina-Simona; Hica, Ştefan; Rancea, Alin; Resiga, Liliana; Csutak, Csaba; Todor, Nicolae; Nagy, Viorica Magdalena

    2014-06-01

    The purpose of this prospective observational study was to evaluate the rate and the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphincter-saving surgery. We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy. The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p5 cm (p35 days (p5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure. Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.

  8. Role of mammography in evaluating residual cancer of locally advanced breast carcinoma after neo-adjuvant chemotherapy : compared with clinical examination

    International Nuclear Information System (INIS)

    Choi, Byoung Wook; Kim, Eun Kyung; Oh, Ki Keun; Cho, Jae Min; Chung, Hyun Cheol; Lee, Byung Chan; Lee, Kyong Sik; Lee, Yong Hee

    1997-01-01

    To compare the usefulness of mammography and clinical examination in the evaluation of residual cancer of locally-advanced breast carcinoma treated with neoadjuvant chemotherapy. Among 67 patients with locally advanced breast carcinoma who were treated with neoadjuvant chemotherapy, 18, aged 35-67 (mean, 48) years, underwent mammography before and after this therapy. The 18 sets of mammographs were analyzed retrospectively and compared with the results of clinical examination based on histologic diagnosis. On histologic examinations, 16 of 18 patients (89%) were found to have residual cancer, but in one of these 16, mammography did not show this same result. On mammography, residual cancer was found in 16 patients, but in one of this group, histologic examination did not reveal the same finding. Clinically, a complete response was shown by four patients, and a partial response by 11 ; three showed no response. On histolgogic examination, three of the four patients with complete clinical response were found to have residual cancer. Post-treatment mammographic findings showed that 11 patients had measurable mass ; all of these had residual cancer (positive predictive value : 100%). However, five of seven patients in whom no measurable mass was evident also had residual cancer. Seven of 8 patients in whom microcalcifications were seen on mammography were found to have residual cancer (positive predictive value : 88%). The sensitivity of mammography in predicting residual cancer was greater than that of clinical examination (94% vs 81%), even when microscopic residual cancer was considered as a complete response (92% vs 77%). The specificity of mammography was the same as that of clinical examination(50% vs 50%, 20% vs 20%). In evaluating residual cancer of locally-advanced breast carcinoma after neoadjuvant chemotheragy, mammography is more accurate and informative than clincal examination. In predicting residual cancer, however, it is not accurate enough to replace

  9. Response to neoadjuvant chemotherapy in locally advanced breast cancer according to tumor subtypes

    International Nuclear Information System (INIS)

    Tabassum, S.; Zahid, N.

    2017-01-01

    To compare the pathological response to neoadjuvant chemotherapy in different molecular subtypes of breast cancer Study Design: Prospective cohort study. Place and Duration of Study: Department of Oncology Liaquat National Hospital Karachi from Jan 2013 to Dec 2014. Material and Methods: A total of 119 patients received neo-adjuvant chemotherapy for locally advanced breast cancer followed by definitive surgery. Demographic, clinical and pathological data of 101 patients were available for analysis. Tumors were divided into different molecular subtypes, luminal A, luminal B human epidermal growth factor receptor 2 (HER 2) was negative, luminal B (HER 2 positive), HER 2 over expressed and triple negative. Neoadjuvant chemotherapy was given for total of eight cycles. Primary end point was pathological response [pathological complete response (PCR) versus no PCR] after surgery. Results: A total of 101 patients data were analyzed. Seventeen (16.8%) were luminal A, thirty eight (37.6%) were luminal B, out of 38 luminal B patients, twenty one (55.2%) were HER 2 + and seventeen (44.7%) were HER 2 -ve. Sixteen (15.8%) patients were HER 2 over expressed and thirty (29.7%) were triple negative. Out of 101 patients, twenty eight (27.72%) achieved PCR. A total of 5.9% achieved PCR in luminal A, 4.8% had PCR in luminal B (HER 2 -ve type), 23.5% had in luminal B (HER 2 +ve type), 50% achieved PCR in HER-2 over expressed type and 46.7% had PCR in triple negative subtype, (p=0.001). There was no significant association of PCR with age, tumor size, lymph node status, histology or grade. Conclusion: Molecular subtypes of breat cancer were found to be statistically significant predictor of PCR after neoadjuvant chemotherapy. (author)

  10. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

    International Nuclear Information System (INIS)

    Chintamani; Singhal, Vinay; Singh, JP; Lyall, Ashima; Saxena, Sunita; Bansal, Anju

    2004-01-01

    Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio). Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide) were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was assessed using chi-square test and coefficient

  11. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer

    NARCIS (Netherlands)

    Lips, Esther H.; Mukhtar, Rita A.; Yau, Christina; de Ronde, Jorma J.; Livasy, Chad; Carey, Lisa A.; Loo, Claudette E.; Vrancken-Peeters, Marie-Jeanne T. F. D.; Sonke, Gabe S.; Berry, Donald A.; van't Veer, Laura J.; Esserman, Laura J.; Wesseling, Jelle; Rodenhuis, Sjoerd; Shelley Hwang, E.

    2012-01-01

    Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene

  12. Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study

    Science.gov (United States)

    De Martini, Paolo; Ceresoli, Marco; Mari, Giulio M.; Costanzi, Andrea; Maggioni, Dario; Pugliese, Raffaele; Ferrari, Giovanni

    2017-01-01

    Background To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Becker’s criteria) and volume change assessed by CT. Results Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52–36.80 months) and 36.60 months (range, 24.3–52.9 months), respectively. The median follow up was 27 months (range, 5.00–68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required. PMID:29299362

  13. Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Fangberget, A.; Holmen, M.M.; Nilsen, L.B.; Hole, K.H.; Engebraaten, O.; Naume, B.; Smith, H.J.; Olsen, D.R.; Seierstad, T.

    2011-01-01

    To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not. Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37-72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated. Before NAC, HER2 overexpression was the single significant predictor of pCR (p = 0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42 x 10 -3 mm 2 /s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%. ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR. (orig.)

  14. Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

    Science.gov (United States)

    Gaß, Paul; Fasching, Peter A.; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W.; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M.; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y.; Beckmann, Matthias W.; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R.

    2016-01-01

    Background Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. PMID:27920623

  15. Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma

    International Nuclear Information System (INIS)

    Kitamura, Kei; Shirato, Hiroki; Sawamura, Yutaka; Suzuki, Keishiro; Ikeda, Jun; Miyasaka, Kazuo

    1999-01-01

    Purpose: To investigate the importance of preirradiation mental and endocrinological evaluation, and the effectiveness of involved-field radiotherapy following neoadjuvant chemotherapy. Methods and Materials: Following etoposide and cisplatin with or without ifosfamide, 13 patients with nondisseminated disease received involved-field irradiation of 24 Gy in 12 fractions within 3 weeks and 2 patients with disseminated germinoma received 24 Gy craniospinal irradiation (CSI). CT simulation was used to cover the tumor bed. Results: Full-scale intelligence quotient (IQ) tests given at the time of the initial radiotherapy showed less than 90 in 7 of 11 patients who had tumors involving the neurohypophyseal region, but the 4 patients who had solitary pineal tumors showed higher scores. Panhypopituitarism was observed in 9 patients with tumors involving the neurohypophyseal region. All patients are alive without disease, with a median follow-up period of 40 months. No in-field relapse was noted after the involved-field radiotherapy. One patient experienced a recurrence outside of the planning target volume. Conclusion: Decline of neurocognitive and endocrine functions were often seen in patients with tumors involving the hypophyseal region, but not in patients with solitary pineal germinoma before radiotherapy. Involved-field radiotherapy using 24 Gy is effective with the help of CT simulation and neoadjuvant chemotherapy

  16. Machine learning for predicting the response of breast cancer to neoadjuvant chemotherapy.

    Science.gov (United States)

    Mani, Subramani; Chen, Yukun; Li, Xia; Arlinghaus, Lori; Chakravarthy, A Bapsi; Abramson, Vandana; Bhave, Sandeep R; Levy, Mia A; Xu, Hua; Yankeelov, Thomas E

    2013-01-01

    To employ machine learning methods to predict the eventual therapeutic response of breast cancer patients after a single cycle of neoadjuvant chemotherapy (NAC). Quantitative dynamic contrast-enhanced MRI and diffusion-weighted MRI data were acquired on 28 patients before and after one cycle of NAC. A total of 118 semiquantitative and quantitative parameters were derived from these data and combined with 11 clinical variables. We used Bayesian logistic regression in combination with feature selection using a machine learning framework for predictive model building. The best predictive models using feature selection obtained an area under the curve of 0.86 and an accuracy of 0.86, with a sensitivity of 0.88 and a specificity of 0.82. With the numerous options for NAC available, development of a method to predict response early in the course of therapy is needed. Unfortunately, by the time most patients are found not to be responding, their disease may no longer be surgically resectable, and this situation could be avoided by the development of techniques to assess response earlier in the treatment regimen. The method outlined here is one possible solution to this important clinical problem. Predictive modeling approaches based on machine learning using readily available clinical and quantitative MRI data show promise in distinguishing breast cancer responders from non-responders after the first cycle of NAC.

  17. State of the art of neoadjuvant chemotherapy in breast cancer: rationale, results and recent developments

    Directory of Open Access Journals (Sweden)

    Solomayer, Erich-Franz

    2005-09-01

    Full Text Available Aims, results, advantages and possible disadvantages of preoperative chemotherapy (pCHT for breast cancer are discussed in this review. Established chemotherapeutic regimens are described with respect to new drugs that are added to combinations now and in the future. Illustrating the potential of new components, trastuzumab and cytotoxic chemotherapy, were combined in neoadjuvant trials for the first time. This approach yielded impressing and unprecedented high pathological response rates. An overview regarding current neoadjuvant cytostatic and immunotherapy trials is given. Established prognostic factors like axillary lymph-nodal status are altered during pCHT, which causes the need for new prognostic markers. The consequences of these changes for clinical decision making are demonstrated. It seems possible that the advances of gene array and protein expression profile technologies will lead to improved prognostic and predictive statements. Tumor tissue can be analyzed before during and after treatment in this regard recent studies investigating the response to specific, chemotherapeutics in correlation to molecular markers are reviewed. These approaches might enable us to identify chemoresistance of specific tumors. Furthermore pCHT allows testing of chemosensitivity in vivo in an early stage, which might lead to a more individualized cancer therapy. We discuss radiotherapy after neoadjuvant therapy and the risk of local relapse after breast conserving surgery, which was made feasible by pCHT. It is shown how the evaluation of efficacy of new cancer drugs, using the neoadjuvant situation, can be done more rapidly than in the metastatic and adjuvant setting.

  18. Impact of Blood Transfusions on Survival of Locally Advanced Cervical Cancer Patients Undergoing Neoadjuvant Chemotherapy Plus Radical Surgery.

    Science.gov (United States)

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Lopez, Carlos; Indini, Alice; Leone Roberti Maggiore, Umberto; Sabatucci, Ilaria; Lorusso, Domenica; Raspagliesi, Francesco

    2017-03-01

    Transfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer. Data of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models. The study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis, we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09-4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95% CI, 0.92-9.63; P = 0.06) and pathological (P = 0.03) response at neoadjuvant chemotherapy as well as parametrial (P = 0.004), vaginal (P < 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95% CI, 1.20-7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00-6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91-8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival. The role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted.

  19. Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

    LENUS (Irish Health Repository)

    Mulsow, J

    2012-02-01

    Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

  20. The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

    Science.gov (United States)

    Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

    2012-04-01

    This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

  1. Intratumoral and peritumoral radiomics for the pretreatment prediction of pathological complete response to neoadjuvant chemotherapy based on breast DCE-MRI.

    Science.gov (United States)

    Braman, Nathaniel M; Etesami, Maryam; Prasanna, Prateek; Dubchuk, Christina; Gilmore, Hannah; Tiwari, Pallavi; Plecha, Donna; Madabhushi, Anant

    2017-05-18

    In this study, we evaluated the ability of radiomic textural analysis of intratumoral and peritumoral regions on pretreatment breast cancer dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). A total of 117 patients who had received NAC were retrospectively analyzed. Within the intratumoral and peritumoral regions of T1-weighted contrast-enhanced MRI scans, a total of 99 radiomic textural features were computed at multiple phases. Feature selection was used to identify a set of top pCR-associated features from within a training set (n = 78), which were then used to train multiple machine learning classifiers to predict the likelihood of pCR for a given patient. Classifiers were then independently tested on 39 patients. Experiments were repeated separately among hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR + , HER2 - ) and triple-negative or HER2 + (TN/HER2 + ) tumors via threefold cross-validation to determine whether receptor status-specific analysis could improve classification performance. Among all patients, a combined intratumoral and peritumoral radiomic feature set yielded a maximum AUC of 0.78 ± 0.030 within the training set and 0.74 within the independent testing set using a diagonal linear discriminant analysis (DLDA) classifier. Receptor status-specific feature discovery and classification enabled improved prediction of pCR, yielding maximum AUCs of 0.83 ± 0.025 within the HR + , HER2 - group using DLDA and 0.93 ± 0.018 within the TN/HER2 + group using a naive Bayes classifier. In HR + , HER2 - breast cancers, non-pCR was characterized by elevated peritumoral heterogeneity during initial contrast enhancement. However, TN/HER2 + tumors were best characterized by a speckled enhancement pattern within the peritumoral region of nonresponders. Radiomic features were found to strongly predict pCR independent of

  2. A meta-analysis of 18F-FDG PET or PET/CT for the evaluation of neoadjuvant chemotherapy in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Xi Yun; Zhang Min; Guo Rui; Zhang Miao; Hu Jiajia; Li Biao

    2012-01-01

    Objective: To evaluate the accuracy and predictive value of 18 F-FDG PET or PET/CT in the assessment of neoadjuvant chemotherapy in locally advanced breast cancer by meta-analysis. Methods: Relevant studies were retrieved from PubMed, Embase, Cochrane and Wanfang, in English or Chinese. To ensure the homogeneity of all included studies, selection criteria were established and all the studies were scored according to a quality assessment of diagnostic accuracy studies (QUADAS) table. The combined Se, Sp, LR, diagnostic odds ratio (DOR), and AUC of PET and other conventional imaging techniques were compared. The assessment standard of neoadjuvant chemotherapy by conventional imaging techniques is tumor size change. Funnel plot and analysis with meta-regression were performed to explore the source of heterogeneity. Results: Sixteen eligible studies were included with a total of 662 subjects. The combined results were: (1) PET: Se PET 86.1% (247/287), Sp PET 69.6% (261/375), LR + PET 3.18, LR - PET 0.23, DOR PET 17.26; (2) Other imaging techniques: Se d 57.2% (91/159), Sp d 48.5% (50/103), LR + d 1.07, LR - d 0.87, DOR d 1.30. ROC analysis showed that Q * values of PET (Q PET * ) and other imaging techniques (Q d * ) were 0.8058 and 0.5328, respectively. Funnel plot showed that publication bias was not the main source of heterogeneity. Meta-regression results suggested that the year of publication might be one of the sources of heterogeneity (P=0.05). Conclusion: This meta-analysis suggests that, in the assessment of treatment response of neoadjuvant chemotherapy for breast cancer, FDG PET or PET/CT in monitoring the changes in glucose metabolism is more accurate than conventional imaging techniques in monitoring tumor size. (authors)

  3. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

    Directory of Open Access Journals (Sweden)

    Singh JP

    2004-08-01

    Full Text Available Abstract Background Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. Methods 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio. Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was

  4. PLANNING PHASE 2 MULTICENTER RANDOMIZED TRIAL OF NEOADJUVANT CHEMO-RADIOTHERAPY FOLLOWED BY D2 GASTRECTOMY AND ADJUVANT CHEMOTHERAPY FOR LOCALLY ADVANCED GASTRIC CANCER

    Directory of Open Access Journals (Sweden)

    V. Yu. Skoropad

    2016-01-01

    Full Text Available Introduction. The prognosis for surgical treatment of locally advanced gastric cancer remains disappointing. Neoadjuvant chemo-radiation therapy is relatively new and the least researched method of treatment, it is attracting more and more attention, mainly abroad in recent years. The aims of neoadjuvant therapy is the earliest start of systemic therapy, damage of the primary tumor and regional metastases, an increase in the percentage of radical operations, improving treatment outcome. Material and methods. The planning study is a multicenter, randomized clinical phase II trial. Patients of the first (experimental group will be treated as the followes: neoadjuvant chemo-radiotherapy (total tumor dose of 46 Gy in 23 fractions with the concurrent modified CapOX scheme followed by D2 gastrectomy and adjuvant chemotherapy. Patients of the second (control group will be treated with D2 gastrectomy and adjuvant chemotherapy. Adjuvant chemotherapy will be carried out under the following schemes (optional for the researchers: CapOX or FOLFOX. Toxicity evaluation of neoadjuvant chemo-radiotherapy and adjuvant chemotherapy will be conducted with NCI CTC Toxicity Scale Version 3.0. The main objectives of the trial are to assess the safety and immediate effectiveness of neoadjuvant chemo-radiotherapy according to the criteria of the frequency and severity of postoperative complications and mortality, and tumor response. We are planning to include 80 patients with morphologically confirmed gastric cancer сT2–4N1–3, сT3–4N0–3; М0. The proposed trial will be carried out in accordance with the principles of the Helsinki Declaration, it has been approved by local ethic committees of the participated institutions. Results. As a result of this multicenter randomized trial it is planned to show the reproducibility of obtained in MRRC and a number of foreign centers results – that is, the safety and high immediate effectiveness of neoadjuvant chemo

  5. Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

    Directory of Open Access Journals (Sweden)

    Sanambar Sadighi

    2015-06-01

    Full Text Available To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years. Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%. No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014. Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes.

  6. Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized Phase III study

    International Nuclear Information System (INIS)

    Lewin, Freddi; Damber, Lena; Jonsson, Haakan; Andersson, Torsten; Berthelsen, Anne; Bioerklund, Anders; Blomqvist, Erik; Evensen, Jan F.; Hansen, Hanne S.; Hansen, Olfred; Jetlund, Olav; Mercke, Claes; Modig, Hans; Overgaard, Marie; Rosengren, Bengt; Tausjoe, Johan; Ringborg, Ulrik

    1997-01-01

    Background and purpose: In 1986 a prospective, randomized, multi-centre trial for evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the treatment of advanced squamous cell carcinoma of the head and neck was initiated. As survival in this group of patients is poor the purpose was to find a possible survival benefit of the chemotherapy in addition to radiotherapy compared to radiotherapy only. Methods. Four-hundred sixty-one patients from Denmark, Norway and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were randomized to receive either standard treatment (radiotherapy or radiotherapy followed by surgery) or neoadjuvant chemotherapy followed by standard treatment. Chemotherapy included three courses of cisplatin 100 mg/m 2 i.v. infusion on day 1 followed by 5-fluorouracil 1000 mg/m 2 per day continuous i.v. infusion for 120 hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to patients in both treatment arms. Results: Response rate was 71% for patients randomized to chemotherapy-radiotherapy and 66% for patients randomized to standard treatment (not statistically significant). Residual tumors were excised if possible. After surgery 62% of the patients randomized to chemotherapy-radiotherapy and 60% of the patients in the standard treatment group were clinically tumor free. Conclusions: No statistically significant benefit in survival was observed for patients treated with neoadjuvant chemotherapy followed by radiotherapy. Nor was there any impact of chemotherapy on the number of patients achieving loco-regional tumor control after primary treatment

  7. Clinical trial of neoadjuvant chemotherapy combined with radiotherapy for primary intracranial germinomas

    International Nuclear Information System (INIS)

    Kitamura, Kei; Suzuki, Keishiro; Shirato, Hiroki; Kagei, Kenji; Aoyama, Hidefumi; Sawamura, Yutaka; Ikeda, Jun; Miyasaka, Kazuo

    1997-01-01

    Purpose/Objective: Since 1992, we have been using neoadjuvant chemotherapy to reduce the radiation dose and irradiated volume in the treatment of intracranial germinomas. This study evaluates the initial response and complications of the treatment and also the IQ score and pituitary function of patients before radiotherapy. Materials and methods: Fifteen patients with histologically confirmed intracranial germinomas were treated between 1992 and 1997. Six patients with solitary pure germinoma received 3 to 4 courses of etoposide and cisplatin (EP regimen) followed by localized irradiation of 24Gy (in 12 fractions within 3 weeks). Three patients with germinoma with syncytiotrophoblastic giant cells (STGC) and 4 patients with multifocal pure germinoma received 3 to 5 courses of ifosfamide, cisplatin and etoposide (ICE regimen), followed by localized irradiation of 24 Gy. Two patients with disseminated pure germinoma received 2 to 4 courses of ICE regimen followed by craniospinal irradiation of 24 Gy. In the planning of localized irradiation, the treatment field was determined so as to cover the tumor with a margin of 2cm. The IQ score and pituitary function before radiotherapy were also examined. MRI was performed in all patients one month after the completion of treatment and every 6 months in the follow-up study. The treatment data of our institute before 1991, as historical control, was analyzed and compared to that of the present study. Results: Complete remission (CR) was obtained in all patients after the treatment. One patient with germinoma with STGC experienced recurrence out of the field at 39 months after surgery. He was re-treated with salvage therapy including the ICE regimen and obtained a second complete remission. All patients are alive without disease with a median follow-up period of 29 months. The examination of IQ score and pituitary function before radiotherapy revealed mental retardation in 2 patients (22%) and hypopituitarism in 13 patients (86

  8. Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial.

    Science.gov (United States)

    Thomas, Jeremy St John; Provenzano, Elena; Hiller, Louise; Dunn, Janet; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Gounaris, Ioannis; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Stephen; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Caldas, Carlos; Bartlett, John Ms; Cameron, David Allan; Hayward, Richard Laurence; Earl, Helena Margaret

    2017-08-01

    The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation

  9. Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer.

    Science.gov (United States)

    Henderson, Shelley; Purdie, Colin; Michie, Caroline; Evans, Andrew; Lerski, Richard; Johnston, Marilyn; Vinnicombe, Sarah; Thompson, Alastair M

    2017-11-01

    To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer. This was a retrospective study of 88 consenting women (age: 30-79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2-3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated. Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%. Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy. • Texture analysis provides a means of measuring lesion heterogeneity on MRI images. • Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response. • Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes. • Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

  10. Predictive value of BRCA1/2 mRNA expression for response to neoadjuvant chemotherapy in BRCA-negative breast cancers.

    Science.gov (United States)

    Xu, Ye; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2018-01-01

    It is well known that BRCA1 and BRCA2 play a central role in DNA repair, but the relationship between BRCA1 and BRCA2 mRNA expression and response to neoadjuvant chemotherapy in sporadic breast cancer patients has not been well established. Here, we investigate the association between BRCA1 or BRCA2 mRNA expression levels and pathological response in 674 BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant chemotherapy. BRCA1 and BRCA2 mRNA expression were assessed using quantitative real-time polymerase chain reaction in core biopsy breast cancer tissue obtained prior to the initiation of neoadjuvant chemotherapy. A total 129 patients (19.1%) achieved pathological complete response (pCR) after neoadjuvant chemotherapy. Among patients treated with anthracycline-based chemotherapy (n = 531), BRCA1 mRNA low expression patients had a significantly higher pCR rate than intermediate or high BRCA1 mRNA expression groups (24.6% vs 16.8% or 14.0%, P = .031) and retained borderline significance (OR = 1.54, 95% CI = 0.93-2.56, P = .094) in multivariate analysis. Among the 129 patients who received a taxane-based regimen, pCR rate showed no differences in BRCA1 low, intermediate, and high mRNA level subgroups (19.6%, 26.8% and 21.4%, respectively; P = .71). BRCA2 mRNA level was not associated with pCR rate in the anthracyline-based treated subgroup (P = .60) or the taxane-based regimen subgroup (P = .82). Taken together, our findings suggested that BRCA1 mRNA expression could be used as a predictive marker in BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant anthracycline-based treatment. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  11. Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Drisis, Stylianos; Stathopoulos, Konstantinos; Chao, Shih-Li; Lemort, Marc [Institute Jules Bordet, Radiology Department, Brussels (Belgium); Metens, Thierry [Erasme University Hospital, Radiology Department, Brussels (Belgium); Ignatiadis, Michael [Institute Jules Bordet, Oncology Department, Brussels (Belgium)

    2016-05-15

    To assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups. Eighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2-, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model. At EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2-. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 - EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER-. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCR Quantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2- group. (orig.)

  12. Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

    Science.gov (United States)

    Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

    2017-06-01

    We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

  13. Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her-2-neu, and GADD45 expression in oral squamous cell carcinoma.

    Science.gov (United States)

    Pandey, Manoj; Kannepali, Krishna Kiran; Dixit, Ruhi; Kumar, Mohan

    2018-01-31

    Head and neck cancers are the commonest cancer in Southeast Asia. Despite being a surface cancer, it is associated with significant morbidity as despite early detection by the patients they often report for treatment late and hence are associated with poor prognosis. The role of neoadjuvant chemotherapy in head and neck cancer is still under evaluation; there is a large subgroup of population that does not respond to chemotherapy, and hence, most studies have failed to show any survival benefit. This study evaluated the role of neoadjuvant therapy with docetaxel and carboplatin in patients with oral cancer and correlated the response to human papilloma virus, EGFR1, EGFR2, and GADD45 expression. A total of 24 locally advanced, non-metastatic oral cancer patients were included in the study. Tumor biopsies were taken prior to the start of neoadjuvant therapy for expression of EGFR, Her-2-Neu, and GADD45 by immunohistochemistry and for HPV by PCR. The response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria after three cycles of chemotherapy. Statistical analysis was performed using correlation and Kaplan-Meier analysis; the difference in survival was calculated with log rank test. A total of 21 male and 3 female with a mean age of 53.12 years were enrolled. Sixty-five percent of these received three cycles of chemotherapy. Five patients were positive for HPV 16 and none for HPV 18. Twenty-two of 24 patients showed GADD45 expression, 3 showed expression of Her-2-Neu while all 24 showed expression for EGFR1 protein. Two-year overall survival was 81%; GADD45 expressions were found to significantly affect the overall and disease-free survival, while any of the other protein expression studied and HPV status was not significant. The result of the present study shows significant downgrading of the oral cancers with neoadjuvant chemotherapy suggesting its utility in borderline operable cases. However, the response of chemotherapy does not

  14. Neoadjuvant intra-arterial chemotherapy with a combination of radiotherapy for the treatment of invasive bladder carcinoma

    International Nuclear Information System (INIS)

    Sumiyoshi, Yoshiteru; Uyama, Takeshi.

    1992-01-01

    Fifty patients with invasive bladder carcinoma were treated with neoadjuvant intra-arterial chemotherapy using doxorubicin or pirarubicin, and this was combined with low dose radiotherapy. All of 50 patients were evaluated for clinical and histological efficacy. Twenty-nine of 50 (58%) patients achieved a clinically complete remission (CR) and 17 of 50 (34%) achieved a clinically partial remission (PR). Twenty-eight of 50 (56%) achieved a histological CR and 13 of 50 (26%) achieved a histological PR. The patients who underwent bladder preservation operations after this treatment and were followed up for longer than 3 years were evaluated for long-term results. The 5-year survival for 35 patients in this group was 74.1%. The 5-year survival for patients with a clinical CR was 93.3%, and for patients with a clinical PR it was 45.3%. The survival for patients with a histological CR was 93.3%, and for patients with a histological PR, it was 85.7%. This study suggests that neoadjuvant intra-arterial chemotherapy plus radiotherapy is a useful regimen that could become the treatment of first choice for patients with invasive bladder carcinoma. Patients who achieved a histological CR or PR with this regimen, might be able to retain the function of their bladders. (author)

  15. Systemic immune–inflammation index as a useful prognostic indicator predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Chen L

    2017-12-01

    Full Text Available Li Chen,1,* Ying Yan,2,* Lihua Zhu,3 Xiliang Cong,1 Sen Li,1 Shubin Song,1 Hongjiang Song,1 Yingwei Xue1 1Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, 2Department of Internal Oncology, Harbin The First Hospital, Harbin, Heilongjiang, 3Department of Pathogen Biology, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei, China *These authors contributed equally to this work Background and objective: A novel systemic immune–inflammation index named SII (SII=N×P/L, which is based on neutrophil (N, platelet (P and lymphocyte (L counts, has emerged and reflects comprehensively the balance of host inflammatory and immune status. We aimed to evaluate the potential prognostic significance of SII in patients with advanced gastric cancer who received neoadjuvant chemotherapy.Subjects and methods: The retrospective analysis included data from 107 patients with advanced gastric cancer undergoing neoadjuvant chemotherapy and 185 patients with pathology-proven gastric cancer. The optimal cutoff value of SII by receiver operating characteristic curve stratified patients into low SII (<600×109/L and high SII (SII ≥600×109/L groups. The clinical outcomes of disease-free survival (DFS and overall survival (OS were calculated by Kaplan–Meier survival curves and compared using log-rank test. Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SII.Results: The results indicated that SII had prognostic significance using the cutoff value of 600×109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Low SII was associated with prolonged DFS and OS, and the mean DFS and OS for patients with low SII were longer than for those with high SII (57.22 vs 41.56 months and 62.25 vs 45.60 months, respectively. Furthermore, we found that patients

  16. Early port-site metastasis during neoadjuvant chemotherapy in advanced stage ovarian cancer: report of two cases

    OpenAIRE

    Özmen, Batuhan; Şükür, Yavuz Emre; Atabekoglu, Cem Somer; Heper, Aylin Okçu; Sönmezer, Murat; Güngör, Mete

    2011-01-01

    Port-site metastases in gynecological malignancies subsequent to laparoscopy have been reported with an incidence of 1.1-16%. These metastases tend to be disappearing after primary debulking surgery and subsequent primary chemotherapy. Local resection, chemotherapy and/or radiotherapy have been defined in the management of these metastases with enhanced clinical success. However, in extremely rare cases these metastases were also defined very early during neoadjuvant chemotherapy. Herein, we ...

  17. Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Shueng, Pei-Wei; Hsieh, Chen-Hsi; Shen, Bing-Jie; Wu, Le-Jung; Liao, Li-Jen; Hsiao, Chi-Huang; Lin, Yu-Chin; Cheng, Po-Wen; Lo, Wu-Chia; Jen, Yee-Min

    2011-01-01

    To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC). Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction. After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively. HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings

  18. Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

    International Nuclear Information System (INIS)

    Hyun, Su Jeong; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung

    2016-01-01

    To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. (orig.)

  19. Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

    Energy Technology Data Exchange (ETDEWEB)

    Hyun, Su Jeong [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of); Hallym University Medical Center, Department of Radiology, Kangnam Sacred Heart Hospital, Seoul (Korea, Republic of); Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung [Yonsei University College of Medicine, Department of Radiology, Breast Cancer Clinic, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of)

    2016-11-15

    To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. (orig.)

  20. Prospective and comparative assessment of toxicity of adjuvant concomitant chemo-radiotherapy after neo-adjuvant chemotherapy in breast cancer; evaluation prospective et comparative de la toxicite de la chimioradiotherapie concomitante adjuvante apres chimiotherapie neoadjuvante dans le cancer du sein

    Energy Technology Data Exchange (ETDEWEB)

    Marchand, V.; Angelergues, A.; Gobaux, V.; Kirova, Y.M.; Campana, F.; Dendale, R.; Reyal, F.; Pierga, J.Y.; Fourquet, A.; Bollet, M.A. [Institut Curie, Paris (France)

    2011-10-15

    The authors report a prospective assessment of toxicity a treatment comprising an adjuvant chemo-radiotherapy after neo-adjuvant chemotherapy and a comparison with a treatment comprising only radiotherapy. Two sets of patients have been treated for a breast cancer between 1997 and 2002 by association of neo-adjuvant chemotherapy, surgery and radiotherapy with or without concomitant chemotherapy. Late toxicity has been assessed prospectively according to Common Terminology Criteria for Adverse Events. Acute toxicity has been noticed in medical files. The analysis of 142 treatments reveals that the concomitant administration of chemotherapy to radiotherapy after neo-adjuvant chemotherapy and surgery is associated with an increase of acute toxicity without increase of long term toxicity. Short communication

  1. Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer.

    Science.gov (United States)

    Yip, Connie; Goh, Vicky; Davies, Andrew; Gossage, James; Mitchell-Hay, Rosalind; Hynes, Orla; Maisey, Nick; Ross, Paul; Gaya, Andrew; Landau, David B; Cook, Gary J; Griffin, Nyree; Mason, Robert

    2014-05-01

    Sarcopenia and changes in body composition following neoadjuvant chemotherapy (NAC) may affect clinical outcome. We assessed the associations between CT body composition changes following NAC and outcomes in oesophageal cancer. A total of 35 patients who received NAC followed by oesophagectomy, and underwent CT assessment pre- and post-NAC were included. Fat mass (FM), fat-free mass (FFM), subcutaneous fat to muscle ratio (FMR) and visceral to subcutaneous adipose tissue ratio (VA/SA) were derived from CT. Changes in FM, FFM, FMR, VA/SA and sarcopenia were correlated to chemotherapy dose reductions, postoperative complications, length of hospital stay (LOS), circumferential resection margin (CRM), pathological chemotherapy response, disease-free survival (DFS) and overall survival (OS). Nine (26 %) patients were sarcopenic before NAC and this increased to 15 (43 %) after NAC. Average weight loss was 3.7 % ± 6.4 (SD) in comparison to FM index (-1.2 ± 4.2), FFM index (-4.6 ± 6.8), FMR (-1.2 ± 24.3) and VA/SA (-62.3 ± 12.7). Changes in FM index (p = 0.022), FMR (p = 0.028), VA/SA (p = 0.024) and weight (p = 0.007) were significant univariable factors for CRM status. There was no significant association between changes in body composition and survival. Loss of FM, differential loss of VA/SA and skeletal muscle were associated with risk of CRM positivity. • Changes in CT body composition occur after neoadjuvant chemotherapy in oesophageal cancer. • Sarcopenia was more prevalent after neoadjuvant chemotherapy. • Fat mass, fat-free mass and weight decreased after neoadjuvant chemotherapy. • Changes in body composition were associated with CRM positivity. • Changes in body composition did not affect perioperative complications and survival.

  2. Prediction of neoadjuvant radiation chemotherapy response and survival using pretreatment [{sup 18}F]FDG PET/CT scans in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Ji-In; Ha, Seunggyun; Kim, Sang Eun [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kang, Sung-Bum; Oh, Heung-Kwon [Seoul National University Bundang Hospital, Department of Surgery, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Lee, Keun-Wook [Seoul National University Bundang Hospital, Department of Internal Medicine, Seongnam (Korea, Republic of); Lee, Hye-Seung [Seoul National University Bundang Hospital, Department of Pathology, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Kim, Jae-Sung [Seoul National University Bundang Hospital, Department of Radiation Oncology, Seongnam (Korea, Republic of); Lee, Ho-Young [Seoul National University Bundang Hospital, Department of Nuclear Medicine, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Seoul National University, Cancer Research Institute, Seoul (Korea, Republic of)

    2016-03-15

    The aim of this study was to investigate metabolic and textural parameters from pretreatment [{sup 18}F]FDG PET/CT scans for the prediction of neoadjuvant radiation chemotherapy response and 3-year disease-free survival (DFS) in patients with locally advanced rectal cancer (LARC). We performed a retrospective review of 74 patients diagnosed with LARC who were initially examined with [{sup 18}F]FDG PET/CT, and who underwent neoadjuvant radiation chemotherapy followed by complete resection. The standardized uptake value (mean, peak, and maximum), metabolic volume (MV), and total lesion glycolysis of rectal cancer lesions were calculated using the isocontour method with various thresholds. Using three-dimensional textural analysis, about 50 textural features were calculated for PET images. Response to neoadjuvant radiation chemotherapy, as assessed by histological tumour regression grading (TRG) after surgery and 3-year DFS, was evaluated using univariate/multivariate binary logistic regression and univariate/multivariate Cox regression analyses. MVs calculated using the thresholds mean standardized uptake value of the liver + two standard deviations (SDs), and mean standard uptake of the liver + three SDs were significantly associated with TRG. Textural parameters from histogram-based and co-occurrence analysis were significantly associated with TRG. However, multivariate analysis revealed that none of these parameters had any significance. On the other hand, MV calculated using various thresholds was significantly associated with 3-year DFS, and MV calculated using a higher threshold tended to be more strongly associated with 3-year DFS. In addition, textural parameters including kurtosis of the absolute gradient (GrKurtosis) were significantly associated with 3-year DFS. Multivariate analysis revealed that GrKurtosis could be a prognostic factor for 3-year DFS. Metabolic and textural parameters from initial [{sup 18}F]FDG PET/CT scans could be indexes to assess

  3. The role of neoadjuvant chemotherapy in the management of locally advanced cervix cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Mohammed Osman

    2014-09-01

    Full Text Available Cervical cancer is the second most common cancer in women. Neoadjuvant chemotherapy for patients with locally advanced cervix cancer has comparable benefits to concurrent chemoradiotherapy (CCRT, but with fewer side effects. This systematic review aims to provide a comprehensive summary of the benefits of neoadjuvant chemotherapy for the management of locally advanced cervix cancer from stage IB2 (tumor >4.0 cm to IIIB (tumor extending to the pelvic wall and/or hydronephrosis. Our primary objective was to assess benefits in terms of survival. The data source included the USA national library of medicine, Medline search, and the National Cancer Institute PDQ Clinical Protocols. Inclusion criteria for consideration in the current systematic review included studies published between January 1997 and December 2012. In terms of histology, they had to be focused on squamous cell carcinoma, adenosquamous carcinoma, and/or adenocarcinoma. Patients should be either chemotherapy naïve or cervix cancer chemotherapy naïve, and have a performance status ≤2. The search in the above-mentioned scientific websites led to identify 49 publications, 19 of which were excluded, as they did not meet the inclusion criteria of this systematic review. Therefore only 30 studies were deemed eligible. Data was collected from 1760 patients enrolled in the current systematic review study. The mean age was 45.2 years. The mean tumor size was 4.7 cm. The most commonly used chemotherapies were cisplatin doublets. Paclitaxel was the most commonly used chemotherapeutic agent in the doublets. The mean chemotherapy cycles were 2.7. After chemotherapy, patients underwent surgery after a mean time of 2.5 weeks. The standard operation was radical hysterectomy with pelvic lymphadenectomy. Chemotherapy achieved an objective response rate of 84%. The 5-year progression-free survival and overall survival were 61.9% and 72.8% respectively. The treatment protocol was associated

  4. Neoadjuvant and adjuvant chemotherapy for locally advanced bladder carcinoma. Development of novel bladder preservation approach, Osaka Medical College regimen

    International Nuclear Information System (INIS)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Ibuki, Naokazu; Nomi, Hayahito; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Ubai, Takanobu

    2012-01-01

    Cisplatin-based chemotherapy has been widely used in a neoadjuvant as well as adjuvant setting. Furthermore, trimodal approaches including complete transurethral resection of the bladder tumor followed by combined chemotherapy and radiation have generally been performed as bladder preservation therapy. However, none of the protocols have achieved a 5-year survival rate of more than 70%. Additionally, the toxicity of chemotherapy and/or a decreased quality of life due to urinary diversion cannot be ignored, as most patients with bladder cancer are elderly. We therefore newly developed the novel trimodal approach of ''combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects (''Osaka Medical College regimen'' referred to as the OMC regimen). We initially applied the OMC regimen as neoadjuvant chemotherapy for locally advanced bladder cancer. However, since more than 85% of patients with histologically-proven urothelial cancer achieved complete response with no evidence of recurrence after a mean follow-up of 170 (range 21-814) weeks, we have been applying the OMC-regimen as a new approach for bladder sparing therapy. We summarize the advantage and/or disadvantage of chemotherapy in neoadjuvant as well as adjuvant settings, and show the details of our newly developed bladder sparing approach OMC regimen in this review. (author)

  5. Gene trio signatures as molecular markers to predict response to doxorubicin cyclophosphamide neoadjuvant chemotherapy in breast cancerpatients

    Directory of Open Access Journals (Sweden)

    M.C. Barros Filho

    2010-12-01

    Full Text Available In breast cancer patients submitted to neoadjuvant chemotherapy (4 cycles of doxorubicin and cyclophosphamide, AC, expression of groups of three genes (gene trio signatures could distinguish responsive from non-responsive tumors, as demonstrated by cDNA microarray profiling in a previous study by our group. In the current study, we determined if the expression of the same genes would retain the predictive strength, when analyzed by a more accessible technique (real-time RT-PCR. We evaluated 28 samples already analyzed by cDNA microarray, as a technical validation procedure, and 14 tumors, as an independent biological validation set. All patients received neoadjuvant chemotherapy (4 AC. Among five trio combinations previously identified, defined by nine genes individually investigated (BZRP, CLPTM1,MTSS1, NOTCH1, NUP210, PRSS11, RPL37A, SMYD2, and XLHSRF-1, the most accurate were established by RPL37A, XLHSRF-1based trios, with NOTCH1 or NUP210. Both trios correctly separated 86% of tumors (87% sensitivity and 80% specificity for predicting response, according to their response to chemotherapy (82% in a leave-one-out cross-validation method. Using the pre-established features obtained by linear discriminant analysis, 71% samples from the biological validation set were also correctly classified by both trios (72% sensitivity; 66% specificity. Furthermore, we explored other gene combinations to achieve a higher accuracy in the technical validation group (as a training set. A new trio, MTSS1, RPL37 and SMYD2, correctly classified 93% of samples from the technical validation group (95% sensitivity and 80% specificity; 86% accuracy by the cross-validation method and 79% from the biological validation group (72% sensitivity and 100% specificity. Therefore, the combined expression of MTSS1, RPL37 and SMYD2, as evaluated by real-time RT-PCR, is a potential candidate to predict response to neoadjuvant doxorubicin and cyclophosphamide in breast cancer

  6. Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Tiffany A. Pompa

    2017-01-01

    Full Text Available Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC, the National Comprehensive Cancer Network (NCCN suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring 6.2×3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles, intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.

  7. [Neoadjuvant Chemotherapy Using S-1 for Pancreatic Cancer - Mid-Term Results].

    Science.gov (United States)

    Homma, Yuki; Honda, Goro; Sakamoto, Katsunori; Kurata, Masanao; Honjo, Masahiko; Hirata, Yoshihiro; Shinya, Satoshi

    2016-10-01

    Although surgical resection is the only curative strategy for pancreatic cancer, the prognosis of patients with pancreatic cancer remains poor. Recently, neoadjuvant treatment has been frequently employed as a promising treatment. Here, the mid-term results of neoadjuvant chemoradiotherapy(NACRT)using S-1, which has been performed in our hospital since 2008, are reported. Seventy-nine patients with resectable or borderline resectable pancreatic ductal adenocarcinoma, who had been intended to undergo NACRT treatment using S-1, were enrolled. The NACRT comprised radiotherapy( 1.8 Gy×28 days)and full-dose twice-daily oral S-1 given on the same days as the radiotherapy. The results of the NACRT and pancreatectomy and the patients' prognoses were evaluated. Fifty-five patients(69.6%)underwent pancreatectomy, with no case of mortality. The curative resection rate was 94.5%. Postoperative adjuvant chemotherapy was administered in 46 patients(83.6%). The 3-year survival rates of all 79 patients and 55 pancreatectomy patients were 40.1% and 50.4%, respectively. NACRT using S-1 was found to be feasible, and good mid-term outcomes were obtained. However, analysis of the long-term outcomes and comparisons with other novel anti-cancer drugs are still required.

  8. Study on the value of color Doppler ultrasound in evaluating the efficacy of neoadjuvant chemotherapy for breast cancer

    Directory of Open Access Journals (Sweden)

    Chao-Xi Li

    2016-05-01

    Full Text Available Objective: To explore the value of color Doppler flow imaging (CDFI in evaluating the efficacy of neoadjuvant chemotherapy (NCT for breast cancer. Methods: A total of 60 patients with breast cancer who were admitted in our hospital from January, 2015 to December, 2015 were included in the study. TC scheme was used for chemotherapy before operation, i.e. cyclophosphamide 600 mg/m2, docetaxel 75 mg/m2, IV. Three-week treatment was regarded as one course, for 2-4 weeks. After chemotherapy for 1-2 week, the operation was performed. CDFI was used to observe the lesion location, number, size, shape, boundary, internal echo, surrounding echo, rear echo, axillary lymph node, and the relation with the surrounding tissues. The lesion resistance index (RI was measured. Results: CDFI results showed that 3 were CF, 35 were PR, 20 were SD, and 2 were PD, with a diagnostic sensitivity of 80.6% and coincidence rate of 68.3%. After NCT, the length, width, thickness, area, and volume of the lesions were significantly reduced when compared with before NCT. The comparison of the evaluation of the boundary resolution and echo of the lesions by CDFI before and after NCT was statistically significant. The pathological results showed that 31 were effective, and 29 were invalid, among which RI in the effective group was significantly reduced when compared with before NCT, while RI in the invalid group was not significantly different from that before NCT. Conclusions: The efficacy evaluation of NCT by CDFI is highly consistent with the pathology. CDFI in evaluating the size, boundary, echo, and blood flow indicators of the lesions is of great scientificity and clinical application value.

  9. MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

    Science.gov (United States)

    Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

    2017-06-01

    Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Clinical outcome of 19 patients with nasopharyngeal cancer. A review of neo-adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Sakamoto, Masayuki; Kitahara, Nobuo; Asanuma, Satoshi; Ichimura, Keiichi; Abe, Kazuya

    2001-01-01

    We clinically examined 19 cases of nasopharyngeal cancer in which primary care was administered in the Department of Otolaryngology, Tokyo Metropolitan Fuchu Hospital between September 1990 and August 1999. The subjects consisted of 11 males and 8 females. Histophathological study revealed 17 cases of WHO type III tumors (14 cases were poorly differentiated squamous cell carcinoma and 3 cases were lymph-epithelioma). The accumulated 5-year survival rate by the Kaplan-Meier method was 50% in T1, 75% in T2, 0% in T4, and 36% overall. Neo-adjuvant chemotherapy was administered in 15 cases and distant metastasis appeared in 3 cases (21%) after definitive radiotherapy. The biological characteristic of WHO type III tumors is a tendency towards early metastasis, and we speculated that this might be the cause of the lower level of effectiveness of the neo-adjuvant chemotherapy in these cases. At present, this therapy is not effective and further improvement is required. (author)

  11. Effect of breast cancer phenotype on diagnostic performance of MRI in the prediction to response to neoadjuvant treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bufi, Enida, E-mail: reagandus@alice.it [Department of Bioimaging and Radiological Sciences, Catholic University, Rome (Italy); Belli, Paolo; Di Matteo, Marialuisa [Department of Bioimaging and Radiological Sciences, Catholic University, Rome (Italy); Terribile, Daniela; Franceschini, Gianluca [Department of Surgery, Breast Unit, Catholic University, Rome (Italy); Nardone, Luigia [Department of Radiotherapy, Catholic University, Rome (Italy); Petrone, Gianluigi [Department of Pathology, Catholic University, Rome (Italy); Bonomo, Lorenzo [Department of Bioimaging and Radiological Sciences, Catholic University, Rome (Italy)

    2014-09-15

    Aim: The estimation of response to neoadjuvant chemotherapy (NAC) is useful in the surgical decision in breast cancer. We addressed the diagnostic reliability of conventional MRI, of diffusion weighted imaging (DWI) and of a merged criterion coupling morphological MRI and DWI. Diagnostic performance was analysed separately in different tumor subtypes, including HER2+ (human epidermal growth factor receptor 2)/HR+ (hormone receptor) (hybrid phenotype). Materials and methods: Two-hundred and twenty-five patients underwent MRI before and after NAC. The response to treatment was defined according to the RECIST classification and the evaluation of DWI with apparent diffusion coefficient (ADC). The complete pathological response – pCR was assessed (Mandard classification). Results: Tumor phenotypes were Luminal (63.6%), Triple Negative (16.4%), HER2+ (7.6%) or Hybrid (12.4%). After NAC, pCR was observed in 17.3% of cases. Average ADC was statistically higher after NAC (p < 0.001) among patients showing pCR vs. those who had not pCR. The RECIST classification showed adequate performance in predicting the pCR in Triple Negative (area under the receiver operating characteristic curve, ROC AUC = 0.9) and in the HER2+ subgroup (AUC = 0.826). Lower performance was found in the Luminal and Hybrid subgroups (AUC 0.693 and 0.611, respectively), where the ADC criterion yielded an improved performance (AUC = 0.787 and 0.722). The coupling of morphological and DWI criteria yielded maximally improved performance in the Luminal and Hybrid subgroups (AUC = 0.797 and 0.761). Conclusion: The diagnostic reliability of MRI in predicting the pCR to NAC depends on the tumor phenotype, particularly in the Luminal and Hybrid subgroups. In these cases, the coupling of morphological MRI evaluation and DWI assessment may facilitate the diagnosis.

  12. Bulky mesonephric adenocarcinoma of the uterine cervix treated with neoadjuvant chemotherapy and radical surgery: report of the first case.

    Science.gov (United States)

    Ditto, Antonino; Martinelli, Fabio; Bogani, Giorgio; Gasparri, Maria L; Donato, Violante Di; Paolini, Biagio; Carcangiu, Maria L; Lorusso, Domenica; Raspagliesi, Francesco

    2016-11-11

    Malignant mesonephric adenocarcinoma of the uterine cervix is a rare occurrence with few cases described in the literature. Although surgery seems to be effective in the treatment of early-stage tumor, no cases describing outcomes of locally advanced stage are available. We report the first case of a patient with International Federation of Obstetrics and Gynecologists stage IIB mesonephric adenocarcinoma undergoing neoadjuvant chemotherapy and radical surgery. Despite the inherent limitation of a single description of a case, our experience supports the utilization of neoadjuvant chemotherapy in patients with malignant mesonephric adenocarcinoma of the uterine cervix. Further prospective multi-institutional studies are needed.

  13. Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction – a prospective cohort pilot study within a randomized clinical trial

    International Nuclear Information System (INIS)

    Lund, Mikael; Alexandersson von Döbeln, Gabriella; Nilsson, Magnus; Winter, Reidar; Lundell, Lars; Tsai, Jon A; Kalman, Sigridur

    2015-01-01

    Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. 40 patients participated (chemoradiotherapy, n = 17; chemotherapy, n = 23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p = 0.02, p = 0.01, and p = 0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p = 0.09 and p = 0.09). NT-proBNP increased following chemoradiotherapy (p = 0.05) but not after chemotherapy (p > 0.99), and there was a trend towards an interaction effect (p = 0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p = 0.03) and was more pronounced after

  14. Contrast-Enhanced Spectral Mammography is Comparable to MRI in the Assessment of Residual Breast Cancer Following Neoadjuvant Systemic Therapy.

    Science.gov (United States)

    Patel, Bhavika K; Hilal, Talal; Covington, Matthew; Zhang, Nan; Kosiorek, Heidi E; Lobbes, Marc; Northfelt, Donald W; Pockaj, Barbara A

    2018-05-01

    To evaluate the performance of contrast-enhanced spectral mammography (CESM) compared to MRI in the assessment of tumor response in breast cancer patients undergoing neoadjuvant systemic therapy (NST). The institutional review board approved this study. From September 2014 to June 2017, we identified patients with pathologically confirmed invasive breast cancer who underwent NST. All patients had both CESM and MRI performed pre- and post-NST with pathological assessment after surgical management. Size of residual malignancy on post-NST CESM and MRI was compared with surgical pathology. Lin concordance and Pearson correlation coefficient were used to assess agreement. Bland-Altman plots were used to visualize the differences between tumor size on imaging and pathology. Sixty-five patients were identified. Mean age was 52.7 (range 30-76) years. Type of NST included chemotherapy in 53 (82%) and endocrine therapy in 12 (18%). Mean tumor size after NST was 14.6 (range 0-105) mm for CESM and 14.2 mm (range 0-75 mm) for MRI compared with 19.6 (range 0-100) mm on final surgical pathology. Equivalence tests demonstrated that mean tumor size measured by CESM (p = 0.009) or by MRI (p = 0.01) was equivalent to the mean tumor size measured by pathology within - 1 and 1-cm range. Comparing CESM versus MRI for assessment of complete response, the sensitivity was 95% versus 95%, specificity 66.7% versus 68.9%, positive predictive value 55.9% versus 57.6%, and negative predictive value 96.7% versus 96.9% respectively. CESM was comparable to MRI in assessing residual malignancy after completion of NST.

  15. Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors

    Directory of Open Access Journals (Sweden)

    I.P.C. Buzatto

    Full Text Available The purpose of this study was to retrospectively review the pathologic complete response (pCR rate from patients (n=86 with stage II and III HER2-positive breast cancer treated with neoadjuvant chemotherapy at our institution from 2008 to 2013 and to determine possible predictive and prognostic factors. Immunohistochemistry for hormone receptors and Ki-67 was carried out. Clinical and pathological features were analyzed as predictive factors of response to therapy. For survival analysis, we used Kaplan-Meier curves to estimate 5-year survival rates and the log-rank test to compare the curves. The addition of trastuzumab to neoadjuvant chemotherapy significantly improved pCR rate from 4.8 to 46.8%, regardless of the number of preoperative trastuzumab cycles (P=0.0012. Stage II patients achieved a higher response rate compared to stage III (P=0.03. The disease-free and overall survivals were not significantly different between the group of patients that received trastuzumab in the neoadjuvant setting (56.3 and 70% at 5 years, respectively and the group that initiated it post-operatively (75.8 and 88.7% at 5 years, respectively. Axillary pCR post neoadjuvant chemotherapy with trastuzumab was associated with reduced risk of recurrence (HR=0.34; P=0.03 and death (HR=0.21; P=0.02. In conclusion, we confirmed that trastuzumab improves pCR rates and verified that this improvement occurs even with less than four cycles of the drug. Hormone receptors and Ki-67 expressions were not predictive of response in this subset of patients. Axillary pCR clearly denotes prognosis after neoadjuvant target therapy and should be considered to be a marker of resistance, providing an opportunity to investigate new strategies for HER2-positive treatment.

  16. Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

    Science.gov (United States)

    Ellingson, Marissa S; Hart, Steven N; Kalari, Krishna R; Suman, Vera; Schahl, Kimberly A; Dockter, Travis J; Felten, Sara J; Sinnwell, Jason P; Thompson, Kevin J; Tang, Xiaojia; Vedell, Peter T; Barman, Poulami; Sicotte, Hugues; Eckel-Passow, Jeanette E; Northfelt, Donald W; Gray, Richard J; McLaughlin, Sarah A; Moreno-Aspitia, Alvaro; Ingle, James N; Moyer, Ann M; Visscher, Daniel W; Jones, Katie; Conners, Amy; McDonough, Michelle; Wieben, Eric D; Wang, Liewei; Weinshilboum, Richard; Boughey, Judy C; Goetz, Matthew P

    2015-09-01

    When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled (median age 51) with the following subtypes: triple negative (n = 43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n = 13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%) patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2 (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n = 1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1). 121/124 (97.6%) patients consented to return of research results. Thirteen (10.5%) had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management.

  17. Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer.

    Science.gov (United States)

    Zhu, Jun; Zhang, Hai-Ping; Jiang, Sen; Ni, Jian

    2017-08-01

    We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC). This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected. A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6-19.4], and the median OS was 25.0 months (95% CI: 19.1-30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated. Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

  18. A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Xun He

    2015-01-01

    Conclusion: Neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve the 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in the patients with locally advanced nasopharyngeal carcinoma.

  19. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

    Science.gov (United States)

    Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

    1998-01-01

    The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

  20. Neoadjuvant chemotherapy with methotrexate and cisplatin prior to radiotherapy for invasive transitional cell carcinoma of the bladder. Assessment of feasibility and toxicity

    International Nuclear Information System (INIS)

    Howard, G.C.W.; Cornbleet, M.A.; Whillis, D.; Hargreave, T.B.; Chisholm, G.D.

    1991-01-01

    A prospective study has been performed to assess the feasibility and toxicity of administering neoadjuvant chemotherapy with methotrexate and cisplatin prior to radical radiotherapy. Twenty patients with advanced transitional cell carcinoma of the bladder were assessed after each of 3 courses of chemotherapy, after radiotherapy and 6 months following treatment. Of particular concern was whether neoadjuvant chemotherapy compromised the ability to give potentially curative radical radiotherapy, delayed effective palliation of distressing urinary symptoms, or allowed local tumour progression prior to definitive treatment. It was concluded that this chemotherapy regimen was well tolerated, did not compromise the ability to give radical radiotherapy and resulted in the prompt palliation of urinary symptoms. This treatment, however, did not stop the development or progression of metastatic disease in some patients. In only 1 patient was there local progression during chemotherapy. (author)

  1. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    Science.gov (United States)

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  2. Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial.

    Science.gov (United States)

    Issa-Nummer, Yasmin; Darb-Esfahani, Silvia; Loibl, Sibylle; Kunz, Georg; Nekljudova, Valentina; Schrader, Iris; Sinn, Bruno Valentin; Ulmer, Hans-Ullrich; Kronenwett, Ralf; Just, Marianne; Kühn, Thorsten; Diebold, Kurt; Untch, Michael; Holms, Frank; Blohmer, Jens-Uwe; Habeck, Jörg-Olaf; Dietel, Manfred; Overkamp, Friedrich; Krabisch, Petra; von Minckwitz, Gunter; Denkert, Carsten

    2013-01-01

    We have recently described an increased lymphocytic infiltration rate in breast carcinoma tissue is a significant response predictor for anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study was to prospectively validate the tumor-associated lymphocyte infiltrate as predictive marker for response to anthracycline/taxane-based NACT. The immunological infiltrate was prospectively evaluated in a total of 313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy), stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer (LPBC) were evaluated by histopathological assessment. Pathological complete response (pCR) rates were analyzed and compared between the defined subgroups using the exact test of Fisher. Patients with lymphocyte-predominant breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to non-LPBC patients (14.3%, pimmunological infiltrate in breast tumor tissue is predictive for response to anthracycline/taxane-based NACT. Patients with LPBC and increased stromal lymphocyte infiltration have significantly increased pCR rates. The lymphocytic infiltrate is a promising additional parameter for histopathological evaluation of breast cancer core biopsies.

  3. Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

    Science.gov (United States)

    Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

    2016-11-01

    To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

  4. Is Technetium-99m Sestamibi Imaging Able to Predict Pathologic Nonresponse to Neoadjuvant Chemotherapy in Breast Cancer? : A Meta-analysis Evaluating Current Use and Shortcomings

    NARCIS (Netherlands)

    Collarino, Angela; de Koster, Elizabeth J.; Valdés Olmos, Renato A.; de Geus-Oei, Lioe Fee; Pereira Arias-Bouda, Lenka M.

    2017-01-01

    Background: Interest in technetium-99m (99mTc)-sestamibi imaging for neoadjuvant chemotherapy (NAC) response monitoring in locally advanced breast cancer (LABC) is increasing but remains matter of discussion. The present study conducted a meta-analysis of the diagnostic performance of

  5. Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: Evaluating the effect of race/ethnicity

    Science.gov (United States)

    Chavez-MacGregor, Mariana; Litton, Jennifer; Chen, Huiqin; Giordano, Sharon H.; Hudis, Clifford A.; Wolff, Antonio C.; Valero, Vicente; Hortobagyi, Gabriel N.; Bondy, Melissa L.; Gonzalez-Angulo, Ana Maria

    2010-01-01

    Purpose To evaluate the influence of race/ethnicity and tumor subtype in pathological complete response (pCR) following treatment with neoadjuvant chemotherapy. Methods 2074 patients diagnosed with breast cancer between 1994 and 2008, treated with neoadjuvant anthracycline- and taxane-based chemotherapy, were included. pCR was defined as no residual invasive cancer in the breast and axilla. Kaplan-Meier product-limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome. Results Median age was 50 years, 14.6% patients were black, 15.2% Hispanic, 64.3% White, and 5.9% other race. There were no differences in pCR rates among race/ethnicity: (12.3% in black, 14.2% in Hispanics, 12.3% in whites and 11.5% in others, p=.788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse RFS and OS (p≤.0001). Differences in RFS by race/ethnicity were seen in the patients with hormone receptor-positive disease, p=.007. In multivariate analysis, Hispanics had improved RFS (HR, 95% CI 0.69; 0.49-0.97) and OS (HR, 95% CI 0.63; 0.41-0.97); blacks had a trend to worse outcomes (RFS:HR, 95% CI 1.28; 0.97-1.68, OS:HR, 1.32; 95% CI; 0.97-1.81) when compared to whites. Conclusions In this cohort of patients, race/ethnicity was not significantly associated with pCR rates. In a multivariate analysis we observed improved outcomes in Hispanics and a trend towards worse outcomes in black patients, when compared to whites. Further research is needed to explore the potential differences in biology and outcomes. PMID:20564153

  6. Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features.

    Directory of Open Access Journals (Sweden)

    Lakshmanan Sannachi

    Full Text Available Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS, textural analysis and molecular features in patients with locally advanced breast cancer.The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR, partial responders (PR, and non-responders (NR. Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times.Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the

  7. Combining antiangiogenic therapy with neoadjuvant chemotherapy increases treatment efficacy in stage IIIA (N2) non-small cell lung cancer without increasing adverse effects.

    Science.gov (United States)

    Zhao, Xiaoliang; Su, Yanjun; You, Jian; Gong, Liqun; Zhang, Zhenfa; Wang, Meng; Zhao, Zhenqing; Zhang, Zhen; Li, Xiaolin; Wang, Changli

    2016-09-20

    To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).

  8. The evaluation of the effect of VAB-6 combination chemotherapy by MRI for a germinal cell tumor originating in the anterior mediastinum

    International Nuclear Information System (INIS)

    Tomioka, Hiromi; Murayama, Takako; Kurasawa, Takuya; Kuze, Fumiyuki; Chihara, Kouji; Wada, Hiromi; Hitomi, Shigeki; Noma, Satoshi.

    1988-01-01

    A 22-year old man with germinal cell tumor originating in the anterior mediastinum was treated with the VAB-6 chemotherapy. Disappearance of tumor cells and degeneration to fibrous necrotic tissue was revealed by MRI performed after chemotherapy, i.e. change of T 2 weighted image of the tumor from high-intensity to iso-intensity. And this pathological change was confirmed by the histological examination of the resected specimen. MRI was considered to be very useful to evaluate the effect of chemotherapy for germinal cell tumor originating in the anterior mediastinum. (author)

  9. Preoperative detection of colorectal liver metastases in fatty liver: MDCT or MRI?

    International Nuclear Information System (INIS)

    Kulemann, Vanessa; Schima, Wolfgang; Tamandl, Dietmar; Kaczirek, Klaus; Gruenberger, Thomas; Wrba, Friedrich; Weber, Michael; Ba-Ssalamah, Ahmed

    2011-01-01

    Objective: To compare the diagnostic value of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative detection of colorectal liver metastases in diffuse fatty infiltration of the liver, associated with neoadjuvant chemotherapy. Materials and methods: Twenty preoperative tri-phasic MDCT (4-64-row, Siemens) and dynamic contrast-enhanced MRI (1.5 T or 3.0 T, Siemens) examinations of patients with colorectal cancer and liver metastases in diffuse steatosis were retrospectively evaluated. All patients underwent surgical resection for liver metastases (time interval 1-60 days). The amount of fatty infiltration of the liver was determined histopathologically by semi-quantitative percent-wise estimation and ranged from 25 to 75%. Results: Overall, 51 metastases were found by histopathology of the resected liver segments/lobes. The size of the metastases ranged from 0.4 to 13 cm, with 18 (35%) being up to 1 cm in diameter. In the overall rating, MDCT detected 33/51 lesions (65%), and MRI 45/51 (88%). For lesions up to 1 cm, MDCT detected only 2/18 (11%) and MRI 12/18 (66%). One false positive lesion was detected by MDCT. Statistical analysis showed that MRI is markedly superior to MDCT, with a statistically significant difference (p 1 cm. Conclusion: For the detection of colorectal liver metastases after neoadjuvant chemotherapy and consecutive diffuse fatty infiltration of the liver, MRI is superior to MDCT, especially for the detection of small lesions.

  10. A priori Prediction of Neoadjuvant Chemotherapy Response and Survival in Breast Cancer Patients using Quantitative Ultrasound.

    Science.gov (United States)

    Tadayyon, Hadi; Sannachi, Lakshmanan; Gangeh, Mehrdad J; Kim, Christina; Ghandi, Sonal; Trudeau, Maureen; Pritchard, Kathleen; Tran, William T; Slodkowska, Elzbieta; Sadeghi-Naini, Ali; Czarnota, Gregory J

    2017-04-12

    Quantitative ultrasound (QUS) can probe tissue structure and analyze tumour characteristics. Using a 6-MHz ultrasound system, radiofrequency data were acquired from 56 locally advanced breast cancer patients prior to their neoadjuvant chemotherapy (NAC) and QUS texture features were computed from regions of interest in tumour cores and their margins as potential predictive and prognostic indicators. Breast tumour molecular features were also collected and used for analysis. A multiparametric QUS model was constructed, which demonstrated a response prediction accuracy of 88% and ability to predict patient 5-year survival rates (p = 0.01). QUS features demonstrated superior performance in comparison to molecular markers and the combination of QUS and molecular markers did not improve response prediction. This study demonstrates, for the first time, that non-invasive QUS features in the core and margin of breast tumours can indicate breast cancer response to neoadjuvant chemotherapy (NAC) and predict five-year recurrence-free survival.

  11. Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status.

    Science.gov (United States)

    Strassburg, Joachim; Junginger, Theo; Trinh, Trong; Püttcher, Olaf; Oberholzer, Katja; Heald, Richard J; Hermanek, Paul

    2008-11-01

    Is it possible to reduce the frequency of neoadjuvant therapy for rectal carcinoma and nevertheless achieve a rate of more than 90% circumferential resection margin (CRM)-negative resection specimens by a novel concept of magnetic resonance imaging (MRI)-based therapy planning? One hundred eighty-one patients from Berlin and Mainz, Germany, with primary rectal carcinoma, without distant metastasis, underwent radical surgery with curative intention. Surgical procedures applied were anterior resection with total mesorectal excision (TME) or partial mesorectal excision (PME; PME for tumours of the upper rectum) or abdominoperineal excision with TME. With MRI selection of the highest-risk cases, neoadjuvant therapy was given to only 62 of 181 (34.3%). The rate of CRM-negative resection specimens on histology was 170 of 181 (93.9%) for all patients, and in Berlin, only 1 of 93 (1%) specimens was CRM-positive. Patients selected for primary surgery had CRM-negative specimens on histology in 114 of 119 (95.8%). Those selected for neoadjuvant therapy had a lower rate of clear margin: 56 of 62 (90%). By applying a MRI-based indication, the frequency of neoadjuvant treatment with its acute and late adverse effects can be reduced to 30-35% without reduction of pathologically CRM-negative resection specimens and, thus, without the danger of worsening the oncological long-term results. This concept should be confirmed in prospective multicentre observation studies with quality assurance of MRI, surgery and pathology.

  12. Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer in a population with a high HIV prevalence in Johannesburg, South Africa.

    Science.gov (United States)

    Ruff, Paul; Cubasch, Herbert; Joffe, Maureen; Rosenbaum, Evan; Murugan, Nivashni; Tsai, Ming-Chih; Ayeni, Oluwatosin; Crew, Katherine D; Jacobson, Judith S; Neugut, Alfred I

    2018-01-01

    Neoadjuvant (primary) chemotherapy (NACT) is the standard of care for locally advanced breast cancer. It also allows for the short-term assessment of chemotherapy response; a pathological complete responses correspond to improved long-term breast cancer outcomes. In sub-Saharan Africa, many patients are diagnosed with large nonresectable tumors. We examined NACT use in breast cancer patients who visited public hospitals in Johannesburg, South Africa. We assessed demographic characteristics, tumor stage and grade, hormone receptor status, and human immunodeficiency virus (HIV) status of female patients diagnosed with nonmetastatic invasive carcinoma of the breast at Chris Hani Baragwanath Academic Hospital between January 1, 2009, and December 31, 2011. The patients received neoadjuvant, adjuvant, or no chemotherapy. Trastuzumab was unavailable. We developed logistic regression models to analyze the factors associated with NACT receipt in these patients. Of 554 women with nonmetastatic breast cancer, the median age at diagnosis was 52 years (range: 28-88 years). Only 5.8% of patients were diagnosed with stage I disease; 49.3% and 44.9% were diagnosed with stages II and III, respectively. Most patients had hormone-responsive tumors: luminal A, 38.1%; luminal B 1 (human epidermal growth factor receptor 2 [HER2]-negative and high grade), 12.5%, and luminal B 2 (HER2-positive any grade), 11.6%; 11.6% had a HER2-enriched tumor and 20.6% a triple-negative tumor. Eighty (14.4%) patients were HIV-positive. In total, 195 patients (35.2%) received NACT, 264 (47.7%) patients received adjuvant chemotherapy, and 95 patients (17.1%) received no chemotherapy, including 62 (11.2%) patients who received only hormonal therapy. Of patients receiving NACT, 125 (64.1%) were evaluable for clinical response. Eighty (64.0%) patients had a clinically significant response; 19 (15.2%) patients had a stable disease, and 26 (20.8%) patients had a progressive disease. Multivariate analysis

  13. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    International Nuclear Information System (INIS)

    Kuremsky, Jeffrey G.; Tepper, Joel E.; McLeod, Howard L. Phar

    2009-01-01

    Locally advanced rectal cancer (LARC) is currently treated with neoadjuvant chemoradiation. Although approximately 45% of patients respond to neoadjuvant therapy with T-level downstaging, there is no effective method of predicting which patients will respond. Molecular biomarkers have been investigated for their ability to predict outcome in LARC treated with neoadjuvant chemotherapy and radiation. A literature search using PubMed resulted in the initial assessment of 1,204 articles. Articles addressing the ability of a biomarker to predict outcome for LARC treated with neoadjuvant chemotherapy and radiation were included. Six biomarkers met the criteria for review: p53, epidermal growth factor receptor (EGFR), thymidylate synthase, Ki-67, p21, and bcl-2/bax. On the basis of composite data, p53 is unlikely to have utility as a predictor of response. Epidermal growth factor receptor has shown promise as a predictor when quantitatively evaluated in pretreatment biopsies or when EGFR polymorphisms are evaluated in germline DNA. Thymidylate synthase, when evaluated for polymorphisms in germline DNA, is promising as a predictive biomarker. Ki-67 and bcl-2 are not useful in predicting outcome. p21 needs to be further evaluated to determine its usefulness in predicting outcome. Bax requires more investigation to determine its usefulness. Epidermal growth factor receptor, thymidylate synthase, and p21 should be evaluated in larger prospective clinical trials for their ability to guide preoperative therapy choices in LARC.

  14. Impact of receptor phenotype on nodal burden in patients with breast cancer who have undergone neoadjuvant chemotherapy

    LENUS (Irish Health Repository)

    Boland, M. R.

    2017-07-31

    Optimal evaluation and management of the axilla following neoadjuvant chemotherapy(NAC) in patients with node-positive breast cancer remains controversial. The aim of this study wasto examine the impact of receptor phenotype in patients with nodal metastases who undergo NAC to seewhether this approach can identify those who may be suitable for conservative axillary management.Methods: Between 2009 and 2014, all patients with breast cancer and biopsy-proven nodal diseasewho received NAC were identied from prospectively developed databases. Details of patients who hadaxillary lymph node dissection (ALND) following NAC were recorded and rates of pathological completeresponse (pCR) were evaluated for receptor phenotype.

  15. Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR.

    Science.gov (United States)

    Generali, Daniele; Corona, Silvia Paola; Pusztai, Lajos; Rouzier, Roman; Allevi, Giovanni; Aguggini, Sergio; Milani, Manuela; Strina, Carla; Frati, Albane

    2018-03-01

    Neoadjuvant hormonal therapy is generally considered a valid option for hormone receptor positive breast cancer (BC) patients who are unfit for chemotherapy or surgery. Whilst numerous studies analyzed efficacy of neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor positive patients, there is a lack of research looking at the usefulness of a preoperative combinatorial approach of CT and HT in this patient subgroup. Using a predictive model previously described in the literature, developed to analyze the probability of benefit from preoperative chemotherapy, we were able to compare pathological complete response (pCR) rates expected with the use of CT alone with the pCR rates reported in a population of 192 patients treated with the combination of tamoxifen plus anthracycline-based CT at Cremona Hospital between 2003 and 2006. Even with a relatively small patient population, this approach provided insightful information for the selection of hormone receptor positive BC patients most likely to benefit from the use of preoperative HT and CT in combination. Whilst no statistically significant benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy in the entire population, or in any of the molecular stratification subgroups, the analysis of the calibration curve showed that a combinatorial approach may improve pCR in patients with luminal B tumors. More specific trials should be designed to confirm our initial results. To the best of our knowledge, this is the first report investigating the efficacy of the combination of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.

  16. An overview of neoadjuvant chemotherapy in the multimodality treatment of malignant pleural mesothelioma.

    Science.gov (United States)

    Pasello, G; Ceresoli, G L; Favaretto, A

    2013-02-01

    Malignant Pleural Mesothelioma (MPM) is an aggressive tumour with poor prognosis and increasing incidence in industrialized countries because of the previous widespread exposure to asbestos fibres and to the long lag period from time of exposure and the diagnosis of the disease. MPM shows high refractoriety to systemic treatment, single-modality treatment was generally ineffective and did not achieve higher results than supportive care. The incidence of local and distant recurrences after surgery remains high and that was the reason for many centres to perform combined treatments. In the attempt of reducing the incidence of local recurrences, a multimodality approach with surgery followed by adjuvant radiotherapy was explored. Extrapleural pneumonectomy (EPP) allows higher doses of radiotherapy to the whole hemithorax by avoiding pulmonary toxicity and the results of this approach is a significant reduction of loco-regional relapses; although, extrathoracic metastasis represent a major problem in the management of the disease because of the impact on overall survival. The success with surgical resection after neoadjuvant chemotherapy in stage IIIA lung cancer has been the impetus for several groups to apply this strategy in MPM aiming at reducing the incidence of distant relapse after surgery. Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3-4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. This review will focus on the main clinical studies and overview the results of different chemotherapy regimens in the neoadjuvant treatment of MPM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Deformable image registration as a tool to improve survival prediction after neoadjuvant chemotherapy for breast cancer: results from the ACRIN 6657/I-SPY-1 trial

    Science.gov (United States)

    Jahani, Nariman; Cohen, Eric; Hsieh, Meng-Kang; Weinstein, Susan P.; Pantalone, Lauren; Davatzikos, Christos; Kontos, Despina

    2018-02-01

    We examined the ability of DCE-MRI longitudinal features to give early prediction of recurrence-free survival (RFS) in women undergoing neoadjuvant chemotherapy for breast cancer, in a retrospective analysis of 106 women from the ISPY 1 cohort. These features were based on the voxel-wise changes seen in registered images taken before treatment and after the first round of chemotherapy. We computed the transformation field using a robust deformable image registration technique to match breast images from these two visits. Using the deformation field, parametric response maps (PRM) — a voxel-based feature analysis of longitudinal changes in images between visits — was computed for maps of four kinetic features (signal enhancement ratio, peak enhancement, and wash-in/wash-out slopes). A two-level discrete wavelet transform was applied to these PRMs to extract heterogeneity information about tumor change between visits. To estimate survival, a Cox proportional hazard model was applied with the C statistic as the measure of success in predicting RFS. The best PRM feature (as determined by C statistic in univariable analysis) was determined for each of the four kinetic features. The baseline model, incorporating functional tumor volume, age, race, and hormone response status, had a C statistic of 0.70 in predicting RFS. The model augmented with the four PRM features had a C statistic of 0.76. Thus, our results suggest that adding information on the texture of voxel-level changes in tumor kinetic response between registered images of first and second visits could improve early RFS prediction in breast cancer after neoadjuvant chemotherapy.

  18. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Victor E. Chen, BS

    2017-04-01

    Conclusions: Patients with TNBC treated with neoadjuvant chemotherapy who have residual disease in the breast or lymph nodes at the time of surgery have significantly higher rates of locoregional failure and lower DFS compared with those with a pCR despite the use of adjuvant radiation therapy. Strategies to intensify therapy for patients with residual disease warrant further investigation.

  19. Correlation between Tumor-Infiltrating Lymphocytes and Pathological Response in Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy in H. Adam Malik General Hospital

    Directory of Open Access Journals (Sweden)

    Kamal Basri Siregar

    2017-08-01

    Full Text Available Background: Tumor-infiltrating lymphocytes (TILs are emerging as biomarkers mediating tumor response to treatments. Earlier studies have provided evidence that the level of TILs has prognostic value, particularly in triple-negative and human epidermal growth factor receptor-2-positive breast cancer. Moreover, the level of TILs has been associated with treatment outcome in patients undergoing neoadjuvant chemotherapy, and there is a strong correlation with pathologically complete response. In this study, we analyzed whether changes in TILs take place after neoadjuvant therapy and if they correlate with pathological response to treatment. Patients and Methods: We retrospectively analyzed the specimen slides from the Department of Anatomic Pathology of H. Adam Malik General Hospital during 2011–2015. We identified 51 patients fulfilling the inclusion criteria of this study. The histological sections had already been evaluated by hematoxylin and eosin slides. They were reassessed by our pathologist for the percentage of intratumoral and stromal TILs. The correlation with pathological response of the tumor after neoadjuvant therapy was also studied in these patients. Each case was also defined as high- or low-TIL breast cancer adopting previously validated cutoffs. Results: The mean age of the 51 patients was 49.22 years. The most frequent type of breast cancer histology was invasive ductal breast carcinoma in 49 (96% patients, and there were 2 (4% patients with lobular carcinoma. The histopathological grading for high TILs was grade 1 in 5 patients, grade 2 in 15 patients, and grade 3 in 3 patients. High TILs that had a pathologically complete response were found in 47.8% of patients, and low TILs were found in 28.8%. There was no significant correlation between TILs and pathological response in patients with neoadjuvant chemotherapy (p = 0.157. Conclusions: This research has not been able to demonstrate a significant correlation between TILs and

  20. Quimioterapia neoadjuvante em câncer localmente avançado do colo do útero Neoadjuvant chemotherapy in locally advanced cancer of the cervix

    Directory of Open Access Journals (Sweden)

    Eduardo Schünemann Jr

    2002-12-01

    Full Text Available OBJETIVOS: avaliar a quimioterapia neoadjuvante no câncer localmente avançado do colo uterino, por meio da sua aceitabilidade, tolerabilidade, toxicidade, taxa de complicações cirúrgicas, taxa de resposta, taxa de operabilidade e sobrevida em 5 anos. MÉTODOS: foram incluídas 60 mulheres com câncer do colo uterino localmente avançado (IIB e IIIB, submetidas à quimioterapia neoadjuvante com doxorrubicina-bleomicina-cisplatina. Aquelas que se tornaram operáveis após a quimioterapia foram submetidas à cirurgia de Wertheim-Meigs, seguida de radioterapia pélvica complementar. Nas pacientes em que a cirurgia não foi possível após a quimioterapia, realizou-se radioterapia. RESULTADOS: o seguimento médio foi de 108 meses. A taxa de resposta global à quimioterapia foi de 80%, sendo 100% para o estádio IIB e 60% para o estádio IIIB. A porcentagem de pacientes operadas, após a quimioterapia foi de 65%. A sobrevida global em 5 anos para todo o grupo foi 62%. No grupo operado (n=34, a sobrevida global foi de 82,14%, independentemente do estádio inicial. No grupo não operado (n=18, a sobrevida em 5 anos foi 16,67%. CONCLUSÕES: A quimioterapia neoadjuvante com doxorrubicina-bleomicina-cisplatina no câncer do colo uterino localmente avançado é segura, com baixo índice de complicações e permitiu uma alta taxa de operabilidade.PURPOSE: to evaluate neoadjuvant chemotherapy in locally advanced cervical cancer as to its acceptability, tolerability, toxicity, surgical complications, operability, response rate, and overall survival in 5 years. METHODS: sixty women with locally advanced cervical cancer (stages IIB and IIIB, who were submitted to neoadjuvant chemotherapy, were included. All patients were treated with doxorubicin-bleomycin-cisplatin. Those who had a good response, allowing a surgical approach, underwent the Wertheim-Meigs procedure. After surgery, they were submitted to pelvic radiotherapy. Those that could not be submitted

  1. Immunological tumor status may predict response to neoadjuvant chemotherapy and outcome after radical cystectomy in bladder cancer.

    Science.gov (United States)

    Tervahartiala, Minna; Taimen, Pekka; Mirtti, Tuomas; Koskinen, Ilmari; Ecke, Thorsten; Jalkanen, Sirpa; Boström, Peter J

    2017-10-04

    Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of patients to chemotherapy that are likely to respond to the treatment. To date, there are no validated molecular markers or baseline clinical characteristics to identify these patients. Different inflammatory markers, including tumor associated macrophages with their plastic pro-tumorigenic and anti-tumorigenic functions, have extensively been under interests as potential prognostic and predictive biomarkers in different cancer types. In this immunohistochemical study we evaluated the predictive roles of three immunological markers, CD68, MAC387, and CLEVER-1, in response to NAC and outcome of BC. 41% of the patients had a complete response (pT0N0) to NAC. Basic clinicopathological variables did not predict response to NAC. In contrast, MAC387 + cells and CLEVER-1 + macrophages associated with poor NAC response, while CLEVER-1 + vessels associated with more favourable response to NAC. Higher counts of CLEVER-1 + macrophages associated with poorer overall survival and CD68 + macrophages seem to have an independent prognostic value in BC patients treated with NAC. Our findings point out that CD68, MAC387, and CLEVER-1 may be useful prognostic and predictive markers in BC.

  2. Multispectral and phase-contrast diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study

    Science.gov (United States)

    Liang, Xiaoping; Zhang, Qizhi; Staal, Stephen; Grobmyer, Stephen; Jiang, Huabei

    2009-02-01

    Multispectral and phase-contrast diffuse optical tomography are used to track treatment progress in a patient with locally advanced invasive carcinoma of the breast cancer during neoadjuvant chemotherapy. Two types of chemotherapy treatment including four cycles of Adriamycin/Cytoxin (AC cycles) and twelve cycles of Taxol/Herceptin (TH cycles) were applied to patient. A total of eight optical exams were performed before and within the chemotherapy. Images of tissue refractive index, and absorption and scattering coefficients, as well as oxy-hemoglobin and deoxy-hemoglobin concentrations along with scattering particle volume fraction and mean diameter of cellular components were all obtained. The tumor was identified through absorption and scattering images. Tumor shrinkage was observed during the course of chemotherapy from all the optical images. Our results show that oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin in tumor decreased after chemotherapy compared to that of before chemotherapy. Significant changes in tumor refractive index along with tumor cellular morphology during the entire chemotherapy are also observed.

  3. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  4. [Radical Resection of Huge Gastrointestinal Stromal Tumor of the Stomach Following Neoadjuvant Chemotherapy with lmatinib - ACase Report].

    Science.gov (United States)

    Hiraki, Yoko; Kato, Hiroaki; Shiraishi, Osamu; Tanaka, Yumiko; Iwama, Mitsuru; Yasuda, Atsushi; Shinkai, Masayuki; Kimura, Yutaka; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

    2017-11-01

    The usefulness and safety of imatinibfor neoadjuvant chemotherapy for resectable gastrointestinal stromal tumor(GIST) has not been established. We reported a case of a huge GIST of the stomach that was safely resected following preoperative imatinibtherapy. A 69-year-old man was hospitalized with abdominal fullness which increased rapidly from a month ago. A CT scan showed a huge tumor containing solid and cystic component which was accompanied by an extra-wall nodule. The tumor was strongly suspected to be originated from the stomach and EUS-FNA revealed GIST. We diagnosed GIST of the stomach and initiated preoperative adjuvant chemotherapy with imatinib because there was a risk for the break of tumor capsule and composite resection of the other organs without prior chemotherapy. After the administration of imatinib4 00 mg/day for 6months, the solid component was decreased in size and its' activity by PET-CT had declined, but the size of the cystic component was not changed and the patient's complaint of fullness was not reduced. Then, after a week cessation of imatinib, we performed surgical removal of the tumor with partial gastrectomy without surgical complication during and after the operation. Imatinibwas resumed 2 weeks later postoperatively and 1 year and 8 months has passed since the operation without recurrence. Neoadjuvant chemotherapy with imatinibhas the potential to become an important therapeutic option for the treatment of huge GISTs.

  5. Prognosis of patients with stage IIIb-IVa squamous cell carcinoma of the cervix following intra-arterial neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fujiwaki, R.; Maede, Y.; Ohnishi, Y.; Watanabe, Y.; Hata, K.; Miyazaki, K.

    1999-01-01

    The aim was to determine the long-term prognosis in patients with stage IIIb-IVa squamous cell carcinoma of the cervix who were treated with intra-arterial neoadjuvant chemotherapy (NAC), and to analyze factors related to prognostic value. The authors assessed the disease-free survival of 21 patients with FIGO stage IIIb-IVa squamous cell carcinoma of the cervix treated with intra-arterial NAC followed by irradiation therapy. Before chemotherapy, five factors (age, clinical stage, histologic type, parametrial involvement and serum level of SCC) were evaluated for their correlation with disease-free survival. Univariate Cox's proportional hazard model also demonstrated that age was a significant prognostic factor as a continuous variable. Intra-arterial NAC thus appeared to be effective in treating older patients with stage IIIb-IVa squamous cell carcinoma of the cervix

  6. Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score

    International Nuclear Information System (INIS)

    Huang, Eugene H.; Strom, Eric A.; Perkins, George H.; Oh, Julia L.; Chen, Allen M.; Meric-Bernstam, Funda; Hunt, Kelly K.; Sahin, Aysegul A.; Hortobagyi, Gabriel N.; Buchholz, Thomas A.

    2006-01-01

    Purpose: We previously developed a prognostic index that stratified patients treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy into groups with different risks for local-regional recurrence (LRR). The purpose of this study was to compare the rates of LRR as a function of prognostic index score for patients treated with BCT or mastectomy plus radiation after neoadjuvant chemotherapy. Methods and Materials: We retrospectively analyzed 815 patients treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were assigned an index score from 0 to 4 and given 1 point for the presence of each factor: clinical N2 to N3 disease, lymphovascular invasion, pathologic size >2 cm, and multifocal residual disease. Results: The 10-year LRR rates were very low and similar between the mastectomy and BCT groups for patients with an index score of 0 or 1. For patients with a score of 2, LRR trended lower for those treated with mastectomy vs. BCT (12% vs. 28%, p = 0.28). For patients with a score of 3 to 4, LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs. 61%, p = 0.009). Conclusions: This analysis suggests that BCT can provide excellent local-regional treatment for the vast majority of patients after neoadjuvant chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT and was <20% with mastectomy. If these findings are confirmed in larger randomized studies, the prognostic index may be useful in helping to select the type of surgical treatment for patients treated with neoadjuvant chemotherapy, surgery, and radiation

  7. Association between SPARC mRNA expression, prognosis and response to neoadjuvant chemotherapy in early breast cancer: a pooled in-silico analysis.

    Directory of Open Access Journals (Sweden)

    Hatem A Azim

    Full Text Available INTRODUCTION: SPARC is an important regulator of the extracellular matrix and has been suggested to improve delivery of albumin-bound cytotoxics. However, little is known regarding its role in breast cancer (BC. METHODS: We conducted a pooled analysis of publically available datasets, in which BC patients who received no systemic therapy or received neoadjuvant chemotherapy were eligible. Patients were assigned to molecular subtypes using PAM-50. We computed a SPARC module (SPARC7, composed of genes with an absolute correlation with SPARC >0.7. In the systemically untreated cohort, we evaluated 1 expression of SPARC/SPARC7 according to breast cancer subtype, 2 association between SPARC/SPARC7 and biological processes related to proliferation, immune and stroma, and 3 association between SPARC/SPARC7 and relapse-free survival in a Cox model in all patients and in the different molecular subtypes adjusted for tumor size, nodal status, histological grade, and age. In the neoadjuvant cohort, we evaluated the association between SPARC and pCR in a logistic regression model, adjusted for the same clinicopathologic factors. RESULTS: 948 (10 datasets, and 791 (8 datasets patients were included in the systemically untreated and neoadjuvant cohorts, respectively. High SPARC expression was associated with small tumor size, low histological grade and luminal-A tumors (all p<0.0001. There was a positive correlation between SPARC and stroma-related modules but negative correlation with proliferation modules. High SPARC expression was associated with poor prognosis in patients with basal and HER2+ breast cancer even after adjusting for clinicopathologic parameters. In the neoadjuvant cohort, a subgroup analysis suggested that high SPARC is associated with low rates of pCR in the HER2 subtype. Same results were observed on replacing SPARC by SPARC7. CONCLUSION: This analysis suggests a potential role of SPARC in determining prognosis and response to primary

  8. Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

    International Nuclear Information System (INIS)

    Petry, V.; Gagliato, D.M.; Leal, A.I.C.; Arai, R.J.; Longo, E.; Andrade, F.; Ricci, M.D.; Piato, J.R.; Barroso-Sousa, R.; Hoff, P.M.; Mano, M.S.

    2015-01-01

    Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m 2 during 8 weeks followed by weekly doxorubicin at 24 mg/m 2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment

  9. Metronomic chemotherapy in the neoadjuvant setting: results of two parallel feasibility trials (TraQme and TAME) in patients with HER2+ and HER2− locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Petry, V.; Gagliato, D.M.; Leal, A.I.C.; Arai, R.J.; Longo, E. [Divisão de Oncologia Médica, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Andrade, F. [Núcleo de Mastologia, Hospital Sírio Libanês, São Paulo, SP (Brazil); Ricci, M.D.; Piato, J.R.; Barroso-Sousa, R.; Hoff, P.M.; Mano, M.S. [Divisão de Oncologia Médica, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-03-06

    Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m{sup 2} during 8 weeks followed by weekly doxorubicin at 24 mg/m{sup 2} for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.

  10. Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Al-Amro, Abdullah; Al-Rajhi, Nasser; Khafaga, Yasser; Memon, Mohammad; Al-Hebshi, Adnan; El-Enbabi, Ashraf; El-Husseiny, Gamal; Radawi, Amer; Belal, Abdulaziz; Allam, Ayman; El-Sebaie, Medhat

    2005-01-01

    Purpose: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Methods and Materials: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m 2 and epirubicin 70 mg/m 2 on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m 2 for 4 days on Days 42, 63, and 84. Results: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient

  11. [A Case of Pathological Complete Response after Neoadjuvant Chemotherapy(S-1 plus Oxaliplatin)and Laparoscopic Low Anterior Resection for Rectal Cancer].

    Science.gov (United States)

    Ichinohe, Daichi; Morohashi, Hajime; Umetsu, Satoko; Yoshida, Tatsuya; Wakasa, Yusuke; Odagiri, Tadashi; Kimura, Toshirou; Suto, Akiko; Saito, Takeshi; Yoshida, Eri; Akasaka, Harue; Jin, Hiroyuki; Miura, Takuya; Sakamoto, Yoshiyuki; Hakamada, Kenichi

    2016-11-01

    We report a case of pathological complete response after neoadjuvant chemotherapy(NAC)(S-1 plus oxaliplatin)for rectal cancer. The patient was a 50-year-old man who had type 3 circumferential rectal cancer. An abdominal CT scan revealed locally advanced rectal cancer(cT3N2H0P0M0, cStage III b)with severe stenosis and oral-side intestinal dilatation. The patient was treated with NAC after loop-ileostomy. After 3 courses of chemotherapy, a CT scan revealed significant tumor reduction. Laparoscopic low anterior resection and bilateral lymph node dissection were performed 5 weeks after the last course of chemotherapy. The pathological diagnosis was a pathological complete response(no residual cancer cells). This case suggests that laparoscopic low anterior resection after NAC with S-1 plus oxaliplatin for locally advanced rectal cancer is a potentially effective procedure.

  12. High-risk bladder cancer: improving outcomes with perioperative chemotherapy

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available Despite treatment with radical cystectomy and pelvic lymph node dissection, muscle invasive bladder cancer has a relapse rate of 50%. Patients can develop regionally advanced or metastatic disease that ultimately leads to death. The addition of neoadjuvant or adjuvant chemotherapy to reduce the risk of relapse and death has been extensively studied over the past two decades. Two contemporary trials coupled with a recent meta-analysis evaluating neoadjuvant chemotherapy demonstrated a modest but real improvement in overall survival. This has made neoadjuvant chemotherapy a standard of care. Clinical trials evaluating adjuvant chemotherapy in patients with high-risk disease have been plagued with statistical flaws and have, therefore, been unable to define the survival impact of this approach. It is hoped that ongoing adjuvant trials that are powered to detect small but meaningful clinical differences will clarify the benefit of chemotherapy after cystectomy. Since there are theoretical advantages and disadvantages to each of these approaches, both are widely used in North America. The evidence behind each approach and potential future developments in this field will be described.

  13. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer – the RAPIDO trial

    International Nuclear Information System (INIS)

    Nilsson, Per J; Marijnen, Corrie AM; Nagtegaal, Iris D; Wiggers, Theo; Glimelius, Bengt; Etten, Boudewijn van; Hospers, Geke AP; Påhlman, Lars; Velde, Cornelis JH van de; Beets-Tan, Regina GH; Blomqvist, Lennart; Beukema, Jannet C; Kapiteijn, Ellen

    2013-01-01

    Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative

  14. [A Case of Emergency Resection of Esophageal Cancer Which is on the Brink of Perforation after Neoadjuvant Chemotherapy].

    Science.gov (United States)

    Yasuda, Atsushi; Yasuda, Takushi; Kimura, Yutaka; Kato, Hiroaki; Hiraki, Yoko; Iwama, Mitsuru; Shiraishi, Osamu; Shinkai, Masayuki; Imano, Motohiro; Imamoto, Haruhiko

    2017-11-01

    According to the Guidelines for Diagnosis and Treatment of Carcinoma of the Esophagus in Japan, the standard treatment of esophageal cancer with cStage II / III is preoperative chemotherapy and radical resection. But when the tumor has deep ulcer, the perforation of it is sometimes occurred due of the anti-tumor effect and we are forced to change the standard treatment. In this time, we report a case of emergency resection of esophageal cancer which is on the brink of perforation after neoadjuvant chemotherapy. A 62-year-old woman had locally advanced esophageal cancer(cT4N2M0)and performed neoadjuvant chemotherapy(NAC). After 2 courses of NAC, the patient got into critical condition that the esophageal cancer was on the brink of perforation, thus we immediately performed emergency resection of the tumor. Unfortunately, the tumor was not completely resected because of invasion to the Botallo ligament, but we were able to avoid a critical state such as mediastinitis or penetration to the aorta. In multimodality therapy for locally advanced tumor, immediate response to oncologic emergency is significantly required, impacting on the prognosis and quality of life.

  15. Impact of neoadjuvant chemotherapy on complications of minimally invasive radical cystectomy.

    Science.gov (United States)

    Lizée, D; Salas, R S; Barret, E; Galiano, M; Di Trapani, E; Montorsi, F; Cathelineau, X

    2017-03-01

    Neoadjuvant chemotherapy (NC) before minimally invasive radical cystectomy (MIRC) is considered a standard of care in muscle-invasive bladder cancer or recurrent high-risk non-muscle-invasive bladder cancer. To evaluate the impact of NC on morbidity and mortality after MIRC. We prospectively evaluated 135 patients who underwent MIRC (laparoscopic: n=100; robotic: n=35) between 2007 and 2013 with ≥90 days of follow-up (median age: 66 year). Complications were analyzed and graded according to the Clavien Dindo classification system. Logistic regression models were used to evaluate the impact of NC on postoperative complications. Kaplan-Meier methods with the log-rank test were used for cancer-specific survival probabilities and differences between the 2groups (MIRC with and without NC). Sixty-two of 135 patients received NC. A total of 118 patients (87.4%) developed 179 complications, chiefly infectious (48.0%) or gastrointestinal (21.2%), ≤90 days after surgery; 3 patients died bladder cancer who had NC versus no NC. We did not find any significant differences in terms of early or late complications, length of stay, or reintervention. The oncologic outcomes regarding NC were encouraging. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  16. Overview of different available chemotherapy regimens combined with radiotherapy for the neoadjuvant and definitive treatment of esophageal cancer.

    Science.gov (United States)

    Tomasello, Gianluca; Ghidini, Michele; Barni, Sandro; Passalacqua, Rodolfo; Petrelli, Fausto

    2017-06-01

    Neoadjuvant chemoradiotherapy (CTRT) is the current standard of care for treatment of locally advanced cancer of the esophagus or gastroesophageal junction. Many efforts have been made over the last years to identify the best chemotherapy and radiotherapy combination regimen, but specific randomized trials addressing this issue are still lacking. Areas covered: A systematic review of the literature was performed searching in PubMed all published studies of combinations CTRT regimens for operable or unresectable esophageal cancer to describe activity and toxicity. Studies considered were prospective series or clinical phase II-III trials including at least 40 patients and published in English language. Expert commentary: Long-term results of CROSS trial have established RT combined with carboplatin plus paclitaxel chemotherapy as the preferred neoadjuvant treatment option for both squamous and adenocarcinoma of the esophagus. More effective multimodal treatment strategies integrating novel biological agents including immunotherapy and based on an extensive molecular tumor characterization are eagerly awaited.

  17. MRI of cervical carcinoma: before and after chemotherapy

    International Nuclear Information System (INIS)

    Kim, Jung Sik; Suh, Soo Jhi; Choi, Tae Jin; Lee, Tae Sung; Suh, Young Wook

    1992-01-01

    To evaluate usefulness of MR in assessment of tumor response to the chemotherapy, we prospectively studied cases of cervical carcinoma with more than 2.5cm in diameter or stage IIb or more. Three courses of chemotherapy were performed with cisplatin and 5 F-U. MR images were obtained both before and after chemotherapy. Nine of 13 patients were undertaken radical hysterectomy after chemotherapy and MR amination. MR volumetry, stage and depth of stromal invasion were compared before and after chemotherapy. And in 9 patients who underwent radical hysterectomy, comparison of pathologic and MR imaging findings were also done. The results were following. 1) All tumors dectrased in volume (m = 80.5%). 2) Five tumors (38.5%) reduced in stage, IB → CIS (1); IIA → CIS (1), IIA → IB (2), IIB → IB (1). 3) Depth of stromal invasion in MRI correlated well with that of histopathologic specimen in 7 of the 9 patients. Conclusively MR imaging is useful in assessment of tumor response to chemotherapy

  18. Expression of the BRCA1 gene in a breast tumor: Correlation with the effect of neoadjuvant chemotherapy

    Science.gov (United States)

    Tsyganov, M. M.; Ibragimova, M. K.; Deryusheva, I. V.; Slonimskaya, E. M.; Litviakov, N. V.

    2017-09-01

    Most current research is limited by only germinal mutations of the BRCA1 gene (more often 5382insC) and the number of studies, which characterize various somatic alterations of the BRCA1 gene in a tumor, namely the expression of this gene and its correlation with the efficiency of chemotherapy, which is scarce. Taking into account the data on the connection between the genetic mutation of BRCA1 with the high efficiency of the platinum medication one may suggest that the expression of the BRCA1 gene is also associated with the high sensitivity of the tumor to the platinum medication. Aim: to evaluate the correlation between the expression of the BRCA1 gene in a breast tumor with the neoadjuvant chemotherapy (NACT) efficiency. The research included 86 patients with BC. We evaluated the expression of BRCA1 in the tumor material before and after NACT. We established that objective response to NACT is connected with a high level of BRCA1 in the general group of patients (p = 0.01) and in case of docetaxel monotherapy (p < 0.05).

  19. Prognostic significance of cancer within 1 mm of the circumferential resection margin in oesophageal cancer patients following neo-adjuvant chemotherapy.

    Science.gov (United States)

    Salih, Tamir; Jose, Paul; Mehta, Samir P; Mirza, Ahmed; Udall, Gavin; Pritchard, Susan A; Hayden, Jeremy D; Grabsch, Heike I

    2013-03-01

    The prognostic significance of the circumferential resection margin (CRM) status in oesophageal cancer patients treated with neo-adjuvant chemotherapy and radical resection is controversial. Furthermore, it is currently unclear whether patients with cancer located at the CRM have a prognosis different from that of those with cancer within 1 mm of the CRM. This is the first study aiming to establish the optimal tumour-free distance from the CRM of an oesophagectomy in patients who have undergone neo-adjuvant chemotherapy. The clinicopathological data of 232 oesophageal cancer patients from two UK centres were analysed. The CRM status was classified as Group A (cancer at the CRM), Group B (cancer within 1 mm but not at the CRM) and Group C (no cancer within 1 mm from the CRM). The relationship between the CRM status and patient survival was investigated. Thirty-eight specimens were classified as Group A, 89 as Group B and 105 as Group C. CRM status was related to the depth of tumour invasion (P CRM or within 1 mm of the CRM of the resected specimen have a significantly worse survival than patients with no cancer cells within 1 mm of the margin. However, this study suggests that the overall prognostic significance of the CRM status is limited in this cohort and the postoperative lymph node status is the most important prognostic factor in oesophageal cancer patients treated with neo-adjuvant chemotherapy and surgery.

  20. Neoadjuvant treatment intensification or adjuvant chemotherapy for locally advanced carcinoma rectum: The optimum treatment approach remains unresolved.

    Science.gov (United States)

    Mallick, Supriya; Benson, Rony; Haresh, K P; Rath, G K

    2015-12-01

    Rectal carcinoma [RC] is often managed with preoperative radiotherapy or radio-chemotherapy followed by total mesorectal excision (TME). Efforts are being made to improve outcome by intensifying the preoperative treatment. However, the optimum therapy remains unclear. There is ongoing controversy regarding the optimum radiation dose, chemotherapy regimen and schedule. In addition there exists growing disagreement regarding the role of adjuvant chemotherapy after neoadjuvant radiation or chemoradiation. We reviewed the recent land mark trials to find a road map in the management of locally advanced rectal carcinoma. Preoperative short course radiotherapy has long been proven to improve local disease control. The initial trials with long course chemoradiotherapy, comparing short course radiotherapy have shown to increase local control and pathological complete response rates. Since then treatment intensification of this neoadjuvant schedule has been tried by many researchers. But initial results of these treatment intensification trials, show no significant benefit and are associated with increased toxicity. There is an unmet need to stratify patients depending on risk to assign them to long course chemoradiotherapy or short course radiotherapy. Current evidence does not support the use of adjuvant chemotherapy in patients who were treated with preoperative (chemo)radiotherapy. Preoperative radiotherapy appears to improve disease control with favorable toxicity profile and there is very little to choose between long course chemoradiotherapy and short course radiotherapy. However, long course chemoradiotherapy may be beneficial for patients with high risk features like positive circumferential resection margin [CRM] and extramural spread of >5mm. There is no role for adjuvant chemotherapy in patients who were treated preoperative (chemo)radiotherapy. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  1. Neoadjuvant treatment intensification or adjuvant chemotherapy for locally advanced carcinoma rectum: The optimum treatment approach remains unresolved

    International Nuclear Information System (INIS)

    Mallick, S.; Benson, R.; Haresh, K.P.; Rath, G.K.

    2015-01-01

    Background: Rectal carcinoma [RC] is often managed with preoperative radiotherapy or radio chemotherapy followed by total meso rectal excision (TME). Efforts are being made to improve outcome by intensifying the preoperative treatment. However, the optimum therapy remains unclear. There is ongoing controversy regarding the optimum radiation dose, chemotherapy regimen and schedule. In addition there exists growing disagreement regarding the role of adjuvant chemotherapy after neoadjuvant radiation or chemo radiation. Methodology: We reviewed the recent land mark trials to find a road map in the management of locally advanced rectal carcinoma. Results: Preoperative short course radiotherapy has long been proven to improve local disease con- trol. The initial trials with long course chemoradiotherapy, comparing short course radiotherapy have shown to increase local control and pathological complete response rates. Since then treatment intensification of this neoadjuvant schedule has been tried by many researchers. But initial results of these treatment intensification trials, show no significant benefit and are associated with increased toxicity. There is an unmet need to stratify patients depending on risk to assign them to long course chemoradiotherapy or short course radiotherapy. Current evidence does not support the use of adjuvant chemotherapy in patients who were treated with preoperative (chemo)radiotherapy. Conclusion: Preoperative radiotherapy appears to improve disease control with favorable toxicity profile and there is very little to choose between long course chemoradiotherapy and short course radiotherapy. However, long course chemoradiotherapy may be beneficial for patients with high risk features like positive circumferential resection margin [CRM] and extramural spread of >5 mm. There is no role for adjuvant chemotherapy in patients who were treated preoperative (chemo)radiotherapy

  2. Value of diffusion-weighted images in differentiating mid-course responders to chemotherapy for osteosarcoma compared to the histological response: preliminary results

    International Nuclear Information System (INIS)

    Baunin, C.; Schmidt, G.; Aschero, A.; Ruocco, A.; Bourliere, B.; Gorincour, G.; Desvignes, C.; Colavolpe, N.; Petit, P.; Baumstarck, K.; Auqier, P.; Bouvier, C.; Gentet, J.C.; Bollini, G.

    2012-01-01

    Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points. Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups. DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy. (orig.)

  3. Value of diffusion-weighted images in differentiating mid-course responders to chemotherapy for osteosarcoma compared to the histological response: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Baunin, C.; Schmidt, G.; Aschero, A.; Ruocco, A.; Bourliere, B.; Gorincour, G.; Desvignes, C.; Colavolpe, N.; Petit, P. [Hopital Timone Enfants, Service d' Imagerie Pediatrique et Prenatale, Marseille Cedex 05 (France); Baumstarck, K.; Auqier, P. [Faculte de Medecine de Marseille, Service de Sante Publique, Marseille Cedex 05 (France); Bouvier, C. [Hopital Timone, Service d' Anatomopathologie, Marseille Cedex 05 (France); Gentet, J.C. [Hopital Timone Enfants, Service d' Oncologie Pediatrique, Marseille Cedex 05 (France); Bollini, G. [Hopital Timone Enfants, Service d' Orthopedie Pediatrique, Marseille Cedex 05 (France)

    2012-09-15

    Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points. Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups. DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy. (orig.)

  4. Neoadjuvant chemotherapy among patients treated for nonmetastatic breast cancer in a population with a high HIV prevalence in Johannesburg, South Africa

    Directory of Open Access Journals (Sweden)

    Ruff P

    2018-02-01

    . Results: Of 554 women with nonmetastatic breast cancer, the median age at diagnosis was 52 years (range: 28–88 years. Only 5.8% of patients were diagnosed with stage I disease; 49.3% and 44.9% were diagnosed with stages II and III, respectively. Most patients had hormone-responsive tumors: luminal A, 38.1%; luminal B1 (human epidermal growth factor receptor 2 [HER2]-negative and high grade, 12.5%, and luminal B2 (HER2-positive any grade, 11.6%; 11.6% had a HER2-enriched tumor and 20.6% a triple-negative tumor. Eighty (14.4% patients were HIV-positive. In total, 195 patients (35.2% received NACT, 264 (47.7% patients received adjuvant chemotherapy, and 95 patients (17.1% received no chemotherapy, including 62 (11.2% patients who received only hormonal therapy. Of patients receiving NACT, 125 (64.1% were evaluable for clinical response. Eighty (64.0% patients had a clinically significant response; 19 (15.2% patients had a stable disease, and 26 (20.8% patients had a progressive disease. Multivariate analysis showed age <40 years and disease stage to be independently associated with the receipt of NACT. Conclusion: Most women receiving NACT with available response data showed a clinical benefit. Stage III disease at diagnosis and age <40 years were predictors of neoadjuvant versus adjuvant chemotherapy treatment. Keywords: breast cancer, chemotherapy, neoadjuvant, South Africa, HIV, LMICs

  5. Incorporating drug delivery into an imaging-driven, mechanics-coupled reaction diffusion model for predicting the response of breast cancer to neoadjuvant chemotherapy: theory and preliminary clinical results

    Science.gov (United States)

    Jarrett, Angela M.; Hormuth, David A.; Barnes, Stephanie L.; Feng, Xinzeng; Huang, Wei; Yankeelov, Thomas E.

    2018-05-01

    Clinical methods for assessing tumor response to therapy are largely rudimentary, monitoring only temporal changes in tumor size. Our goal is to predict the response of breast tumors to therapy using a mathematical model that utilizes magnetic resonance imaging (MRI) data obtained non-invasively from individual patients. We extended a previously established, mechanically coupled, reaction-diffusion model for predicting tumor response initialized with patient-specific diffusion weighted MRI (DW-MRI) data by including the effects of chemotherapy drug delivery, which is estimated using dynamic contrast-enhanced (DCE-) MRI data. The extended, drug incorporated, model is initialized using patient-specific DW-MRI and DCE-MRI data. Data sets from five breast cancer patients were used—obtained before, after one cycle, and at mid-point of neoadjuvant chemotherapy. The DCE-MRI data was used to estimate spatiotemporal variations in tumor perfusion with the extended Kety–Tofts model. The physiological parameters derived from DCE-MRI were used to model changes in delivery of therapy drugs within the tumor for incorporation in the extended model. We simulated the original model and the extended model in both 2D and 3D and compare the results for this five-patient cohort. Preliminary results show reductions in the error of model predicted tumor cellularity and size compared to the experimentally-measured results for the third MRI scan when therapy was incorporated. Comparing the two models for agreement between the predicted total cellularity and the calculated total cellularity (from the DW-MRI data) reveals an increased concordance correlation coefficient from 0.81 to 0.98 for the 2D analysis and 0.85 to 0.99 for the 3D analysis (p  <  0.01 for each) when the extended model was used in place of the original model. This study demonstrates the plausibility of using DCE-MRI data as a means to estimate drug delivery on a patient-specific basis in predictive models and

  6. Low Estrogen Receptor (ER)-Positive Breast Cancer and Neoadjuvant Systemic Chemotherapy: Is Response Similar to Typical ER-Positive or ER-Negative Disease?

    Science.gov (United States)

    Landmann, Alessandra; Farrugia, Daniel J; Zhu, Li; Diego, Emilia J; Johnson, Ronald R; Soran, Atilla; Dabbs, David J; Clark, Beth Z; Puhalla, Shannon L; Jankowitz, Rachel C; Brufsky, Adam M; Ahrendt, Gretchen M; McAuliffe, Priscilla F; Bhargava, Rohit

    2018-05-08

    Pathologic complete response (pCR) rate after neoadjuvant chemotherapy was compared between 141 estrogen receptor (ER)-negative (43%), 41 low ER+ (13%), 47 moderate ER+ (14%), and 98 high ER+ (30%) tumors. Human epidermal growth factor receptor 2-positive cases, cases without semiquantitative ER score, and patients treated with neoadjuvant endocrine therapy alone were excluded. The pCR rate of low ER+ tumors was similar to the pCR rate of ER- tumors (37% and 26% for low ER and ER- respectively, P = .1722) but significantly different from the pCR rate of moderately ER+ (11%, P = .0049) and high ER+ tumors (4%, P < .0001). Patients with pCR had an excellent prognosis regardless of the ER status. In patients with residual disease (no pCR), the recurrence and death rate were higher in ER- and low ER+ cases compared with moderate and high ER+ cases. Low ER+ breast cancers are biologically similar to ER- tumors. Semiquantitative ER H-score is an important determinant of response to neoadjuvant chemotherapy.

  7. Effect of Postmastectomy Radiotherapy in Patients <35 Years Old With Stage II-III Breast Cancer Treated With Doxorubicin-Based Neoadjuvant Chemotherapy and Mastectomy

    International Nuclear Information System (INIS)

    Garg, Amit K.; Oh, Julia L.; Oswald, Mary Jane; Huang, Eugene; Strom, Eric A.; Perkins, George H.; Woodward, Wendy A.; Yu, T. Kuan; Tereffe, Welela; Meric-Bernstam, Funda; Hahn, Karin; Buchholz, Thomas A.

    2007-01-01

    Purpose: Postmastectomy radiotherapy (PMRT) improves locoregional control (LRC) in patients with high-risk features after mastectomy. Young age continues to evolve as a potentially important risk factor. The objective of this study was to assess the benefits of PMRT in patients <35 years old treated with doxorubicin-based neoadjuvant chemotherapy for Stage II-III breast cancer. Patients and Methods: We retrospectively analyzed 107 consecutive breast cancer patients <35 years old with Stage IIA-IIIC disease treated at our institution with doxorubicin-based neoadjuvant chemotherapy and mastectomy, with or without PMRT. The treatment groups were compared in terms of LRC and overall survival. Results: Despite more advanced disease stages, the patients who received PMRT (n = 80) had greater rates of LRC (5-year rate, 88% vs. 63%, p = 0.001) and better overall survival (5-year rate, 67% vs. 48%, p = 0.03) than patients who did not receive PMRT (n = 27). Conclusion: Among breast cancer patients <35 years old at diagnosis, the use of PMRT after doxorubicin-based neoadjuvant chemotherapy and mastectomy led to a statistically greater rate of LRC and overall survival compared with patients without PMRT. The benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions after mastectomy

  8. Effects of core needle biopsy and subsequent neoadjuvant chemotherapy on molecular alterations and outcome in breast cancer

    Directory of Open Access Journals (Sweden)

    Xie L

    2018-02-01

    Full Text Available Lingmin Xie,1 Xiaolei Li,2 Qinchuan Wang,1 Jichun Zhou,1 Jun Shen,1 Lixi Luo,1 Yi Lu,1 Linbo Wang1 1Division of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, 2Division of Surgical Oncology, The First People’s Hospital of Wenling, Zhejiang, China Objectives: The aim of our study is to evaluate the effect of core needle biopsy (CNB and subsequent neoadjuvant chemotherapy (NAC on the expression of estrogen receptor (ER, progesterone receptor (PR, human epidermal growth hormone receptor 2 (HER2 and Ki67 in breast cancer, and the associated influencing factors.Materials and methods: In this retrospective cohort study, 143 patients with primary operable breast cancer who received NAC were included. ER, PR, HER2 and Ki67 statuses were compared between pretreatment and posttreatment residual samples. A control group of paired core and excision tumors from 123 patients who did not receive NAC within the same study period was also assessed. Data on patients’ clinicopathologic features were collected to identify associated influencing factors.Results: Ki67 value significantly increased in excision tumors compared with paired core samples in controls without presurgery treatment (P<0.01, which was associated with the pathologic lymph node status and the interaction of PR and HER2 status (P=0.008 and 0.028, respectively. In 143 patients who underwent NAC, a significant decrease was observed in the expression of PR and Ki67 after NAC (P=0.003 and P<0.01, respectively. Further subgroup analysis showed that PR decrease was more obvious in premenopausal patients and Luminal A patients (P=0.006 and 0.002, respectively.Conclusion: Core samples could provide more reliable information on determination of molecular subtype than surgical excisions. Decreases in PR and Ki67 expression following NAC could be used as positive prognostic factors. We recommend repeat testing of these biologic markers following NAC for

  9. Comparison of diffusion-weighted MR imaging and FDG PET/CT to predict pathological complete response to neoadjuvant chemotherapy in patients with breast cancer

    International Nuclear Information System (INIS)

    Park, Sang Hee; Moon, Woo Kyung; Cho, Nariya; Chang, Jung Min; Im, Seock-Ah; Park, In Ae; Kang, Keon Wook; Han, Wonshik; Noh, Dong-Young

    2012-01-01

    To compare the use of diffusion-weighted MR imaging (DWI) and 18 F-FDG PET/CT to predict pathological complete response (pCR) in breast cancer patients receiving neoadjuvant chemotherapy. Thirty-four women with 34 invasive breast cancers underwent DWI and PET/CT before and after chemotherapy and before surgery. The percentage changes in the apparent diffusion coefficient (ADC) and the standardised uptake value (SUV) were calculated, and the diagnostic performances for predicting pCR were evaluated using receiver operating characteristic (ROC) curve analysis. After surgery, 7/34 patients (20.6%) were found to have pCR. A z values for DWI, PET/CT and the combined use of DWI and PET/CT were 0.910, 0.873 and 0.944, respectively. The best cut-offs for differentiating pCR from non-pCR were a 54.9% increase in the ADC and a 63.9% decrease in the SUV. DWI showed 100% (7/7) sensitivity and 70.4% (19/27) specificity and PET/CT showed 100% sensitivity and 77.8% (21/27) specificity. When DWI and PET/CT were combined, there was a trend towards improved specificity compared with DWI. DWI and FDG PET/CT show similar diagnostic accuracy for predicting pCR to neoadjuvant chemotherapy in breast cancer patients. The combined use of DWI and FDG PET/CT has the potential to improve specificity in predicting pCR. (orig.)

  10. 18F-fluorodeoxyglucose positron emission tomography optimizes neoadjuvant chemotherapy for primary breast cancer to achieve pathological complete response

    International Nuclear Information System (INIS)

    Ueda, Shigeto; Saeki, Toshiaki; Shigekawa, Takashi

    2012-01-01

    The background of this study was to assess the usefulness of positron emission tomography combined with computed tomography using 18 F-fluorodeoxyglucose (FDG positron emission tomography (PET)/CT) for optimizing chemotherapy during neoadjuvant chemotherapy for primary breast cancer. One hundred and eight patients (110 tumors) with breast cancer (≥2 cm, stages II and III) received neoadjuvant chemotherapy consisting of an anthracycline-based regimen and taxane. The maximal value of the baseline standardized uptake value (SUV) and the change in SUV after four cycles of an anthracycline-based regimen relative to baseline SUV were assessed for predicting pathological complete response (pCR) after sequential taxane. Tumors with pCR had significantly higher baseline SUV (9.3±3.7 SD) compared to those with non-pCR (7.2±3.8 SD) (p=0.02), but there was a considerable overlap between two groups. On PET scan after four cycles of chemotherapy, thirty-three patients (33.7%) with a 72.1% or greater reduction in SUV were considered as responders and the performance in predicting pCR had a sensitivity of 88.9% and specificity of 78.7%. The baseline SUV could not be a useful indicator for predicting pCR due to the wide range in sensitivity. On the other hand, a relative change in SUV after completion of an anthracycline-based regimen could be useful for predicting pCR. (author)

  11. A phase I/II study of neoadjuvant chemotherapy followed by radiation with boost chemotherapy for advanced T-stage nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Johnson, Faye M.; Garden, Adam S.; Palmer, J. Lynn; Shin, Dong M.; Morrison, William; Papadimitrakopoulou, Vassiliki; Khuri, Fadlo; Clayman, Gary; Goepfert, Helmuth; Ang, K. Kian; Hong, Waun K.; Glisson, Bonnie S.

    2005-01-01

    Purpose: Local recurrence is the most common site of failure for locally advanced nasopharyngeal carcinoma (NPC) treated with neoadjuvant cisplatin/5-fluorouracil (PF) and definitive radiation at our center. Based on this, we studied the addition of chemotherapy during the boost phase of radiation after neoadjuvant PF for advanced T-stage (T3-T4) NPC. This strategy was based on theoretical radiosensitization with chemotherapy during accelerated repopulation of the tumor with relatively radioresistant clonogens. Methods and Materials: Three cycles of neoadjuvant PF was followed by conventionally fractionated radiation with additional PF during the boost portion of the radiation course. An initial Phase I study was done to establish the maximum tolerated dose of concurrent PF. Results: Forty-four patients were enrolled. Six patients in Phase I defined the MTD for concurrent PF as: cisplatin 10 mg/m 2 /day and PF 320 mg/m 2 /day, on Days 1-5 during Weeks 6 and 7 of radiation therapy based on dose-limiting toxicities of mucositis, neutropenia, and thrombocytopenia. Forty-one patients were treated with concurrent therapy per protocol: complete, partial, and minor responses were seen in 23, 16, and 2 patients, respectively. Progression-free and overall survival rates at 5 years were 55% (95% CI, 41-75%) and 66% (95% CI, 52-85%), respectively. Seven of 11 tumor-related deaths were due to local recurrence. Nine of 10 patients with local recurrence had T4-stage disease at presentation. Local control of T4 disease was achieved in 74% of patients overall, and in 25% (1/4) with World Health Organization (WHO) type 1, 76% (16/21) with WHO type 2, and 90% (9/10) with WHO type 3 histology. Common toxicities included mucositis, dermatitis, fatigue, vomiting, and weight loss. Conclusions: This regimen was feasible and associated with promising overall survival. Local recurrence remains the major reason for treatment failure in advanced T-stage NPC, especially WHO types 1 and 2

  12. Relief of dysphagia during neoadjuvant treatment for cancer of the esophagus or gastroesophageal junction.

    Science.gov (United States)

    Sunde, B; Ericson, J; Kumagai, K; Lundell, L; Tsai, J A; Lindblad, M; Rouvelas, I; Friesland, S; Wang, N; Nilsson, M

    2016-07-01

    Dysphagia is the main symptom of cancer of the esophagus and gastroesophageal junction and causing nutritional problems and weight loss, often counteracted by insertion of self-expandable metal stents or nutrition via an enteral route. Clinical observations indicate that neoadjuvant therapy may effectively and promptly alleviate dysphagia, making such nutrition supportive interventions redundant before surgical resection. The objective of the current study was to carefully study the effects of induction neoadjuvant therapy on dysphagia and its subsequent course and thereby investigate the actual need for alimentary gateways for nutritional support. Thirty-five consecutive patients scheduled for neoadjuvant therapy were recruited and assessed regarding dysphagia and appetite at baseline, after the first cycle of preoperative treatment with either chemotherapy alone or with chemoradiotherapy and before surgery. Platinum-based therapy in combination with 5-fluorouracil was administered intravenously days 1-5 every 3 weeks and consisted of three treatments. Patients receiving combined chemoradiotherapy started radiotherapy on day one of second chemotherapy cycle. They received fractions of 2 Gy/day each up to a total dose of 40 Gy. Watson and Ogilvie dysphagia scores were used to assess dysphagia, while appetite was assessed by the Edmonton Assessment System Visual analogue scale-appetite questionnaire. Patients were evaluated at regular outpatient clinic visits or by telephone. The histological tumor response in the surgical specimen was assessed using the Chirieac scale. Ten patients scheduled for neoadjuvant chemotherapy and 25 patients scheduled for chemoradiotherapy were included in the analysis. There was a significant improvement in dysphagia in both treatment groups, according to both scales, already from baseline to the completion of the first chemotherapy cycle which remained to the end of the neoadjuvant treatment (P dysphagia and the degree of

  13. Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy

    International Nuclear Information System (INIS)

    Fristachi, Carlos Elias

    2005-01-01

    Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

  14. Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response.

    Science.gov (United States)

    Díaz-Expósito, R; Martí-Bonmatí, L; Burgués, O; Casáns-Tormo, I; Bermejo-de Las Heras, B; Julve-Parreño, A; Caballero-Garate, A

    Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, pcancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  15. Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

    Science.gov (United States)

    Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

    2016-01-01

    The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  16. Robotic Stereotactic Radioablation Concomitant With Neo-Adjuvant Chemotherapy for Breast Tumors

    International Nuclear Information System (INIS)

    Bondiau, Pierre-Yves; Bahadoran, Phillipe; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Chamorey, Emmanuel; Courdi, Adel; Quielle-Roussel, Catherine; Thariat, Juliette; Ferrero, Jean-Marc

    2009-01-01

    Purpose: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation of thoracic tumors; however, it has never been used for breast tumors and may have a real potential. We conducted a Phase I study, including neoadjuvant chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and 7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by conventional radiotherapy. Materials and Methods: To define toxicity, we performed a dermatologic exam (DE) including clinical examination by two independent observers and technical examination by colorimetry, dermoscopy, and skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was performed 4-8 weeks after the last chemotherapy session. A pathologic examination was also performed. Results: There were two clinical complete responses and four clinical partial responses at D56 and D85. Maximum tolerable dose was not reached. All patients tolerated RSR with no fatigue; 2 patients presented with mild pain after the third fraction of the treatment. There was no significant toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation (50 Gy) has been delivered without toxicity. Conclusion: The study showed the feasibility of irradiation with RSR combined with chemotherapy and surgery for breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy delivered in three fractions combined with chemotherapy. Lack of toxicity suggested that the dose could be increased further. Pathologic response was acceptable.

  17. Non-Hodgkin lymphoma response evaluation with MRI texture classification

    Directory of Open Access Journals (Sweden)

    Heinonen Tomi T

    2009-06-01

    Full Text Available Abstract Background To show magnetic resonance imaging (MRI texture appearance change in non-Hodgkin lymphoma (NHL during treatment with response controlled by quantitative volume analysis. Methods A total of 19 patients having NHL with an evaluable lymphoma lesion were scanned at three imaging timepoints with 1.5T device during clinical treatment evaluation. Texture characteristics of images were analyzed and classified with MaZda application and statistical tests. Results NHL tissue MRI texture imaged before treatment and under chemotherapy was classified within several subgroups, showing best discrimination with 96% correct classification in non-linear discriminant analysis of T2-weighted images. Texture parameters of MRI data were successfully tested with statistical tests to assess the impact of the separability of the parameters in evaluating chemotherapy response in lymphoma tissue. Conclusion Texture characteristics of MRI data were classified successfully; this proved texture analysis to be potential quantitative means of representing lymphoma tissue changes during chemotherapy response monitoring.

  18. Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

    International Nuclear Information System (INIS)

    Bacci, Gaetano; Longhi, Alessandra; Forni, Cristiana R.N.; Fabbri, Nicola; Briccoli, Antonio; Barbieri, Enza; Mercuri, Mario; Balladelli, Alba B.A.; Ferrari, Stefano; Picci, Piero

    2007-01-01

    Purpose: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. Patients and Methods: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. Results: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. Conclusion: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01)

  19. Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Wesolowski, Robert; Duggan, Megan C; Stiff, Andrew; Markowitz, Joseph; Trikha, Prashant; Levine, Kala M; Schoenfield, Lynn; Abdel-Rasoul, Mahmoud; Layman, Rachel; Ramaswamy, Bhuvaneswari; Macrae, Erin R; Lustberg, Maryam B; Reinbolt, Raquel E; Mrozek, Ewa; Byrd, John C; Caligiuri, Michael A; Mace, Thomas A; Carson, William E

    2017-11-01

    This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively. 45.8% had pCR. Mean M-MDSC% were types. G-MDSC levels at the last draw were numerically lower in patients with pCR (1.15; 95% CI 0.14-2.16) versus patients with no pCR (2.71; 95% CI 0-5.47). There was no significant rise in G-MDSC from draw 1 to 3 in African American patients, and at draw 3 G-MDSC levels were significantly lower in African Americans versus Caucasians (p < 0.05). It was concluded that G-MDSC% increased during doxorubicin and cyclophosphamide therapy, but did not significantly differ between patients based on pathologic complete response.

  20. Prognostic value of the 99mTc-Isonitrile washout rate in neoadjuvant chemotherapy in patients with locally advanced breast cancer

    International Nuclear Information System (INIS)

    Silva, N. Jr.; Anselmi, C.E.; Foppa, M.; Batista, L.; Grobocopatel, D.; Hunsche, A.; Fernandes, D.; Berdichevski, E.; Madke, R.; Baptista, I.; Martini, J.; Obando, A.

    2004-01-01

    Full text: Neoadjuvant chemotherapy is the pre-surgical treatment of choice in patients with locally advanced breast tumor for better disease control and breast conservation. Resistance to chemotherapy may be seen in about 18%-51% of the cancers. The term multi drug resistance (MDR) is commonly used to indicate the expression of the transmembrane glycoprotein (P-glycoprotein). This protein removes some very important chemotherapeutic drugs from inside the cell and is responsible for the clinical manifestation of the MDR. The knowledge of MDR before the initiation of chemotherapy can help choosing the best treatment. 99mTc-Isonitrile is a radiotracer largely used in nuclear medicine. It enters cells, is identified by the P-glycoprotein as a substrate and is, therefore, expelled from the neoplastic cell. Various studies have demonstrated direct correlation between the 99mTc-Isonitrile efflux, P-glycoprotein expression and MDR. On the other hand, 99mTc-Isonitrile retention in the tumor suggests chemosensitivity. The objective of this study was to monitor the response to neoadjuvant chemotherapy in breast cancer by the use of 99mTc-Sestamibi scintimammography and its washout rate in a pilot study. Five patients with locally advanced breast cancer were subjected to neoadjuvant chemotherapy. Inclusion criteria were locally advanced tumor, biopsy results, no distant metastasis, and completion of the whole chemotherapy protocol. Exclusion criteria were any previous cancer treatment or other primary tumor. All the patients underwent 99mTc-Sestamibi scintimammography before and after completion of the chemotherapy protocol. For scintimammography, 740MBq of radiotracer was injected in the arm contra lateral to the side of lesion. Planar images were acquired at 10 and 240 minutes, in anterior supine position as well as in both lateral projections in prone position. Regions of interest of same size were drawn over the tumor and in the contra lateral breast to correct for

  1. Ultrasound guided pO2 measurement of breast cancer reoxygenation after neoadjuvant chemotherapy and hyperthermia treatment.

    Science.gov (United States)

    Vujaskovic, Z; Rosen, E L; Blackwell, K L; Jones, E L; Brizel, D M; Prosnitz, L R; Samulski, T V; Dewhirst, M W

    2003-01-01

    The objective of this study was to determine whether neoadjuvant chemotherapy in combination with hyperthermia (HT) would improve oxygenation in locally advanced breast tumours. The study describes a new optimized ultrasound guided technique of pO2 measurement using Eppendorf polarographic oxygen probes in 18 stage IIB-III breast cancer patients. Prior to treatment, tumour hypoxia (median pO2pO2=3.2 mmHg). Seven patients had well oxygenated tumours (median pO2 of 48.3 mmHg). Eight patients with hypoxic tumours prior to treatment had a significant improvement (p=0.0008) in tumour pO2 after treatment (pO2 increased to 19.2 mmHg). In three patients, tumours remained hypoxic (average median pO2=4.5 mmHg). The advantages of the ultrasound guided pO2 probe are in the accuracy of the Eppendorf electrode placement in tumour tissue, the ability to monitor electrode movement through the tumour tissue during the measurement and the ability to avoid electrode placement near or in large blood vessels by using colour Doppler imaging. The results of this preliminary study suggest that the combination of neoadjuvant chemotherapy and hyperthermia improves oxygenation in locally advanced breast tumours that are initially hypoxic.

  2. Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer

    DEFF Research Database (Denmark)

    Bernsdorf, Mogens; Balslev, Eva; Lykkesfeldt, Anne

    2011-01-01

    The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor α (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the Erb......B receptors or downstream effectors may repress ER expression. Here the authors investigated whether gefitinib, given neoadjuvant in combination with epirubicin and cyclophosphamide (EC), could restore ER expression. Eligible patients in the NICE trial were women with unilateral, primary operable, ER negative...... to positive. A change was seen in three patients in the gefitinib (5.1%) and in two patients in the placebo (3.6%) group with a difference of 1.51% (95% CI, -6.1-9.1). Results of the NICE trial have been reported previously. Post-operative reassessment of ER expression changed the assessment of ER status...

  3. The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer

    Directory of Open Access Journals (Sweden)

    Teleki Ivett

    2013-02-01

    Full Text Available Abstract Background Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST are still missing. Deregulation of gap junction channel forming connexins (Cx has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems. Methods The expression of Cx26, Cx32, Cx43, Cx46 and Ki67 was evaluated in 96 breast cancer patients prior to and after neoadjuvant chemotherapy using duplicate cores in tissue microarrays (TMA. Cx plaques of Results In our cohort dominated by hormone receptor (ER/PR positive and HER2 negative cases, only the CPS-EG classification showed prognostic relevance: cases with scores 1–2 had significantly better overall survival (p=0.015 than cases with scores 3–5. Pre-chemotherapy Cx43 expression correlated positively with hormone receptor status both before and after chemotherapy and had a negative correlation with HER2 expression pre-chemotherapy. There was a positive correlation between Cx32 and HER2 expression pre-chemotherapy and between Cx32 and Ki67 expression post-chemotherapy. A negative correlation was found between post-chemotherapy Cx46 and Ki67 expression. Decreased post-chemotherapy Cx26 expression (20% pre- and post-chemotherapy correlated with significantly better survival in the intermediate prognostic subgroups of EWGBSP TR2b (ppre-chemo=0.006; Sataloff TB (ppre-chemo=0.005; ppost-chemo=0.029 and in Miller-Payne G3 (ppre-chemo=0.002; ppost-chemo=0.012 classifications. Pre-chemotherapy, Cx46 expression was the only marker that correlated with overall survival within these subgroups. Conclusion Our results suggest that Cx46 and Cx26 expression

  4. Feasibility of Breast Conservation after Neoadjuvant Chemotherapy in 58 Patients with Locally Advanced Breast Cancer Using p53 and MDRI Genes as Predictors of Response

    International Nuclear Information System (INIS)

    Elsawy, W.H.; Abdel Kader, M.; Abdulla, M.H.

    2002-01-01

    The aim of this prospective trial was to evaluate the feasibility and outcome of breast conservation therapy for patients with locally advanced breast cancer after neoadjuvant chemotherapy. We studied also the value of p53 and MDR1 as predictors to neoadjuvant chemotherapy. Patients and methods: Bet ween August 1997 and May 2000, 58 patients with locally advanced breast carcinoma (stages IlIA and lllB) completed treatment consisting of 5 fluorouracil 600 mg/m 2 , epirubicin 60 mg/m 2 and cyclophosphamide 600 mg/m 2 (FEC) administered intravenously, at intervals of 3 weeks. The number of cycles of chemotherapy given depended on the clinical tumor response. Surgery (local excision if sufficiently down staged, or mastectomy if not, both with axillary dissection) was performed. Surgery was followed by radiation therapy and 4 more cycles of FEC chemotherapy as an adjuvant therapy. P53 and MDR1 were assessed in the initial tissue biopsy by means of reverse transcriptase-mediated polymerase chain reaction (RT-PCR). p53 and MDR1 findings were correlated with treatment response and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Results: The overall response (CR+PR) was 87.9%, with a clinical complete response rate of 29.3%. Six patients had a pathological complete response and 10 patients had only minimal residual disease. Median followup from the start of chemotherapy was 24 months (range 6 to 40). Twenty two patients (43%) underwent BCS with actuarial 3-year disease-free and overall survival of 58% and 75% respectively. Cosmetic results were good to excellent in 77.2% of the patients. Modified radical mastectomy was done in 29/51 (56.9%) patients with actuarial 3 year disease-free and overall survival of 60% and 78% respectively.In 13 out of 58 patients (22.4%), p53 mutations could be identified, including eight point mutations, three minor deletions and two complex deletions

  5. Role of Postmastectomy Radiation After Neoadjuvant Chemotherapy in Stage II-III Breast Cancer

    International Nuclear Information System (INIS)

    Fowble, Barbara L.; Einck, John P.; Kim, Danny N.; McCloskey, Susan; Mayadev, Jyoti; Yashar, Catheryn; Chen, Steven L.; Hwang, E. Shelley

    2012-01-01

    Purpose: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). Methods and Materials: Seven breast cancer physicians from University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. Results: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having ≤10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. Conclusions: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within University of California Athena Breast Health Network.

  6. NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer.

    Science.gov (United States)

    Palmieri, C; Cleator, S; Kilburn, L S; Kim, S B; Ahn, S-H; Beresford, M; Gong, G; Mansi, J; Mallon, E; Reed, S; Mousa, K; Fallowfield, L; Cheang, M; Morden, J; Page, K; Guttery, D S; Rghebi, B; Primrose, L; Shaw, J A; Thompson, A M; Bliss, J M; Coombes, R C

    2014-12-01

    Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE₁₀₀C or endocrine therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95% CI 36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and 0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole 1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.

  7. Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer : Results of the Dutch national breast cancer audit

    NARCIS (Netherlands)

    Spronk, Pauline E.R.; van Bommel, A.C.M.; Siesling, S.; Wouters, M. W.J.M.; Vrancken Peeters, M.T.F.D.; Smorenburg, Carolien H.

    2017-01-01

    Objectives Neoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care.

  8. Study on predictive role of AR and EGFR family genes with response to neoadjuvant chemotherapy in locally advanced breast cancer in Indian women.

    Science.gov (United States)

    Singh, L C; Chakraborty, Anurupa; Mishra, Ashwani K; Devi, Thoudam Regina; Sugandhi, Nidhi; Chintamani, Chintamani; Bhatnagar, Dinesh; Kapur, Sujala; Saxena, Sunita

    2012-06-01

    Locally advanced breast cancer (LABC) remains a clinical challenge as the majority of patients with this diagnosis develop distant metastases despite appropriate therapy. We analyzed expression of steroid and growth hormone receptor genes as well as gene associated with metabolism of chemotherapeutic drugs in locally advanced breast cancer before and after neoadjuvant chemotherapy (NACT) to study whether there is a change in gene expression induced by chemotherapy and whether such changes are associated with tumor response or non-response. Fifty patients were included with locally advanced breast cancer treated with cyclophosphamide, adriamycin, 5-fluorouracil (CAF)-based neoadjuvant chemotherapy before surgery. Total RNA was extracted from 50 match samples of pre- and post-NACT tumor tissues. RNA expression levels of epidermal growth factor receptor family genes including EGFR, ERBB2, ERBB3, androgen receptor (AR), and multidrug-resistance gene 1 (MDR1) were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Responders show significantly high levels of pre-NACT AR gene expression (P = 0.016), which reduces following NACT (P = 0.008), and hence can serve as a useful tool for the prediction of the success of neoadjuvant chemotherapy in individual cancer patients with locally advanced breast carcinoma. Moreover, a significant post-therapeutic increase in the expression levels of EGFR and MDR1 gene in responders (P = 0.026 and P < 0.001) as well as in non-responders (P = 0.055, P = 0.001) suggests that expression of these genes changes during therapy but they do not have any impact on tumor response, whereas a post-therapeutic reduction was observed in AR in responders. This indicates an independent predictive role of AR with response to NACT.

  9. Incidence of venous thromboembolism following the neoadjuvant chemotherapy regimen for epithelial type of ovarian cancer.

    Science.gov (United States)

    Chavan, Devendra Manik; Huang, Zhen; Song, Kun; Parimi, Leela Rani Haricharan; Yang, Xing Sheng; Zhang, Xiangning; Liu, Peishu; Jiang, Jie; Zhang, Youzhong; Kong, Beihua; Li, Li

    2017-10-01

    This study aims to analyze the risk of venous thromboembolism (VTE) in patients receiving neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC).A retrospective audit was conducted examining 147 patients treated for EOC. Surgical treatment with curative intent, with or without NACT and adjuvant chemotherapy, is the treatment approach, which was modified according to the patient's condition. The incidence of VTE with the most commonly used chemotherapy regimen, carboplatin, cisplatin, paclitaxel, docetaxel, and others were evaluated.This study found a 13.6% incidence of VTE in patients undergoing therapy with curative intent for EOC. No association was seen between NACT and VTE compared to VTE after standard treatment: 2/16 (12.5%) vs 5/131 (3.8%) (P = .16). Univariate and multivariate analyses also demonstrated that NACT has no risk for VTE with odds ratio (OR) = 0.89 (95% CI = 0.18-4.28) and P = 1. Results did not vary significantly with the type of chemotherapy used. Furthermore, increased incidence of VTE as an incidental finding supports the well-established role of malignancy in VTE occurrence. Univariate and multivariate analyses demonstrated that VTE occurred more frequently in menopausal women than nonmenopausal women (17.9% vs 5.8%) with OR = 3.55 (95% CI = 0.99-12.78) and P = .04 in patients aged ≥60 (19.3% vs 10%) with OR = 2.15 (95% CI = 0.83-5.57) and P = .13 but is not statistically significant.We conclude that NACT has no association with VTE and the currently used common chemotherapeutic drug combinations for ovarian cancer carry the minimal risk of thromboembolic events.

  10. A Feasibility Study of Neoadjuvant XELOX Without Radiotherapy for Locally Advanced Lower Rectal Cancer.

    Science.gov (United States)

    Ueki, Takashi; Manabe, Tatsuya; Inoue, Shigetaka; Ienaga, Jun; Yamanaka, Naoki; Egami, Takuya; Ishikawa, Mikimasa; Konomi, Hiroyuki; Ikubo, Akashi; Nagayoshi, Kinuko; Nakamura, Masafumi; Tanaka, Masao

    2016-02-01

    This study was planned to evaluate the efficacy and safety of preoperative capecitabine and oxaliplatin (XELOX) without radiation in patients with locally advanced lower rectal cancer. Patients with clinical stage II/III lower rectal cancer underwent three cycles of XELOX followed by radical surgery. The primary end-point was the R0 resection rate. Thirty-one patients were recruited between February 2012 and August 2014. The completion rate of neoadjuvant chemotherapy was 96.5% among the 29 patients who received it; the remaining two refused chemotherapy and underwent immediate surgery. Grade 3-4 adverse events occurred in nine patients (31%). All 29 patients who received chemotherapy underwent radical resection. The R0 resection rate was 96.5% among these 29 patients. Pathological complete responses were achieved in three patients (10.3%) and downstaging occurred in 13 (44.8%). This pilot study found that neoadjuvant XELOX for locally advanced lower rectal cancer is feasible and safe. This neoadjuvant treatment improved resection margin status. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Association of primary tumour FDG uptake with clinical, histopathological and molecular characteristics in breast cancer patients scheduled for neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, B.B.; Aukema, T.S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vrancken Peeters, M.J.T.F.D.; Rutgers, E.J.T. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Wesseling, J.; Lips, E.H. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Pathology and Experimental Therapy, Amsterdam (Netherlands); Vogel, W.V.; Valdes Olmos, R.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Werkhoven, E. van [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, K.G.A. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, S. [Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

    2012-12-15

    The aim of this study was to evaluate the association of primary tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake with clinical, histopathological and molecular characteristics of breast cancer patients scheduled for neoadjuvant chemotherapy. Second, we wished to establish for which patients pretreatment positron emission tomography (PET)/CT could safely be omitted because of low FDG uptake. PET/CT was performed in 214 primary stage II or III breast cancer patients in the prone position with hanging breasts. Tumour FDG uptake was qualitatively evaluated to determine the possibility of response monitoring with PET/CT and was quantitatively assessed using maximum standardized uptake values (SUV{sub max}). FDG uptake was compared with age, TNM stage, histology, hormone and human epidermal growth factor receptor 2 status, grade, Ki-67 and molecular subtype in univariable and multivariable analyses. In 203 tumours (95 %) FDG uptake was considered sufficient for response monitoring. No subgroup of patients with consistently low tumour FDG uptake could be identified. In a univariable analysis, SUV{sub max} was significantly higher in patients with distant metastases at staging examination, non-lobular carcinomas, tumours with negative hormone receptors, triple negative tumours, grade 3 tumours, and in tumours with a high proliferation index (Ki-67 expression). After multiple linear regression analysis, triple negative and grade 3 tumours were significantly associated with a higher SUV{sub max}. Primary tumour FDG uptake in breast cancer patients scheduled for neoadjuvant chemotherapy is significantly higher in tumours with prognostically unfavourable characteristics. Based on tumour characteristics associated with low tumour FDG uptake, this study was unable to identify a subgroup of patients unlikely to benefit from pretreatment PET/CT. (orig.)

  12. The Longitudinal Transcriptional Response to Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer.

    Science.gov (United States)

    Silwal-Pandit, Laxmi; Nord, Silje; von der Lippe Gythfeldt, Hedda; Møller, Elen K; Fleischer, Thomas; Rødland, Einar; Krohn, Marit; Borgen, Elin; Garred, Øystein; Olsen, Tone; Vu, Phuong; Skjerven, Helle; Fangberget, Anne; Holmen, Marit M; Schlitchting, Ellen; Wille, Elisabeth; Nordberg Stokke, Mette; Moen Vollan, Hans Kristian; Kristensen, Vessela; Langerød, Anita; Lundgren, Steinar; Wist, Erik; Naume, Bjørn; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise; Engebraaten, Olav

    2017-08-15

    Purpose: Chemotherapy-induced alterations to gene expression are due to transcriptional reprogramming of tumor cells or subclonal adaptations to treatment. The effect on whole-transcriptome mRNA expression was investigated in a randomized phase II clinical trial to assess the effect of neoadjuvant chemotherapy with the addition of bevacizumab. Experimental Design: Tumor biopsies and whole-transcriptome mRNA profiles were obtained at three fixed time points with 66 patients in each arm. Altogether, 358 specimens from 132 patients were available, representing the transcriptional state before treatment start, at 12 weeks and after treatment (25 weeks). Pathologic complete response (pCR) in breast and axillary nodes was the primary endpoint. Results: pCR was observed in 15 patients (23%) receiving bevacizumab and chemotherapy and 8 patients (12%) receiving only chemotherapy. In the estrogen receptor-positive patients, 11 of 54 (20%) treated with bevacizumab and chemotherapy achieved pCR, while only 3 of 57 (5%) treated with chemotherapy reached pCR. In patients with estrogen receptor-positive tumors treated with combination therapy, an elevated immune activity was associated with good response. Proliferation was reduced after treatment in both treatment arms and most pronounced in the combination therapy arm, where the reduction in proliferation accelerated during treatment. Transcriptional alterations during therapy were subtype specific, and the effect of adding bevacizumab was most evident for luminal-B tumors. Conclusions: Clinical response and gene expression response differed between patients receiving combination therapy and chemotherapy alone. The results may guide identification of patients likely to benefit from antiangiogenic therapy. Clin Cancer Res; 23(16); 4662-70. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Clinical efficacy of breast-conserving surgery combined with neoadjuvant chemotherapy for locally advanced breast cancer: a report of 81 cases

    Directory of Open Access Journals (Sweden)

    Zhi-yu CAO

    2015-07-01

    Full Text Available Objective To investigate the clinical efficacy of neoadjuvant chemotherapy combined with breast-conserving surgery for locally advanced breast cancer. Methods Eighty-one patients with locally advanced breast cancer were selected from those who were admitted into 309 Hospital of PLA from January 2009 to October 2013, consisting of 65 patients in stage Ⅲa and 16 in stage Ⅲb, and they were treated with neoadjuvant chemotherapy combined with breast-conserving surgery. The clinical efficacy [complete response (CR, partial response (PR, stable disease (SD and progress disease (PD] was observed during follow-up. Results All the patients were followed-up for 12-60 months with a median of 34 months. There were 12 CR patients (14.8%, including 4 with pathological complete response (4.9%, and 52 PR patients (64.2%, 17 SD patients (21.0%. No PD was observed. The overall response rate(ORR was 79.0%(64/81. After follow-up for 12-60 months (median 34 months, distant metastasis to the lung, liver, meninges and bone occurred in 3 patients (3.7%, 3/81 and 1 of them died. Forty-eight patients received breastconserving surgery. The local recurrence rate was 6.3% (3/48. Assessment of cosmetic result was carried out in 48 patients who received breast-conserving surgery and comprehensive treatment for one year, and excellent results were obtained in 14.6% (7/48, good in 43.8% (21/48, and poor in 41.7% (20/48. Conclusions The therapeutic efficacy of locally advanced breast cancer is satisfactory by neoadjuvant chemotherapy and breast-conserving surgery. Standardization of excision and postoperative radiotherapy, systemic comprehensive treatment is the key to the success of the treatment. DOI: 10.11855/j.issn.0577-7402.2015.06.14

  14. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer.

    Science.gov (United States)

    Lips, Esther H; Mukhtar, Rita A; Yau, Christina; de Ronde, Jorma J; Livasy, Chad; Carey, Lisa A; Loo, Claudette E; Vrancken-Peeters, Marie-Jeanne T F D; Sonke, Gabe S; Berry, Donald A; Van't Veer, Laura J; Esserman, Laura J; Wesseling, Jelle; Rodenhuis, Sjoerd; Shelley Hwang, E

    2012-11-01

    Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.

  15. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial.

    Science.gov (United States)

    van Meurs, Hannah S; Tajik, Parvin; Hof, Michel H P; Vergote, Ignace; Kenter, Gemma G; Mol, Ben Willem J; Buist, Marrije R; Bossuyt, Patrick M

    2013-10-01

    To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule. The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy. Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory

  16. Can we eliminate neoadjuvant chemoradiotherapy in favor of neoadjuvant multiagent chemotherapy for select stage II/III rectal adenocarcinomas: Analysis of the National Cancer Data base.

    Science.gov (United States)

    Cassidy, Richard J; Liu, Yuan; Patel, Kirtesh; Zhong, Jim; Steuer, Conor E; Kooby, David A; Russell, Maria C; Gillespie, Theresa W; Landry, Jerome C

    2017-03-01

    Stage II and III rectal cancers have been effectively treated with neoadjuvant chemoradiotherapy (NCRT) followed by definitive resection. Advancements in surgical technique and systemic therapy have prompted investigation of neoadjuvant multiagent chemotherapy (NMAC) regimens with the elimination of radiation (RT). The objective of the current study was to investigate factors that predict for the use of NCRT versus NMAC and compare outcomes using the National Cancer Data Base (NCDB) for select stage II and III rectal cancers. In the NCDB, 21,707 patients from 2004 through 2012 with clinical T2N1 (cT2N1), cT3N0, or cT3N1 rectal cancers were identified who had received NCRT or NMAC followed by low anterior resection. Kaplan-Meier analyses, log-rank tests, and Cox-proportional hazards regression analyses were conducted along with propensity score matching analysis to reduce treatment selection bias. The 5-year actuarial overall survival (OS) rate was 75% for patients who received NCRT versus 67.2% for those who received NMAC (P elimination of neoadjuvant RT for select patients with stage II and III rectal adenocarcinoma was associated with worse OS and should not be recommended outside of a clinical trial. Cancer 2017;123:783-93. © 2016 American Cancer Society. © 2016 American Cancer Society.

  17. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.

  18. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun

    2015-01-01

    The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited

  19. A prospective cohort study of patient-reported vomiting, retching, nausea and antiemetic use during neoadjuvant long-course radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Kristopher Dennis

    2018-03-01

    Full Text Available Background and purpose: Antiemetic guidelines suggest daily prophylaxis with a serotonin3 receptor antagonist (5-HT3RA as an option for patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal cancer, despite the risks that 5-HT3RA-induced constipation may pose. We explored the incidence of patient-reported vomiting, retching, nausea and antiemetic intake among patients in this setting to determine if these risks are justified. Materials and methods: We carried out a single-centre non-randomised prospective cohort study of adult patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma. Patients recorded symptoms and medication intake daily until 7 days following treatment completion. Results: From 33 evaluable patients, we collected 1407 days of patient-reported data. Vomiting was reported by 7 patients (21%, retching by 5(15% and nausea by 21(64%. No patients were administered prophylactic antiemetics. The median number of days with vomiting was 2, and the cumulative number of days for all affected patients was 22 (1.6% of 1407 evaluable days. There were no differences in PTV or small bowel loop V15Gy, V45Gy and V50Gy volumes between patients that did and did not vomit. Conclusions: The cumulative incidence of days with vomiting was only 1.6%. 5-HT3RA prophylaxis during long-course neoadjuvant treatment seems unnecessary. Keywords: Antiemetic, Nausea, Patient-reported outcome, Radiation therapy, Rectal cancer, Vomiting

  20. Sentinel Lymph Node Biopsy Following Neoadjuvant Chemotherapy: Review of the Literature and Recommendations for Use in Patient Management

    Directory of Open Access Journals (Sweden)

    Yan Xing

    2004-10-01

    Full Text Available Breast cancer is a significant health problem worldwide and is one of the leading causes of cancer-related mortality in women. Preoperative chemotherapy has become the standard of care for patients with locally advanced disease and is being used more frequently in patients with early-stage breast cancer. Sentinel lymph node biopsy has shown great promise in the surgical management of breast cancer patients, but its use following preoperative chemotherapy is yet to be determined. Eleven studies have been published with respect to the accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy. Ten studies showed favourable results, with the ability to identify a sentinel lymph node in 84% to 98% of cases, and reported false negative rates ranging from 0% to 20%. The accuracy of sentinel lymph node biopsy following preoperative chemotherapy for breast cancer ranges from 88% to 100%, with higher rates when specific techniques and inclusion criteria are applied. The published literature supports the use of sentinel lymph node biopsy for assessment of the axilla in patients with clinically node-negative disease following preoperative chemotherapy.

  1. A gene expression signature of Retinoblastoma loss-of-function predicts resistance to neoadjuvant chemotherapy in ER-positive/HER2-positive breast cancer patients.

    Science.gov (United States)

    Risi, Emanuela; Grilli, Andrea; Migliaccio, Ilenia; Biagioni, Chiara; McCartney, Amelia; Guarducci, Cristina; Bonechi, Martina; Benelli, Matteo; Vitale, Stefania; Biganzoli, Laura; Bicciato, Silvio; Di Leo, Angelo; Malorni, Luca

    2018-07-01

    HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients. We selected clinical trials of neoadjuvant chemotherapy ± anti-HER2 therapy in HER2+ breast cancer patients with available information on gene expression data, hormone receptor status, and pathological complete response (pCR) rates. RBsig expression was computed in silico and correlated with pCR. Ten studies fulfilled the inclusion criteria and were included in the analysis (514 patients). Overall, of 211 ER+/HER2+ breast cancer patients, 49 achieved pCR (23%). The pCR rate following chemotherapy ± anti-HER2 drugs in patients with RBsig low expression was significantly lower compared to patients with RBsig high expression (16% vs. 30%, respectively; Fisher's exact test p = 0.015). The area under the ROC curve (AUC) was 0.62 (p = 0.005). In the 303 ER-negative (ER-)/HER2+ patients treated with chemotherapy ± anti-HER2 drugs, the pCR rate was 43%. No correlation was found between RBsig expression and pCR rate in this group. Low expression of RBsig identifies a subset of ER+/HER2+ patients with low pCR rates following neoadjuvant chemotherapy ± anti-HER2 therapy. These patients may potentially be spared chemotherapy in favor of anti-HER2, endocrine therapy, and CDK 4/6 inhibitor combinations.

  2. Association of PTP1B with Outcomes of Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Rivera Franco, Monica M; Leon Rodriguez, Eucario; Martinez Benitez, Braulio; Villanueva Rodriguez, Luisa G; de la Luz Sevilla Gonzalez, Maria; Armengol Alonso, Alejandra

    2016-01-01

    PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR ( P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens ( P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B over-expression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

  3. Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Monica M. Rivera Franco

    2016-01-01

    Full Text Available PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR. Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5% and overexpression (≥5%. Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2. However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02. Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B overexpression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

  4. Effect of preoperative neoadjuvant chemotherapy on the expression of malignant molecules in colon cancer tissue and the degree of trauma caused by radical operation

    Directory of Open Access Journals (Sweden)

    Yan-Cheng Wang

    2017-09-01

    Full Text Available Objective: To study the effect of preoperative neoadjuvant chemotherapy on the expression of malignant molecules in colon cancer tissue and the degree of trauma caused by radical operation. Methods: Patients who were diagnosed with colon cancer in Fengrun People’s Hospital between March 2014 and February 2017 were selected and randomly divided into the XELOX group who accepted XELOX neoadjuvant chemotherapy combined with radical operation for colon cancer and the control group who accepted radical operation for colon cancer alone. Surgically removed colon cancer tissue was collected to test the expression of proliferation, apoptosis and invasion genes, and serum was collected to detect the contents of liver and kidney function indicators as well as inflammatory factors. Results: Rac1, PLD2, CHD1L, Snail, Vimentin and N-cadherin mRNA expression levels in surgically removed colon cancer lesions of XELOX group were significantly lower than those of control group while MS4A12 and ASPP2 mRNA expression levels were significantly higher than those of control group; serum ALT, AST, β2-MG, Cys-C, sICAM-1, sVCAM-1, sTM and sE-selectin contents were not significantly different between the two groups of patients 1 day and 3 days after surgery. Conclusion: Preoperative neoadjuvant chemotherapy can inhibit the proliferation, apoptosis and invasion gene expression in colon cancer tissues without increasing the trauma of operation.

  5. Incidence of chemotherapy-induced neutropenia in HIV-infected and uninfected patients with breast cancer receiving neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Sithembile Ngidi

    2017-07-01

    Full Text Available Background. Chemotherapy-induced neutropenia (CIN can result in poor tolerance of chemotherapy, leading to dose reductions, delays in therapy schedules, morbidity and mortality. Actively identifying predisposing risk factors before treatment is of paramount importance. We hypothesised that chemotherapy is associated with a greater increase in CIN and its complications in HIV-infected patients than in those who are not infected. Objective. To establish the incidence of CIN in HIV-infected and uninfected patients undergoing chemotherapy. Methods. A retrospective chart review and analysis was conducted in the oncology departments at Inkosi Albert Luthuli Central Hospital and Addington Hospital, Durban, South Africa. The study population consisted of 65 previously untreated women of all ages with stage II - IV breast cancer and known HIV status treated with neoadjuvant chemotherapy from January 2012 to December 2015. Results. HIV-infected patients formed 32.3% of the group, and 95.2% of them were on antiretroviral therapy. The mean age (standard deviation (SD of the cohort was 48.5 (13.2 years (40.6 (9.6 years for the HIV-infected group v. 52.0 (13.1 years for the uninfected group; p<0.001. Ninety-five neutropenia episodes were observed (rate 0.85 per 1 year of follow-up time. Following multivariate adjustment, patients with HIV infection were almost two times more likely to develop CIN (hazard ratio (HR 1.76, 95% confidence interval (CI 1.06 - 2.92; p=0.029. A high baseline absolute neutrophil count (ANC (HR 0.80, 95% CI 0.68 - 0.95; p=0.005 remained significantly associated with protection against CIN. Conclusions. HIV-infected patients were younger than those who were not infected, and presented at a more locally advanced stage of disease. HIV infection was an independent predictor for CIN. HIV-infected patients had an almost two-fold increased risk of developing CIN and developed neutropenia at a much faster rate. A high baseline white cell

  6. Breast conserving treatment of breast carcinoma T2 ({<=} 4 cm) and T3 by neoadjuvant chemotherapy, quadrantectomy, high dose rate brachytherapy as a boost, external beam radiotherapy and adjuvant chemotherapy: local control and overall survival analysis; Tratamento conservador do cancer de mama T2 ({<=} 4 cm) e T3 por quimioterapia neoadjuvante, quadrantectomia, braquiterapia com alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante: analise de controle local e sobrevida global

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Celia Regina; Miziara Filho, Miguel Abrao; Fogaroli, Ricardo Cesar; Baraldi, Helena Espindola; Pellizzon, Antonio Cassio Assis; Pelosi, Edilson Lopes [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia], e-mail: celiarsoares@terra.com.br; Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia; Paes, Roberto Pinto [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil)

    2008-12-15

    Objective: to assess the treatment of breast cancer T2 ({<=} 4 cm) and T3 through neoadjuvant chemotherapy, quadrantectomy and high dose rate brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering local control and overall survival. Material and method: this clinical prospective descriptive study was based on the evaluation of 88 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIb and IIIa, responsive to the neoadjuvant chemotherapy, treated from June/1995 to December/2006. Median follow-up was 58 months. Using clinical methods the tumor was evaluated before and after three or four cycles of chemotherapy based on anthracyclines. Overall survival and local control were assessed according to Kaplan-Meier methodology. Results: Local control and overall survival in five years were 90% and 73.5%, respectively. Conclusion: local control and overall survival were comparable to other forms of treatment. (author)

  7. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial.

    Science.gov (United States)

    Gronchi, Alessandro; Ferrari, Stefano; Quagliuolo, Vittorio; Broto, Javier Martin; Pousa, Antonio Lopez; Grignani, Giovanni; Basso, Umberto; Blay, Jean-Yves; Tendero, Oscar; Beveridge, Robert Diaz; Ferraresi, Virginia; Lugowska, Iwona; Merlo, Domenico Franco; Fontana, Valeria; Marchesi, Emanuela; Donati, Davide Maria; Palassini, Elena; Palmerini, Emanuela; De Sanctis, Rita; Morosi, Carlo; Stacchiotti, Silvia; Bagué, Silvia; Coindre, Jean Michelle; Dei Tos, Angelo Paolo; Picci, Piero; Bruzzi, Paolo; Casali, Paolo Giovanni

    2017-06-01

    Previous trials from our group suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference in overall survival benefit between three cycles versus five cycles of the same neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant administration of histotype-tailored regimen to standard chemotherapy. For this international, open-label, randomised, controlled, phase 3, multicentre trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and Poland. Eligible patients were aged 18 years or older with localised, high-risk (high malignancy grade, 5 cm or longer in diameter, and deeply located according to the investing fascia), soft-tissue sarcoma of the extremities or trunk wall and belonging to one of five histological subtypes: high-grade myxoid liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumour, and undifferentiated pleomorphic sarcoma. Patients were randomly assigned (1:1) to receive three cycles of full-dose standard chemotherapy (epirubicin 60 mg/m 2 per day [short infusion, days 1 and 2] plus ifosfamide 3 g/m 2 per day [days 1, 2, and 3], repeated every 21 days) or histotype-tailored chemotherapy: for high-grade myxoid liposarcoma, trabectedin 1·3 mg/m 2 via 24-h continuous infusion, repeated every 21 days; for leiomyosarcoma, gemcitabine 1800 mg/m 2 on day 1 intravenously over 180 min plus dacarbazine 500 mg/m 2 on day 1 intravenously over 20 min, repeated every 14 days; for synovial sarcoma, high-dose ifosfamide 14 g/m 2 , given over 14 days via an external infusion pump, every 28 days; for malignant peripheral nerve sheath tumour, intravenous etoposide 150 mg/m 2 per day (days 1, 2, and 3) plus intravenous ifosfamide 3 g/m 2 per day (days 1, 2, and 3), repeated every 21 days; and for undifferentiated pleomorphic sarcoma, gemcitabine 900 mg/m 2 on days 1 and

  8. Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Icro Meattini

    2014-01-01

    Full Text Available Neoadjuvant chemotherapy (NAC is widely used in locally advanced breast cancer (BC treatment. The role of postmastectomy radiotherapy (PMRT after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6% underwent PMRT and 72 cases (42.4% did not receive radiation. At a median follow-up period of 7.7 years (range 2–16 for the whole cohort, median time to locoregional recurrence (LRR was 3.3 years (range 0.7–12.4. The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P=0.035, extracapsular extension (HR 2.18, 1.37–3.46; P=0.009, and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P=0.003. Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P=0.015. Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy.

  9. Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.

    Science.gov (United States)

    Lacava, J A; Leone, B A; Machiavelli, M; Romero, A O; Perez, J E; Elem, Y L; Ferreyra, R; Focaccia, G; Suttora, G; Salvadori, M A; Cuevas, M A; Acuña, L R; Acuña, J R; Langhi, M; Amato, S; Castaldi, J; Arroyo, A; Vallejo, C T

    1997-02-01

    To evaluate the efficacy and toxicity of vinorelbine (VNB) as single-agent neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between December 1993 and October 1995, 43 untreated patients with stages IIB to IVA squamous cell cervical cancer were entered onto this study. Forty-two patients are assessable for response and 43 for toxicity. The median age was 46 years (range, 28 to 65). Distribution by stages (International Federation of Gynecology and Obstetrics [FIGO]) was as follows: IIB, 18 patients; IIIA, one; IIIB, 19; and IVA, five. Therapy consisted of VNB 30 mg/m2 by 20-minute intravenous (IV) infusion repeated weekly for 12 injections and followed by radical surgery if feasible or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. One patient was considered not assessable for response. A total of 493 cycles of therapy were administered and objective remissions were observed in 19 of 42 patients (45%; 95% confidence interval, 30% to 60%). Two patients (5%) had a complete response (CR) and 17 (40%) a partial response (PR); no change (NC) was observed in 16 (38%) and progressive disease (PD) in seven (17%). Six of 19 patients (32%) who achieved objective responses (ORs) underwent surgery. The median time to failure and median survival time have not been reached yet. There were no therapy-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (81%) and was grade 3 or 4 in seven (17%). Twelve patients (28%) developed peripheral neuropathy, while myalgias occurred in 10 (23%). Constipation was observed in nine patients (21%), one with a prolonged ileum. Phlebitis was recorded in 18 patients (41%). In contrast, emesis and mucositis were rarely observed. No patient developed alopecia grade 3. By the end of the twelfth course of treatment, the average received dose-intensity was 85.4% of that projected. VNB is an active drug against ACC with moderate

  10. Preoperative evaluation and monitoring chemotherapy in patients with high-grade osteogenic and Ewing's sarcoma: review of current imaging modalities

    International Nuclear Information System (INIS)

    Woude, H.-J. van der; Bloem, J.L.; Hogendoorn, P.C.W.

    1998-01-01

    Diagnostic imaging is pivotal in the initial detection, characterization, staging and post-treatment follow-up of patients with high-grade osteogenic and Ewing's sarcoma. In the present review article, conventional and new imaging modalities are discussed with regard to the monitoring of the effect of neoadjuvant chemotherapy in such patients. Presurgical monitoring of response to chemotherapy may have an impact on modification of neoadjuvant treatment protocols, on patient selection for the performance and timing of limb-salvage surgery and on planning of radiation therapy (in non-operated Ewing's sarcomas) and selection of postoperative chemotherapy regimens. Dynamic contrast-enhanced MR imaging, as part of a routine MR protocol, assists in the detection of the most viable parts of the tumour and serves as an initial standard for follow-up of the metabolic activity of the tumour during and after chemotherapy, both in small intraosseous tumours and in tumours with an associated soft tissue mass. In combination with selected morphological features, dynamic imaging parameters are therefore advocated for monitoring the effect of neoadjuvant chemotherapy in patients with osteogenic and Ewing's sarcoma. (orig.)

  11. Evaluation of tolerability and efficacy of incorporating carboplatin in neoadjuvant anthracycline and taxane based therapy in a BRCA1 enriched triple-negative breast cancer cohort.

    Science.gov (United States)

    Sella, Tal; Gal Yam, Einav Nili; Levanon, Keren; Rotenberg, Tal Shapira; Gadot, Moran; Kuchuk, Iryna; Molho, Rinat Bernstein; Itai, Amit; Modiano, Tami Mekel; Gold, Raya; Kaufman, Bella; Shimon, Shani Paluch

    2018-05-22

    The addition of carboplatin (Cb) to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) has been demonstrated to improve pathologic complete response (pCR) at the expense of increased toxicity. We aimed to evaluate the effectiveness and tolerability of dose-dense anthracycline & cyclophosphamide (ddAC) followed by weekly paclitaxel (wT) in combination with weekly Cb. Retrospective data was collected on patients with clinical stage I-III TNBC treated with neoadjuvant ddAC-wTCb (four cycles of ddA 60 mg/m 2 and ddC 600 mg/m 2 every 2 weeks followed by 12 cycles of wT 80 mg/m 2 with Cb AUC 1.5). Indices of tolerability and pCR were evaluated and compared to a historical cohort (n = 76) treated with ddAC-T. A secondary objective was to evaluate the rates of pCR by BRCA status. For 43 eligible patients, mean age was 41.5 years, 51% had clinical stage II disease, 81.4% were clinically node positive and 32.6% carried a deleterious BRCA1 mutation. Only 35% completed all scheduled doses of chemotherapy. Grade 3/4 neutropenia was observed in 42.5% of patients. Overall pCR was 51.2%; 44.8% in BRCA wild-type compared to 64.3% in BRCA-associated TNBC (p = 0.232). pCR rates with ddAC-wTCb were similar to historic institutional rates with ddAC-T (51.2% vs. 51.3%, p = 0.987) and were comparable when stratified by BRCA status. In pooled multivariate analysis, only BRCA status (HR 4.00, 95%CI 1.65-9.75, p = 0.002) was significantly associated with pCR. Neoadjuvant ddAC-wTCb is less tolerable in clinical practice compared to most clinical trials, with a pCR comparable to historic rates using non-platinum regimen. The role of Cb in neoadjuvant chemotherapy for BRCA mutated TNBC remains uncertain. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Does the pretreatment tumor sampling location correspond with metabolic activity on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Koolen, Bas B., E-mail: b.koolen@nki.nl [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Elshof, Lotte E. [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Loo, Claudette E. [Department of Radiology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Wesseling, Jelle [Department of Pathology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Vrancken Peeters, Marie-Jeanne T.F.D. [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Vogel, Wouter V. [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Rutgers, Emiel J.Th. [Department of Surgical Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Valdés Olmos, Renato A. [Department of Nuclear Medicine, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2013-12-01

    Purpose: To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II–III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling. Methods: A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥2 cm and a relative difference in SUV ≥25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed. Results: Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p = 0.028), diffuse (non-mass) and multifocal tumors on MRI (p = 0.001), diffuse and multifocal tumors on PET/CT (p < 0.001), tumors >3 cm (p < 0.001), and lobular carcinomas (p < 0.001). No association was found with other features. Conclusion: Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II–III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3 cm, lobular carcinomas, and diffuse and multifocal tumors.

  13. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial

    Directory of Open Access Journals (Sweden)

    Shen Kui

    2012-11-01

    Full Text Available Abstract Background The purpose of this study is to assess the predictive accuracy of a multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and cyclophosphamide combination chemotherapy on gene expression data from patients who received these drugs as neoadjuvant treatment. Methods Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC followed by four cycles of docetaxel/capecitabine (TX on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H. The chemotherapy predictor (TFEC-MGP was developed from publicly available gene expression data of 42 breast cancer cell-lines with corresponding in vitro chemotherapy sensitivity results for the four chemotherapy drugs. No predictor was developed for treatment with trastuzumab. The predictive performance of TFEC-MGP in distinguishing cases with pathologic complete response from those with residual disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area under the receiver-operating characteristic curve (AU-ROC was used as the metric of predictive performance. Genomic predictions were performed blinded to clinical outcome. Results The AU-ROC was 0.70 (95% CI: 0.57-0.82 for the FEC/TX group (n=66 and 0.43 (95% CI: 0.20-0.66 for the FEC/TX plus H group (n=25. Among the patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86 for estrogen receptor (ER-negative (n=28 and it was 0.59 (95% CI: 0.36-0.82 for ER-positive cancers (n=37. ER status was not reported for one patient. Conclusions Our results indicate that the cell line derived 291-probeset genomic predictor of response to FEC/TX combination chemotherapy shows good performance in a blinded validation study, particularly in ER-negative patients.

  14. Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.

    Science.gov (United States)

    Samrao, Damanzoopinder; Wang, Dan; Ough, Faith; Lin, Yvonne G; Liu, Song; Menesses, Teodulo; Yessaian, Annie; Turner, Nicole; Pejovic, Tanja; Mhawech-Fauceglia, Paulette

    2012-12-01

    The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen's kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of 20 months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.

  15. Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance)

    Science.gov (United States)

    Ellis, Matthew J.; Suman, Vera J.; Hoog, Jeremy; Goncalves, Rodrigo; Sanati, Souzan; Creighton, Chad J.; DeSchryver, Katherine; Crouch, Erika; Brink, Amy; Watson, Mark; Luo, Jingqin; Tao, Yu; Barnes, Michael; Dowsett, Mitchell; Budd, G. Thomas; Winer, Eric; Silverman, Paula; Esserman, Laura; Carey, Lisa; Ma, Cynthia X.; Unzeitig, Gary; Pluard, Timothy; Whitworth, Pat; Babiera, Gildy; Guenther, J. Michael; Dayao, Zoneddy; Ota, David; Leitch, Marilyn; Olson, John A.; Allred, D. Craig; Hunt, Kelly

    2017-01-01

    Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) –positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for

  16. Multiparametric MRI in the assessment of response of rectal cancer to neoadjuvant chemoradiotherapy: A comparison of morphological, volumetric and functional MRI parameters

    International Nuclear Information System (INIS)

    Hoetker, Andreas M.; Tarlinton, Lisa; Gollub, Marc J.; Mazaheri, Yousef; Woo, Kaitlin M.; Goenen, Mithat; Saltz, Leonard B.; Goodman, Karyn A.; Garcia-Aguilar, Julio

    2016-01-01

    To compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer. This retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant K"t"r"a"n"s on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). For both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR. Tumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement. (orig.)

  17. Multiparametric MRI in the assessment of response of rectal cancer to neoadjuvant chemoradiotherapy: A comparison of morphological, volumetric and functional MRI parameters

    Energy Technology Data Exchange (ETDEWEB)

    Hoetker, Andreas M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Universitaetsmedizin Mainz, Department of Diagnostic and Interventional Radiology, Mainz (Germany); Tarlinton, Lisa; Gollub, Marc J. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Mazaheri, Yousef [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Woo, Kaitlin M.; Goenen, Mithat [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Saltz, Leonard B. [Memorial Sloan Kettering Cancer Center, Department of Medicine, Gastrointestinal Oncology Service, New York, NY (United States); Goodman, Karyn A. [Memorial Sloan Kettering Cancer Center, Department of Radiation Oncology, New York, NY (United States); Garcia-Aguilar, Julio [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States)

    2016-12-15

    To compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer. This retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant K{sup trans} on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC). For both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR. Tumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement. (orig.)

  18. CCR 20th Anniversary Commentary: Simpson's Paradox and Neoadjuvant Trials.

    Science.gov (United States)

    Carey, Lisa A

    2015-09-15

    The research article by Carey and colleagues, published in the April 15, 2007, issue of Clinical Cancer Research, described the relationship between response to neoadjuvant chemotherapy and outcome by tumor subtype. Today neoadjuvant clinical trials are often designed to provide correlative data to help identify predictive biomarkers or to focus on poor-risk patients identified by residual disease after neoadjuvant treatment. ©2015 American Association for Cancer Research.

  19. The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer

    International Nuclear Information System (INIS)

    Teleki, Ivett; Varga, Zsuzsanna; Krenacs, Tibor; Szasz, Marcell A; Kulka, Janina; Wichmann, Barna; Leo, Cornelia; Papassotiropoulos, Barbel; Riemenschnitter, Cosima; Moch, Holger

    2013-01-01

    Several classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST) are still missing. Deregulation of gap junction channel forming connexins (Cx) has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems. The expression of Cx26, Cx32, Cx43, Cx46 and Ki67 was evaluated in 96 breast cancer patients prior to and after neoadjuvant chemotherapy using duplicate cores in tissue microarrays (TMA). Cx plaques of <1μm were detected with multilayer, multichannel fluorescence digital microscopy. Current classifications to assess residual tumour burden after primary systemic therapy included the EWGBSP, CPS-EG, Miller-Payne, Sataloff and NSABP systems. In our cohort dominated by hormone receptor (ER/PR) positive and HER2 negative cases, only the CPS-EG classification showed prognostic relevance: cases with scores 1–2 had significantly better overall survival (p=0.015) than cases with scores 3–5. Pre-chemotherapy Cx43 expression correlated positively with hormone receptor status both before and after chemotherapy and had a negative correlation with HER2 expression pre-chemotherapy. There was a positive correlation between Cx32 and HER2 expression pre-chemotherapy and between Cx32 and Ki67 expression post-chemotherapy. A negative correlation was found between post-chemotherapy Cx46 and Ki67 expression. Decreased post-chemotherapy Cx26 expression (<5%) statistically correlated with better overall survival (p=0.011). Moderate or higher Cx46 expression (>20%) pre- and post-chemotherapy correlated with significantly better survival in the intermediate prognostic subgroups of EWGBSP TR2b (p pre-chemo =0

  20. Evaluation of paclitaxel and carboplatin versus combination chemotherapy with fluorouracil doxorubicin and cyclophosphamide as a neoadjuvant therapy in patients with inoperable breast cancer

    International Nuclear Information System (INIS)

    Akhtar, M.S.; Kausar, F.

    2010-01-01

    To compare the results of patients with locally advanced breast cancer receiving two different regimens Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) and Paclitaxel and Carboplatin. Study Design: Comparative study. Place and Duration of Study: The Oncology Department, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from March 2007 to September 2008. Methodology: Patients with inoperable locally advanced breast cancer of stage were included. Sixteen patients were given FAC regimen and 9 patients were given Paclitaxel and Carboplatin, each combination was cycled after 21 days for four times. Before enrollment, detailed medical histories, physical examinations and performance status assessments were done as well as post chemotherapy evaluation with regular follow-up visits was done. Complete Response (CR, 100%) is defined as the disappearance of all known disease parameter i.e. disappearance in detectable tumour size, node free disease and surgery is possible. Paratial Response (PR, > 50%) was defined by 50% or greater decrease in the sum of the areas of bidimensionally measured lesions i.e. change of N2 to N1 or no status and some surgical procedure is possible to down stage the disease. Minor Response (MR) was defined as a decrease in the tumour insufficient to quality for partial resp once. Static disease or no evaluable reflected no significant change in disease and no evidence of new disease. Progression of disease (> 25%) was defined as a 25% or greater increase in the area of any lesion > 2 cm or in the sum of the products of the individual lesions or the appearance of new malignant lesions, surgery not possible. Results: Twenty five patients completed neoadjuvant chemotherapy. Sixteen (66%) patients received FAC and 9 (37%) patients received PC chemotherapy. Overall CR (breast and axilla) was 54%, PR was 16% and minor response (MR) was 8%. FAC treatment induced more emesis, mucositis, alopecia and cardiotoxicity. No death occurred

  1. Is Tc99m-MIBI scintigraphy a predictor of response to pre-operative neoadjuvant chemotherapy in Osteosarcoma?

    Directory of Open Access Journals (Sweden)

    Vahidreza Dabbagh Kakhki

    2013-10-01

    Full Text Available Objectives: Multidrug resistance (MDR, which may be due to the over expression of P-glycoprotein (Pgp and/or MRP, is a major problem in neoadjuvant chemotherapy of osteosarcoma. The aim of this study was to investigate the role of Tc-99m MIBI scan for predicting the response to pre-operative chemotherapy. Materials and Methods: Twenty-five patients (12 males and 13 females, aged between 8 and 52y with osteosarcoma were studied. Before the chemotherapy, planar 99mTc-MIBI anterior and posterior images were obtained 10-min [tumor-to-background ratio: (T1/B110min] and 3-hr after tracer injection. After completion of chemotherapy, again 99mTc-MIBI scan was performed at 10-min after tracer injection. In addition to calculation of decay corrected tumor to background (T/B ratios ,  using the 10-min and 3-hr images of the pre-chemotherapy scintigraphy , percent wash-out rate (WR% of 99mTc-MIBI was calculated. Using the 10-min images of the pre- and post-chemotherapy scans, the percent reduction in uptake at the tumor site after treatment (Red% was also calculated. Then after surgical resection, tumor response was assessed by percentage of necrosis. Results: All patients showed significant 99mTc-MIBI uptake in early images. Only 9 patients showed good response to chemotherapy (necrosis≥90% while 16 patients were considered as non-responder (necrosis

  2. Neo-adjuvant chemotherapy with cisplatin induces low expression of NMDA receptors and postoperative cognitive impairment.

    Science.gov (United States)

    Cheng, Jing; Liu, Xiaoqing; Cao, Longhui; Zhang, Tianhua; Li, Huiting; Lin, Wenqian

    2017-01-10

    Whether Neo-adjuvant chemotherapy can affect patients' postoperative brain function is not clear. In this study, we investigated the effect of preoperative cisplatin treatment on postoperative cognitive function and its possible mechanism in rats. Moreover, we also tested whether the NMDAR inhibitor memantine could attenuate cisplatin-induced alterations. 12-month-oldSprague-Dawley rats randomly received an intraperitoneal injection of either cisplatin once a week at a dose of 3mg/kg for three consecutive weeks or an equivalent volume of normal saline. After the injections, the normal saline injection group was divided into 3 groups (n=5 each): a normal saline group (group S), normal saline+pentobarbital group (group SP), and normal saline+pentobarbital+operation group (group SPO).The cisplatin injection group was divided into 3 groups: a cisplatin group (group C), cisplatin+pentobarbital group (group CP), and cisplatin+pentobarbital+operation group (group CPO).Rats in the group SP, SPO,CP and CPO were anaesthetized with sodium pentobarbital and then the SPO and CPO groups underwent a simple laparotomy operation. The effects of memantine were tested through two additional groups of rats (cisplatin+memantine group (group CM) and cisplatin+pentobarbital+operation+memantine group (group CPOM)). A Morris water maze test was performed to evaluate the spatial learning and memory ability five days after anesthesia or operation. After the test, the hippocampi were removed for detection of the expression of NMDAR by western bloting. The relevant protein expression levels of PSD95 and ERK1/2 were detected by western blot analysis. Rats treated with cisplatin had a longer mean escape latency and spent a shorter amount of time in the target quadrant than did the normal saline injection rats. Furthermore, the protein expression levels of NMDA receptors, PSD95 and ERK1/2 were decreased in cisplatin group and memantine could up-regulate their expression. These results suggest

  3. Gradient phenomenon of multidrug resistance gene expression in breast cancer during neoadjuvant chemotherapy is related to disease progression

    Directory of Open Access Journals (Sweden)

    N. V. Litviakov

    2013-01-01

    Full Text Available The paper examined 106 patients with breast cancer (BC treated with neoadjuvant chemotherapy (NАС. In the biopsy material, derived from primary tumor before NAC and surgical samples after chemotherapy the expression of 8 multidrug resistance genes (MDR ABCB1, АВСВ2, ABCC1, ABCC2, АВСС5, ABCG1, ABCG2 и MVP was evaluated using quantitative RT-PCR. During the NAC course 75 % of patients manifested gradient phenomenon for gene expression that means a unidirectional change in the expression of all five MDR genes ABCB1, ABCC1, ABCC2, ABCG1 и ABCG2 closely associated with the NAC efficacy: the reduction in MDR gene expression was related to good response to NAC while the expression increase associated with poor response to NAC. In 25% of patients there was no such change in studied gene expression that means the lack of a gradient phenomenon. The objective was to study whether gradient phenomenon for MDR gene expression during NAC is related to disease free survival in breast cancer patients. Five-year metastasis-free survival in patients having a gradient phenomenon was 73 % versus 39 % in patients who lack a gradient phenomenon (log-rank test p=0,0018. So, the presence of a gradient phenomenon in patients is appeared to be associated with a good disease prognosis. It is assumed that the gradiThe paper examined 106 patients with breast cancer (BC treated with neoadjuvant chemotherapy (NАС. In the biopsy material, derived from primary tumor before NAC and surgical samples after chemotherapy the expression of 8 multidrug resistance genes (MDR ABCB1, АВСВ2, ABCC1, ABCC2, АВСС5, ABCG1, ABCG2 и MVP was evaluated using quantitative RT-PCR. During the NAC course 75 % of patients manifested gradient phenomenon for gene expression that means a unidirectional change in the expression of all five MDR genes ABCB1, ABCC1, ABCC2, ABCG1 и ABCG2 closely associated with the NAC efficacy: the reduction in MDR gene expression was related to good

  4. Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus

    International Nuclear Information System (INIS)

    Minsky, Bruce D.; Neuberg, Donna; Kelsen, David P.; Pisansky, Thomas M.; Ginsberg, Robert J.; Pajak, Thomas; Salter, Merle; Benson, Al

    1999-01-01

    Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (100 mg/m 2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m 2 /24 h x 5 days) and cisplatin (75 mg/m 2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123

  5. Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

    Science.gov (United States)

    Sada, Yvonne H; Tran Cao, Hop S; Chang, George J; Artinyan, Avo; Musher, Benjamin L; Smaglo, Brandon G; Massarweh, Nader N

    2018-06-01

    For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment. Published by Elsevier Inc.

  6. Protocol and result of neoadjuvant chemotherapy for locally advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    Isono, Kaichi; Koide, Yoshio

    1996-01-01

    The protocol and result were described of chemotherapy and radiotherapy for locally advanced esophageal carcinoma, especially for A3 stage one with metastasis at neighboring tissues such as aorta, trachea and bronchia. Chemotherapy was done with 5-FU and CDDP and radiotherapy, with 30 Gy/15 fx/3 wk. Double contrast roentgenography, dynamic CT and MRI were performed to follow the process. The efficacy rate was 55.0% with 4 CR and 7 PR in 20 cases. Three CR patients survived at present. Major adverse effects were leukopenia and thrombocytopenia, of which grade 4 were found in 14 and 12% cases, respectively. Low-dose FP therapy might be useful for lowering the adverse effects and for elevating the efficacy rates. (K.H.)

  7. [A Case of Retroperitoneal Abscess Due to Acute Appendicitis during Neo-Adjuvant Chemotherapy for Breast Cancer].

    Science.gov (United States)

    Oba, Takaaki; Maeno, Kazuma; Ito, Kenichi; Ishizone, Satoshi; Hanaoka, Takaomi

    2017-11-01

    When acute appendicitis occurs in patients treated with chemotherapy, neutropenia and abdominal complaints caused by chemotherapy can contribute to the diagnostic difficulty, masking the increase in white blood cell(WBC)counts and physical findings of acute appendicitis. A 43-year-old premenopausal woman who was diagnosed with stage IIIA left breast cancer was scheduled for neoadjuvant chemotherapy includingfluorouracil plus epirubicin plus cyclophosphamide(FEC), followed by docetaxel and trastuzumab(DOC plus HER). The patient developed fever and lower abdominal pain on day 17 of DOC plus HER cycle 1, and was diagnosed with acute gastroenteritis in the emergency room. These symptoms were almost improved 4 days later, and then cycle 2 was performed as scheduled. WBC counts decreased to 1,530 cells/mL due to DOCinduced myelosuppression on day 8 of cycle 2 when the patient developed lower abdominal pain again. However, WBC counts increased to 21,680 cells/mL on day 13 of cycle 2. Computed tomography scans revealed an intraperitoneal abscess due to acute appendicitis, and consequently urgent operation was performed. It is necessary to understand that patients with acute appendicitis duringchemotherapy can present less clinical findings.

  8. Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

    Directory of Open Access Journals (Sweden)

    Guilherme Freire Angotti Carrara

    Full Text Available OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04. A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01. CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

  9. MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Franklin, J.M., E-mail: jamiemfranklin@hotmail.com [Churchill Hospital, Headington, Oxford (United Kingdom); Anderson, E.M.; Gleeson, F.V. [Churchill Hospital, Headington, Oxford (United Kingdom)

    2012-06-15

    Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having {>=}80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

  10. MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy

    International Nuclear Information System (INIS)

    Franklin, J.M.; Anderson, E.M.; Gleeson, F.V.

    2012-01-01

    Aim: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). Materials and methods: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. Results: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having ≥80% low signal, and 3/13 with 100% low signal. Conclusion: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

  11. Clinical efficacy of local targeted chemotherapy for triple-negative breast cancer

    International Nuclear Information System (INIS)

    He, Jinsong; Wang, Xianming; Guan, Hong; Chen, Weicai; Wang, Ming; Wu, Huisheng; Wang, Zun; Zhou, Ruming; Qiu, Shuibo

    2011-01-01

    The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m 2 ]; E: epirubicin [90 mg/m 2 ]; F: 5-fluorouracil [600 mg/m 2 ]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses

  12. Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients : Identification rate and influence on axillary treatment

    NARCIS (Netherlands)

    van der Heiden-van der Loo, M.; de Munck, L.; Sonke, G. S.; van Dalen, T.; van Diest, P. J.; van den Bongard, H. J. G. D.; Peeters, P. H. M.; Rutgers, E. J. T.

    The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The

  13. Chemotherapy related toxicity in locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Bahl Amit

    2006-01-01

    Full Text Available Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0 Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients. Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

  14. HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

    International Nuclear Information System (INIS)

    Tiezzi, Daniel G; Andrade, Jurandyr M; Ribeiro-Silva, Alfredo; Zola, Fábio E; Marana, Heitor RC; Tiezzi, Marcelo G

    2007-01-01

    Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. Sixty patients received preoperative docetaxel (75 mg/m 2 ) in combination with epirubicin (50 mg/m 2 ) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination

  15. Comparison of Pathologic Response Evaluation Systems after Anthracycline with/without Taxane-Based Neoadjuvant Chemotherapy among Different Subtypes of Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Hee Jin Lee

    Full Text Available Several methods are used to assess the pathologic response of breast cancer after neoadjuvant chemotherapy (NAC to predict clinical outcome. However, the clinical utility of these systems for each molecular subtype of breast cancer is unclear. Therefore, we applied six pathologic response assessment systems to specific subtypes of breast cancer and compared the results.Five hundred and eighty eight breast cancer patients treated with anthracycline with/without taxane-based NAC were retrospectively analyzed, and the ypTNM stage, residual cancer burden (RCB, residual disease in breast and nodes (RDBN, tumor response ratio, Sataloff's classification, and Miller-Payne grading system were evaluated. The results obtained for each assessment system were analyzed in terms of patient survival.In triple-negative tumors, all systems were significantly associated with disease-free survival and Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. For HR+/HER2- tumors, systems assessing the residual tumor (ypTNM stage, RCB, and RDBN had prognostic significance. However, for HER2+ tumors, the association between patient survival and the pathologic response assessment results varied according to the system used, and none resulted in distinct Kaplan-Meier curves.Most of the currently available pathologic assessment systems used after anthracycline with/without taxane-based NAC effectively classified triple-negative breast cancers into groups showing different prognoses. The pathologic assessment systems evaluating residual tumors only also had prognostic significance in HR+/HER2- tumors. However, new assessment methods are required to effectively evaluate the pathologic response of HR+/HER2+ and HR-/HER2+ tumors to anthracycline with/without taxane-based NAC.

  16. Circulating tumour cells and pathological complete response: independent prognostic factors in inflammatory breast cancer in a pooled analysis of two multicentre phase II trials (BEVERLY-1 and -2) of neoadjuvant chemotherapy combined with bevacizumab.

    Science.gov (United States)

    Pierga, J-Y; Bidard, F-C; Autret, A; Petit, T; Andre, F; Dalenc, F; Levy, C; Ferrero, J-M; Romieu, G; Bonneterre, J; Lerebours, F; Bachelot, T; Kerbrat, P; Campone, M; Eymard, J-C; Mouret-Reynier, M-A; Gligorov, J; Hardy-Bessard, A-C; Lortholary, A; Soulie, P; Boher, J-M; Proudhon, C; Charafe-Jaufret, E; Lemonnier, J; Bertucci, F; Viens, P

    2017-01-01

    We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials. © The Author 2016

  17. Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

    Science.gov (United States)

    Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

    2016-04-01

    The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect. © 2015 UICC.

  18. Percentage of pathological complete response in patients with rectal cancer that received neoadjuvant therapy with chemotherapy and radiotherapy at the Servicio de Radioterapia from Hospital Mexico, in the period from January 2009 to December 2013

    International Nuclear Information System (INIS)

    Lopez Mena, Stephanie

    2015-01-01

    Percentage of pathologic complete response is determined in patients with rectal cancer, treated with neoadjuvant chemotherapy and radiotherapy, in the Servicio de Radioterapia from Hospital Mexico, in the period between January 2009 and December 2013. Tumor histology is determined. The distance of the tumor is identified with respect to the anal margin. The correlation between the TNM staging and the response received in this type of neoadjuvant therapy is described. Radiotherapy dose used in each case is described. Different schemes of chemotherapy used are characterized. The acute side effects most common are determined in the study population [es

  19. Preoperative chemotherapy of bone and soft tissue sarcomas. Evaluation with dynamic MR imaging

    International Nuclear Information System (INIS)

    Ando, Yoko; Fukatsu, Hiroshi; Isomura, Takayuki; Itoh, Shigeki; Ishigaki, Takeo; Yamamura, Shigeki; Sugiura, Hideshi; Satoh, Keiji.

    1995-01-01

    Dynamic MR imaging and conventional angiography were performed in eleven patients with musculoskeletal malignant tumors before and after preoperative chemotherapy in order to evaluate its effect. Dynamic MRI was obtained with GRASS (TR/TE/FA=50/10-13/30) or SE (TR/TE=150-350/20). Although resected specimen in one case of osteosarcoma had the necrotic ratio of more than 90%, it had marked early enhancement in dynamic MRI, and microscopic examination revealed fibrotic necrosis with many capillaries. In soft tissue sarcomas with hemorrhage and/or cystic change, dynamic MRI findings did not necessarily correlate with the chemotherapy effect. Dynamic MRI was more useful than angiography because of its ability to show tumor vascularity and of its non-invasiveness. (author)

  20. Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

    Directory of Open Access Journals (Sweden)

    Hardes Jendrik

    2010-12-01

    Full Text Available Abstract Background Bone mineral density (BMD accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA after completion of neoadjuvant chemotherapy. Methods DXA measurements of the lumbar spine (L2-4, both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years. Mean Z-scores, areal BMD (g/cm2, calculated volumetric BMD (g/cm3 and bone mineral content (BMC, g were determined. Results Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18, areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082 and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347 which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36, the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9 in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0 for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ρ = 0.55 to ρ = 0.80. Conclusions The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis

  1. Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

    OpenAIRE

    Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas; Hatschek, Thomas

    2017-01-01

    Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advance...

  2. Neoadjuvant chemotherapy for breast cancer: correlation between the baseline MR imaging findings and responses to therapy

    International Nuclear Information System (INIS)

    Uematsu, Takayoshi; Yuen, Sachiko; Kasami, Masako

    2010-01-01

    To retrospectively evaluate the magnetic resonance (MR) imaging findings of breast cancer before neoadjuvant chemotherapy (NAC) and to compare findings of chemosensitive breast cancer with those of chemoresistant breast cancer. The MR imaging findings before NAC in 120 women undergoing NAC were reviewed. The MR imaging findings were compared with the pathological findings and responses. A complete response (pCR) and marked response were achieved in 12 and 35% of 120 breast cancers in 120 women respectively. Breast cancers with a pCR or marked response were classified as chemosensitive breast cancer. The remaining 64 breast cancers (53%) were classified as chemoresistant breast cancer. Large tumour size, a lesion without mass effect, and very high intratumoural signal intensity on T2-weighted MR images were significantly associated with chemoresistant breast cancer. Lesions with mass effect and washout enhancement pattern were significantly associated with chemosensitive breast cancer. Areas with very high intratumoural signal intensity on T2-weighted images corresponded pathologically to areas of intratumoural necrosis. Several MR imaging features of breast cancer before NAC can help predict the efficacy of NAC. (orig.)

  3. Neoadjuvant chemotherapy for breast cancer: correlation between the baseline MR imaging findings and responses to therapy

    Energy Technology Data Exchange (ETDEWEB)

    Uematsu, Takayoshi; Yuen, Sachiko [Shizuoka Cancer Center Hospital, Breast Imaging and Breast Intervention Section, Naga-izumi, Shizuoka (Japan); Kasami, Masako [Shizuoka Cancer Center Hospital, Department of Pathology, Naga-izumi, Shizuoka (Japan)

    2010-10-15

    To retrospectively evaluate the magnetic resonance (MR) imaging findings of breast cancer before neoadjuvant chemotherapy (NAC) and to compare findings of chemosensitive breast cancer with those of chemoresistant breast cancer. The MR imaging findings before NAC in 120 women undergoing NAC were reviewed. The MR imaging findings were compared with the pathological findings and responses. A complete response (pCR) and marked response were achieved in 12 and 35% of 120 breast cancers in 120 women respectively. Breast cancers with a pCR or marked response were classified as chemosensitive breast cancer. The remaining 64 breast cancers (53%) were classified as chemoresistant breast cancer. Large tumour size, a lesion without mass effect, and very high intratumoural signal intensity on T2-weighted MR images were significantly associated with chemoresistant breast cancer. Lesions with mass effect and washout enhancement pattern were significantly associated with chemosensitive breast cancer. Areas with very high intratumoural signal intensity on T2-weighted images corresponded pathologically to areas of intratumoural necrosis. Several MR imaging features of breast cancer before NAC can help predict the efficacy of NAC. (orig.)

  4. Clinical Initial Response of Neoadjuvant Chemotheraphy in Triple Negative, HER-2, and Luminal Types of Breast Cancer in Denpasar (A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Kristianto Yuli Yarso

    2012-01-01

    Full Text Available Objectives: Triple Negative, Luminal, HER-2 subtypes of breast cancer are markers to predict behavior, aggressiveness, and response to chemotherapy. The aim of this study is to understand character and response to standard neoadjuvant chemotherapy in different subtypes of breast cancer. Method: This is a descriptive study of breast cancer subtypes. From 687 patients (2003-2010 351 patients have IHC data which divided into 3 groups, Triple negative, Luminal, and HER-2. We used 10% as a cut off point for ER, PR, while 30% & positive 3 for HER-2. We determined initial clinical response after 3 cycles of neoadjuvant chemotherapy although only 77 got standard neoadjuvant chemotherapy and had clinical response data. We used 50% diameters depreciation & no metastasis as cut off point for respond group. Results: There were 116 (33% Triple Negative, 60 (17% HER-2, and 175 (50% Luminal Subtypes. The mean of age for 351 patients are 48.32 (23-82 years. In this study, it was obtained that no significant difference of means of age (p=0.24 in these 3 groups. Triple negative group significantly more advance in grade if compared with the other two groups (p=0.02. HER-2 group had highest response with standard neoadjuvant chemotherapy (50%, Luminal group had (49%, and Triple negative group had only (15% response. One pCR in HER-2 group. There were no difference ages in subtypes. Triple negative has more advances in grade. HER-2 group has highest response to standard neoadjuvant chemotherapy and Triple negative has lowest response to standard neoadjuvant chemotherapy.

  5. Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy

    Science.gov (United States)

    Castaneda, Carlos A; Mittendorf, Elizabeth; Casavilca, Sandro; Wu, Yun; Castillo, Miluska; Arboleda, Patricia; Nunez, Teresa; Guerra, Henry; Barrionuevo, Carlos; Dolores-Cerna, Ketty; Belmar-Lopez, Carolina; Abugattas, Julio; Calderon, Gabriela; De La Cruz, Miguel; Cotrina, Manuel; Dunstan, Jorge; Gomez, Henry L; Vidaurre, Tatiana

    2016-01-01

    AIM To determine influence of neoadjuvant-chemotherapy (NAC) over tumor-infiltrating-lymphocytes (TIL) in triple-negative-breast-cancer (TNBC). METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays (TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response (pCR) (P = 0.0251) and outcome (P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections (ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. Post-NAC lesions with pCR had similar TIL levels than those without pCR (P = 0.6331). NAC produced a TIL decrease in full-face sections (P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival (DFS). Higher counts of CD3 in pre-NAC samples had longer overall-survival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR. CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related. PMID:27777881

  6. Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won Tae; Kim, Yong Kan; Lee, Ju Hye; Kim, Dong Hyun; Park, Dahl; Cho, Kyu Sup; Kim, Dong Won [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Ji Ho; Roh, Hwan Jung [Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2013-09-15

    The optimal treatment of advanced maxillary sinus cancer has been challenging for several decades. Intra-arterial chemotherapy (IAC) for head and neck cancer has been controversial. We have analyzed the long-term outcome of neoadjuvant IAC followed by radiation therapy (RT) and surgery. Twenty-seven patients with advanced maxillary sinus cancer were treated between 1989 and 2002. Five-fluorouracil (5-FU, 500 mg/m2) was infused intra-arterially, and followed by RT (total 50.4 Gy/28 fractions). A planned surgery was performed 3 to 4 weeks after completion of IAC and RT. At a median follow-up of 77 months (range, 12 to 169 months), the 5-year rates of overall survival in all patients were 63%. The 5-year rates of overall survival of stage T3/T4 patients were 70.0% and 58.8%, respectively. Seven of fourteen patients with disease recurrence had a local recurrence alone. The 5-year actuarial local control rates in patients with stage T3/T4, and in all patients were 20.0%, 32.3%, and 27.4%, respectively. Overall response rate after the completion of IAC and RT was 70.3%. During the follow-up, seven patients (25.9%) showed mild to moderate late complications. The tumor extent (i.e., the involvement of either orbit and/or base of skull) appeared to be related with local recurrence. Neoadjuvant IAC with 5-FU followed by RT and surgery may be effective to improve local tumor control in the patients with advanced maxillary sinus cancer. However, local failure was still the major cause of death. Further investigations are required to determine the optimal treatment schedule, radiotherapy techniques and chemotherapy regimens.

  7. Diffusion-weighted magnetic resonance imaging for pretreatment prediction and monitoring of treatment response of patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy

    International Nuclear Information System (INIS)

    Nilsen, Line; Olsen, Dag Rune; Seierstad, Therese; Fangberget, Anne; Geier, Oliver

    2010-01-01

    Background. For patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy (NACT), the European Guidelines for Breast Imaging recommends magnetic resonance imaging (MRI) to be performed before start of NACT, when half of the NACT has been administered and prior to surgery. This is the first study addressing the value of flow-insensitive apparent diffusion coefficients (ADCs) obtained from diffusion-weighted (DW) MRI at the recommended time points for pretreatment prediction and monitoring of treatment response. Materials and methods. Twenty-five LABC patients were included in this prospective study. DW MRI was performed using single-shot spin-echo echo-planar imaging with b-values of 100, 250 and 800 s/mm 2 prior to NACT, after four cycles of NACT and at the conclusion of therapy using a 1.5 T MR scanner. ADC in the breast tumor was calculated from each assessment. The strength of correlation between pretreatment ADC, ADC changes and tumor volume changes were examined using Spearman's rho correlation test. Results. Mean pretreatment ADC was 1.11 ± 0.21 x 10 -3 mm 2 /s. After 4 cycles of NACT, ADC was significantly increased (1.39 ± 0.36 x 10 -3 mm 2 /s; p=0.018). There was no correlation between individual pretreatment breast tumor ADC and MR response measured after four cycles of NACT (p=0.816) or prior to surgery (p=0.620). Conclusion. Pretreatment tumor ADC does not predict treatment response for patients with LABC undergoing NACT. Furthermore, ADC increase observed mid-way in the course of NACT does not correlate with tumor volume changes.

  8. Comparison of mediastinal lymph node status and relapse pattern in clinical stage IIIA non-small cell lung cancer patients treated with neoadjuvant chemotherapy versus upfront surgery: A single center experience.

    Science.gov (United States)

    Savic, Milan; Kontic, Milica; Ercegovac, Maja; Stojsic, Jelena; Bascarevic, Slavisa; Moskovljevic, Dejan; Kostic, Marko; Vesovic, Radomir; Popevic, Spasoje; Laban, Marija; Markovic, Jelena; Jovanovic, Dragana

    2017-09-01

    In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. The rate of N2 disease was significantly higher in the upfront surgery group ( P   0.05). There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  9. [Application of decision curve on evaluation of MRI predictive model for early assessing pathological complete response to neoadjuvant therapy in breast cancer].

    Science.gov (United States)

    He, Y J; Li, X T; Fan, Z Q; Li, Y L; Cao, K; Sun, Y S; Ouyang, T

    2018-01-23

    Objective: To construct a dynamic enhanced MR based predictive model for early assessing pathological complete response (pCR) to neoadjuvant therapy in breast cancer, and to evaluate the clinical benefit of the model by using decision curve. Methods: From December 2005 to December 2007, 170 patients with breast cancer treated with neoadjuvant therapy were identified and their MR images before neoadjuvant therapy and at the end of the first cycle of neoadjuvant therapy were collected. Logistic regression model was used to detect independent factors for predicting pCR and construct the predictive model accordingly, then receiver operating characteristic (ROC) curve and decision curve were used to evaluate the predictive model. Results: ΔArea(max) and Δslope(max) were independent predictive factors for pCR, OR =0.942 (95% CI : 0.918-0.967) and 0.961 (95% CI : 0.940-0.987), respectively. The area under ROC curve (AUC) for the constructed model was 0.886 (95% CI : 0.820-0.951). Decision curve showed that in the range of the threshold probability above 0.4, the predictive model presented increased net benefit as the threshold probability increased. Conclusions: The constructed predictive model for pCR is of potential clinical value, with an AUC>0.85. Meanwhile, decision curve analysis indicates the constructed predictive model has net benefit from 3 to 8 percent in the likely range of probability threshold from 80% to 90%.

  10. Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer.

    Science.gov (United States)

    Shrestha, Bikram; Sun, Yifei; Faisal, Farzana; Kim, Victoria; Soares, Kevin; Blair, Alex; Herman, Joseph M; Narang, Amol; Dholakia, Avani S; Rosati, Lauren; Hacker-Prietz, Amy; Chen, Linda; Laheru, Daniel A; De Jesus-Acosta, Ana; Le, Dung T; Donehower, Ross; Azad, Nilofar; Diaz, Luis A; Murphy, Adrian; Lee, Valerie; Fishman, Elliot K; Hruban, Ralph H; Liang, Tingbo; Cameron, John L; Makary, Martin; Weiss, Matthew J; Ahuja, Nita; He, Jin; Wolfgang, Christopher L; Huang, Chiung-Yu; Zheng, Lei

    2017-07-01

    The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL-PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL-PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL-PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13-0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19-0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long-term survival in a subpopulation of patients with BL-PDAC. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. The role of {sup 18}F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Amandeep; Seenu, Vathalaru; Mehta, Sada Nand [All India Institute of Medical Sciences, Department of Surgical disciplines, New Delhi (India); Kumar, Rakesh; Chawla, Madhavi; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Gupta, Sidharatha Datta [All India Institute of Medical Sciences, Department of Pathology, New Delhi (India)

    2009-06-15

    We evaluated the role of 18F-FDG PET/CT for the assessment of response after two cycles of neo-adjuvant chemotherapy (NACT) for breast cancer. Twenty-three women with locally advanced breast cancer were included in this study. Early response to NACT was evaluated after two cycles using clinical examination, CT, and 18F-FDG PET/CT. Final histopathology following surgery after six cycles of NACT served as reference. Baseline PET/CT demonstrated a total of 26 lesions in 23 patients. The size of the primary tumor ranged from 1.90 cm to 11.60 cm, and the maximum value of the standardized uptake value of FDG (SUVmax) ranged from 3.6 to 38.6 (mean, 11.7). Post-chemotherapy PET/CT examinations were done after two cycles of NACT. The size of the primary tumor on follow-up PET/CT examinations ranged from 0.0 cm to 7.6 cm, and SUVmax ranged from 0.0 to 12.0 (mean, 3.96). On clinical, CT, and PET/CT examinations, 50% reduction in the parameters was taken as the cutoff value to differentiate between responders and non-responders. Post-NACT PET/CT demonstrated that 16 patients were responders and 7 non-responders. Among 16 responders on PET/CT scan, 14 were true positive and 2 were false positive when compared with histopathology. Among seven non-responder patients, six were true negative, and one was false negative. The sensitivity, specificity, and accuracy of PET/CT in detecting responders were 93%, 75%, and 87%, respectively. In conclusion, 18F-FDG PET/CT can differentiate responders from non-responders with high accuracy after two cycles of NACT in patients with LABC. (orig.)

  12. Docetaxel as neoadjuvant chemotherapy in patients with advanced cervical carcinoma.

    Science.gov (United States)

    Vallejo, Carlos T; Machiavelli, Mario R; Pérez, Juan E; Romero, Alberto O; Bologna, Fabrina; Vicente, Hernán; Lacava, Juan A; Ortiz, Eduardo H; Cubero, Alberto; Focaccia, Guillermo; Suttora, Guillermo; Scenna, Mirna; Boughen, José M; Leone, Bernardo A

    2003-10-01

    The purpose of this study was to evaluate the efficacy and toxicity of docetaxel as single-agent neoadjuvant chemotherapy in locoregionally advanced cervical carcinoma. Between April 1998 and August 2000, 38 untreated patients with International Federation of Gynecology and Obstetrics stages IIB to IVA were entered onto this study. The median age was 44 years (range: 25-66 years). Stages: IIB 22 patients, IIIB 15 patients, and IVA 1 pt. Treatment consisted of docetaxel 100 mg/m2 IV infusion during 1 hour. Standard premedication with dexamethasone, diphenhydramine, and ranitidine was used. Cycles were repeated every 3 weeks for three courses, followed by radical surgery when it was judged appropriate, or definitive radiotherapy. Both staging and response assessment were performed by a multidisciplinary team. 106 cycles of therapy were administered; all patients were evaluable for TX, whereas 35 were evaluable for response (3 patients refused further treatment after the first cycle of therapy). Complete response (CR): 1 patient (3%); partial response: 11 patients (31%), for an overall objective response rate of 34% (95% CI: 15-53%); no change (NC): 16 patients (46%); and progressive disease: 7 patients (20%). Six patients (17%) underwent surgery and a pathologic CR was confirmed in 1 of them. The median time to treatment failure and the median survival have not been reached yet. The limiting toxicity was leukopenia in 25 patients (69%) (G1-G2: 14 patients, G3: 10 patients, and G4: 1 patient). Neutropenia: 28 patients (78%) (G1-G2: 10 patients, G3: 8 and G4: 10). Myalgias: 17 patients (47%) (G1-G2: 15 patients and G3: 2 patients). Emesis: 21 patients (55%) (G1-G2: 19 patients and G3: 2 patients). Alopecia G3: 13 patients (36%); rash cutaneous 26 patients (68%) (G1-G2: 22 patients and G3: 4 patients). There were no hypersensitivity reactions or fluid-retention syndrome. The received dose intensity was 91% of that projected. Docetaxel is an active drug against advanced

  13. Intraindividual variability in reaction time before and after neoadjuvant chemotherapy in women diagnosed with breast cancer.

    Science.gov (United States)

    Yao, Christie; Rich, Jill B; Tirona, Kattleya; Bernstein, Lori J

    2017-12-01

    Women treated with chemotherapy for breast cancer experience subtle cognitive deficits. Research has focused on mean performance level, yet recent work suggests that within-person variability in reaction time performance may underlie cognitive symptoms. We examined intraindividual variability (IIV) in women diagnosed with breast cancer and treated with neoadjuvant chemotherapy. Patients (n = 28) were assessed at baseline before chemotherapy (T1), approximately 1 month after chemotherapy but prior to surgery (T2), and after surgery about 9 months post chemotherapy (T3). Healthy women of similar age and education (n = 20) were assessed at comparable time intervals. Using a standardized regression-based approach, we examined changes in mean performance level and IIV (eg, intraindividual standard deviation) on a Stroop task and self-report measures of cognitive function from T1 to T2 and T1 to T3. At T1, women with breast cancer were more variable than controls as task complexity increased. Change scores from T1 to T2 were similar between groups on all Stroop performance measures. From T1 to T3, controls improved more than women with breast cancer. IIV was more sensitive than mean reaction time in capturing group differences. Additional analyses showed increased cognitive symptoms reported by women with breast cancer from T1 to T3. Specifically, change in language symptoms was positively correlated with change in variability. Women with breast cancer declined in attention and inhibitory control relative to pretreatment performance. Future studies should include measures of variability, because they are an important sensitive indicator of change in cognitive function. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Post-mastectomy radiation therapy and overall survival after neoadjuvant chemotherapy.

    Science.gov (United States)

    Kantor, Olga; Pesce, Catherine; Singh, Puneet; Miller, Megan; Tseng, Jennifer; Wang, Chi-Hsiung; Winchester, David J; Yao, Katharine

    2017-05-01

    The role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) and mastectomy is unclear, especially in patients that have post-treatment tumor negative axillary nodes (ypN0). The National Cancer Data Base was used to identify women that had PMRT after NAC and mastectomy for clinically node positive (cN1-2) disease from 2004 to 2008. Median follow-up time was 69 months. 8,321 patients were included for analysis, and 6140 (65.6%) had cN1 disease and 2181 (23.3%) had cN2 disease. On adjusted survival analysis, PMRT was associated with an overall survival (OS) benefit in both patients with cN1 (5-yr OS 75.8% vs. 71.9%, P  0.11) for PMRT compared to those patients who were not ypN0, except for patients with hormone-receptor negative tumors, who had improved OS with PMRT (HR 0.65, P < 0.01). PMRT is associated with improved OS in patients with cN1 and cN2 disease after NAC and mastectomy. However, in the subgroup of patients that were ypN0 after NAC, PMRT improved OS for hormone-receptor negative patients but not hormone-receptor positive patients. © 2017 Wiley Periodicals, Inc.

  15. Combined radiotherapy and chemotherapy for head and neck cancer

    International Nuclear Information System (INIS)

    Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

    1988-01-01

    There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

  16. Prospective Phase II Study of Brachytherapy Boost as a Component of Neo-Adjuvant Chemotherapy and External Beam Radiation Therapy in Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    EL-SAYED, M.E.; EL-TAHER, Z.H.

    2008-01-01

    The aim of the current study is to assess the response rate and toxicity profile in patients with locally advanced rectal cancer using brachytherapy (BT) boost following external beam radiotherapy (EBRT), concomitant with chemotherapy as a component of the neoadjuvant treatment. Patients and Methods: This is a prospective phase II study of neoadjuvant chemo-radiation therapy for patients with locally advanced rectal cancer who presented to the department of radiation oncology, King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Seventeen patients had been included in the study. Radiation therapy was given as: phase I,45 Gy/25 fractions/5 weeks of EBRT, followed by brachytherapy boost (within one week after the end of EBRT) using high dose rate iridium 192 (Ir 192 ) aiming at 800 c Gy given in 2 fractions (each 400 c Gy) separated by 1 week. All patients received the same concomitant chemotherapy in the form of Capecitabine and Oxaliplatin. The clinical and pathological response rates, together with the toxicity profile were assessed. Results: Seventeen patients had been studied; the majority (14; 82%) were males, while 3 only (18%) were females, their mean age was 57.4 years. All patients had low anterior resection (LAR). The clinical response rate, assessed by digital rectal examination ± endoscopy examination 4 weeks after the end of EBRT and BT, revealed that complete clinical response (cCR) was noted in 3 patients (18%), clinical partial response (cPR) in 14 patients (82%); while the pathological response rate was: complete pathological response (pCR) in 8 patients (47%), pathological partial response (pPR) in 9 patients (53%). The toxicity profile showed that grade III radiation proctitis was seen in one patient (6%), grade III dermatitis in 2 (12%), while no patients developed grade III cystitis. For chemotherapy toxicities, three patients (18%) developed grade III nausea and/or vomiting, 2 (12%) developed grade III diarrhea. Conclusion

  17. Expression characteristic of CXCR1 in different breast tissues and the relevance between its expression and efficacy of neo-adjuvant chemotherapy in breast cancer.

    Science.gov (United States)

    Xue, Miao-Qun; Liu, Jun; Sang, Jian-Feng; Su, Lei; Yao, Yong-Zhong

    2017-07-25

    To investigate chemokine receptor CXCR1 expression characteristic in different breast tissues and analyze the relationship between CXCR1 expression changes in breast cancer tissue and efficacy of neo-adjuvant chemotherapy. Chemokine receptor CXCR1 was lowly expressed in normal breast tissues and breast fibroadenoma, but highly expressed in breast cancer. It was significantly correlated with pathological stage, tumor cell differentiation, and lymph node metastasis (P breast cancer tissues decreased. Among these 104 breast cancer patients with different molecular subtypes, the survival rate with Luminal A was the highest, followed by the Luminal B breast cancer, TNBC was the worst. 104 cases with breast carcinoma, 20 cases with normal breast and 20 cases with breast fibroadenoma were included and followed up. Immunohistochemistry was used to detect the expression of CXCR1 in the various tissues. The relationship between the CXCR1 expression changes in breast cancer biopsies and surgical specimens, as well as the efficacy of neo-adjuvant chemotherapy, was analyzed. Chemokine receptor CXCR1 could be used as an indicator to predict benign or malignant breast disease, and it can even predict the malignancy degree of breast cancer, as well as its invasive ability and prognosis.

  18. Peripheral inflammation/immune indicators of chemosensitivity and prognosis in breast cancer patients treated with neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Qian Y

    2018-03-01

    Full Text Available Yi Qian,1,* Jing Tao,1,2,* Xiuqing Li,3 Hua Chen,1 Qi Lu,1 Junzhe Yang,1 Hong Pan,1 Cong Wang,4 Wenbin Zhou,1 Xiaoan Liu1 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; 2Department of General Surgery, Nanjing Pukou Hospital, Nanjing, China; 3Department of Pathology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China; 4Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Introduction: Neoadjuvant chemotherapy (NAC has become a standard treatment for locally advanced breast cancer. The present study was designed to investigate the predictive value of different peripheral inflammation/immune biomarker responses to NAC and prognosis in breast cancer patients. Materials and methods: A total of 180 breast cancer patients treated with NAC in the First Affiliated Hospital with Nanjing Medical University between January 2008 and March 2015 were enrolled in the study. The associations between inflammation/immune indicators and pathological complete response (pCR were determined, and the prognostic value of inflammation/immune indicators was also evaluated. Results: In the univariate analysis, patients with a high pretreatment peripheral lymphocyte count (>2.06×109/L showed a higher pCR rate than those with a low lymphocyte count (23.9% vs 10.4%, P=0.023. The pCR rate of patients with a neutrophil: lymphocyte ratio ≤2.15 was significantly higher than that of patients with a high neutrophil: lymphocyte ratio (20% vs 7.8%; P=0.03. However, multivariate analysis revealed that only the high lymphocyte count was predictive for pCR (odds ratio: 4.375, 95% CI: 1.429–13.392, P=0.010. In the survival analysis, patients with a higher neutrophil count (>2.65×109/L were confirmed to have a shorter disease-free survival (hazard ratio: 4.322, 95% CI: 1.028–18.174, P=0.046, and the

  19. Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

    Energy Technology Data Exchange (ETDEWEB)

    Denecke, Timm; Misch, Daniel; Steffen, Ingo G.; Plotkin, Michail; Stoever, Brigitte [Charite - Universitaetsmedizin Berlin, Klinik fuer Strahlenheilkunde, Campus Virchow-Klinikum, Berlin (Germany); Hundsdoerfer, Patrick; Henze, Guenter [Charite - Universitaetsmedizin Berlin, Klinik fuer Paediatrie m.S. Onkologie und Haematologie, Otto-Heubner-Zentrum, Campus Virchow-Klinikum, Berlin (Germany); Schoenberger, Stefan [Universitaetsklinikum der Heinrich-Heine-Universitaet Duesseldorf, Klinik fuer Kinder-Onkologie, -Haematologie und -Immunologie, Duesseldorf (Germany); Furth, Christian; Ruf, Juri [Otto-von-Guericke-Universitaet Magdeburg, Klinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany); Hautzel, Hubertus [Universitaetsklinikum der Heinrich Heine Universitaet Duesseldorf, Nuklearmedizinische Klinik, Duesseldorf (Germany); Kluge, Regine [Universitaetsklinikum Leipzig A.oe.R., Klinik und Poliklinik fuer Nuklearmedizin, Leipzig (Germany); Bierbach, Uta [Universitaetsklinikum Leipzig A.oe.R., Abteilung fuer Kinder-Haematologie, -Onkologie und -Haemostaseologie, Leipzig (Germany); Otto, Sylke [Universitaetsklinikum Greifswald, Institut fuer Diagnostische Radiologie und Neuroradiologie, Greifswald (Germany); Beck, James F. [Universitaetsklinikum Greifswald, Abteilung fuer Paediatrische Haematologie und Onkologie, Greifswald (Germany); Franzius, Christiane [MR- und PET/CT-Zentrum, Bremen-Mitte (Germany); Universitaetsklinikum Muenster, Klinik und Poliklinik fuer Nuklearmedizin, Muenster (Germany); Amthauer, Holger [Charite - Universitaetsmedizin Berlin, Klinik fuer Strahlenheilkunde, Campus Virchow-Klinikum, Berlin (Germany); Otto-von-Guericke-Universitaet Magdeburg, Klinik fuer Radiologie und Nuklearmedizin, Universitaetsklinikum Magdeburg A.oe.R., Magdeburg (Germany)

    2010-10-15

    The objective of this study was to evaluate positron emission tomography (PET) using {sup 18}F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients. FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik. FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population ({nabla}SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients ({nabla}SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS. FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment. (orig.)

  20. Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the German Retinoblastoma Referral Centre.

    Science.gov (United States)

    Künkele, Annette; Wilm, Josephine; Holdt, Markus; Lohmann, Dietmar; Bornfeld, Norbert; Eggert, Angelika; Temming, Petra; Schulte, Johannes H

    2015-07-01

    Retinoblastoma can extend beyond the structures of the eye, where cells can enter the bloodstream and cause metastases. Various types of protocols for adjuvant treatment risk-adapted according to histopathological risk factors are used worldwide. Between 1997 and 2009, 420 children were diagnosed with retinoblastoma at the German Retinoblastoma Referral Centre and risk factors were assessed. Patients with post-laminar optic nerve infiltration or choroid or minor scleral invasion received six courses of adjuvant chemotherapy using vincristine, etoposide, carboplatin and cyclophosphamide (group 1). Patients with microscopic extension beyond the sclera to the resection margin of the optic nerve or potential spread due to vitrectomy received chemotherapy plus orbital radiotherapy (group 2). Neoadjuvant chemotherapy was performed in patients with local extraocular invasion detected on MRI. Following this protocol, 42 of the 420 patients and 21 referred from other centres showed high-risk histopathological factors qualifying for adjuvant therapy (57 in group 1 and 6 in group 2). Seven of the 63 patients received neoadjuvant and adjuvant treatment. During a mean follow-up of 5.8 (range 0.4-15.4) years, one of six patients in group 2 developed metastases and died. No patients died from toxicity. The 5-year overall survival was 100% for group 1 and 80% for group 2. This retrospective single-site study reveals a 10% incidence of high-risk features in children with retinoblastoma diagnosed at the German Retinoblastoma Referral Centre. Overall survival rates of 98.3% underline the safety of this adjuvant chemotherapy protocol and its efficiency in preventing metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01)

    NARCIS (Netherlands)

    Charehbili, A.; Hamdy, N. A. T.; Smit, V. T. H. B. M.; Kessels, L.; van Bochove, A.; van Laarhoven, H. W.; Putter, H.; Meershoek-Klein Kranenbarg, E.; van Leeuwen-Stok, A. E.; van der Hoeven, J. J. M.; van de Velde, C. J. H.; Nortier, J. W. R.; Kroep, J. R.

    2016-01-01

    Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the

  2. Circulating tumor cells in patients with breast cancer: monitoring chemotherapy success.

    Science.gov (United States)

    Ušiaková, Zuzana; Mikulová, Veronika; Pintérová, Daniela; Brychta, Milan; Valchář, Josef; Kubecová, Martina; Tesařová, Petra; Bobek, Vladimír; Kološtová, Katarína

    2014-01-01

    Circulating tumor cells (CTCs) are an independent prognostic factor for patients with metastatic breast cancer (MBC). However, the role of CTCs in early breast cancer management is not yet clearly defined. The aim of this study was to assess the CTC-positivity rate in patients undergoing chemotherapy depending on breast cancer stage in the adjuvant and neoadjuvant setting. We evaluated the ability to confirm therapy response by CTC analysis. CTCs isolated from blood by means of immunomagnetic separation were further characterized by means of reverse transcriptase - polymerase chain reaction (RT-PCR) for epithelial cell adhesion molecule (EPCAM), mucin 1 (MUC1) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2) transcripts with the AdnaTest™. This prospective study included 179 patients; altogether 419 blood samples were evaluated. Patients with primary tumors were divided into neoadjuvant (n=38), and adjuvant (n=100) groups. Forty-one patients with MBC were evaluated under palliative treatment. CTC positivity was described in 35% of patients with early breast cancer without detected metastases before neoadjuvant chemotherapy; similarly, a 26% positivity rate was found in the adjuvant group. In patients with MBC, we detected CTCs in 43% of them. After completing the therapy, the CTC positivity rate decreased to 5% in the neoadjuvant group, to 13% in the adjuvant group and to 12% in the MBC group. CTC positivity after the therapy may classify a subgroup of patients at high risk of developing metastatic disease. This was even true when a patient was evaluated as being CTC-negative before chemotherapy. The multivariate analysis evaluating the correlation of CTC positivity with clinicopathological characteristics such as tumor size, nodal involvement, hormone receptor status, HER2 expression and number of metastatic sites revealed no statistically significant relationships. CTC status may have a significant impact on early BC management

  3. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy.

    Science.gov (United States)

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-11-13

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2-3 disease, plasma Epstein-Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤ 46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0-1 risk factors; and 2) high-risk group: 2-4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT.

  4. Randomized study of the clinical effects of ω-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer.

    Science.gov (United States)

    Miyata, Hiroshi; Yano, Masahiko; Yasuda, Takushi; Yamasaki, Makoto; Murakami, Kohei; Makino, Tomoki; Nishiki, Kohei; Sugimura, Keijiro; Motoori, Masaaki; Shiraishi, Osamu; Mori, Masaki; Doki, Yuichiro

    2017-01-01

    Omega-3 (ω-3) fatty acids have potential positive effects during chemotherapy, such as body weight maintenance and muscle mass preservation. However, little is known about the effect this supplement might have on reducing chemotherapy-induced toxicities. The aim of this study was to determine the usefulness of ω-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities. Sixty-one patients undergoing neoadjuvant chemotherapy for esophageal cancer randomly received ω-3-rich enteral nutrition (EN; n = 31) or ω-3-poor EN support (n = 30) for 15 d during chemotherapy. The daily dosage of ω-3 fatty acids was 900 mg in the ω-3-rich group and 250 mg in the ω-3-poor group. The primary endpoint was the frequency of grade 3/4 neutropenia, and secondary endpoints included other chemotherapy-related adverse events, body weight, and inflammatory markers. The total and dietary intake calories during chemotherapy were equal in both groups. There was no significant difference in the body weight change after chemotherapy between the two groups. There was no significant difference in the incidence of grade 3/4 leukopenia and neutropenia (P > 0.05). However, stomatitis was significantly less frequent in the ω-3-rich group, than in the ω-3-poor group (P = 0.018). Grade 3/4 diarrhea occurred relatively less frequently in the ω-3-rich group than in the ω-3-poor group; however, this difference was not significant (16.1% versus 36.7%, respectively, P = 0.068). Increases in the aspartate aminotransferase and alanine aminotransferase levels were seen significantly less frequently in the ω-3-rich group than in the ω-3-poor group (P = 0.012 and P = 0.015, respectively). ω-3-rich EN support decreased the frequency of chemotherapy-induced mucosal toxicities, such as stomatitis and diarrhea, and exhibited a hepatoprotective effect during chemotherapy, compared with the ω-3-poor EN support. Copyright © 2016 Elsevier Inc. All rights

  5. The Role of Redox-Regulating Enzymes in Inoperable Breast Cancers Treated with Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Nelli Roininen

    2017-01-01

    Full Text Available Although validated predictive factors for breast cancer chemoresistance are scarce, there is emerging evidence that the induction of certain redox-regulating enzymes may contribute to a poor chemotherapy effect. We investigated the possible association between chemoresistance and cellular redox state regulation in patients undergoing neoadjuvant chemotherapy (NACT for breast cancer. In total, 53 women with primarily inoperable or inflammatory breast cancer who were treated with NACT were included in the study. Pre-NACT core needle biopsies and postoperative tumor samples were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2, Kelch-like ECH-associated protein 1 (Keap1, thioredoxin (Trx, and peroxiredoxin I (Prx I. The expression of all studied markers increased during NACT. Higher pre-NACT nuclear Prx I expression predicted smaller size of a resected tumor (p=0.00052; r=−0.550, and higher pre-NACT cytoplasmic Prx I expression predicted a lower amount of evacuated nodal metastasis (p=0.0024; r=−0.472. Pre-NACT nuclear Trx expression and pre-NACT nuclear Keap1 expression had only a minor prognostic significance as separate factors, but when they were combined, low expression for both antibodies before NACT predicted dismal disease-free survival (log-rank p=0.0030. Our results suggest that redox-regulating enzymes may serve as potential prognostic factors in primarily inoperable breast cancer patients.

  6. Analysis of Perioperative Chemotherapy in Resected Pancreatic Cancer: Identifying the Number and Sequence of Chemotherapy Cycles Needed to Optimize Survival.

    Science.gov (United States)

    Epelboym, Irene; Zenati, Mazen S; Hamad, Ahmad; Steve, Jennifer; Lee, Kenneth K; Bahary, Nathan; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

    2017-09-01

    Receipt of 6 cycles of adjuvant chemotherapy (AC) is standard of care in pancreatic cancer (PC). Neoadjuvant chemotherapy (NAC) is increasingly utilized; however, optimal number of cycles needed alone or in combination with AC remains unknown. We sought to determine the optimal number and sequence of perioperative chemotherapy cycles in PC. Single institutional review of all resected PCs from 2008 to 2015. The impact of cumulative number of chemotherapy cycles received (0, 1-5, and ≥6 cycles) and their sequence (NAC, AC, or NAC + AC) on overall survival was evaluated Cox-proportional hazard modeling, using 6 cycles of AC as reference. A total of 522 patients were analyzed. Based on sample size distribution, four combinations were evaluated: 0 cycles = 12.1%, 1-5 cycles of combined NAC + AC = 29%, 6 cycles of AC = 25%, and ≥6 cycles of combined NAC + AC = 34%, with corresponding survival. 13.1, 18.5, 37, and 36.8 months. On MVA (P cycles AC, receipt of 0 cycles [HR 3.57, confidence interval (CI) 2.47-5.18] or 1-5 cycles in any combination (HR 2.37, CI 1.73-3.23) was associated with increased hazard of death, whereas receipt of ≥6 cycles in any sequence was associated with optimal and comparable survival (HR 1.07, CI 0.78-1.47). Receipt of 6 or more perioperative cycles of chemotherapy either as combined neoadjuvant and adjuvant or adjuvant alone may be associated with optimal and comparable survival in resected PC.

  7. Copy number aberrations landscape of a breast tumor, connection with the efficiency of neoadjuvant chemotherapy

    Science.gov (United States)

    Ibragimova, M. K.; Tsyganov, M. M.; Slonimskaya, E. M.; Litviakov, N. V.

    2017-09-01

    The research involved 80 patients diagnosed with breast cancer (BC). Each patient had their tumor biopsy material sampled before their treatment. We studied the tumor tissue using the CytoScan HD Array (Affymetrix, USA) microarray to evaluate the CNA landscape. We studied the frequency of segmental and numerical CNA occurrence, their association with the efficiency of neoadjuvant chemotherapy (NAC). We found that the biggest number of amplifications (with frequency over 60%) were found on in the following locuses; 1q32.1 1q32.3, 1q42.13, 1q42.2, 1q43. The biggest frequency of deletions (more than in 58% of the patients) was found in these locuses: 16q21, 16q23.2, 16q23.3, 17p12, 17p13.1. However, we found the locuses with full absence of segmental chromosome anomalies. We observed trisomy most frequently in the 7, 8, 12, and 17 chromosomes, and monosomy in the 3, 4, 9, 11, 18, and X-chromosomes. We demonstrated the connection between the high frequency of cytobands with CNA in the patients' tumors and the efficiency of NAC. We also identified the cytobands, whose CNA are linked to the response to NAC.

  8. Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer.

    Science.gov (United States)

    Sasaki, Tomohiko; Motoyama, Satoru; Komatsuda, Atsushi; Shibata, Hiroyuki; Sato, Yusuke; Yoshino, Kei; Wakita, Akiyuki; Saito, Hajime; Anbai, Akira; Jin, Mario; Minamiya, Yoshihiro

    2016-01-01

    We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5-fluorourasil. After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Xuemei Ji

    Full Text Available BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC treated by intensity modulated radiotherapy (IMRT and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS, metastasis-free survival (MFS, relapse-free survival (RFS, and disease-free survival (DFS were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03, patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03, neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.

  10. Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

    Science.gov (United States)

    Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

    2018-06-01

    To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

  11. Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial

    NARCIS (Netherlands)

    van Meurs, Hannah S.; Tajik, Parvin; Hof, Michel H. P.; Vergote, Ignace; Kenter, Gemma G.; Mol, Ben Willem J.; Buist, Marrije R.; Bossuyt, Patrick M.

    2013-01-01

    To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. We used data of the European Organisation for Research and

  12. The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy.

    Science.gov (United States)

    Kim, Grace J; Koshy, Matthew; Hanlon, Alexandra L; Horiba, M Naomi; Edelman, Martin J; Burrows, Whitney M; Battafarano, Richard J; Suntharalingam, Mohan

    2016-04-01

    The objective of this retrospective study was to determine the potential benefits of chemotherapy in esophageal cancer patients treated with chemoradiation followed by surgery. At our institution, 145 patients completed trimodality therapy from 1993 to 2009. Neoadjuvant treatment predominantly consisted of 5-fluorouracil and cisplatin with a concurrent median radiation dose of 50.4 Gy. Sixty-two patients received chemotherapy postoperatively. The majority (49/62) received 3 cycles of docetaxel. Within the entire cohort, a 5-year overall survival (OS) benefit was found in those who received postoperative chemotherapy, OS 37.1% versus 18.0% (P=0.024). The response after neoadjuvant chemoradiation was as follows: 33.8% had a pathologic complete response and 62.8% with residual disease. A 5-year OS and cause-specific survival (CSS) advantage were associated with postoperative chemotherapy among those with macroscopic residual disease after neoadjuvant therapy: OS 38.7% versus 13.9% (P=0.016), CSS 42.8% versus 18.8% (P=0.048). This benefit was not seen in those with a pathologic complete response or those with microscopic residual. A stepwise multivariate Cox regression model evaluating the partial response group revealed that postoperative chemotherapy and M stage were independent predictors of overall and CSS. This analysis revealed that patients with gross residual disease after trimodality therapy for esophageal cancer who received postoperative chemotherapy had an improved overall and CSS. These data suggest that patients with residual disease after trimodality therapy and a reasonable performance status may benefit from postoperative chemotherapy. Prospective trials are needed to confirm these results to define the role of postoperative treatment after trimodality therapy.

  13. Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki [Shimane Medical Univ., Izumo (Japan)

    1998-03-01

    Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

  14. Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

    International Nuclear Information System (INIS)

    Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki

    1998-01-01

    Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

  15. Preoperative radio-chemotherapy for rectal cancer: Forecasting the next steps through ongoing and forthcoming studies

    International Nuclear Information System (INIS)

    Crehange, G.; Maingon, P.; Bosset, J.F.

    2011-01-01

    Protracted preoperative radio-chemotherapy with a 5-FU-based scheme, or a short course of preoperative radiotherapy without chemotherapy, are the standard neo-adjuvant treatments for resectable stage II-III rectal cancer. Local failure rates are low and reproducible, between 6 and 15% when followed with a 'Total Meso-rectal Excision'. Nevertheless, the therapeutic strategy needs to be improved: distant metastatic recurrence rates remain stable around 30 to 35%, while both sphincter and sexual sequels are still significant. The aim of the present paper was to analyse the ongoing trials listed on the following search engines: the Institut National du Cancer in France, the National Cancer Institute and the National Institute of Health in the United States, and the major cooperative groups. Keywords for the search were: 'rectal cancer', 'preoperative radiotherapy', 'phase II-III', 'preoperative chemotherapy', 'adjuvant chemotherapy' and 'surgery'. Twenty-three trials were selected and classified in different groups, each of them addressing a question of strategy: (1) place of adjuvant chemotherapy; (2) optimization of preoperative radiotherapy; (3) evaluation of new radiosensitization protocols and/or neo-adjuvant chemotherapy; (4) optimization of techniques and timing of surgery; (5) place of radiotherapy for non resectable or metastatic tumors. (authors)

  16. Computer-aided global breast MR image feature analysis for prediction of tumor response to chemotherapy: performance assessment

    Science.gov (United States)

    Aghaei, Faranak; Tan, Maxine; Hollingsworth, Alan B.; Zheng, Bin; Cheng, Samuel

    2016-03-01

    Dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) has been used increasingly in breast cancer diagnosis and assessment of cancer treatment efficacy. In this study, we applied a computer-aided detection (CAD) scheme to automatically segment breast regions depicting on MR images and used the kinetic image features computed from the global breast MR images acquired before neoadjuvant chemotherapy to build a new quantitative model to predict response of the breast cancer patients to the chemotherapy. To assess performance and robustness of this new prediction model, an image dataset involving breast MR images acquired from 151 cancer patients before undergoing neoadjuvant chemotherapy was retrospectively assembled and used. Among them, 63 patients had "complete response" (CR) to chemotherapy in which the enhanced contrast levels inside the tumor volume (pre-treatment) was reduced to the level as the normal enhanced background parenchymal tissues (post-treatment), while 88 patients had "partially response" (PR) in which the high contrast enhancement remain in the tumor regions after treatment. We performed the studies to analyze the correlation among the 22 global kinetic image features and then select a set of 4 optimal features. Applying an artificial neural network trained with the fusion of these 4 kinetic image features, the prediction model yielded an area under ROC curve (AUC) of 0.83+/-0.04. This study demonstrated that by avoiding tumor segmentation, which is often difficult and unreliable, fusion of kinetic image features computed from global breast MR images without tumor segmentation can also generate a useful clinical marker in predicting efficacy of chemotherapy.

  17. Rapidly Growing Esophageal Carcinosarcoma Reduced by Neoadjuvant Radiotherapy Alone

    Directory of Open Access Journals (Sweden)

    Naotaka Ogasawara

    2014-06-01

    Full Text Available Esophageal carcinosarcoma is a rare malignant neoplasm consisting of both carcinomatous and sarcomatous components. It is generally treated by surgery, radiotherapy and chemotherapy according to the protocols used for other esophageal cancers. However, the treatment of esophageal carcinosarcoma by radiotherapy alone before surgery has not been previously described. We report a patient with a rapidly growing esophageal carcinosarcoma that was efficiently reduced by neoadjuvant radiotherapy alone. A previously healthy 69-year-old man was admitted with dysphagia. Initial esophagogastroduodenoscopy (EGD revealed a small nodular polypoid lesion of about 10 mm in the middle esophagus. A second EGD 1 month later showed that the tumor had expanded into a huge mass. A biopsy specimen revealed that the tumor comprised squamous cell carcinoma with spindle cell components, and the tumor was diagnosed as carcinosarcoma which was diagnosed as stage I (T1bN0M0. Due to renal dysfunction, the patient was treated with neoadjuvant radiotherapy (40 Gy without chemotherapy. A third EGD 1 month later revealed remarkable tumor reduction. He then underwent total esophagectomy with regional lymph node dissection (pStage 0, pT1aN0M0. After surgical operation, the patient was followed up without adjuvant therapy. Whole body computed tomography revealed lung metastasis 14 months after surgery, and the patient died 2 months later. The neoadjuvant radiotherapy for esophageal carcinosarcoma was considered to have contributed to the subsequent surgery and his prolonged survival time. Thus, radiotherapy alone might be a suitable neoadjuvant therapy for esophageal carcinosarcomas.

  18. Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

    Science.gov (United States)

    Matsuda, S; Tsubosa, Y; Sato, H; Takebayashi, K; Kawamorita, K; Mori, K; Niihara, M; Tsushima, T; Yokota, T; Onozawa, Y; Yasui, H; Takeuchi, H; Kitagawa, Y

    2017-02-01

    Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5

  19. Cisplatin Loaded Hyaluronic Acid Modified TiO2 Nanoparticles for Neoadjuvant Chemotherapy of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Enling Liu

    2015-01-01

    Full Text Available Novel tumor-targeting titanium dioxide (TiO2 nanoparticles modified with hyaluronic acid (HA were developed to explore the feasibility of exploiting the pH-responsive drug release property of TiO2 and the tumor-targeting ability of HA to construct a tumor-targeting cisplatin (CDDP delivery system (HA-TiO2 for potential neoadjuvant chemotherapy of ovarian cancer. The experimental results indicated that CDDP release from the HA-TiO2 nanoparticles was significantly accelerated by decreasing pH from 7.4 to 5.0, which is of particular benefit to cancer therapy. CDDP-loaded HA-TiO2 nanoparticles increased the accumulation of CDDP in A2780 ovarian cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo real-time imaging assay revealed that HA-TiO2 nanoparticles possessed preferable tumor-targeting ability which might potentially minimize the toxic side effects of CDDP in clinical application.

  20. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

    2012-01-01

    Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

  1. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    Science.gov (United States)

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. MRI at the completion of chemoradiotherapy can accurately evaluate the extent of disease in women with advanced urethral carcinoma undergoing anterior pelvic exenteration

    Energy Technology Data Exchange (ETDEWEB)

    Gourtsoyianni, S.; Hudolin, T. [Department of Radiology, Memorial Sloan-Kettering Cancer Centre, 1275 York Avenue, New York, NY (United States); Sala, E. [Department of Radiology, Box 218, Addenbrooke' s Hospital, Hills Road, Cambridge (United Kingdom); Goldman, D. [Department of Radiology, Memorial Sloan-Kettering Cancer Centre, 1275 York Avenue, New York, NY (United States); Bochner, B.H. [Department of Urology, Memorial Sloan-Kettering Cancer Centre, 1275 York Avenue, New York, NY (United States); Hricak, Hedvig, E-mail: muellnea@mskcc.org [Department of Radiology, Memorial Sloan-Kettering Cancer Centre, 1275 York Avenue, New York, NY (United States)

    2011-11-15

    Aim: To demonstrate the value of pelvic magnetic resonance imaging (MRI) in mapping tumour extension after chemoradiotherapy and before anterior pelvic exenteration in patients with primary carcinoma of the urethra. Materials and methods: The Institutional Review Board approved and issued a waiver of informed consent for this retrospective study, which was compliant with the Health Insurance Portability and Accountability Act. Six women (median age 51 years, range 39-63 years) with histopathology-proven urethral carcinoma who underwent neoadjuvant chemoradiotherapy before anterior pelvic exenteration were included in the study. All had MRI performed at first presentation and after completion of chemoradiotherapy. MRI images were analysed by an experienced reader, who was blinded to the clinical data. The tumour location, signal intensity, size, local extension, and presence of enlarged lymph nodes were recorded for each patient at baseline and after chemoradiotherapy. Surgical histopathology constituted the reference standard. Results: All tumours were locally advanced (stage T3) at baseline MRI. The mean maximum diameter of the tumour at baseline MRI was 3.7 cm (range 2.4-5 cm). After chemoradiotherapy, the mean reduction in maximum tumour diameter on MRI was 44% (range 13-67%), but only three cases were down-staged. MRI was accurate in the evaluation of tumour extension after completion of chemoradiotherapy in all cases. Persistence of bladder neck and anterior vaginal wall invasion was correctly identified in three cases. Conclusion: In women with advanced primary urethral cancer, MRI is an excellent tool for monitoring neo-adjuvant chemoradiotherapy changes and evaluating the extent of disease before exenterative surgery.

  3. MRI at the completion of chemoradiotherapy can accurately evaluate the extent of disease in women with advanced urethral carcinoma undergoing anterior pelvic exenteration

    International Nuclear Information System (INIS)

    Gourtsoyianni, S.; Hudolin, T.; Sala, E.; Goldman, D.; Bochner, B.H.; Hricak, Hedvig

    2011-01-01

    Aim: To demonstrate the value of pelvic magnetic resonance imaging (MRI) in mapping tumour extension after chemoradiotherapy and before anterior pelvic exenteration in patients with primary carcinoma of the urethra. Materials and methods: The Institutional Review Board approved and issued a waiver of informed consent for this retrospective study, which was compliant with the Health Insurance Portability and Accountability Act. Six women (median age 51 years, range 39-63 years) with histopathology-proven urethral carcinoma who underwent neoadjuvant chemoradiotherapy before anterior pelvic exenteration were included in the study. All had MRI performed at first presentation and after completion of chemoradiotherapy. MRI images were analysed by an experienced reader, who was blinded to the clinical data. The tumour location, signal intensity, size, local extension, and presence of enlarged lymph nodes were recorded for each patient at baseline and after chemoradiotherapy. Surgical histopathology constituted the reference standard. Results: All tumours were locally advanced (stage T3) at baseline MRI. The mean maximum diameter of the tumour at baseline MRI was 3.7 cm (range 2.4-5 cm). After chemoradiotherapy, the mean reduction in maximum tumour diameter on MRI was 44% (range 13-67%), but only three cases were down-staged. MRI was accurate in the evaluation of tumour extension after completion of chemoradiotherapy in all cases. Persistence of bladder neck and anterior vaginal wall invasion was correctly identified in three cases. Conclusion: In women with advanced primary urethral cancer, MRI is an excellent tool for monitoring neo-adjuvant chemoradiotherapy changes and evaluating the extent of disease before exenterative surgery.

  4. Study comparing sequential (neo-adjuvant) versus concurrent chemo-radiotherapy in patients with squamous cell carcinoma

    International Nuclear Information System (INIS)

    Okawa, Tomohiko; Karasawa, Kumiko; Kaneyasu, Yuko; Tanaka, Makiko; Kita-Okawa, Midori; Ishii, Tetsuo

    1994-01-01

    Radiotherapy combined with chemotherapy is still used for standard treatment in patients with locally advanced unresectable cancer. A study was undertaken to compare a sequential (neo-adjuvant) with a simultaneous (concurrent) chemotherapy and radiotherapy program. Neo-adjuvant chemotherapy with cisplatin (80 mg/m 2 i.v. day 1) and 5FU (600 mg/m 2 continuous i.v. day 1-5) every 3 weeks prior to definitive conventional radiotherapy (60-65 Gy), or cisplatin (20 mg/m 2 i.v. day 1-5) and 5FU (250 mg/m 2 continuous i.v. infusion. day 1-14) were given simultaneously for same radiotherapy. Complete response rate was 45% in the sequential treatment and 43% in the simultaneous arm. Leukopenia and other adverse effects were slightly more frequent in the simultaneous arm, but there were no significant differences. These results suggested that individualization of treatment planning and establishment of optimum treatment were most important for combination of chemotherapy and radiotherapy. (author)

  5. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    Directory of Open Access Journals (Sweden)

    Zhang MM

    2016-06-01

    Full Text Available Minmin Zhang,* Wei Wei,* Jianlun Liu, Huawei Yang, Yi Jiang, Wei Tang, Qiuyun Li, Xiaoming Liao Department of Breast Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC, followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT vs taxotere (T, in axillary lymph node (LN-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1 who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1 to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027 and objective remission rate (87% vs 73%, P=0.048 compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001 and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034 but less phlebitis (3% vs 14%, P=0.035. XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. Keywords: breast cancer, capecitabine, docetaxel, neoadjuvant chemotherapy, curative effect, toxic side effects

  6. Clinical Assessment of Sarcopenia and Changes in Body Composition During Neoadjuvant Chemotherapy for Esophageal Cancer.

    Science.gov (United States)

    Miyata, Hiroshi; Sugimura, Keijiro; Motoori, Masaaki; Fujiwara, Yoshiyuki; Omori, Takeshi; Yanagimoto, Yoshitomo; Ohue, Masayuki; Yasui, Masayoshi; Miyoshi, Norikatsu; Tomokuni, Akira; Akita, Hirofumi; Kobayashi, Shogo; Takahashi, Hidenori; Yano, Masahiko

    2017-06-01

    The aim of this study was to assess changes in body composition during neoadjuvant chemotherapy (NAC) and investigate whether chemotherapy-related toxicities affect body composition in patients with esophageal cancer. In ninety-four patients who underwent NAC for esophageal cancer, body composition was assessed before and after NAC. Associations between the incidence of toxicities and change in body composition during NAC were investigated. Forty-four (46.8%) and 50 (53.2%) out of 94 patients were defined as having sarcopenia before and after NAC, respectively. There was no significant difference in the incidence of any toxicity pre-treatment between patients with sarcopenia and those without sarcopenia. No significant reduction in skeletal muscle mass or fat mass was observed in the patients during NAC (p=0.501 and p=0.072). However, patients who experienced grade 4 neutropenia or febrile neutropenia during NAC showed a significantly larger decrease in change of skeletal muscle mass compared to patients who did not experience those toxicities (p=0.013 and 0.036, respectively). The incidence of serious adverse events such as febrile neutropenia and grade 4 neutropenia is associated with a significant reduction of skeletal muscle mass during NAC. We should make an effort to reduce the incidence of adverse events in order to maintain an appropriate body composition during NAC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Digital expression profiling identifies RUNX2, CDC5L, MDM2, RECQL4, and CDK4 as potential predictive biomarkers for neo-adjuvant chemotherapy response in paediatric osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Martin

    Full Text Available Osteosarcoma is the most common malignancy of bone, and occurs most frequently in children and adolescents. Currently, the most reliable technique for determining a patients' prognosis is measurement of histopathologic tumor necrosis following pre-operative neo-adjuvant chemotherapy. Unfavourable prognosis is indicated by less than 90% estimated necrosis of the tumor. Neither genetic testing nor molecular biomarkers for diagnosis and prognosis have been described for osteosarcomas. We used the novel nanoString mRNA digital expression analysis system to analyse gene expression in 32 patients with sporadic paediatric osteosarcoma. This system used specific molecular barcodes to quantify expression of a set of 17 genes associated with osteosarcoma tumorigenesis. Five genes, from this panel, which encoded the bone differentiation regulator RUNX2, the cell cycle regulator CDC5L, the TP53 transcriptional inactivator MDM2, the DNA helicase RECQL4, and the cyclin-dependent kinase gene CDK4, were differentially expressed in tumors that responded poorly to neo-adjuvant chemotherapy. Analysis of the signalling relationships of these genes, as well as other expression markers of osteosarcoma, indicated that gene networks linked to RB1, TP53, PI3K, PTEN/Akt, myc and RECQL4 are associated with osteosarcoma. The discovery of these networks provides a basis for further experimental studies of role of the five genes (RUNX2, CDC5L, MDM2, RECQL4, and CDK4 in differential response to chemotherapy.

  8. High levels of X-linked Inhibitor-of-Apoptosis Protein (XIAP) are indicative of radio chemotherapy resistance in rectal cancer

    International Nuclear Information System (INIS)

    Flanagan, L.; Kehoe, J.; Fay, J.; Bacon, O.; Lindner, A.U.; Kay, E.W.; Deasy, J.; McNamara, D.A.; Prehn, J.H.M.

    2015-01-01

    The mainstay of treatment in rectal cancer is neoadjuvant radio chemotherapy prior to surgery, in an attempt to downstage the tumour, allowing for more complete removal during surgery. In 40 % of cases however, this neoadjuvant radio chemotherapy fails to achieve tumour regression, partly due insufficient apoptosis signaling. X-linked Inhibitor of Apoptosis Protein (XIAP) is an anti-apoptotic protein that has been reported to contribute to disease progression and chemotherapy resistance. We obtained rectal biopsy normal and matched tumour tissue from 29 rectal cancer patients with varying degrees of tumour regression, and using Western blot, examined anti-apoptotic XIAP and pro-apoptotic Smac protein levels in these tissues, with the aim to examine whether disturbed XIAP/Smac levels may be an indicator of neoadjuvant radio chemotherapy resistance. Expression of inhibitor of apoptosis proteins cIAP-1 and cIAP-2 was also examined. We found that levels of XIAP increased in accordance with the degree of radio chemotherapy resistance of the tissue. Levels of this protein were also significantly higher in tumour tissue, compared to matched normal tissue in highly resistant tissue. In contrast, Smac protein levels did not increase with radio chemotherapy resistance, and the protein was similarly expressed in normal and tumour tissue, indicating a shift in the balance of these proteins. Post treatment surgical resection tissue was available for 8 patients. When we compared matched tissue pre- and post- radio chemotherapy we found that XIAP levels increased significantly during treatment in both normal and tumour tissue, while Smac levels did not change. cIAP-1 and cIAP-2 levels were not differentially expressed in varying degrees of radio chemotherapy resistance, and neoadjuvant therapy did not alter expression of these proteins. These data indicate that disturbance of the XIAP/Smac balance may be a driver of radio chemotherapy resistance, and hence high levels of XIAP may

  9. Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); Imaging 2, Level 1, Lambeth Wing, St Thomas' Hospital, London (United Kingdom); Goh, Vicky [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Davies, Andrew; Gossage, James; Mason, Robert [Guy' s and St Thomas' NHS Foundation Trust, Department of Upper Gastrointestinal and General Surgery, London (United Kingdom); Mitchell-Hay, Rosalind; Griffin, Nyree [Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Hynes, Orla [Department of Dietetics, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Maisey, Nick; Ross, Paul; Gaya, Andrew [Department of Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Department of Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2014-05-15

    Sarcopenia and changes in body composition following neoadjuvant chemotherapy (NAC) may affect clinical outcome. We assessed the associations between CT body composition changes following NAC and outcomes in oesophageal cancer. A total of 35 patients who received NAC followed by oesophagectomy, and underwent CT assessment pre- and post-NAC were included. Fat mass (FM), fat-free mass (FFM), subcutaneous fat to muscle ratio (FMR) and visceral to subcutaneous adipose tissue ratio (VA/SA) were derived from CT. Changes in FM, FFM, FMR, VA/SA and sarcopenia were correlated to chemotherapy dose reductions, postoperative complications, length of hospital stay (LOS), circumferential resection margin (CRM), pathological chemotherapy response, disease-free survival (DFS) and overall survival (OS). Nine (26 %) patients were sarcopenic before NAC and this increased to 15 (43 %) after NAC. Average weight loss was 3.7 % ± 6.4 (SD) in comparison to FM index (-1.2 ± 4.2), FFM index (-4.6 ± 6.8), FMR (-1.2 ± 24.3) and VA/SA (-62.3 ± 12.7). Changes in FM index (p = 0.022), FMR (p = 0.028), VA/SA (p = 0.024) and weight (p = 0.007) were significant univariable factors for CRM status. There was no significant association between changes in body composition and survival. Loss of FM, differential loss of VA/SA and skeletal muscle were associated with risk of CRM positivity. (orig.)

  10. Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer

    International Nuclear Information System (INIS)

    Yip, Connie; Goh, Vicky; Davies, Andrew; Gossage, James; Mason, Robert; Mitchell-Hay, Rosalind; Griffin, Nyree; Hynes, Orla; Maisey, Nick; Ross, Paul; Gaya, Andrew; Landau, David B.; Cook, Gary J.

    2014-01-01

    Sarcopenia and changes in body composition following neoadjuvant chemotherapy (NAC) may affect clinical outcome. We assessed the associations between CT body composition changes following NAC and outcomes in oesophageal cancer. A total of 35 patients who received NAC followed by oesophagectomy, and underwent CT assessment pre- and post-NAC were included. Fat mass (FM), fat-free mass (FFM), subcutaneous fat to muscle ratio (FMR) and visceral to subcutaneous adipose tissue ratio (VA/SA) were derived from CT. Changes in FM, FFM, FMR, VA/SA and sarcopenia were correlated to chemotherapy dose reductions, postoperative complications, length of hospital stay (LOS), circumferential resection margin (CRM), pathological chemotherapy response, disease-free survival (DFS) and overall survival (OS). Nine (26 %) patients were sarcopenic before NAC and this increased to 15 (43 %) after NAC. Average weight loss was 3.7 % ± 6.4 (SD) in comparison to FM index (-1.2 ± 4.2), FFM index (-4.6 ± 6.8), FMR (-1.2 ± 24.3) and VA/SA (-62.3 ± 12.7). Changes in FM index (p = 0.022), FMR (p = 0.028), VA/SA (p = 0.024) and weight (p = 0.007) were significant univariable factors for CRM status. There was no significant association between changes in body composition and survival. Loss of FM, differential loss of VA/SA and skeletal muscle were associated with risk of CRM positivity. (orig.)

  11. Analysis of clinical factors for pathological complete response after preoperative neoadjuvant chemoradiotherapy for rectal cancer

    International Nuclear Information System (INIS)

    Ayiguli Hare; Palida Apizi; Iskandar Abulimiti; Zhang Jinrong; Tian Hanhan

    2014-01-01

    Objective: To evaluate the clinical factors associated with pathological complete response (pCR) after preoperative neoadjuvant chemoradiotherapy for rectal cancer. Methods: A retrospective analysis was performed on the clinical data of 116 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy followed by radical surgery from January 2009 to December 2012. All patients received pelvic intensity-modulated radiotherapy (50 Gy/25 fractions) with concurrent fluorouracil based chemotherapy and then underwent radical surgery 4-8 weeks later. The clinical factors associated with pCR or non-pCR were analyzed by Logistic regression. Results: Of the 116 patients, 20 (17.2%) achieved a pCR after neoadjuvant chemoradiotherapy. The univariate analysis showed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum carcinoembryonic antigen (CEA) level, T stage, N stage, distance from the anal verge, degree of tumor differentiation, and maximum tumor diameter were associated with pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. The multivariate analysis revealed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum CEA level,and T stage were predictive factors for pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. Conclusions: Non-circumferential tumor (percentage of circumference of the rectal tube invaded by the tumor <75 %), low CEA level, and early T stage before treatment may be associated with pCR after neoadjuvant chemoradiotherapy for rectal cancer. (authors)

  12. Sarcopenic obesity: A probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients.

    Science.gov (United States)

    Anandavadivelan, Poorna; Brismar, Torkel B; Nilsson, Magnus; Johar, Asif M; Martin, Lena

    2016-06-01

    Profound weight loss and malnutrition subsequent to severe dysphagia and cancer cachexia are cardinal symptoms in oesophageal cancer (OC). Low muscle mass/sarcopenia has been linked to toxicity during neo-adjuvant therapy in other cancers, with worser effects in sarcopenic obesity. In this study the association between sarcopenia and/or sarcopenic obesity and dose limiting toxicity (DLT) during cycle one chemotherapy in resectable OC patients was evaluated. Body composition was assessed from computed tomography scans of 72 consecutively diagnosed OC patients. Lean body mass and body fat mass were estimated. Patients were grouped as sarcopenic or non-sarcopenic based on pre-defined gender-specific cut-offs for sarcopenia, and as underweight/normal (BMI sarcopenia combined with overweight and obesity. DLT was defined as temporary reduction/delay or permanent discontinuation of drugs due to adverse effects. Odds ratios for developing toxicity were ascertained using multiple logistic regression. Of 72 patients, 85% (n = 61) were males. Sarcopenia and sarcopenic obesity were present in 31 (43%) and 10 (14%), respectively, prior to chemotherapy. Sarcopenic patients had significantly lower adipose tissue index (p = 0.02) compared to non-sarcopenic patients. Patients with DLT (n = 24) had lower skeletal muscle mass (p = 0.04) than those without DLT. Sarcopenic patients (OR = 2.47; 95% CI: 0.88-6.93) showed a trend towards increased DLT risk (p < 0.10). Logistic regression with BMI as an interaction term indicated higher DLT risk in sarcopenic patients with normal BMI (OR = 1.60; 95% CI 0.30-8.40), but was non-significant. In the sarcopenic obese, risk of DLT increased significantly (OR = 5.54; 95% CI 1.12-27.44). Sarcopenic and sarcopenic obese OC patients may be at a higher risk for developing DLT during chemotherapy compared to non-sarcopenic OC patients. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All

  13. Effects of CO(2) pneumoperitoneum on anastomotic healing in rats receiving preoperative 5-fluorouracil neoadjuvant chemotherapy.

    Science.gov (United States)

    Ulas, Murat; Ozer, Ilter; Ercan, Metin; Ozogul, Yusuf B; Bostanci, E Birol; Keklik, Tulay Temucin; Turkcu, Ummuhani Ozel; Bilgihan, Ayse; Akoglu, Musa

    2009-01-01

    When used separately, antineoplastic agents and carbon dioxide (CO(2)) pneumoperitoneum have been reported to impair anastomotic healing in experimental animals. However, the effects of their combined use have not been previously investigated. The aim of this study was to investigate the possibility that neoadjuvant chemotherapy with 5-fluorouracil followed by CO(2) pneumoperitoneum would affect the healing of anastomoses in the colon. Sprague-Dawley rats (n = 48) were given 5-fluorouracil (20 mg/kg/day) for 5 days, and were then assigned to one of the three groups. Prior to surgery, the control group received no pneumoperitoneum. The other two groups received pneumoperitoneum at 6 and 12 mmHg, respectively, for 2 hr. The large intestine was transected and anastomosis was performed via median laparotomy. On postoperative days 3 and 7, relaparotomy was performed in half of the rats in each group. From the colon, a segment including the anastomosis was excised. Tissue hydroxyproline levels were measured. For histological evaluation, the Verhofstad scale was modified and used. No significant differences in hydroxyproline levels were seen across the groups on postoperative days 3 or 7. However, by postoperative day 7, polymorphonuclear leukocytes and necrosis in the 6-mmHg group had decreased markedly, and granulation had improved. Overall, these findings suggest that preoperative 5-fluorouracil therapy followed by pneumoperitoneum at 6 or 12 mmHg does not impair anastomotic healing.

  14. [Effect of postoperative precision nutrition therapy on postoperative recovery for advanced gastric cancer after neoadjuvant chemotherapy].

    Science.gov (United States)

    Zhao, Q; Li, Y; Yu, B; Yang, P G; Fan, L Q; Tan, B B; Tian, Y; Yang, A B

    2018-02-23

    Objective: To investigate the effect of postoperative precision nutrition therapy on postoperative recovery (PR) of patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NC). Methods: 71 subjects were randomly divided into 2 groups. The 34 patients of research group were treated with postoperative precision nutrition treatment according to the indirect energy measurement method. The 31 patients of control group were treated with traditional postoperative nutrition treatment. All participants were measured for body mass index (BMI), NRS2002, PG-SGA and relevant laboratory test within the 1st day before surgery and 7th day after surgery. Moreover, the difference between two groups in short-term effects were evaluated. Results: The daily energy supply of control group was 30.1%-43.74% higher than that of the experimental group ( P nutritional risk became lower in the research group ( P recovery of patients in the research group was comparable to that of the control group ( P >0.05). Moreover, the complication rate and hospitalization costs of in research group were significantly lower than that of in control group ( P nutritional risks before surgery, the nutritional index and inflammatory index in the research group were better than those in the control group. Conclusion: Postoperative precision nutrition therapy may improve the postoperative nutritional status and short-term effects of patients with AGC after NC.

  15. Impact of body fat distribution on neoadjuvant chemotherapy outcomes in advanced breast cancer patients

    International Nuclear Information System (INIS)

    Iwase, Toshiaki; Sangai, Takafumi; Nagashima, Takeshi; Sakakibara, Masahiro; Sakakibara, Junta; Hayama, Shouko; Ishigami, Emi; Masuda, Takahito; Miyazaki, Masaru

    2015-01-01

    Obesity is known to decrease the efficacy of neoadjuvant chemotherapy (NAC) against breast cancer; however, the relationship between actual body composition and NAC outcomes remains unknown. Therefore, we determined the effect of body composition on NAC outcomes. A total of 172 advanced breast cancer patients who underwent surgery after NAC were retrospectively analyzed. Body composition parameters including abdominal circumference (AC), subcutaneous fat area (SFA), visceral fat area (VFA), and skeletal muscle area (SMA) were calculated using computed tomography volume-analyzing software. VFA/SFA ratio was used to evaluate visceral obesity. The associations of body composition parameters with pathological complete remission (pCR) and survival were analyzed. AC, SFA, and VFA were significantly correlated with body mass index (BMI) (all P < 0.05; r = 0.82, r = 0.71, and r = 0.78, respectively). AC, SFA, and VFA increased significantly and SMA decreased significantly after menopause (all P < 0.05). VFA/SFA ratio increased significantly after menopause, even though BMI remained unchanged. Body composition parameters were not associated with pCR. Distant disease-free survival (DDFS) was significantly worse in the high VFA group than in the low VFA group (P < 0.05). Furthermore, in the high VFA group, postmenopausal patients had significantly shorter DDFS than premenopausal patients (P < 0.05). VFA was independently associated with DDFS in the multivariate analysis (P < 0.05). High visceral fat is associated with worse NAC outcomes in breast cancer patients, especially postmenopausal patients. Interventions targeting visceral fat accumulation will likely improve NAC outcomes

  16. Correlation between response to neoadjuvant chemotherapy and survival in locally advanced breast cancer patients.

    Science.gov (United States)

    Romero, A; García-Sáenz, J A; Fuentes-Ferrer, M; López Garcia-Asenjo, J A; Furió, V; Román, J M; Moreno, A; de la Hoya, M; Díaz-Rubio, E; Martín, M; Caldés, T

    2013-03-01

    Measurement of residual disease following neoadjuvant chemotherapy that accurately predicts long-term survival in locally advanced breast cancer (LABC) is an essential requirement for clinical trials development. Several methods to assess tumor response have been described. However, the agreement between methods and correlation with survival in independent cohorts has not been reported. We report survival and tumor response according to the measurement of residual breast cancer burden (RCB), the Miller and Payne classification and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in 151 LABC patients. Kappa Cohen's coefficient (К) was used to test the agreement between methods. We assessed the correlation between the treatment outcome and overall survival (OS) and relapse-free survival (RFS) by calculating Harrell's C-statistic (c). The agreement between Miller and Payne classification and RCB classes was very high (К = 0.82). In contrast, we found a moderate-to-fair agreement between the Miller and Payne classification and RECIST criteria (К = 0.52) and RCB classes and RECIST criteria (К = 0.38). The adjusted C-statistic to predict OS for RCB index (0.77) and RCB classes (0.75) was superior to that of RECIST criteria (0.69) (P = 0.007 and P = 0.035, respectively). Also, RCB index (c = 0.71), RCB classes (c = 0.71) and Miller and Payne classification (c = 0.67) predicted better RFS than RECIST criteria (c = 0.61) (P = 0.005, P = 0.006 and P = 0.028, respectively). The pathological assessment of tumor response might provide stronger prognostic information in LABC patients.

  17. Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging.

    Science.gov (United States)

    Wu, Shulian; Huang, Yudian; Tang, Qinggong; Li, Zhifang; Horng, Hannah; Li, Jiatian; Wu, Zaihua; Chen, Yu; Li, Hui

    2018-03-01

    Preoperative neoadjuvant treatment in locally advanced breast cancer is recognized as an effective adjuvant therapy, as it improves treatment outcomes. However, the potential complications remain a threat, so there is an urgent clinical need to assess both the tumor response and changes in its microenvironment using non-invasive and precise identification techniques. Here, two-photon microscopy was employed to detect morphological alterations in breast cancer progression and recession throughout chemotherapy. The changes in structure were analyzed based on the autofluorescence and collagen of differing statuses. Parameters, including optical redox ratio, the ratio of second harmonic generation and auto-fluorescence signal, collagen density, and collagen shape orientation, were studied. Results indicate that these parameters are potential indicators for evaluating breast tumors and their microenvironment changes during progression and chemotherapy. Combined analyses of these parameters could provide a quantitative, novel method for monitoring tumor therapy.

  18. Systemic Chemotherapy as Salvage Treatment for Locally Advanced Rectal Cancer Patients Who Fail to Respond to Standard Neoadjuvant Chemoradiotherapy.

    Science.gov (United States)

    Sclafani, Francesco; Brown, Gina; Cunningham, David; Rao, Sheela; Tekkis, Paris; Tait, Diana; Morano, Federica; Baratelli, Chiara; Kalaitzaki, Eleftheria; Rasheed, Shahnawaz; Watkins, David; Starling, Naureen; Wotherspoon, Andrew; Chau, Ian

    2017-06-01

    The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question. Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy. Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively. Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy. High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is

  19. Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

    Science.gov (United States)

    Seiler, Roland; Ashab, Hussam Al Deen; Erho, Nicholas; van Rhijn, Bas W G; Winters, Brian; Douglas, James; Van Kessel, Kim E; Fransen van de Putte, Elisabeth E; Sommerlad, Matthew; Wang, Natalie Q; Choeurng, Voleak; Gibb, Ewan A; Palmer-Aronsten, Beatrix; Lam, Lucia L; Buerki, Christine; Davicioni, Elai; Sjödahl, Gottfrid; Kardos, Jordan; Hoadley, Katherine A; Lerner, Seth P; McConkey, David J; Choi, Woonyoung; Kim, William Y; Kiss, Bernhard; Thalmann, George N; Todenhöfer, Tilman; Crabb, Simon J; North, Scott; Zwarthoff, Ellen C; Boormans, Joost L; Wright, Jonathan; Dall'Era, Marc; van der Heijden, Michiel S; Black, Peter C

    2017-10-01

    An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Gene expression analysis was used to assign subtypes. Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Different molecular

  20. Breast Cancer Spatial Heterogeneity in Near-Infrared Spectra and the Prediction of Neoadjuvant Chemotherapy Response

    Science.gov (United States)

    Santoro, Ylenia

    Breast cancer accounts for more than 20% of all female cancers. Many of these patients receive neoadjuvant chemotherapy (NAC) to reduce the size of the tumor before surgery and to anticipate the efficacy of treatments for after the procedure. Breast cancer is a heterogeneous disease that comes in several clinical and histological forms. The prediction of the efficacy of chemotherapy would potentially select good candidates who would respond while excluding poor candidates who would not benefit from treatment. In this work we investigate the possibility of noninvasively predicting chemotherapy response prior to treatment based on optical biomarkers obtained from tumor spatial heterogeneities of spectral features measured using Diffuse Optical Spectroscopy. We describe an algorithm to calculate an index that characterizes spatial differences in broadband near-infrared absorption spectra of tumor-containing breast tissue. Patient-specific tumor spatial heterogeneities are visualized through a Heterogeneity Spectrum (HS). HS is a biomarker that can be attributed to different molecular distributions within the tumor. To classify lesion heterogeneities, we built a Heterogeneity Index (HI) from the HS by weighing specific absorption bands. It has been shown that NAC response is potentially related to tumor heterogeneity. Therefore, we correlate the HI obtained prior to treatment with the final response to NAC. In this thesis we also present a novel digital parallel frequency domain system for tissue imaging. The systems employs a supercontinuum laser with high brightness, and a photomultiplier with a large detection area, both allowing a deep penetration with extremely low power on the sample. The digital parallel acquisition is performed through the use of the Flimbox and it decreases the time required for standard serial systems that need to scan through all modulation frequencies. The all-digital acquisition removes analog noise, avoids the analog mixer and it does not

  1. Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer.

    Science.gov (United States)

    Phillips, Andrew; Sundar, Sudha; Singh, Kavita; Nevin, James; Elattar, Ahmed; Kehoe, Sean; Balega, Janos

    2018-06-01

    To assess the impact of 5 or more cycles of neoadjuvant chemotherapy (NACT) and cytoreductive outcomes on overall survival (OS) in patients undergoing interval debulking surgery (IDS) for advanced ovarian cancer. A retrospective review of patients receiving NACT followed by IDS between 2007 and 2017. Patients were analysed according to number of NACT cycles received: group 1 consisted of patients receiving ≤4 cycles and group 2 consisted of those receiving ≥5 cycles. Outcomes were stratified by cytoreductive outcome, surgical complexity, stage and chemotherapy exposure. 231 patients in group 1 and 167 in group 2 were identified. In group 1, the OS for those achieving Complete (R0), Optimalcycles to 24.3 (95%CI 14.4-34.2)months with ≥6 cycles. Surgery with utilisation of cytoreductive procedures to achieve complete clearance should be offered to all patients even after ≥5 cycles if R0 can be achieved. R1 cytoreduction has questionable value in those receiving ≤4 cycles and no value in those receiving ≥5 cycles. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  2. Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

    Science.gov (United States)

    2015-11-01

    the acoustic output power for SHAPE has been developed on the scanner. Briefly, the optimization algorithm steps the ultrasound scanner from 0 to... ultrasound contrast agents to improve the monitoring of breast cancer treatment response to neoadjuvant therapies in women diagnosed with LABC by imaging...estimation (SHAPE). Software for analyzing RF data from a Logiq 9 ultrasound scanner (GE Healthcare, Milwauke, WI) to produce 3D SHAPE pressure

  3. Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Zinser-Sierra Juan

    2009-07-01

    Full Text Available Abstract Background Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC, 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh after neoadjuvant chemotherapy (NCT in patients with LABC. Methods One hundred twelve patients with LABC (stage IIB-IIIB were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC, or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC IV in four 21-day courses followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg, and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR in the breast was 42% (95% CI, 33.2–50.5% and, 29.5% (95% CI, 21.4–37.5% if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016. The 5-year disease-free survival (DFS was 76.9% (95% CI, 68.2–84.7%. No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04. Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%. The toxicity profile was acceptable. Conclusion This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

  4. Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer.

    Science.gov (United States)

    Tanaka, Satoru; Iwamoto, Mitsuhiko; Kimura, Kosei; Matsunami, Nobuki; Morishima, Hirotaka; Yoshidome, Katsuhide; Nomura, Takashi; Morimoto, Takashi; Yamamoto, Daigo; Tsubota, Yu; Kobayashi, Toshihiro; Uchiyama, Kazuhisa

    2015-06-01

    We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with

  5. MR volumetric analysis of the course of nephroblastomatosis under chemotherapy in childhood

    International Nuclear Information System (INIS)

    Guenther, Patrick; Waag, Karl Ludwig; Troeger, Jochen; Schenk, Jens-Peter; Graf, Norbert

    2004-01-01

    Nephroblastomatosis is a paediatric renal disease that may undergo malignant transformation. When neoadjuvant chemotherapy is indicated for nephroblastomatosis or bilateral Wilms' tumours, exact volumetric analysis using high-speed data processing and visualization may aid in determining tumour response. Using 3D-volume-rendering software, the 0.5-T MRI data of a 2-year-old girl with bilateral nephroblastomatosis was analysed. Exact volume determination of foci of nephroblastomatosis was performed by automatic and manual segmentation, and the relation to normal renal parenchyma was determined over a 12-month period. At the first visit, 80% (460/547 ml) of the extremely enlarged right kidney was due to nephroblastomatosis. Total tumour volume within the right kidney decreased to 74 ml under chemotherapy. Volume analysis of the two emerging right-sided masses after treatment correctly suggested Wilms' tumour. Three-dimensional rendering of the growing masses aided the surgeon in nephron-sparing surgery during tumour resection. (orig.)

  6. MR volumetric analysis of the course of nephroblastomatosis under chemotherapy in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, Patrick; Waag, Karl Ludwig [Department of Paediatric Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Troeger, Jochen; Schenk, Jens-Peter [Department of Paediatric Radiology, University of Heidelberg (Germany); Graf, Norbert [Department of Paediatric Oncology, Children' s Hospital, University of Homburg/Saar (Germany)

    2004-08-01

    Nephroblastomatosis is a paediatric renal disease that may undergo malignant transformation. When neoadjuvant chemotherapy is indicated for nephroblastomatosis or bilateral Wilms' tumours, exact volumetric analysis using high-speed data processing and visualization may aid in determining tumour response. Using 3D-volume-rendering software, the 0.5-T MRI data of a 2-year-old girl with bilateral nephroblastomatosis was analysed. Exact volume determination of foci of nephroblastomatosis was performed by automatic and manual segmentation, and the relation to normal renal parenchyma was determined over a 12-month period. At the first visit, 80% (460/547 ml) of the extremely enlarged right kidney was due to nephroblastomatosis. Total tumour volume within the right kidney decreased to 74 ml under chemotherapy. Volume analysis of the two emerging right-sided masses after treatment correctly suggested Wilms' tumour. Three-dimensional rendering of the growing masses aided the surgeon in nephron-sparing surgery during tumour resection. (orig.)

  7. MR volumetric analysis of the course of nephroblastomatosis under chemotherapy in childhood.

    Science.gov (United States)

    Günther, Patrick; Tröger, Jochen; Graf, Norbert; Waag, Karl Ludwig; Schenk, Jens-Peter

    2004-08-01

    Nephroblastomatosis is a paediatric renal disease that may undergo malignant transformation. When neoadjuvant chemotherapy is indicated for nephroblastomatosis or bilateral Wilms' tumours, exact volumetric analysis using high-speed data processing and visualization may aid in determining tumour response. Using 3D-volume-rendering software, the 0.5-T MRI data of a 2-year-old girl with bilateral nephroblastomatosis was analysed. Exact volume determination of foci of nephroblastomatosis was performed by automatic and manual segmentation, and the relation to normal renal parenchyma was determined over a 12-month period. At the first visit, 80% (460/547 ml) of the extremely enlarged right kidney was due to nephroblastomatosis. Total tumour volume within the right kidney decreased to 74 ml under chemotherapy. Volume analysis of the two emerging right-sided masses after treatment correctly suggested Wilms' tumour. Three-dimensional rendering of the growing masses aided the surgeon in nephron-sparing surgery during tumour resection.

  8. Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast cancer.

    Science.gov (United States)

    Yang, Su-Jin; Wang, Dan-Dan; Li, Jian; Xu, Han-Zi; Shen, Hong-Yu; Chen, Xiu; Zhou, Si-Ying; Zhong, Shan-Liang; Zhao, Jian-Hua; Tang, Jin-Hai

    2017-08-05

    Anthracycline/taxane-based chemotherapy regimens are usually used as neoadjuvant chemotherapies to decrease tumour size and prevent metastasis of advanced breast cancer. However, patients have a high risk of developing chemo-resistance during treatment through still unknown mechanisms. Glutathione S-transferase P1 (GSTP1), which belongs to the family of phase II metabolic enzymes, has been reported to function in detoxifying several anti-cancer drugs by conjugating them with glutathione. Previous studies have identified GSTP1 as a predictor of prognosis and chemo-resistance in breast cancer patients, but the mechanisms governing GSTP1-dependent drug resistance are still unclear. We have found that GSTP1 expression is much higher in adriamycin-resistant cells and their corresponding exosomes. The role of GSTP1-containing exosomes in conferring drug resistance was analysed through cell apoptosis and immunofluorescence staining assays. Furthermore, we analysed 42 cases of paired breast cancer tissues collected before and after anthracycline/taxane-based neoadjuvant chemotherapy by immunohistochemistry. Higher GSTP1 expression was shown in the progressive disease (PD)/stable disease (SD) group than in the partial response (PR)/complete response (CR) group both in the samples collected before and after the chemotherapy treatment. Interestingly, GSTP1 partly re-localized from the cell nucleus to the cytoplasm upon treatment, and similar results were obtained for the exosomal marker Tumour susceptibility gene 101 protein (TSG101), which also increased in the cytoplasm after chemotherapy. After analysing the serum exosomes of 30 patients treated with anthracycline/taxane-based neoadjuvant chemotherapy, we discovered that the levels of GSTP1 in exosomes from patients in the PD/SD group were significantly higher than those in the PR/CR group. Here, for the first time, we investigated a novel role for GSTP1-containing exosomes and their capability to transfer drug resistance

  9. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    International Nuclear Information System (INIS)

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-01-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  10. Phase 1 Clinical Trial of Stereotactic Body Radiation Therapy Concomitant With Neoadjuvant Chemotherapy for Breast Cancer

    International Nuclear Information System (INIS)

    Bondiau, Pierre-Yves; Courdi, Adel; Bahadoran, Phillipe; Chamorey, Emmanuel; Queille-Roussel, Catherine; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Pacquelet-Cheli, Sandrine; Ferrero, Jean-Marc

    2013-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer. Methods and Materials: To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate. Results: Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported. Conclusions: This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial

  11. Phase 1 Clinical Trial of Stereotactic Body Radiation Therapy Concomitant With Neoadjuvant Chemotherapy for Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bondiau, Pierre-Yves, E-mail: pierre-yves.bondiau@nice.unicancer.fr [Department of Radiotherapy, Centre Antoine Lacassagne, Nice (France); Courdi, Adel [Department of Radiotherapy, Centre Antoine Lacassagne, Nice (France); Bahadoran, Phillipe [Department of Dermatology, University Hospital of Nice, Nice (France); Chamorey, Emmanuel [Department of Radiotherapy, Centre Antoine Lacassagne, Nice (France); Queille-Roussel, Catherine [Centre de Pharmacologie Clinique Appliquée à la Dermatologie, Nice (France); Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Pacquelet-Cheli, Sandrine; Ferrero, Jean-Marc [Department of Radiotherapy, Centre Antoine Lacassagne, Nice (France)

    2013-04-01

    Purpose: Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer. Methods and Materials: To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate. Results: Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported. Conclusions: This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial.

  12. Can quantitative contrast-enhanced ultrasonography predict cervical tumor response to neoadjuvant chemotherapy?

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Chuan; Liu, Long-Zhong; Zheng, Wei [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China); Xie, Yan-Jun [Department of Gynecology and Obstetrics, Zhongcun Town hospital, 140 Renmin Road, Zhongcun Town, Panyu District, Guangzhou, 511400 (China); Xiong, Yong-Hong; Li, An-Hua [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China); Pei, Xiao-Qing, E-mail: peixq@sysucc.org.cn [Department of Ultrasound, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060 (China)

    2016-11-15

    Highlights: • We assessed the clinical value of quantitative CEUS for prediction of cervical tumor perfusion response to NACT. • IMAX, RT, and TTP changed significantly after one NACT cycle. • Pre-treatment IMAX positively correlated with the absolute and percentage changes in all cervical tumor IMAX after NACT. • Pre-treatment IMAX may be predictive of NACT perfusion response in cervical tumor. - Abstract: Objective: To evaluate the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for predicting and assessing cervical tumor response to neoadjuvant chemotherapy (NACT). Methods: Thirty-eight cases with stage IB2 or IIA cervical cancer were studied using CEUS before and after one cycle of NACT. The quantitative CEUS parameters maximum intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (MTT) were compared between cervical tumors and myometrium (reference zone) using Sonoliver software. Absolute and relative changes in quantitative CEUS parameters were also compared among complete response, partial response, and non-responsive groups. Correlations between pre-treatment IMAX and changes in quantitative parameters were assessed after one cycle of NACT. Results: There were significant changes in cervical tumor IMAX (P < 0.001), RT (P < 0.05), and TTP (P < 0.05) after one cycle of NACT. According to the Response Evaluation Criteria In Solid Tumors guidelines, the enrollments were divided into complete response, partial response, stable disease and progressive disease groups. There were no significant differences in quantitative CEUS parameters among complete response, partial response, and non-responsive groups (P > 0.05). In the stable disease group (n = 17), cervical tumor IMAX, RT, and TTP decreased significantly after NACT (P < 0.001). The absolute and percentage changes in IMAX were positively correlated with pre-treatment IMAX in all 38 patients (r = 0.576, P < 0.001 and r = 0.429, P < 0.001). Conclusion

  13. Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Songliang ZHANG

    2015-06-01

    Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

  14. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    International Nuclear Information System (INIS)

    Alexander, Brian M.; Wang Xiaozhe; Niemierko, Andrzej; Weaver, David T.; Mak, Raymond H.; Roof, Kevin S.; Fidias, Panagiotis; Wain, John; Choi, Noah C.

    2012-01-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  15. Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

    International Nuclear Information System (INIS)

    Gao, Yuan-Hong; Lin, Jun-Zhong; An, Xin; Luo, Jie-Lin; Cai, Mu-Yan; Cai, Pei-Qiang; Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong; Ding, Pei-Rong

    2014-01-01

    Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen

  16. Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuan-Hong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Lin, Jun-Zhong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); An, Xin [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Luo, Jie-Lin [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); Cai, Mu-Yan [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou (China); Cai, Pei-Qiang [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou (China); Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); Ding, Pei-Rong, E-mail: dingpr@mail.sysu.edu.cn [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China)

    2014-12-01

    Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen

  17. When Does Neoadjuvant Chemotherapy Really Avoid Radiotherapy? Clinical Predictors of Adjuvant Radiotherapy in Cervical Cancer.

    Science.gov (United States)

    Papadia, Andrea; Bellati, Filippo; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Lorusso, Domenica; Donfrancesco, Cristina; Gasparri, Maria Luisa; Raspagliesi, Francesco

    2015-12-01

    The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate- and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate- and/or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate- and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.

  18. ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    David Vrana

    2018-03-01

    Full Text Available The prognosis of esophageal cancer (EC is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome.

  19. Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Yutaka Yonemura

    2012-01-01

    Full Text Available Novel multidisciplinary treatment combined with neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS and peritonectomy was developed. Ninety-six patients were enrolled. Peritoneal wash cytology was performed before and after NIPS through a port system. Patients were treated with 60 mg/m2 of oral S-1 for 21 days, followed by a 1-week rest. On days 1, 8, and 15, 30 mg/m2 of Taxotere and 30 mg/m2 of cisplatin with 500 mL of saline were introduced through the port. NIPS is done 2 cycles before surgery. Three weeks after NIPS, 82 patients were eligible to intend cytoreductive surgery (CRS by gastrectomy + D2 dissection + periotnectomy to achieve complete cytoreduction. Sixty-eight patients showed positice cytology before NIPS, and the positive cytology results became negative in 47 (69% patients after NIPS. Complete pathologic response on PC after NIPS was experienced in 30 (36.8% patients. Stage migration was experienced in 12 patients (14.6%. Complete cytoreduction was achieved in 58 patients (70.7%. By the multivariate analysis, complete cytoreduction and pathologic response became a significantly good survival. However the high morbidity and mortality, stringent patient selection is important. The best indications of the therapy are patients with good pathologic response and PCI≤6, which are supposed to be removed completely by peritonectomy.

  20. Assessment of early response biomarkers in relation to long‐term survival in patients with HER2‐negative breast cancer receiving neoadjuvant chemotherapy plus bevacizumab: Results from the Phase II PROMIX trial

    Science.gov (United States)

    Kimbung, Siker; Markholm, Ida; Bjöhle, Judith; Lekberg, Tobias; von Wachenfeldt, Anna; Azavedo, Edward; Saracco, Ariel; Hellström, Mats; Veerla, Srinivas; Paquet, Eric; Bendahl, Pär‐Ola; Fernö, Mårten; Bergh, Jonas; Loman, Niklas

    2017-01-01

    Pathologic complete response (pCR) is a predictor for favorable outcome after neoadjuvant treatment in early breast cancer. Modulation of gene expression may also provide early readouts of biological activity and prognosis, offering the possibility for timely response‐guided treatment adjustment. The role of early transcriptional changes in predicting response to neoadjuvant chemotherapy plus bevacizumab was investigated. One‐hundred‐and‐fifty patients with large, operable and locally advanced HER2‐negative breast cancer received epirubicin and docetaxel, with the addition of bevacizumab. Patients underwent tumor biopsies at baseline, after Cycle 2 and at the time of surgery. The primary end point, pCR, and its relation with the secondary endpoints event‐free survival (EFS), overall survival (OS) and gene expression profiles, are reported. The pCR rate was 13% (95% CI 8.6–20.2), with significantly more pCRs among triple‐negative [28% (95% CI 14.8–45.4)] than among hormone receptor positive (HR+) tumors [9% (95% CI 4.6–16.3); (OR = 3.9 [CI = 1.5–10.3])]. pCR rates were not associated with EFS or OS. PAM50 subtypes significantly changed after Cycle 2 (p = 0.03) and an index of absolute changes in PAM50 correlations between these time‐points was associated with EFS [HR = 0.62 (CI = 0.3–1.1)]. In univariable analyses, signatures for angiogenesis, proliferation, estrogen receptor signaling, invasion and metastasis, and immune response, measured after Cycle 2, were associated with pCR in HR+ tumors. Evaluation of changes in molecular subtypes and other signatures early in the course of neoadjuvant treatment may be predictive of pCR and EFS. These factors may help guide further treatment and should be considered when designing neoadjuvant trials. PMID:28940389

  1. Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

    Science.gov (United States)

    Naiken, Surennaidoo P; Toso, Christian; Rubbia-Brandt, Laura; Thomopoulos, Theodoros; Roth, Arnaud; Mentha, Gilles; Morel, Philippe; Gervaz, Pascal

    2014-01-17

    Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy

  2. Tumor residual pós-quimioterapia neoadjuvante para câncer de mama: impacto sobre o tratamento cirúrgico conservador Residual tumor after neoadjuvant chemotherapy for breast cancer: impact on conservative surgical treatment

    Directory of Open Access Journals (Sweden)

    Edison Mantovani Barbosa

    1999-05-01

    Full Text Available Objetivo: analisar as alterações histopatológicas provocadas pela ação da quimioterapia neoadjuvante (fluoracil, epirrubicina e ciclofosfamida; FEC -- 4 ciclos na área tumoral, no tecido mamário adjacente e nos linfonodos homolaterais, em peças cirúrgicas obtidas de pacientes portadoras de carcinomas primários da mama. Método: estudo histológico detalhado de 30 peças cirúrgicas obtidas por mastectomia radical (Patey de pacientes portadoras de carcinomas primários da mama, previamente submetidas a esse tipo de terapêutica sistêmica. Resultados: observamos regressão tumoral, de grau variável, em todas as peças analisadas. Esta regressão ocorreu de forma irregular, restando inúmeros focos refratários na área ocupada pelo tumor primário. Observamos focos celulares resistentes independentes do tumor primário no tecido mamário. Detalhamos outros achados histopatológicos decorrentes da ação quimioterápica nos tecidos tumoral e mamário, como calcificações e fibrose, e nos linfonodos axilares homolaterais. Conclusão: concluímos que a ação da quimioterapia neoadjuvante não é uniforme, restando focos tumorais refratários, tanto na área do tumor inicial, quanto à distância. A regressão do tumor independe da resposta de regressão dos linfonodos axilares metastáticos. A utilização da cirurgia conservadora pós-quimioterapia neoadjuvante (FEC deve ser evitada.Purpose: analysis of histopathologic alterations caused by neoadjuvant chemotherapy (fluorouracil, epirubicine, cyclophosphamide; FEC - 4 cycles at the tumor site, adjacent mammary tissue and homolateral lymph nodes, as observed in sections of patients with primary breast carcinomas. Method: histological studies performed on 30 surgical sections obtained from radical mastectomy (Patey of patients with primary breast carcinomas, who underwent prior neoadjuvant systemic therapy. Results: all sections showed tumor regression with variable intensity. This

  3. The accuracy of {sup 18}F-FDG PET/CT in predicting the pathological response to neoadjuvant chemotherapy in patients with breast cancer. A meta-analysis and systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Fangfang; Shen, Guohua; Diao, Wei; Jia, Zhiyun [West China Hospital of Sichuan University, Department of Nuclear Medicine, Chengdu, Sichuan (China); Deng, Yunfu [West China Hospital of Sichuan University, Department of Oncology, Chengdu (China)

    2017-11-15

    The aim of this meta-analysis was to evaluate the accuracy of {sup 18}F-FDG PET/CT in predicting the pathological response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients. PubMed, Embase, the Cochrane Library (Central), and the Web of Science (SCI-Expanded) were systematically searched to identify pertinent studies. The methodologic quality of the included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2. The Spearman correlation coefficient was used to explore the existence of a threshold effect. Heterogeneity was assessed by the likelihood ratio I {sup 2} index. The pooled values calculated with a mixed-effects model for the sensitivity, specificity and diagnostic odds ratio with 95% confidence intervals were 81.9% (76.0-86.6%), 79.3% (72.1-85.1%) and 17.35 (10.98-27.42), respectively. {sup 18}F-FDG PET/CT has a moderate accuracy in predicting the pathological response during the early process of NAC in breast cancer patients. To increase the role of {sup 18}F-FDG PET/CT in monitoring the therapy response, future prospective studies are needed to explore how chemotherapy regimens and different subtypes affect the levels of glucose metabolism. (orig.)

  4. Disappearing or residual tiny (≤5 mm) colorectal liver metastases after chemotherapy on gadoxetic acid-enhanced liver MRI and diffusion-weighted imaging: Is local treatment required?

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Cheonan Hospital, Department of Radiology, Soonchunhyang University College of Medicine, Cheonan-si, Chungcheongnam-do (Korea, Republic of); Song, Kyoung Doo; Kim, Young Kon [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Hee Cheol; Huh, Jung Wook [Sungkyunkwan University School of Medicine, Department of Surgery, Samsung Medical Center, Seoul (Korea, Republic of); Park, Young Suk; Park, Joon Oh; Kim, Seung Tae [Sungkyunkwan University School of Medicine, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Seoul (Korea, Republic of)

    2017-07-15

    To evaluate the clinical course of disappearing colorectal liver metastases (DLM) or residual tiny (≤5 mm) colorectal liver metastases (RTCLM) on gadoxetic acid-enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in patients who had colorectal liver metastases (CLM) and received chemotherapy. Among 137 patients who received chemotherapy for CLM and underwent gadoxetic acid-enhanced MRI and DWI between 2010 and 2012, 43 patients with 168 DLMs and 48 RTCLMs were included. The cumulative in situ recurrence rate of DLM and progression rate of RTCLM and their predictive factors were evaluated. A total of 150 DLMs and 26 RTCLMs were followed up without additional treatment. At 1 and 2 years, respectively, the cumulative in situ recurrence rates for DLM were 10.9 % and 15.7 % and the cumulative progression rates for RTCLM were 27.2 % and 33.2 %. The in situ recurrence rate at 2 years was 4.9 % for the DLM group that did not show reticular hypointensity of liver parenchyma on hepatobiliary phase. DLM on gadoxetic acid-enhanced liver MRI and DWI indicates a high possibility of clinical complete response, especially in patients without chemotherapy-induced sinusoidal obstruction syndrome. Thirty-three percent of RTCLMs showed progression at 2 years. (orig.)

  5. Postmastectomy radiotherapy reduces locoregional and disease recurrence in patients with stage II–III triple-negative breast cancer treated with neoadjuvant chemotherapy and mastectomy

    Directory of Open Access Journals (Sweden)

    Chen XX

    2018-04-01

    Full Text Available Xingxing Chen,1,2,* Fan Xia,1,2,* Jurui Luo,1,2,* Jinli Ma,1,2 Zhaozhi Yang,1,2 Li Zhang,1,2 Yan Feng,1,2 Zhimin Shao,2,3 Xiaoli Yu,1,2 Xiaomao Guo1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 3Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China *These authors contributed equally to this work Background: This study investigated the effect of postmastectomy radiotherapy (PMRT in patients with stage II–III triple-negative breast cancer (TNBC after neoadjuvant chemotherapy (NAC and modified radical mastectomy (MRM.Patients and methods: A total of 104 women with stage II–III TNBC who received NAC and MRM at our institution between January 2000 and July 2007 were identified. Patients were divided into 2 groups (PMRT and non-PMRT for statistical analysis.Results: The median follow-up time was 64 months (range 12–123 months. The 5 year cumulative locoregional recurrence (LRR and disease recurrence (DR rates were 26.5% and 49.6%, respectively. Despite their more adverse prognostic features, patients with PMRT had lower 5 year cumulative LRR and DR rates than those without PMRT (LRR: 18.3% vs 52.2%, respectively, p=0.0005; DR: 45% vs 69.1%, p=0.0334, respectively. On multivariate analysis of the entire study cohort, forgoing PMRT was significantly associated with developing LRR and DR. Subset analysis revealed that PMRT significantly reduced the 5 year LRR rate in patients with pre-chemotherapy clinical stages IIA (8.3% vs 46.2%, p=0.019 and IIIA (16% vs 66.7%, p=0.003. PMRT also significantly reduced the 5 year DR rate in patients with pre-chemotherapy clinical stage IIA (24.5% vs 69.3%, p=0.0151 and ≥IIIB (70.8% vs 100%, p=0.0481.Conclusion: In our cohort of patients with TNBC treated with NAC and MRM, PMRT significantly improved locoregional control and disease

  6. Patients' experiences with decisions on timing of chemotherapy for breast cancer

    NARCIS (Netherlands)

    de Ligt, K. M.; Spronk, Pauline E.R.; van Bommel, A.C.M.; Vrancken Peeters, M.T.F.D.; Siesling, S.; Smorenburg, Carolien H.

    2018-01-01

    Introduction Despite potential advantages, application of chemotherapy in the neo-adjuvant (NAC) instead of adjuvant (AC) setting for breast cancer (BC) patients varies among hospitals. The aim of this study was to gain insight in patients' experiences with decisions on the timing of chemotherapy

  7. MRI evaluation of the contralateral breast in patients with recently diagnosed breast cancer

    International Nuclear Information System (INIS)

    Taneja, Sangeeta; Jena, Amarnath; Zaidi, Syed Mohd. Shuaib; Khurana, Anuj

    2012-01-01

    Contralateral breast cancer can be synchronous and/or metachronous in patients with cancer of one breast. Detection of a synchronous breast cancer may affect patient management. Dynamic contrast-enhanced MRI of the breast (DCE-MRI) is a sensitive technique for detecting contralateral lesions occult on the other imaging modalities in women already diagnosed with cancer of one breast. The aim was to assess the incidence of mammographically occult synchronous contralateral breast cancer in patients undergoing MRI mammography for the evaluation of a malignant breast lesion. A total of 294 patients with recently diagnosed breast cancer who underwent MRI of the breast were evaluated for lesions in the opposite breast. The incidence of synchronous contralateral malignancy detected by preoperative MRI mammography done for evaluation of extent of disease was 4.1%. Preoperative breast MRI may detect clinically and mammographically occult synchronous contralateral cancer, and can help the patient avoid an additional second surgery or a second course of chemotherapy later; also, as theoretically these lesions are smaller, there may be a survival benefit as well

  8. Sentinel lymph node biopsy using dye alone method is reliable and accurate even after neo-adjuvant chemotherapy in locally advanced breast cancer - a prospective study

    Directory of Open Access Journals (Sweden)

    Mishra Ashwani

    2011-02-01

    Full Text Available Abstract Background Sentinel lymph node biopsy (SLNB is now considered a standard of care in early breast cancers with N0 axillae; however, its role in locally advanced breast cancer (LABC after neo-adjuvant chemotherapy (NACT is still being debated. The present study assessed the feasibility, efficacy and accuracy of sentinel lymph node biopsy (SLNB using "dye alone" (methylene blue method in patients with LABC following NACT. Materials and methods Thirty, biopsy proven cases of LABC that had received three cycles of neo-adjuvant chemotherapy (cyclophosphamide, adriamycin, 5-fluorouracil were subjected to SLNB (using methylene blue dye followed by complete axillary lymph node dissection (levels I-III. The sentinel node(s was/were and the axilla were individually assessed histologically. The SLN accuracy parameters were calculated employing standard definitions. The SLN identification rate in the present study was 100%. The sensitivity of SLNB was 86.6% while the accuracy was 93.3%, which were comparable with other studies done using dual lymphatic mapping method. The SLN was found at level I in all cases and no untoward reaction to methylene blue dye was observed. Conclusions This study confirms that SLNB using methylene blue dye as a sole mapping agent is reasonably safe and almost as accurate as dual agent mapping method. It is likely that in the near future, SLNB may become the standard of care and provide a less morbid alternative to routine axillary lymph node dissection even in patients with LABC that have received NACT.

  9. Prognostic factors in operable breast cancer treated with neoadjuvant chemotherapy: towards a quantification of residual disease.

    Science.gov (United States)

    Mombelli, Sarah; Kwiatkowski, Fabrice; Abrial, Catherine; Wang-Lopez, Qian; de Boissieu, Paul; Garbar, Christian; Bensussan, Armand; Curé, Hervé

    2015-01-01

    Neoadjuvant chemotherapy (NACT) allows for a more frequent use of breast-conservative surgery; it is also an in vivo model of individual tumor sensitivity which permits to determine new prognostic factors to personalize the therapeutic approach. Between 2000 and 2012, 318 patients with primary invasive breast cancer were treated with a median of 6 cycles of NACT; they received either an anthracycline-based FEC 100 protocol (31.1%), or anthracyclines + taxanes (53.5%), with trastuzumab if indicated (15.4%). After a median follow-up of 44.2 months, the pathological complete response rate according to the classification of Chevallier et al. [Am J Clin Oncol 1993;16:223-228] was 19.3%, and overall (OS) and disease-free survival (DFS) at 10 years were 60.2 and 69.6%, respectively. Univariate analyses demonstrated that the Residual Disease in Breast and Nodes (RDBN) index was the most significant prognostic factor for OS (p = 0.0082) and DFS (p = 0.0022), and multivariate analyses mainly revealed that the residual tumor size, residual involved node number and post-chemotherapy Scarff-Bloom-Richardson (SBR) grading were the most significant prognostic factors. In a cohort of patients who were all homogeneously treated with some of the most common drugs for breast cancer, we demonstrate that NACT may provide additional prognostic factors and confirm the RDBN index. As this index allows for the prediction of survival with different breast cancer subtypes, we suggest that it should be calculated routinely to help clinicians to select patients who need adjuvant treatments. 2015 S. Karger AG, Basel

  10. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management

    International Nuclear Information System (INIS)

    Smith, J. Joshua; Chow, Oliver S.; Gollub, Marc J.; Nash, Garrett M.; Temple, Larissa K.; Weiser, Martin R.; Guillem, José G.; Paty, Philip B.; Avila, Karin; Garcia-Aguilar, Julio

    2015-01-01

    Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or—in patients treated with NOM—the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment

  11. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.

    Science.gov (United States)

    Smith, J Joshua; Chow, Oliver S; Gollub, Marc J; Nash, Garrett M; Temple, Larissa K; Weiser, Martin R; Guillem, José G; Paty, Philip B; Avila, Karin; Garcia-Aguilar, Julio

    2015-10-23

    Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying patients who could safely undergo rectal preservation without sacrificing survival benefit and QoL. This multi-institutional, phase II study investigates the efficacy of total neoadjuvant therapy (TNT) and selective non-operative management (NOM) in LARC. Patients with MRI-staged Stage II or III rectal cancer amenable to TME will be randomized to receive FOLFOX/CAPEOX: a) before induction neoadjuvant chemotherapy (INCT); or b) after consolidation neoadjuvant chemotherapy (CNCT), with 5-FU or capecitabine-based chemoradiation. Patients in both arms will be re-staged after completing all neoadjuvant therapy. Those with residual tumor at the primary site will undergo TME. Patients with clinical complete response (cCR) will receive non-operative management (NOM). NOM patients will be followed every 3 months for 2 years, and every 6 months thereafter. TME patients will be followed according to NCCN guidelines. All will be followed for at least 5 years from the date of surgery or--in patients treated with NOM--the last day of treatment. The studies published thus far on the safety of NOM in LARC have compared survival between select groups of patients with a cCR after NOM, to patients with a pathologic complete response (pCR) after TME. The current study compares 3-year disease-free survival (DFS) in an entire population of patients with LARC, including those with cCR and those with pCR. We will compare the two arms of the study with respect to organ preservation at 3 years, treatment compliance

  12. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer

    Science.gov (United States)

    Homann, Nils; Pauligk, Claudia; Illerhaus, Gerald; Martens, Uwe M.; Stoehlmacher, Jan; Schmalenberg, Harald; Luley, Kim B.; Prasnikar, Nicole; Egger, Matthias; Probst, Stephan; Messmann, Helmut; Moehler, Markus; Fischbach, Wolfgang; Hartmann, Jörg T.; Mayer, Frank; Höffkes, Heinz-Gert; Koenigsmann, Michael; Arnold, Dirk; Kraus, Thomas W.; Grimm, Kersten; Berkhoff, Stefan; Post, Stefan; Jäger, Elke; Bechstein, Wolf; Ronellenfitsch, Ulrich; Mönig, Stefan; Hofheinz, Ralf D.

    2017-01-01

    Importance Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. Objective To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. Design, Setting, and Participants The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie–fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Interventions Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. Main Outcomes and Measures The primary end point was overall survival. Results In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized

  13. Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis.

    Science.gov (United States)

    Ruano Pérez, R; Rebollo Aguirre, A C; García-Talavera San Miguel, P; Díaz Expósito, R; Vidal-Sicart, S; Cordero García, J M; Carrera Salazar, D; Rioja Martín, M E

    The role of the selective sentinel node biopsy (SNB) is increasing in relevance in breast cancer women with indication of neoadjuvant chemotherapy (NAC). The Radiosurgery Working Group of the SEMNIM is aware of the necessity of establishing the need for SNB before or after NAC, and also how to manage patients with axillary node-negative or node-positive. There is sufficient data to assess that the SNB with radioisotope techniques are feasible and safe in all these scenarios. An adequate axilla evaluation prior to surgery and the possibility of marking prior to NAC the nodes infiltrated must be the two main pillars to guarantee the success of the SNB. It has been shown that to incorporate the SNB in breast cancer women with indication of NAC increases the rate of a conservative treatment of the axilla that will be a clear benefit for these patients. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  14. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Katz, Matthew S.; Minsky, Bruce D.; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-01-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  15. [Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes].

    Science.gov (United States)

    Ruano, R; Ramos, M; García-Talavera, J R; Ramos, T; Rosero, A S; González-Orus, J M; Sancho, M

    2014-01-01

    To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  16. The Impact of Skin-Sparing Mastectomy With Immediate Reconstruction in Patients With Stage III Breast Cancer Treated With Neoadjuvant Chemotherapy and Postmastectomy Radiation

    International Nuclear Information System (INIS)

    Prabhu, Roshan; Godette, Karen; Carlson, Grant; Losken, Albert; Gabram, Sheryl; Fasola, Carolina; O’Regan, Ruth; Zelnak, Amelia; Torres, Mylin

    2012-01-01

    Purpose: The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non–SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT). Methods and Materials: Between October 1997 and March 2010, 100 consecutive patients (40 SSM with IR vs. 60 non-SSM) with Stage III breast cancer received anthracycline- and/or taxane-based neoadjuvant chemotherapy, mastectomy, and adjuvant XRT. Clinical stage (SSM with IR vs. for non-SSM) was IIIA (75% vs. 67%), IIIB (8% vs. 18%), and IIIC (8% vs. 8%). Tumors greater than 5 cm were found in 74% vs. 69%; 97% of patients in both groups were clinically node positive; and 8% vs. 18% had T4b disease. Results: The time from initial biopsy to XRT was prolonged for SSM–IR patients (274 vs. 254 days, p = 0.04), and there was a trend toward XRT delay of more than 8 weeks (52% vs. 31%, p = 0.07) after surgery. The rate of complications requiring surgical intervention was higher in the SSM–IR group (37.5% vs. 5%, p < 0.001). The 2-year actuarial locoregional control, breast cancer–specific survival, and overall survival rates for SSM with IR vs. non-SSM were 94.7% vs. 97.4%, 91.5% vs. 86.3%, and 87.4% vs. 84.8%, respectively (p = not significant). Conclusions: In our small study with limited follow-up, SSM with IR prolonged overall cancer treatment time and trended toward delaying XRT but did not impair oncologic outcomes. Complication rates were significantly higher in this group. Longer follow-up is needed.

  17. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

    Directory of Open Access Journals (Sweden)

    Petros-Pavlos Ypsilantis

    Full Text Available Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

  18. The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc-IV high-grade serous ovarian cancer.

    Science.gov (United States)

    Xu, Xia; Deng, Fei; Lv, Mengmeng; Chen, Xiaoxiang

    2017-02-01

    No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1-8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p cycles was shorter than those of patients who underwent cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

  19. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

    Science.gov (United States)

    Newman, Neil B; Sidhu, Manpreet K; Baby, Rekha; Moss, Rebecca A; Nissenblatt, Michael J; Chen, Ting; Lu, Shou-En; Jabbour, Salma K

    2016-04-01

    To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Newman, Neil B.; Sidhu, Manpreet K.; Baby, Rekha [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Moss, Rebecca A.; Nissenblatt, Michael J. [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Chen, Ting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States); Lu, Shou-En [Department of Biostatistics, School of Public Health, Rutgers University, Piscataway, New Jersey (United States); Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey (United States)

    2016-04-01

    Purpose/Objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer. Methods and Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM). Dose volume histograms (DVH) measured the mean doses and percentage of BM volume receiving between 5-40 Gy (i.e.: PBM-V5, LPBM-V5). The Wilcoxon signed rank tests evaluated the differences in absolute hematologic nadirs during neoadjuvant vs. adjuvant treatment. Logistic regressions evaluated the association between dosimetric parameters and ≥ grade 3 hematologic toxicity (HT3) and hematologic event (HE) defined as ≥ grade 2 HT and a dose reduction in OxF. Receiver Operator Characteristic (ROC) curves were constructed to determine optimal threshold values leading to HT3. Results: During OxF chemotherapy, 40.0% (n=14) and 48% (n=17) of rectal cancer patients experienced HT3 and HE, respectively. On multivariable logistic regression, increasing pelvic mean dose (PMD) and lower pelvis mean dose (LPMD) along with increasing PBM-V (25-40), LPBM-V25, and LPBM-V40 were significantly associated with HT3 and/or HE during postoperative chemotherapy. Exceeding ≥36.6 Gy to the PMD and ≥32.6 Gy to the LPMD strongly correlated with causing HT3 during postoperative chemotherapy. Conclusions: Neoadjuvant RT for rectal cancer has lasting effects on the pelvic BM, which are demonstrable during adjuvant OxF. Sparing of the BM during preoperative CRT can aid in reducing significant hematologic adverse events and aid in tolerance of postoperative chemotherapy.

  1. Radiological evaluation of the response to chemotherapy for osteosarcoma

    International Nuclear Information System (INIS)

    Miwa, Shinji; Taki, Junichi; Yamamoto, Norio

    2011-01-01

    Sixty-one patients with osteosarcoma were examined by radiographs, angiograms, MRI, 201 Tl and 99m Tc-methoxyisobutyl-isonitrile (MIBI) scintigram to evaluate their response to preoperative chemotherapy. All patients were classified as either responders or non-responder according based on the imaging findings. The radiographs were evaluated according to the degree of sclerotic change and cortical recovery, and the angiograms were evaluated according to the degree of vascular change. MR images were evaluated according to the rate of extraskeletal mass reduction. The 201 Tl and 99m Tc-MIBI scans were evaluated by the percentage reduction of the uptake ratio. All patients were evaluated on the basis of a pathological examination of the resected specimens. We also devised a combined radiological scoring system according to the predictive power of each type of diagnostic image and investigated the correlation between the radiological evaluation and the pathological evaluation. Sensitivity, specificity, and accuracy were 81.0%, 19.0%, and 60.3%, respectively for the radiographs; 77.1%, 20.0%, and 60.0%, respectively, for angiograms; 82.1%, 69.0%, and 75.4%, respectively for MRI; 81.5%, 68.0%, and 75.0%, respectively, for 201 Tl scans; 76.7%, 70.6%, and 74.5% for 99m Tc-MIBI scans; and 88.9%, 84.0%, and 86.9%, respectively, for the combined radiological evaluation. (author)

  2. Longitudinal, intermodality registration of quantitative breast PET and MRI data acquired before and during neoadjuvant chemotherapy: Preliminary results

    International Nuclear Information System (INIS)

    Atuegwu, Nkiruka C.; Williams, Jason M.; Li, Xia; Arlinghaus, Lori R.; Abramson, Richard G.; Chakravarthy, A. Bapsi; Abramson, Vandana G.; Yankeelov, Thomas E.

    2014-01-01

    Purpose: The authors propose a method whereby serially acquired DCE-MRI, DW-MRI, and FDG-PET breast data sets can be spatially and temporally coregistered to enable the comparison of changes in parameter maps at the voxel level. Methods: First, the authors aligned the PET and MR images at each time point rigidly and nonrigidly. To register the MR images longitudinally, the authors extended a nonrigid registration algorithm by including a tumor volume-preserving constraint in the cost function. After the PET images were aligned to the MR images at each time point, the authors then used the transformation obtained from the longitudinal registration of the MRI volumes to register the PET images longitudinally. The authors tested this approach on ten breast cancer patients by calculating a modified Dice similarity of tumor size between the PET and MR images as well as the bending energy and changes in the tumor volume after the application of the registration algorithm. Results: The median of the modified Dice in the registered PET and DCE-MRI data was 0.92. For the longitudinal registration, the median tumor volume change was −0.03% for the constrained algorithm, compared to −32.16% for the unconstrained registration algorithms (p = 8 × 10 −6 ). The medians of the bending energy were 0.0092 and 0.0001 for the unconstrained and constrained algorithms, respectively (p = 2.84 × 10 −7 ). Conclusions: The results indicate that the proposed method can accurately spatially align DCE-MRI, DW-MRI, and FDG-PET breast images acquired at different time points during therapy while preventing the tumor from being substantially distorted or compressed

  3. Dynamic contrast-enhanced MRI and sonography in patients receiving primary chemotherapy for breast cancer

    International Nuclear Information System (INIS)

    Montemurro, Filippo; Aglietta, Massimo; Martincich, Laura; Rosa, Giovanni De; Cirillo, Stefano; Marra, Vincenzo; Regge, Daniele; Biglia, Nicoletta; Sismondi, Piero; Gatti, Marco

    2005-01-01

    We compared dynamic contrast-enhanced MRI (DCE-MRI) and sonography (US) for monitoring tumour size in 21 patients with breast cancer undergoing primary chemotherapy (PCT) followed by surgery. The correlation between DCE-MRI and US measurements of tumour size, defined as the product of the two major diameters, was 0.555 (P=0.009), 0.782 (P 2 , P 2 , P=0.009). After PCT, the median tumour size measured by the two techniques was similar (256 vs 289 mm 2 for DCE-MRI and US, respectively, P=0.859). The correlation with the histopathological major tumour diameter was 0.824 (P<0.001) and 0.705 (P<0.001) for post-treatment DCE-MRI and US, respectively. Measurements of the final major tumour diameter by DCE-MRI tended to be more precise, including cases achieving a pathological complete response. Randomized trials are warranted to establish the clinical impact of the initial discrepancy in tumour size estimates between DCE-MRI and US, and the trend towards a better definition of the final tumour size provided by DCE-MRI in this clinical setting. (orig.)

  4. A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

    Science.gov (United States)

    Alsina, Maria; Rivera, Fernando; Ramos, Francisco Javier; Galán, Maica; López, Rafael; García-Alfonso, Pilar; Alés-Martinez, José Enrique; Queralt, Bernardo; Antón, Antonio; Carrato, Alfredo; Grávalos, Cristina; Méndez-Vidal, Maria José; López, Carlos; de Mena, Inmaculada Ruiz; Tabernero, Josep; Giralt, Jordi; Aranda, Enrique

    2018-02-01

    Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

  5. Assessment of Pathological Response of Breast Carcinoma in Modified Radical Mastectomy Specimens after Neoadjuvant Chemotherapy

    Directory of Open Access Journals (Sweden)

    Dhanya Vasudevan

    2015-01-01

    Full Text Available Aim. Paclitaxel based neoadjuvant chemotherapy regimen (NAT in the setting of locally advanced breast cancer (LABC can render inoperable tumor (T4, N2/N3 resectable. The aim of this study was to assess the status of carcinoma in the breast and lymph nodes after paclitaxel based NAT in order to find out the patient and the tumor characteristics that correspond to the pathological responses which could be used as a surrogate biomarker to assess the treatment response. Materials and Methods. Clinical and tumor characteristics of patients with breast carcinoma (n=48 were assessed preoperatively. These patients were subjected to modified radical mastectomy after 3 courses of paclitaxel based NAT regimen. The pathological responses of the tumor in the breast and the lymph nodes were studied by using Chevallier’s system which graded the responses into pathological complete response (pCR, pathological partial response (pPR, and pathological no response (pNR. Results. Our studies showed a pCR of 27.1% and a pPR of 70.9% . Clinically small sized tumors (2–5 cms and Bloom Richardson’s grade 1 tumors showed a pCR. Mean age at presentation was 50.58 yrs. 79.2% of cases were invasive ductal carcinoma NOS; only 2.1% were invasive lobular carcinoma, their response to NAT being the same. There was no downgrading of the tumor grades after NAT. Ductal carcinoma in situ and lymphovascular invasion were found to be resistant to chemotherapy. The histopathological changes noted in the lymph nodes were similar to that found in the tumor bed. Discussion and Conclusion. From our study we conclude that histopathological examination of the tumor bed is the gold standard for assessing the chemotherapeutic tumor response. As previous studies have shown pCR can be used as a surrogate biomarker to assess the tumor response.

  6. Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy

    Directory of Open Access Journals (Sweden)

    Talita Garcia do Nascimento

    2014-04-01

    Full Text Available OBJECTIVES: to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer.METHODS: observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant.RESULTS: 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia.CONCLUSION: neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care.

  7. The value of diffusion kurtosis magnetic resonance imaging for assessing treatment response of neoadjuvant chemoradiotherapy in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jing; Xu, Qing; Song, Jia-Cheng; Li, Yan; Dai, Xin; Zhang, Ling; Shi, Hai-Bin [First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing (China); Huang, Dong-Ya [First Affiliated Hospital of Nanjing Medical University, Department of General Surgery, Nanjing (China); Li, Yang [First Affiliated Hospital of Nanjing Medical University, Department of Pathology, Nanjing (China)

    2017-05-15

    To evaluate the feasibility and value of diffusion kurtosis (DK) imaging in assessing treatment response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Forty-one patients were included. All patients underwent pre- and post-CRT DCE-MRI on a 3.0-Tesla MRI scanner. Imaging indices (D{sub app}, K{sub app} and ADC values) were measured. Change value (∇X) and change ratio (r ∇X) were calculated. Pathological tumour regression grade scores (Mandard) were the standard reference (good responders: pTRG 1-2; poor responders: pTRG 3-5). Diagnostic performance was compared using ROC analysis. For the pre-CRT measurements, pre-D{sub app-10th} was significantly lower in the good responder group than that of the poor responder group (p = 0.036). For assessing treatment response to neoadjuvant CRT, pre-D{sub app-10th} resulted in AUCs of 0.753 (p = 0.036) with a sensitivity of 66.67 % and a specificity of 77.78 %. The r ∇D{sub app} had a relatively high AUC (0.859) and high sensitivity (100 %) compared with other image indices. DKI is feasible for selecting good responders for neoadjuvant CRT for LARC. (orig.)

  8. Breast conserving treatment of locally advanced carcinoma T2 and T3 after neoadjuvant chemotherapy followed by quadrantectomy and high dose-rate brachytherapy, as a boost, complementary teletherapy and adjuvant chemotherapy; Tratamento conservador dos carcinomas de mama localmente avancados T2 e T3, apos quimioterapia neoadjuvante, com quadrantectomia e braquiterapia de alta taxa de dose como reforco de dose, teleterapia complementar e quimioterapia adjuvante

    Energy Technology Data Exchange (ETDEWEB)

    Fristachi, Carlos Elias [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Onco-Ginecologia e Mastologia]. E-mail: cefristachi@uol.com.br; Miziara Filho, Miguel Abrao; Soares, Celia Regina; Fogaroli, Ricardo Cesar; Pelosi, Edilson Lopes; Martins, Homero Lavieri Martins [Instituto do Cancer Dr. Arnaldo Vieira de Carvalho (ICAVC), Sao Paulo, SP (Brazil). Servico de Radioterapia; Baracat, Fausto Farah [Hospital do Servidor Publico Estadual de Sao Paulo (HSPE), SP (Brazil). Servico de Ginecologia e Mastologia; Piato, Sebastiao [Irmandade da Santa Casa de Misericordia de Sao Paulo, SP (Brazil). Dept. de Obstetricia e Ginecologia (DOGI)

    2005-07-01

    Objective: to assess the treatment of breast cancer T2 and T3(T > = 4 cm), through neoadjuvant chemotherapy, quadrantectomy and high-dose-rate (HDR) brachytherapy as a boost, complementary radiotherapy and adjuvant chemotherapy, considering its method problems, its esthetics results, the aspect of local control, overall survival, and disease-free survival. Patients and method: this clinical prospective descriptive study was based on the evaluation of 26 patients ranging from 30 to 70 years old, with infiltrating ductal carcinoma, clinical stage IIB and IIIA, responsive to the neoadjuvant chemotherapy. Early and late radiotherapy complications were evaluated according to the criteria established by the RTOG/EORTC (Radiotherapy and Oncology Group /European Organization for Research and Treatment of Cancer) groups. Esthetics evaluation was done in accordance with the criteria set by a plastic surgeon. Local control was evaluated by clinical method, mammography and ultrasonography. Overall survival (OS) and the disease-free survival (DFS) were assessed according to Kaplan-Meier methodology. All the patients were treated at the Dr. Arnaldo Vieira de Carvalho Cancer Institute, from June/1995 to November/2001, and evaluated in March, 2002, with median follow-up of 28.7 months. Results: early complications were observed in 8 patients (30.6%). Two patients were classified as G3 and G4 (RTOG/EORTC). Six patients had late complications and three of them (11.5%) were classified as G3 and G4. One patient (3.8%) had local recurrence, 64 months after having local treatment. Esthetics results were considered good or regular in 16 patients (60.5%) out of 24 patients who were examined. Overall survival and disease-free survival in 24, 36 and 60 months were 100%, 92.3% and 83.1% respectively. Conclusion: early and late radiotherapy complications were considerate high when compared to literature, but esthetic results were considered acceptable. RL, OS and DFS were comparable to other

  9. Early Evaluation of Response Using 18F-FDG PET Influences Management in Gastrointestinal Stromal Tumor Patients Treated with Neoadjuvant Imatinib.

    Science.gov (United States)

    Farag, Sheima; Geus-Oei, Lioe-Fee de; van der Graaf, Winette T; van Coevorden, Frits; Grunhagen, Dirk; Reyners, Anna K L; Boonstra, Pieter A; Desar, Ingrid; Gelderblom, Hans; Steeghs, Neeltje

    2018-02-01

    18 F-FDG PET has previously been proven effective as an early way to evaluate the response of gastrointestinal stromal tumors (GISTs) to imatinib treatment. However, it is unclear whether early evaluation of response affects treatment decisions in GIST patients treated with neoadjuvant intent. Methods: We retrospectively scored changes in management based on early evaluation of response by 18 F-FDG PET in patients in the Dutch GIST registry treated with neoadjuvant imatinib. Results: Seventy 18 F-FDG PET scans were obtained for 63 GIST patients to evaluate for an early response to neoadjuvant imatinib. The scans led to a change in management in 27.1% of the patients. Change in management correlated strongly with lack of metabolic response ( P PET for early evaluation of response often results in a change of management in GIST patients harboring the non- KIT exon 11 mutation and should be considered the standard of care in GIST patients treated with neoadjuvant intent. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  10. Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

    International Nuclear Information System (INIS)

    Hulshof, M.C.C.M; Crezee, J.; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J.J.B.; Richel, D.J.

    2005-01-01

    Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m 2 ) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea ≤ grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients with

  11. Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, M C.C.M; Crezee, J; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J J.B.; Richel, D J [Academical Medical Center of Amsterdam (Netherlands)

    2005-07-01

    Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m{sup 2}) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea {<=} grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients

  12. Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zheng Jijun; Wang Ge; Yang, G.Y.

    2010-01-01

    This Phase II study was conducted to evaluate the activity and feasibility of a regimen of nedaplatin and 5-fluorouracil as induction chemotherapy, followed by intensity-modulated radiotherapy concurrent with chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Patients received neoadjuvant chemotherapy comprised two cycles of 5-fluorouracil at 700 mg/m 2 /day administered on days 1-4 as continuous intravenous infusion and nedaplatin (100 mg/m 2 administered intravenous (i.v.) over 2 h) given after the administration of 5-fluorouracil on day 1, repeated every 3 weeks, followed by intensity-modulated radiotherapy concurrent with nedaplatin. During intensity-modulated radiotherapy, nedaplatin was administered at a dose of 100 mg/m 2 intravenous infusion on days 1, 22 and 43, given -60 min before radiation. Fifty-nine (95.8%) of the 60 patients were assessable for response. Thirty-eight cases of complete response and 14 cases of partial response were confirmed after completion of chemoradiation, with the objective response rate of 86.7% (95% confidence interval (CI), 78.1-95.3%). The median follow-up period was 48 months (range, 30-62 months). The 3-year progression-free survival and overall survival were 75.0% (95% CI, 63.0-87.0%) and 85.5% (95% CI, 75.9-95.1%). No patient showed Grade 3 or higher renal dysfunction. The most commonly observed late effect was xerostomia, but the severity diminished over time, and the detectable xerostomia at 24 months was 10.2%. There were no treatment-related deaths during this study. Neoadjuvant chemotherapy with nedaplatin and 5-fluorouracil followed by concomitant nedaplatin and intensity-modulated radiotherapy is an effective and safe treatment for Southern China patients affected by locoregionally advanced nasopharyngeal carcinoma. (author)

  13. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular breast cancer

    NARCIS (Netherlands)

    Truin, W.; Voogd, A.C.; Vreugdenhil, G.; van der Heiden-van der Loo, M.; Siesling, Sabine; Roumen, R.M.

    2012-01-01

    Background On the basis of the lack of response of invasive lobular breast cancer to neoadjuvant chemotherapy, we questioned the effectiveness of adjuvant chemotherapy in relation to histology. Patients and methods Women with primary nonmetastatic invasive ductal or (mixed type) lobular breast

  14. Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes.

    Science.gov (United States)

    Pareja, Rene; Rendón, Gabriel J; Vasquez, Monica; Echeverri, Lina; Sanz-Lomana, Carlos Millán; Ramirez, Pedro T

    2015-06-01

    Radical trachelectomy is the treatment of choice in women with early-stage cervical cancer wishing to preserve fertility. Radical trachelectomy can be performed with a vaginal, abdominal, or laparoscopic/robotic approach. Vaginal radical trachelectomy (VRT) is generally not offered to patients with tumors 2cm or larger because of a high recurrence rate. There are no conclusive recommendations regarding the safety of abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) in such patients. Several investigators have used neoadjuvant chemotherapy in patients with tumors 2 to 4cm to reduce tumor size so that fertility preservation may be offered. However, to our knowledge, no published study has compared outcomes between patients with cervical tumors 2cm or larger who underwent immediate radical trachelectomy and those who underwent neoadjuvant chemotherapy followed by radical trachelectomy. We conducted a literature review to compare outcomes with these 2 approaches. Our main endpoints for evaluation were oncological and obstetrical outcomes. The fertility preservation rate was 82.7%, 85.1%, 89%; and 91.1% for ART (tumors larger than >2cm), ART (all sizes), NACT followed by surgery and VRT (all sizes); respectively. The global pregnancy rate was 16.2%, 24% and 30.7% for ART, VRT, and NACT followed by surgery; respectively. The recurrence rate was 3.8%, 4.2%, 6%, 7.6% and 17% for ART (all sizes), VRT (all sizes), ART (tumors>2cm), NACT followed by surgery, and VRT (tumors>2cm). These outcomes must be considered when offering a fertility sparing technique to patients with a tumor larger than 2cm. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Selective sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: results of the GEICAM 2005-07 study.

    Science.gov (United States)

    Piñero-Madrona, Antonio; Escudero-Barea, María J; Fernández-Robayna, Francisco; Alberro-Adúriz, José A; García-Fernández, Antonio; Vicente-García, Francisco; Dueñas-Rodriguez, Basilio; Lorenzo-Campos, Miguel; Caparrós, Xavier; Cansado-Martínez, María P; Ramos-Boyero, Manuel; Rojo-Blanco, Roberto; Serra-Genís, Constantí

    2015-01-01

    A controversial aspect of breast cancer management is the use of sentinel lymph node biopsy (SLNB) in patients requiring neoadjuvant chemotherapy (NCT). This paper discusses the detection rate (DT) and false negatives (FN) of SLNB after NCT to investigate the influence of initial nodal disease and the protocols applied. Prospective observational multicenter study in women with breast cancer, treated with NCT and SLNB post-NCT with subsequent lymphadenectomy. DT and FN rates were calculated, both overall and depending on the initial nodal status or the use of diagnostic protocols pre-SLNB. No differences in DT between initial node-negative cases and positive cases were found (89.8 vs. 84.4%, P=.437). Significant differences were found (94.1 vs. 56.5%, P=0,002) in the negative predictive value, which was lower when there was initial lymph node positivity, and a higher rate of FN, not significant (18.2 vs. 43.5%, P=.252) in the same cases. The axillary study before SLNB and after the NCT, significantly decreased the rate of FN in patients with initial involvement (55.6 vs 12.5, P=0,009). NCT means less DT and a higher rate of FN in subsequent SLNB, especially if there is initial nodal involvement. The use of protocols in axillary evaluation after administering the NCT and before BSGC, decreases the FN rate in these patients. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. MRI in staging of rectal carcinoma

    International Nuclear Information System (INIS)

    Gourtsoyianni, S.

    2012-01-01

    Full text: MRI of the rectum is performed for initial local staging of primary rectal cancer in order to identify locally advanced rectal cancers and for assessment of treatment response after completion of neoadjuvant therapy. Introduction of new generation MRI scanners with optimal phased array body coils, resulting in improved contrast and spatial resolution images due to better signal to noise ratio, have contributed to production of high resolution images in which visualization of anatomical details such as the mesorectal fascia and the bowel wall layers are feasible. Pre-operative MRI of the rectum using mainly high resolution T2 weighted sequences has gained significant accreditation, especially after the introduction of total mesorectal excision (TME) surgery and neoadjuvant therapy in the treatment regimen of rectal cancer. MR Imaging is so far the only method that can preoperatively identify patients most likely to benefit from neoadjuvant therapy as well as demonstrate high risk patients for local recurrence. Regarding N stage besides of mesorectal lymph nodes which are removed during TME, especially in case of low lying rectal cancers, MRI may provide information regarding external/internal iliac lymph node involvement. High resolution MRI images may demonstrate lymph nodes with a diameter down to 2 mm, however these are still characterized based on their morphological features. Patients identified at initial MRI staging as having locally advanced rectal cancer undergo neoadjuvant chemoradiation therapy (CRT) in order for their tumor to be downsized and downstaged, especially in low rectal cancers so that sphincter sparing surgery may be performed. In 15-30% of patients complete pathological response is achieved. Reimaging with MRI at 6 weeks post treatment is of great importance for assessing tumor response. Conventional MRI has a reported moderate accuracy for prediction of mesorectal fascia (MF) involvement after CRT therapy, mainly due to its

  17. Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study.

    Science.gov (United States)

    Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

    2017-01-01

    To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

  18. 18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

    International Nuclear Information System (INIS)

    Eschmann, Susanne M.; Reimold, Matthias; Bares, Roland; Friedel, Godehard; Paulsen, Frank; Hehr, Thomas; Budach, Wilfried; Langen, Heinz-Jakob

    2007-01-01

    The aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy (NARCT) of advanced non-small cell lung cancer (NSCLC). Seventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NARCT. Changes in FDG uptake and PET findings after completion of NARCT were compared with (1) the histology of tumour samples obtained at surgery or repeat mediastinoscopy, and (2) treatment results in terms of achieved operability and long-term survival. The mean average FDG uptake of the primary tumours in the patient group decreased significantly during NARCT (p = 0.004). Sensitivity, specificity and overall accuracy of FDG-PET were 94.5%, 80% and 91%, respectively, for the detection of residual viable primary tumour, and 77%, 68% and 73%, respectively, for the presence of lymph node metastases. A negative PET scan or a reduction in the standardised uptake value (SUV) of more than 80% was the best predictive factor for a favourable outcome of further treatment. Progressive disease according to PET (new tumour manifestations or increasing SUV) was significantly correlated with an unfavourable outcome (p = 0.005). In this subgroup, survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery, whereas for the whole patient group, complete tumour resection had a significant influence on outcome. FDG-PET is suitable to assess response to NARCT in patients with stage III NSCLC accurately. It was highly predictive for treatment outcome and patient survival. PET may be helpful in improving restaging after NARCT by allowing reliable assessment of residual tumour viability. (orig.)

  19. Prospective Biomarker Analysis of the Randomized CHER-LOB Study Evaluating the Dual Anti-HER2 Treatment With Trastuzumab and Lapatinib Plus Chemotherapy as Neoadjuvant Therapy for HER2-Positive Breast Cancer.

    Science.gov (United States)

    Guarneri, Valentina; Dieci, Maria Vittoria; Frassoldati, Antonio; Maiorana, Antonino; Ficarra, Guido; Bettelli, Stefania; Tagliafico, Enrico; Bicciato, Silvio; Generali, Daniele Giulio; Cagossi, Katia; Bisagni, Giancarlo; Sarti, Samanta; Musolino, Antonino; Ellis, Catherine; Crescenzo, Rocco; Conte, PierFranco

    2015-09-01

    The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. A biomarker program was prospectively planned to identify potential predictors of sensitivity to different treatments and to evaluate treatment effect on tumor biomarkers. Overall, 121 breast cancer patients positive for human epidermal growth factor 2 (HER2) were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib. Pre- and post-treatment samples were centrally evaluated for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations. Fresh-frozen tissue samples were collected for genomic analyses. A mutation in PIK3CA exon 20 or 9 was documented in 20% of cases. Overall, the pCR rates were similar in PIK3CA wild-type and PIK3CA-mutated patients (33.3% vs. 22.7%; p = .323). For patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p = .06). Ki67, pAKT, and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade. The integrated analysis of gene expression and copy number data demonstrated that a 50-gene signature specifically predicted the lapatinib-induced pCR. PIK3CA mutations seem to identify patients who are less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of phosphoinositide 3-kinase pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib. HER2 is currently the only validated marker to select breast cancer patients for anti-HER2 treatment; however, it is becoming evident that HER2-positive breast cancer is a heterogeneous disease. In addition, more

  20. Systemic Chemotherapy using FLOT - Regimen Combined with Cytoreductive Surgery plus HIPEC for Treatment of Peritoneal Metastasized Gastric Cancer. .

    Science.gov (United States)

    Müller, H; Hotopp, Th; Tofeili, A; Wutke, K

    2014-05-01

    The aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy using FLOT - protocol followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) followed by systemic chemotherapyand in patients with peritoneal carciriomatosis (PC) from gastric cancer. Twenty six (median age 53 years, range 39 - 71) were scheduled for three cycles of neoadjuvant systemic chemotherapy using bi-weekly FLOT - protocol followed by CRS + HIPEC. Thereafter 3 additional cycles of FLOT were given. During HIPEC in Colliseum technique Oxaliplatin was given in a dosage of 200 mg/m2 and Docetaxel in a dosage of 80 mg/m2. All patients underwent cytoreductive surgery plus HIPEC. Peritoneal Cancer index was > 15 in 3 cases only. Complete resection could be carried out in all cases (CC-O 18, CC-18). Postoperative complication rate was 23% with no mortality within 30 days. Anastomotic leakage rate was 3.2%. Overall survival was 19.0 months with a 2-year survival rate 38%. Regression analysis demonstrated a Peritoneal Cancer Index PCI > 12 as negative factor for survival. Neoadju- vant chemotherapy using FLOT - protocol followed by CRS + HIPEC seems to be associated with prolonged OS in patients with peritoneal carcinomatosis from gastric cancer. This treatment is not recommended for patients with extensive peritoneal involvement and PCI > 12.

  1. Feasibility of Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer Patients With Diminished Renal Function.

    Science.gov (United States)

    Koshkin, Vadim S; Barata, Pedro C; Rybicki, Lisa A; Zahoor, Haris; Almassi, Nima; Redden, Alicia M; Fergany, Amr F; Kaouk, Jihad; Haber, Georges-Pascal; Stephenson, Andrew J; Ornstein, Moshe C; Gilligan, Timothy; Garcia, Jorge A; Rini, Brian I; Grivas, Petros

    2018-02-22

    Cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy is the standard of care in muscle-invasive bladder cancer. There are limited data regarding chemotherapy tolerability and outcomes for patients with low glomerular filtration rate (GFR) who receive cisplatin-based NAC. A retrospective analysis of patients who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was undertaken. Patients with pre-NAC GFR < 60 mL/min by either Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula were compared to patients with GFR ≥ 60 mL/min for NAC tolerability, pathologic complete and partial response (pPR), and the ability to undergo radical cystectomy. Thirty patients with low GFR (34-59 mL/min) and 94 patients with normal GFR (≥ 60 mL/min) were identified. Low GFR patients were older (median, 71 vs. 65 years), but other demographic and transurethral resection of bladder tumor characteristics were comparable. Low GFR patients more frequently had early NAC discontinuation (30% vs. 13%), NAC modifications (delays, dose reduction, or discontinuation, 66% vs. 40%), and cisplatin-based NAC administered in split doses (37% vs. 16%). No differences in NAC tolerability or outcomes were noted among low GFR patients receiving split-dose versus standard regimens. No differences were noted between low and normal GFR patients in NAC cycles (median, 3 for each), cystectomy rates (93% for each), time to cystectomy, and GFR change from baseline to after NAC. Pathologic complete response was higher among normal GFR patients (24% vs. 14%). Patients with low GFR had more NAC discontinuations and modifications, but most completed planned NAC cycles. For carefully selected patients with GFR < 60 mL/min, cisplatin-based NAC remains a treatment option. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Intravoxel incoherent motion (IVIM histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Gene Y. Cho

    Full Text Available Objective: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM metrics and their ability to predict response to neoadjuvant treatment (NAT. Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. Methods: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions. Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12–14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT, excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. Results: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased (∼70% and VTT% values generally decreased (∼20% post-treatment. Conclusion: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT. Keywords: Breast cancer, Diffusion weighted MRI, Intravoxel incoherent motion, Neoadjuvant treatment, Response evaluation criteria in solid tumors

  3. Standardized Index of Shape (SIS): a quantitative DCE-MRI parameter to discriminate responders by non-responders after neoadjuvant therapy in LARC

    Energy Technology Data Exchange (ETDEWEB)

    Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Radiology; Sansone, Mario [Naples Univ. ' ' Federico II' ' (Italy). Dept. of Biomedical, Electronics and Telecommunications Engineering; Avallone, Antonio [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Gastrointestinal Medical Oncology; Delrio, Paolo [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Gastrointestinal surgical Oncology; Pecori, Biagio [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Radiotherapy; Tatangelo, Fabiana [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy). Div. of Diagnostic Pathology; Ciliberto, Gennaro [Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS, Naples (Italy)

    2015-07-15

    To investigate the potential of DCE-MRI to discriminate responders from non-responders after neoadjuvant chemo-radiotherapy (CRT) for locally advanced rectal cancer (LARC). We investigated several shape parameters for the time-intensity curve (TIC) in order to identify the best combination of parameters between two linear parameter classifiers. Seventy-four consecutive patients with LARC were enrolled in a prospective study approved by our ethics committee. Each patient gave written informed consent. After surgery, pathological TNM and tumour regression grade (TRG) were estimated. DCE-MRI semi-quantitative analysis (sqMRI) was performed to identify the best parameter or parameter combination to discriminate responders from non-responders in response monitoring to CRT. Percentage changes of TIC shape descriptors from the baseline to the presurgical scan were assessed and correlated with TRG. Receiver operating characteristic analysis and linear classifier were applied. Forty-six patients (62.2 %) were classified as responders, while 28 subjects (37.8 %) were considered as non-responders. sqMRI reached a sensitivity of 93.5 % and a specificity of 82.1 % combining the percentage change in Maximum Signal Difference (ΔMSD) and Wash-out Slope (ΔWOS), the Standardized Index of Shape (SIS). SIS obtains the best result in discriminating responders from non-responders after CRT in LARC, with a cut-off value of -3.0 %. (orig.)

  4. Ovarian preservation in locally advanced cervical cancer undergoing neoadjuvant chemotherapy and radical surgery: our experience and analysis of the literature.

    Science.gov (United States)

    Signorelli, Mauro; Bogani, Giorgio; Chiappa, Valentina; Ditto, Antonino; Scaffa, Cono; Martinelli, Fabio; Lorusso, Domenica; Raspagliesi, Francesco

    2018-03-30

    The aim of this study was to estimate the rate of ovarian metastases and recurrences among patients affected by locally advanced stage cancer patients (LACC), undergoing neoadjuvant chemotherapy (NACT) and radical surgery with conservation of ovaries. Retrospective evaluation of consecutive patients affected by LACC (stage IB2- IIB), treated by NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990-2015. Overall, 331 patients were included. Stage at presentation included stage IB2, IIA and IIB in 120 (36.3%), 63 (19%) and 148 (44.7%) patients, respectively. Main histotype was squamous cell carcinoma (n=265, 80.1%) followed by adenocarcinoma/adenosquamous (n=51, 15.4%), and more than half of patients had a grade 3 carcinoma . Overall, 102 (30.8%) women had at least one ovary preserved during surgery, while 229 (69.2%) had bilateral salpingo-oophorectomy. Comparing patients who had ovarian preservation with patients who had not, we observed that the two groups were comparable in terms of baseline characteristics. Survival outcomes were not influenced by ovarian preservation (disease-free (p=0.93) and overall (p=0.65) survivals). One (1%) woman had a localized ovarian recurrence. Our data suggest that ovarian preservation at the time of surgery is a safe option among women with LACC after NACT with no detrimental impact on oncologic outcome. Further prospective studies are warranted.

  5. Default from neoadjuvant chemotherapy in premenopausal female ...

    African Journals Online (AJOL)

    Seventeen (38.6%) patients dropped out of treatment, before, during or after completing NAC. Ten of these defaulted due to inadequate funds to procure chemotherapy, three patients because they insisted on immediate mastectomy, and four of these patients refused surgery when they achieved complete clinical response, ...

  6. Assessing residual cancer cells using MRI and US after preoperative chemotherapy in primary breast cancer to omit surgery.

    Science.gov (United States)

    Iwase, Madoka; Sawaki, Masataka; Hattori, Masaya; Yoshimura, Akiyo; Ishiguro, Junko; Kotani, Haruru; Gondo, Naomi; Adachi, Yayoi; Kataoka, Ayumi; Onishi, Sakura; Sugino, Kayoko; Iwata, Hiroji

    2018-04-04

    Enhanced magnetic resonance imaging (MRI) and ultrasonography (US) are used to assess residual lesions after preoperative chemotherapy before surgery. However, residual lesion assessments based on preoperative imaging often differ from postoperative pathologic diagnoses. We retrospectively reviewed the accuracy of preoperative residual lesion assessments, including ductal carcinoma in situ (DCIS) cases to find criteria for cases in which surgery can be omitted. We reviewed 201 patients who received preoperative chemotherapy and surgery in our hospital from January 2013 to November 2016. Presurgical evaluations regarding the possible existence of residual lesions, and clinical Complete Response (cCR) or non-cCR, were compared with postoperative pathological diagnoses. Of the 201 patients, 52 were diagnosed with cCR, and 39 with pathological complete response (pCR). Predictions for residual lesions were 86.4% sensitive, 76.9% specific, and 84.6% accurate. When patients were divided into 4 groups by estrogen receptor (ER) and HER2 status, sensitivity in each group was ER + /HER2 - : 91.4%; ER - /HER2 - : 94.1%; ER + /HER2 + : 78.6%; and ER - /HER2 + : 78.5%. Of the 22 patients preoperatively assessed with cCR, but diagnosed with non-pCR, the median invasive residual tumor size was 2 mm (range 0-46 mm); 5 patients (22.7%) had only DCIS. Predicting residual lesions after preoperative chemotherapy by using MRI and US is a reasonable strategy. However, current methods are inadequate for identifying patients who can omit surgery; therefore, a new strategy for detecting small tumors in these patients is needed.

  7. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    International Nuclear Information System (INIS)

    Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin; Hollingsworth, Alan B.; Qian, Wei

    2015-01-01

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy

  8. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin, E-mail: Bin.Zheng-1@ou.edu [School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019 (United States); Hollingsworth, Alan B. [Mercy Women’s Center, Mercy Health Center, Oklahoma City, Oklahoma 73120 (United States); Qian, Wei [Department of Electrical and Computer Engineering, University of Texas, El Paso, Texas 79968 (United States)

    2015-11-15

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.

  9. Assessment of a Chemotherapy Response Score (CRS) System for Tubo-Ovarian High-Grade Serous Carcinoma (HGSC)

    DEFF Research Database (Denmark)

    Ditzel, Helena M; Strickland, Kyle C; Meserve, Emily E

    2018-01-01

    A chemotherapy response score (CRS) system was recently described to assess the histopathologic response and prognosis of patients with tubo-ovarian high-grade serous carcinoma (HGSC) receiving neoadjuvant chemotherapy. The current study was performed as an independent assessment of this CRS syst...

  10. Controversies in breast cancer: adjuvant and neoadjuvant therapy.

    Science.gov (United States)

    Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

    2005-06-01

    Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

  11. Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Guancial

    Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

  12. Preliminary Experience with Locoregional Intraarterial Chemotherapy of Uterine Cervical or Endometrial Cancer Using the Peripheral Implantable Port System (PIPSTM): A Feasibility Study

    International Nuclear Information System (INIS)

    Strecker, Ernst-Peter; Heber, Ralf; Boos, Irene; Goettmann, Dieter; Heinrich, Dirk

    2003-01-01

    The purpose of this study was to assess the suitability of a percutaneously implantable catheter port system (PIPS)for repeated intraarterial locoregional chemotherapy (ILC) for cervical and endometrial carcinoma. In 30 patients with advanced, recurrent, or high-risk cervical (n 23) or endometrial(n = 7) carcinoma, PIPS for ILC was implanted via a femoral access, the catheter localized in the infrarenal abdominal aorta. Chemotherapy was performed adjuvantly after surgery(n = 14) or neo-adjuvantly to enable surgery, or for palliation (n = 16). Port implantation, catheter placement, and repeated port puncture was uneventful in all patients.Complications included catheter dislocation (n = 1),catheter thrombosis (n = 2), subcutaneous infection(n = 1), port-bed skin atrophy (n = 1),requiring port explantation in 3 patients. At 2 years follow-up,complete remission was observed in 7/14 patients with adjuvant chemotherapy, partial remission in 3/14. Successful down-staging could be achieved in 4/8 patients with neo-adjuvant chemotherapy. The PIPS is suitable for repeated ILC which may be a valuable method for pre- and post-surgical therapy of advanced or high-risk cervical and endometrial cancer, for adjuvant chemotherapy as well as neo-adjuvantly for down-staging, or for palliation

  13. A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

    Directory of Open Access Journals (Sweden)

    Takatori E

    2016-09-01

    Full Text Available Eriko Takatori, Tadahiro Shoji, Anna Takada, Takayuki Nagasawa, Hideo Omi, Masahiro Kagabu, Tatsuya Honda, Fumiharu Miura, Satoshi Takeuchi, Toru Sugiyama Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, Iwate, Japan Objective: In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group with patients who underwent RH without NAC (Ope group. Patients and methods: The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS and overall survival (OS between the groups. Results: There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days in the NAC group and 25 days (21–34 days in the Ope group; the patients in the NAC group were discharged earlier (P=0.032. The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91, and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028. Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24, and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101. Conclusion: NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous

  14. Circumferential resection margin (CRM) positivity after MRI assessment and adjuvant treatment in 189 patients undergoing rectal cancer resection.

    Science.gov (United States)

    Simpson, G S; Eardley, N; McNicol, F; Healey, P; Hughes, M; Rooney, P S

    2014-05-01

    The management of rectal cancer relies on accurate MRI staging. Multi-modal treatments can downstage rectal cancer prior to surgery and may have an effect on MRI accuracy. We aim to correlate the findings of MRI staging of rectal cancer with histological analysis, the effect of neoadjuvant therapy on this and the implications of circumferential resection margin (CRM) positivity following neoadjuvant therapy. An analysis of histological data and radiological staging of all cases of rectal cancer in a single centre between 2006 and 2011 were conducted. Two hundred forty-one patients had histologically proved rectal cancer during the study period. One hundred eighty-two patients underwent resection. Median age was 66.6 years, and male to female ratio was 13:5. R1 resection rate was 11.1%. MRI assessments of the circumferential resection margin in patients without neoadjuvant radiotherapy were 93.6 and 88.1% in patients who underwent neoadjuvant radiotherapy. Eighteen patients had predicted positive margins following chemoradiotherapy, of which 38.9% had an involved CRM on histological analysis. MRI assessment of the circumferential resection margin in rectal cancer is associated with high accuracy. Neoadjuvant chemoradiotherapy has a detrimental effect on this accuracy, although accuracy remains high. In the presence of persistently predicted positive margins, complete resection remains achievable but may necessitate a more radical approach to resection.

  15. Textural features of 18F-FDG PET after two cycles of neoadjuvant chemotherapy can predict pCR in patients with locally advanced breast cancer.

    Science.gov (United States)

    Cheng, Lin; Zhang, Jianping; Wang, Yujie; Xu, Xiaoli; Zhang, Yongping; Zhang, Yingjian; Liu, Guangyu; Cheng, Jingyi

    2017-08-01

    This study was designed to evaluate the utility of textural features for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Sixty-one consecutive patients with locally advanced breast cancer underwent 18 F-FDG PET/CT scanning at baseline and after the second course of NAC. Changes to imaging parameters [maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV), total lesion glycolysis (TLG)] and textural features (entropy, coarseness, skewness) between the 2 scans were measured by two independent radiologists. Pathological responses were reviewed by one pathologist, and the significance of the predictive value of each parameter was analyzed using a Chi-squared test. Receiver operating characteristic curve analysis was used to compare the area under the curve (AUC) for each parameter. pCR was observed more often in patients with HER2-positive tumors (22 patients) than in patients with HER2-negative tumors (5 patients) (71.0 vs. 16.7%, p textural features of 18 F-FDG PET images after two cycles of NAC are predictive of pCR in both HER2-negative and HER2-positive patients; this evidence warrants confirmation by further research.

  16. A Patient with a Large Gastric Tumor and Protein-Losing Gastroenteropathy Successfully Treated with Neoadjuvant TS-1 Combined with CDDP Therapy

    Directory of Open Access Journals (Sweden)

    Tatsuya Hashimoto

    2014-11-01

    Full Text Available Gastric cancer with protein-losing gastroenteropathy is relatively rare worldwide. The most important problem for the treatment of these patients is their low nutritional status and protein level, which can cause severe postoperative complications. We report a 49-year-old Japanese female with a large gastric tumor and protein-losing gastroenteropathy successfully treated with neoadjuvant TS-1 combined with CDDP therapy. She had a type 5 tumor with partially cauliflower-like appearance. Her blood chemistry revealed low serum total protein (3.3 g/dl and low albumin (1.7 g/dl. She was additionally diagnosed with protein-losing gastroenteropathy based on 99mTc-human serum albumin scintigraphy. Initial neoadjuvant chemotherapy decreased the size of the tumor and led to a marked improvement in her serum protein levels. She then underwent a total gastrectomy and lymph node dissection (D2 with a combined resection of the spleen and gallbladder. Therefore, neoadjuvant chemotherapy may provide a safe treatment before definitive surgery for gastric cancer with protein-losing gastroenteropathy.

  17. Evaluation of the response to preoperative chemotherapy with PET image in osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Dae Geun; Lee, Jong Seok; Kim, Sug Jun; Lee, Soo Yong

    1999-12-01

    F18 FDG PET scan has an advantage in evaluating the biologic status of the tumors. The purpose of this study is evaluate the role of PET scan in pre- and post chemotherapeutic osteosarcomas and correlate the findings with pathologic examination. Nine cases of osteosarcoma had biopsy and preoperative chemotherapy at our department. There were 4 distal femur, 4 proximal tibia and 1 distal ulna. All case had initial MRI and PET scan and these were repeated after 2 cycles of chemotherapy. Under PET image parameters such as VOI (volume of interest), total activity, degree of necrosis and T/N (tumor/normal tissue) ratio were analyzed. There was a significant correlation between the calculated necrosis in PET and observed one on pathologic specimen (r2=0.78, p<0.05). Cross correlation among identified variables revealed meaningful result between T/N ration and tumor necrosis (r2=0.45, p<0.05). As the T/N ratio decrease, so much more the tumor necrosis was. F18 FDG PET scan could get objective data such as volume, degree of necrosis and total activity and was also useful in estimating the contribution of chemotherapy in tumor necrosis over the innate necrosis before treatment.

  18. Evaluation of the response to preoperative chemotherapy with PET image in osteosarcoma

    International Nuclear Information System (INIS)

    Jeon, Dae Geun; Lee, Jong Seok; Kim, Sug Jun; Lee, Soo Yong

    1999-12-01

    F18 FDG PET scan has an advantage in evaluating the biologic status of the tumors. The purpose of this study is evaluate the role of PET scan in pre- and post chemotherapeutic osteosarcomas and correlate the findings with pathologic examination. Nine cases of osteosarcoma had biopsy and preoperative chemotherapy at our department. There were 4 distal femur, 4 proximal tibia and 1 distal ulna. All case had initial MRI and PET scan and these were repeated after 2 cycles of chemotherapy. Under PET image parameters such as VOI (volume of interest), total activity, degree of necrosis and T/N (tumor/normal tissue) ratio were analyzed. There was a significant correlation between the calculated necrosis in PET and observed one on pathologic specimen (r2=0.78, p<0.05). Cross correlation among identified variables revealed meaningful result between T/N ration and tumor necrosis (r2=0.45, p<0.05). As the T/N ratio decrease, so much more the tumor necrosis was. F18 FDG PET scan could get objective data such as volume, degree of necrosis and total activity and was also useful in estimating the contribution of chemotherapy in tumor necrosis over the innate necrosis before treatment

  19. Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial.

    Science.gov (United States)

    Karoui, Mehdi; Rullier, Anne; Luciani, Alain; Bonnetain, Franck; Auriault, Marie-Luce; Sarran, Antony; Monges, Geneviève; Trillaud, Hervé; Le Malicot, Karine; Leroy, Karen; Sobhani, Iradj; Bardier, Armelle; Moreau, Marie; Brindel, Isabelle; Seitz, Jean François; Taieb, Julien

    2015-07-10

    In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22--ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and

  20. Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.

    Science.gov (United States)

    Hemdan, Tammer; Malmström, Per-Uno; Jahnson, Staffan; Segersten, Ulrika

    2015-12-01

    Neoadjuvant chemotherapy before cystectomy is recommended. To our knowledge the subset of patients likely to benefit has not been identified. We validate emmprin and survivin as markers of chemotherapy response. Tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry. Expression was categorized according to predefined cutoffs reported in the literature. Data were analyzed with the Kaplan-Meier method and Cox models. Patients in the chemotherapy cohort with negative emmprin expression had significantly higher down staging overall survival than those with positive expression (71% vs 38%, pemmprin expression was not associated with overall survival (46% vs 35%, p=0.23) or cancer specific survival (55% vs 51%, p=0.64). Emmprin negative patients had an absolute risk reduction of 25% in overall survival (95% CI 11-40) and a number needed to treat of 4 (95% CI 2.5-9.3). Survivin expression was not useful as a biomarker in this study. Limitations were the retrospective design and heterogeneity coupled with the time difference between the trials. Patients with emmprin negative tumors have a better response to neoadjuvant chemotherapy before cystectomy than those with positive expression. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  1. Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study

    Directory of Open Access Journals (Sweden)

    Filipe Ramos Barra

    Full Text Available Abstract Objective: To assess the feasibility of contrast-enhanced spectral mammography (CESM of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC. Materials and methods: In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM. We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. Results: The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively. The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886. The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598. Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88. Conclusion: CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

  2. A retrospective comparative exploratory study on two Methylentetrahydrofolate Reductase (MTHFR) polymorphisms in esophagogastric cancer: the A1298C MTHFR polymorphism is an independent prognostic factor only in neoadjuvantly treated gastric cancer patients

    International Nuclear Information System (INIS)

    Blank, Susanne; Kumar, Rajiv; Ott, Katja; Rachakonda, Sivaramakrishna; Keller, Gisela; Weichert, Wilko; Lordick, Florian; Langer, Rupert; Springfeld, Christoph; Bruckner, Thomas; Becker, Karen

    2014-01-01

    Methylentetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism and consequently could be an important factor for the efficacy of a treatment with 5-fluorouracil. Our aim was to evaluate the prognostic and predictive value of two well characterized constitutional MTHFR gene polymorphisms for primarily resected and neoadjuvantly treated esophagogastric adenocarcinomas. 569 patients from two centers were analyzed (gastric cancer: 218, carcinoma of the esophagogastric junction (AEG II, III): 208 and esophagus (AEG I): 143). 369 patients received neoadjuvant chemotherapy followed by surgery, 200 patients were resected without preoperative treatment. The MTHFR C677T and A1298C polymorphisms were determined in DNA from peripheral blood lymphozytes. Associations with prognosis, response and clinicopathological factors were analyzed retrospectively within a prospective database (chi-square, log-rank, cox regression). Only the MTHFR A1298C polymorphisms had prognostic relevance in neoadjuvantly treated patients but it was not a predictor for response to neoadjuvant chemotherapy. The AC genotype of the MTHFR A1298C polymorphisms was significantly associated with worse outcome (p = 0.02, HR 1.47 (1.06-2.04). If neoadjuvantly treated patients were analyzed based on their tumor localization, the AC genotype of the MTHFR A1298C polymorphisms was a significant negative prognostic factor in patients with gastric cancer according to UICC 6 th edition (gastric cancer including AEG type II, III: HR 2.0, 95% CI 1.3-2.0, p = 0.001) and 7 th edition (gastric cancer without AEG II, III: HR 2.8, 95% CI 1.5-5.7, p = 0.003), not for AEG I. For both definitions of gastric cancer the AC genotype was confirmed as an independent negative prognostic factor in cox regression analysis. In primarily resected patients neither the MTHFR A1298C nor the MTHFR C677T polymorphisms had prognostic impact. The MTHFR A1298C polymorphisms was an independent prognostic factor in patients

  3. Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

    Science.gov (United States)

    Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R

    2017-10-01

    To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a

  4. Suboptimal use of neoadjuvant chemotherapy in radical cystectomy patients: A population-based study.

    Science.gov (United States)

    Schiffmann, Jonas; Sun, Maxine; Gandaglia, Giorgio; Tian, Zhe; Popa, Ioana; Larcher, Alessandro; Meskawi, Malek; Briganti, Alberto; McCormack, Michael; Shariat, Shahrokh F; Montorsi, Francesco; Graefen, Markus; Saad, Fred; Karakiewicz, Pierre I

    2016-01-01

    We aimed to assess contemporary rates of neoadjuvant chemotherapy (NC) use. We relied on the Surveillance, Epidemiology and End Results (SEER)-Medicare database for non-metastatic, muscle-invasive (T2-T4a) urothelial carcinoma of the urinary bladder (UCUB) patients who underwent radical cystectomy (RC) between 1991 and 2009. Multivariable logistic regression analyses tested predictors of NC use, such as: T-stage, N-stage, year of diagnosis, age at diagnosis, gender, race, use of radiotherapy (RT), marital status, urban status, socioeconomic status, tumour grade, and Charlson comorbidity index (CCI). Overall, 5207 patients treated with RC were identified. Of those, 332 (6.4%) received NC. The rate of NC increased over time from 6.1% (1991) to 15.0% (2009) (pvs. T2: OR: 0.7; p=0.003), married status (OR: 1.5; p=0.006), and younger age at diagnosis (≥80 vs. 66-69: OR: 0.6; p=0.006) were associated with a higher odds of NC; all represented independent predictors of NC use. Neither race nor CCI demonstrated statistical significance. We reported lower than anticipated overall (6.4%) use of NC. Nonetheless, the rate increased from 6.1% (1991) to 15.0% (2009). Older and unmarried individuals were less likely to receive NC. NC rates were higher in T2 UCUB patients. Some of the observed discrepancies, such as lower use in unmarried individuals, may require correction. Better adherence to guidelines should be encouraged and implemented, especially based on the confirmed benefits of NC according to randomized, controlled trials. The study is limited by a retrospective design and limited variables.

  5. Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Baum, R.P.; Schmuecking, M.; Bonnet, R.; Presselt, N.; Przetak, C.; Junker, K.; Schneider, C.P.; Hoeffken, K.; Wendt, T.G.

    2002-01-01

    Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m 2 ) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m 2 ) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

  6. Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial – the PRODIGE 22 - ECKINOXE trial

    International Nuclear Information System (INIS)

    Karoui, Mehdi; Rullier, Anne; Luciani, Alain; Bonnetain, Franck; Auriault, Marie-Luce; Sarran, Antony; Monges, Geneviève; Trillaud, Hervé; Le Malicot, Karine; Leroy, Karen; Sobhani, Iradj; Bardier, Armelle; Moreau, Marie; Brindel, Isabelle; Seitz, Jean François; Taieb, Julien

    2015-01-01

    In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30 % of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22 - ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and

  7. Novel biomarkers in primary breast core biopsies to predict poor response to neoadjuvant chemotherapy and appearance of metastases.

    Science.gov (United States)

    Novell, Anna; Morales, Serafin; Valls, Joan; Panadés, Maria José; Salud, Antonieta; Iglesias, Edelmiro; Vilardell, Felip; Matias-Guiu, Xavier; Llombart-Cussac, Antonio

    2017-09-01

    Drug resistance has been one of the major obstacles limiting the success of cancer chemotherapy. In two thirds of breast cancer patients, large (>1cm) residual tumors are present after neoadjuvant chemotherapy (NCT). The residual tumor and involved nodes have been indicators of relapse and survival very important in breast cancer. The goal of this preliminary study was to assess the predictive significance of a panel of molecular biomarkers, related with the response to treatment or drug resistance to NCT, as determined on the diagnostic tumor. The expression of 22 proteins was examined using immunohistochemistry in tissue microarrays (TMA) from 115 patients of stage II-III breast cancer, treated with NCT. Among studied proteins, there are some that are anti-apoptotic, pro-proliferative, cancer stem cell markers and the Vitamin D Receptor. Other proteins are involved in the identification of molecular subtype, cell cycle regulation or DNA repair. Next, a predictive signature of poor response was generated from independent markers of predictive value. Tumors that expressed four or five conditions (biomarkers of chemoresistance with a determinated cutoff) were associated with a 9-fold increase in the chances of these patients of having a poor response to NCT. Additionally, we also found a worse prognostic signature, generated from independent markers of prognostic value. Tumors which expressed two or three conditions of worst prognostic, were associated with a 6-fold reduction in Distant Disease Free Survival. In conclusion, finding biomarkers of chemoresitance (ypTNM II-III) and metastases can become a stepping stone for future studies that will need to be assessed in a bigger scale.

  8. Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer.

    Science.gov (United States)

    Liu, Hui; Zhang, Tiantuo; Ye, Jin; Li, Hongtao; Huang, Jing; Li, Xiaodong; Wu, Benquan; Huang, Xubing; Hou, Jinghui

    2012-10-01

    Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

  9. Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

    Science.gov (United States)

    Mabuchi, Yasushi; Yahata, Tamaki; Kobayashi, Aya; Tanizaki, Yuko; Minami, Sawako; Ino, Kazuhiko

    2015-06-01

    Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  10. The role of quantitative estrogen receptor status in predicting tumor response at surgery in breast cancer patients treated with neoadjuvant chemotherapy.

    Science.gov (United States)

    Raphael, Jacques; Gandhi, Sonal; Li, Nim; Lu, Fang-I; Trudeau, Maureen

    2017-07-01

    Estrogen receptor (ER) negative (-) breast cancer (BC) patients have better tumor response rates than ER-positive (+) patients after neoadjuvant chemotherapy (NCT). We conducted a retrospective review using the institutional database "Biomatrix" to assess the value of quantitative ER status in predicting tumor response at surgery and to identify potential predictors of survival outcomes. Univariate followed by multivariable regression analyses were conducted to assess the association between quantitative ER and tumor response assessed as tumor size reduction and pathologic complete response (pCR). Predictors of recurrence-free survival (RFS) were identified using a cox proportional hazards model (CPH). A log-rank test was used to compare RFS between groups if a significant predictor was identified. 304 patients were included with a median follow-up of 43.3 months (Q1-Q3 28.7-61.1) and a mean age of 49.7 years (SD 10.9). Quantitative ER was inversely associated with tumor size reduction and pCR (OR 0.99, 95% CI 0.99-1.00, p = 0.027 and 0.98 95% CI 0.97-0.99, p Quantitative ER status is inversely associated with tumor response in BC patients treated with NCT. A cut-off of 60 and 80% predicts best the association with tumor size reduction and pCR, respectively. Therefore, patients with an ER status higher than the cut-off might benefit from a neoadjuvant endocrine therapy approach. Patients with pCR had better survival outcomes independently of their tumor phenotype. Further prospective studies are needed to validate the clinical utility of quantitative ER as a predictive marker of tumor response.

  11. ACR Appropriateness Criteria® Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer.

    Science.gov (United States)

    Slanetz, Priscilla J; Moy, Linda; Baron, Paul; diFlorio, Roberta M; Green, Edward D; Heller, Samantha L; Holbrook, Anna I; Lee, Su-Ju; Lewin, Alana A; Lourenco, Ana P; Niell, Bethany; Stuckey, Ashley R; Trikha, Sunita; Vincoff, Nina S; Weinstein, Susan P; Yepes, Monica M; Newell, Mary S

    2017-11-01

    Patients with locally advanced invasive breast cancers are often treated with neoadjuvant chemotherapy prior to definitive surgical intervention. The primary aims of this approach are to: 1) reduce tumor burden thereby permitting breast conservation rather than mastectomy; 2) promptly treat possible metastatic disease, whether or not it is detectable on preoperative staging; and 3) potentially tailor future chemotherapeutic decisions by monitoring in-vivo tumor response. Accurate radiological assessment permits optimal management and planning in this population. However, assessment of tumor size and response to treatment can vary depending on the modality used, the measurement technique (such as single longest diameter, 3-D measurements, or calculated tumor volume), and varied response of different tumor subtypes to neoadjuvant chemotherapy (such as concentric shrinkage or tumor fragmentation). As discussed in further detail, digital mammography, digital breast tomosynthesis, US and MRI represent the key modalities with potential to help guide patient management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  12. [A case of gastric cancer with N2 lymph node metastasis and pancreatic invasion effectively treated with docetax-el/S-1 as a neoadjuvant chemotherapy].

    Science.gov (United States)

    Omori, Keita; Wakabayashi, Kazuhiko; Ishibashi, Yuji; Ito, Yutaka

    2014-08-01

    A 74-year-old man was diagnosed with advanced gastric cancer(cStage III B). Laparotomy showed N2 lymph node metastasis and pancreatic invasion. Radical resection appeared impossible and was thus not performed. Chemotherapy consisting of a combination of S-1(80mg/m 2, 2-week administration and 1-week rest), and docetaxel(40mg/m2day 1)was administered with the expectation of tumor downstaging. A partial response(PR)was obtained after five courses of this regimen in which the primary lesion and lymph node swelling remarkably improved. Total gastrectomy, splenectomy, partial colectomy, and D2 lymph node dissection were then performed. Pathological analysis revealed very few cancer cells in the primary lesion and that the lymph nodes had become scarred and fibrotic. The histological appearance was judged to be grade 2 and the final diagnosis was T1N0H0P0CY0M0, fStage I A, curability A. Currently, more than 6 years and 4 months after the operation, the patient is alive without any evidence of recurrence. Thus, docetaxel/S-1 combination therapy was an effective neoadjuvant chemotherapy for this case of advanced gastric cancer.

  13. Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance)

    Energy Technology Data Exchange (ETDEWEB)

    Haffty, Bruce G., E-mail: hafftybg@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); McCall, Linda M. [Alliance Statistics and Data Center, Duke University, Durham, North Carolina (United States); Ballman, Karla V. [Weill Medical College of Cornell University, New York, New York (United States); McLaughlin, Sarah [Mayo Clinic, Jacksonville, Florida (United States); Jagsi, Reshma [University of Michigan, Ann Arbor, Michigan (United States); Ollila, David W. [University of North Carolina, Chapel Hill, North Carolina (United States); Hunt, Kelly K. [Department of Breast Surgical Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Buchholz, Thomas A. [MD Anderson Cancer Center, Houston, Texas (United States); Boughey, Judy C. [Mayo Clinic, Rochester, Minnesota (United States)

    2016-03-01

    Purpose: American College of Surgeons Oncology Group Z1071 was a prospective trial evaluating the false negative rate of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were made at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC. Methods and Materials: Of 756 patients enrolled from July 2009 to June 2011, 685 met all eligibility requirements. Surgical approach, RT, and radiation field design were analyzed based on presenting clinical and pathologic factors. Results: Of 401 node-positive patients, mastectomy was performed in 148 (36.9%), mastectomy with immediate reconstruction in 107 (26.7%), and breast-conserving surgery (BCS) in 146 patients (36.4%). Of the 284 pathologically node-negative patients, mastectomy was performed in 84 (29.6%), mastectomy with immediate reconstruction in 69 (24.3%), and BCS in 131 patients (46.1%). Bilateral mastectomy rates were higher in women undergoing reconstruction than in those without (66.5% vs 32.2%, respectively, P<.0001). Use of internal mammary RT was low (7.8%-11.2%) and did not differ between surgical approaches. Supraclavicular RT rate ranged from 46.6% to 52.2% and did not differ between surgical approaches but was omitted in 193 or 408 node-positive patients (47.3%). Rate of axillary RT was more frequent in patients who remained node-positive (P=.002). However, 22% of patients who converted to node-negative still received axillary RT. Post-mastectomy RT was more frequently omitted after reconstruction than mastectomy (23.9% vs 12.1%, respectively, P=.002) and was omitted in 19 of 107 patients (17.8%) with residual node-positive disease in the reconstruction group. Conclusions: Most clinically node-positive patients treated with NAC undergoing mastectomy receive RT. RT is less common in patients undergoing reconstruction. There

  14. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    Science.gov (United States)

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  15. Long-term results of a randomized controlled trial evaluating preoperative chemotherapy in resectable non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chen ZW

    2013-06-01

    Full Text Available Zhiwei Chen,* Qingquan Luo,* Hong Jian, Zhen Zhou, Baijun Cheng, Shun Lu, Meilin LiaoShanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equallyObjective: We aimed to evaluate whether preoperative chemotherapy provides benefits in the survival and prognosis of patients with non-small cell lung cancer (NSCLC in resectable stages I to IIIA, except T1N0. Methods: In this randomized, controlled trial, 356 patients with stage I (except for T1N0, II and IIIA NSCLC were assigned to either the preoperative chemotherapy plus surgery arm (179 patients or the primary surgery arm (177 patients. Both treatments were followed by adjuvant chemotherapy. The end point of this study included overall survival (OS, progression-free survival (PFS, and survival rate associated with clinical remission. Results: Statistical survival difference was found between the preoperative chemotherapy plus surgery arm and the surgery-alone arm. However, the median survival time (MST in the preoperative chemotherapy arm was lower than that of surgery-alone arm (MST, 45.42 months vs 57.59 months (P = 0.016. When comparing the effect of preoperative chemotherapy at each stage of NSCLC, a statistical survival difference was found in stage II NSCLC but not in stage I and IIIA (MST 40.86 months vs 80.81 months (P = 0.044. However, no statistically significant difference in PFS was noticed between the two arms, except for stage I NSCLC (hazard radio [HR] = 0.87; 95% CI, 0.561−1.629; P = 0.027. The survival rate was higher for patients who had clinical remission after preoperative chemotherapy, but the differences did not reach statistical significance (MST 42.10 months vs 35.33 months (P = 0.630. Conclusion: Preoperative chemotherapy did not show benefits in OS and PFS for stage I-IIIA NSCLC patients. Keywords: NSCLC, neoadjuvent, mitomycin, cisplatin, vindesine

  16. Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

    International Nuclear Information System (INIS)

    Kim, Jisun; Kim, Lee Su; Han, Sehwan; Nam, Seok Jin; Kang, Han-Sung; Kim, Seung Il; Yoo, Young Bum; Jeong, Joon; Kim, Tae Hyun; Kang, Taewoo; Kim, Sung-Won; Lim, Woosung; Jung, Yongsik; Lee, Jeong Eon; Kim, Ku Sang; Yu, Jong-Han; Chae, Byung Joo; Jung, So-Youn; Kang, Eunyoung; Choi, Su Yun; Moon, Hyeong-Gon; Noh, Dong-Young; Kim, Eun-Kyu; Han, Wonshik; Kim, Min-Kyoon; Paik, Nam-Sun; Jeong, Sang-Seol; Yoon, Jung-han; Park, Chan Heun; Ahn, Sei Hyun

    2014-01-01

    Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. ClinicalTrials.gov Identifier http://clinicaltrial.gov/ct2/show/NCT01589367?term

  17. Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial.

    Science.gov (United States)

    Denkert, C; Loibl, S; Müller, B M; Eidtmann, H; Schmitt, W D; Eiermann, W; Gerber, B; Tesch, H; Hilfrich, J; Huober, J; Fehm, T; Barinoff, J; Jackisch, C; Prinzler, J; Rüdiger, T; Erbstösser, E; Blohmer, J U; Budczies, J; Mehta, K M; von Minckwitz, G

    2013-11-01

    The proliferation marker Ki67 has been suggested as a promising cancer biomarker. As Ki67 needs an exact quantification, this marker is a prototype of a new generation of tissue-based biomarkers. In this study, we have systematically evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort. We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial. We used the standardized cutoff-finder algorithm for three end points [response to neoadjuvant chemotherapy (pCR), disease-free (DFS) and overall-survival (OS)]. The analyses were stratified for hormone receptor (HR) and HER2 status by molecular subtype radar diagrams (MSRDs). A wide range of Ki67 cut points between 3%-94% (for pCR), 6%-46% (for DFS) and 4%-58% (for OS) were significant. The three groups of Ki67 ≤ 15% versus 15.1%-35% versus >35% had pCR-rates of 4.2%, 12.8%, and 29.0% (P strength of this marker. MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer. The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers.

  18. Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer.

    Directory of Open Access Journals (Sweden)

    Sheng Chen

    Full Text Available BACKGROUND: To evaluate the relationship between body mass index (BMI and response to neoadjuvant chemotherapy (NCT for breast cancer among Chinese women. PATIENTS AND METHODS: A total of 307 eligible patients were assigned to receive four cycles of paclitaxel and carboplatin before standard surgery for breast cancer from 2007 to 2011 at Shanghai Cancer Hospital. The patients were categorized as obese, overweight, normal weight, or underweight based on BMI according to World Health Organization (WHO criteria. Pathological complete response (pCR was defined as no invasive cancer in the breast or axillary tissue. A logistic regression and the Chi-squared test were used for detecting the predictors of pCR and determining the relationship between BMI category and pCR rate in the subgroup analysis with respect to other variables. RESULTS: Categorical BMI, estrogen receptor (ER, and progesterone receptor (PR status were independent predictors of pCR according to the multivariate analysis. Patients with BMI≥25 were less likely to achieve a pCR to NCT compared with patients with BMI<25 (Odds ratio: 0.454, p = 0.033, multivariate analysis. In the subgroup analysis, the predictive value of BMI for pCR to NCT was significantly shown in post-menopausal patients (p = 0.004 and hormonal receptor status-negative patients (p = 0.038. The incidence of treatment-induced toxicity was similar among the different BMI categories. CONCLUSION: Higher BMI was associated with worse pCR to NCT. Further approaches to investigating the mechanism of this influence of BMI on treatment response and a more appropriate schedule for calculating NCT dose for high-BMI-patients should be considered.

  19. Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases

    Directory of Open Access Journals (Sweden)

    Hawkes Eliza A

    2012-08-01

    Full Text Available Abstract Background Surgery is often advocated in patients with resectable pulmonary metastases from colorectal cancer (CRC. Our study aims to evaluate peri-operative chemotherapy in patients with metastastic CRC undergoing pulmonary metastasectomy. Methods Patients treated for CRC who underwent pulmonary metastasectomy by a single surgeon were identified. Outcome measures included survival, peri-operative complications, radiological and histological evidence of chemotherapy-induced lung toxicities. Results Between 1997 and 2009, 51 eligible patients were identified undergoing a total of 72 pulmonary resections. Thirty-eight patients received peri-operative chemotherapy, of whom 9 received an additional biological agent. Five-year overall survival rate was 72% in the whole cohort - 74% and 68% in those who received peri-operative chemotherapy (CS and those who underwent surgery alone (S respectively. Five-year relapse free survival rate was 31% in the whole cohort - 38% and ≤18% in CS and S groups respectively. Only 8% had disease progression during neoadjuvant chemotherapy. There were no post-operative deaths. Surgical complications occurred in only 4% of patients who received pre-operative chemotherapy. There was neither radiological nor histological evidence of lung toxicity in resected surgical specimens. Conclusions Peri-operative chemotherapy can be safely delivered to CRC patients undergoing pulmonary metastasectomy. Survival in this selected group of patients was favourable.

  20. Comparison of long-term efficacy between intensity-modulated radiotherapy with concurrent chemotherapy and neoadjuvant chemotherapy followed by intensity-modulated radiotherapy with concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Guan Ying; Sun Xueming; Zeng Lei; Chen Chunyan; Han Fei; Lu Taixiang

    2014-01-01

    Objective: To compare the long-term efficacy between two radiochemotherapy regimens for locally advanced nasopharyngeal carcinoma (NPC): intensity-modulated radiotherapy with concurrent chemotherapy (CCRT) versus neoadjuvant chemotherapy (NACT) followed by CCRT. Methods: A retrospective analysis was performed on the clinical data of 278 patients with locally advanced NPC who were admitted to our hospital from 2001 to 2008. Of the 278 patients, 133 received CCRT, and 145 received NACT followed by CCRT (NACT + CCRT). Results: The follow-up rate was 96.6%. The 5-year overall survival (OS),distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and progression-free survival (PFS) were 78.1%, 78.0%, 90.6%, and 72.0%, respectively. There were no significant differences between the CCRT group and NACT + CCRT group in 5-year OS (79.9% vs. 76.4%, P=0.443), DMFS (77.1% vs. 78.9%, P=0.972), RFS (91.6% vs. 89.8%, P=0.475), and PFS (71.6% vs. 72.2%, P=0.731). Subgroup analysis showed that compared with CCRT, NACT + CCRT did not significantly improve 5-year RFS in T 3-4 N 0-1 patients (90.7% vs. 86.9%, P=0.376) and did not significantly improve 5-year DMFS in patients with advanced N-stage disease (57.6% vs. 69.7%, P=0.275). There were significantly higher numbers of individuals with neutropenia,decrease in hemoglobin, and upper gastrointestinal reactions in patients treated with NACT + CCRT than in those treated with CCRT (100 vs. 52, P=0.000; 64 vs. 35, P=0.010; 90 vs. 63, P=0.044). Conclusions: Compared with CCRT,NACT + CCRT does not significantly improve the prognosis in patients with locally advanced NPC and leads to significant increases in grade ≥ 3 toxicities (neutropenia, decrease in hemoglobin, and upper gastrointestinal reactions). The role of NACT in the treatment of locally advanced NPC needs further study. (authors)

  1. Phase II study of gemcitabine plus cisplatin chemotherapy combined with intensity modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Ou Dan; He Xiayun; Hu Chaosu; Ying Hongmei; Zhu Guopei

    2012-01-01

    Objective: To evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP) chemotherapy combined with intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: 71 patients (Stage III: 41, Stage IV A : 30) with locoregionally advanced NPC were entered this study. Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m 2 intravenously on d1-3 and gemcitabine 1000 mg/m 2 in 30 minutes intravenous infusion on days 1 and 8, every 3 weeks for 2 cycles. Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy. The prescription doses was 66.0-70.4 Gy to the gross tumor volume, 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume, 54 Gy to the low-risk clinical target volume. Results: The overall response rate to neoadjuvant chemotherapy was 91.2%, acute toxicity was mainly grade 1-2 myleosuppression. All patients completed IMRT. The median follow-up duration was 38 months. The 3-year nasopharyngeal local control, regional control, distant metastasis-free survival rate and overall survival rate were 93%, 99%, 91%, 90%, respectively. Severe late toxicities included grade 3 trismus in 1 patient, grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients, respectively. No grade 4 late toxicities were observed. Conclusions: The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated, convenient, effective, and warrants further studies of more proper cycles of GP regimen. (authors)

  2. Preoperative radio-chemotherapy for rectal cancer: Forecasting the next steps through ongoing and forthcoming studies; Chimioradiotherapie preoperatoire des cancers du rectum: ce que laissent presager les etudes en cours et a venir

    Energy Technology Data Exchange (ETDEWEB)

    Crehange, G.; Maingon, P. [Departement de radiotherapie, centre Georges-Francois-Leclerc, 1, rue du Professeur-Marion, 21000 Dijon (France); Bosset, J.F. [Service d' oncologie radiotherapie, CHU Jean-Minjoz, boulevard Flemming, 25000 Besancon (France)

    2011-10-15

    Protracted preoperative radio-chemotherapy with a 5-FU-based scheme, or a short course of preoperative radiotherapy without chemotherapy, are the standard neo-adjuvant treatments for resectable stage II-III rectal cancer. Local failure rates are low and reproducible, between 6 and 15% when followed with a 'Total Meso-rectal Excision'. Nevertheless, the therapeutic strategy needs to be improved: distant metastatic recurrence rates remain stable around 30 to 35%, while both sphincter and sexual sequels are still significant. The aim of the present paper was to analyse the ongoing trials listed on the following search engines: the Institut National du Cancer in France, the National Cancer Institute and the National Institute of Health in the United States, and the major cooperative groups. Keywords for the search were: 'rectal cancer', 'preoperative radiotherapy', 'phase II-III', 'preoperative chemotherapy', 'adjuvant chemotherapy' and 'surgery'. Twenty-three trials were selected and classified in different groups, each of them addressing a question of strategy: (1) place of adjuvant chemotherapy; (2) optimization of preoperative radiotherapy; (3) evaluation of new radiosensitization protocols and/or neo-adjuvant chemotherapy; (4) optimization of techniques and timing of surgery; (5) place of radiotherapy for non resectable or metastatic tumors. (authors)

  3. Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer

    Science.gov (United States)

    Tabchy, Adel; Valero, Vicente; Vidaurre, Tatiana; Lluch, Ana; Gomez, Henry; Martin, Miguel; Qi, Yuan; Barajas-Figueroa, Luis Javier; Souchon, Eduardo; Coutant, Charles; Doimi, Franco D; Ibrahim, Nuhad K; Gong, Yun; Hortobagyi, Gabriel N; Hess, Kenneth R; Symmans, W Fraser; Pusztai, Lajos

    2010-01-01

    Purpose We examined in a prospective, randomized, international clinical trial the performance of a previously defined 30-gene predictor (DLDA-30) of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil, doxorubicin, cyclophosphamide (T/FAC) chemotherapy, and assessed if DLDA-30 also predicts increased sensitivity to FAC-only chemotherapy. We compared the pCR rates after T/FAC versus FAC×6 preoperative chemotherapy. We also performed an exploratory analysis to identify novel candidate genes that differentially predict response in the two treatment arms. Experimental Design 273 patients were randomly assigned to receive either weekly paclitaxel × 12 followed by FAC × 4 (T/FAC, n=138), or FAC × 6 (n=135) neoadjuvant chemotherapy. All patients underwent a pretreatment FNA biopsy of the tumor for gene expression profiling and treatment response prediction. Results The pCR rates were 19% and 9% in the T/FAC and FAC arms, respectively (pcancers. PMID:20829329

  4. Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

    Science.gov (United States)

    Power, D G; Ilson, D H

    2009-11-01

    Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

  5. Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

    Directory of Open Access Journals (Sweden)

    Albouzidi Abderrahmane

    2011-09-01

    Full Text Available Abstract We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2 by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively. We conclude that resectable gastric carcinoma with overexpression of the c-erbB-2 protein should ideally be managed with perioperative combination of trastuzumab with chemotherapy. Further research to evaluate trastuzumab in combination with chemotherapy regimens in the perioperative and adjuvant setting is urgently needed.

  6. Preoperative balloon occluded arterial infusion chemotherapy for locally invasive bladder cancer. Accurate staging for bladder preservation

    International Nuclear Information System (INIS)

    Hayashi, Norio; Arima, Kiminobu; Kawamura, Juichi; Tochigi, Hiromi

    1999-01-01

    The possibility of bladder preservation by preoperative balloon occluded arterial infusion (BOAI) chemotherapy was studied in 111 patients with locally invasive bladder cancer. BOAI was performed by blocking the blood flow of the internal iliac artery and by performing intra-arterial infusion of adriamycin (50 mg/body) and cisplatin (100 mg/body). Before BOAI the clinical diagnosis was T2 in 36, T3a in 29, T3b in 27, T4 in 11 and after BOAI it was T0 in 1, T1 in 27, T2 in 25, T3a in 20, T3b in 20, and T4 in 10. Down staging was observed on diagnostic images in 46.6%. Thirty patients (27.0%) received transurethral resection of bladder tumor (TUR-Bt) and their bladder could be preserved. The 5-year cancer-specific survival rate was 100% in pT0 (n=9), 97.5% in pT1 (n=47), 79.9% in pT2 (n=21), 80.0% in pT3a (n=6), 39.9% in pT3b (n=18) and 51.9% in pT4 cases (n=9). For the bladder preservation, accurate staging diagnosis is required. Since 1992, endorectal magnetic resonance imaging (MRI) has been used in addition to imaging diagnosis for improving the accuracy of staging diagnosis. The accuracies of staging diagnosis with and without endorectal MRI were 62.5% and 44.0%, respectively. BOAI as a neoadjuvant chemotherapy has the possibility of bladder-preserving therapy in locally invasive bladder cancer. Also, the endorectal MRI can improve the accuracy of staging diagnosis, which is important for the bladder preservation. (author)

  7. Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes.

    Science.gov (United States)

    Yamaguchi, Hironori; Kitayama, Joji; Ishigami, Hironori; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Hata, Keisuke; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Ishihara, Soichiro; Sunami, Eiji; Watanabe, Toshiaki

    2015-11-15

    The effect of chemotherapy on peritoneal carcinomatosis (PC) of gastric cancer remains unclear. Recently, the intraperitoneal (IP) administration of taxanes [e.g., paclitaxel (PTX) and docetaxel (DOC)] during the perioperative period has shown promising results. Herein, we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results. IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h. The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects, making it ideal for IP chemotherapy. There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy (SPIC). In SPIC, patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery (CRS) until disease progression. Usually, a taxane dissolved in 500-1000 mL of saline at ordinary temperature is administered through an IP access port on an outpatient basis. According to phase I studies, the recommended doses (RD) are as follows: IP DOC, 45-60 mg/m(2); IP PTX [without intravenous (IV) PTX], 80 mg/m(2); and IP PTX (with IV PTX), 20 mg/m(2). Phase II studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%. A phase III study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011. The prognosis of patients who underwent CRS was better than that of those who did not; however, this was partly due to selection bias. Although several phase II studies have shown promising results, a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

  8. Differences in Response and Surgical Management with Neoadjuvant Chemotherapy in Invasive Lobular Versus Ductal Breast Cancer.

    Science.gov (United States)

    Truin, W; Vugts, G; Roumen, R M H; Maaskant-Braat, A J G; Nieuwenhuijzen, G A P; van der Heiden-van der Loo, M; Tjan-Heijnen, V C G; Voogd, A C

    2016-01-01

    This study was conducted to determine the impact of neoadjuvant chemotherapy (NAC) on the likelihood of breast-conserving surgery (BCS) performed for patients with invasive lobular breast carcinoma (ILC) and invasive ductal carcinoma (IDC). Female patients with a diagnosis of ILC or IDC in The Netherlands between July 2008 and December 2012 were identified through the population-based Netherlands Cancer Registry. A total of 466 ILC patients received NAC compared with 3622 IDC patients. Downstaging by NAC was seen in 49.7 % of the patients with ILC and in 69.6 % of the patients with IDC, and a pathologic complete response (pCR) was observed in 4.9 and 20.2 % of these patients, respectively (P Lobular histology was independently associated with a higher mastectomy rate (odds ratio 1.91; 95 % confidence interval 1.49-2.44). Among the patients with clinical T2 and T3 disease, BCS was achieved more often when NAC was administered in ILC as well as IDC. The patients with ILC receiving NAC were less likely to experience a pCR and less likely to undergo BCS than the patients with IDC. With regard to BCS, the impact of NAC for ILC patients was lower than for patients receiving surgery without NAC. However, despite the high number to treating in order to achieve BCS, a small subset of ILC patients, especially cT2 and cT3 patients, still may benefit from NAC.

  9. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    Energy Technology Data Exchange (ETDEWEB)

    Sclafani, Francesco; Peckitt, Clare [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Cunningham, David, E-mail: david.cunningham@rmh.nhs.uk [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Tait, Diana [The Royal Marsden NHS Foundation Trust, London (United Kingdom); Giralt, Jordi [Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona (Spain); Glimelius, Bengt [University of Uppsala, Uppsala (Sweden); Keränen, Susana Roselló [Biomedical Research Institute INCLIVA, Department of Hematology and Medical Oncology, University of Valencia (Spain); Bateman, Andrew [Southampton General Hospital, Cancer Sciences Unit, University of Southampton (United Kingdom); Hickish, Tamas [Poole Hospital NHS Foundation Trust, Department of Medical Oncology, Bournemouth University (United Kingdom); Tabernero, Josep [Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Department of Medical Oncology, Barcelona (Spain); Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian [The Royal Marsden NHS Foundation Trust, London (United Kingdom)

    2015-10-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term.

  10. Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial

    International Nuclear Information System (INIS)

    Sclafani, Francesco; Peckitt, Clare; Cunningham, David; Tait, Diana; Giralt, Jordi; Glimelius, Bengt; Keränen, Susana Roselló; Bateman, Andrew; Hickish, Tamas; Tabernero, Josep; Thomas, Janet; Brown, Gina; Oates, Jacqueline; Chau, Ian

    2015-01-01

    Objective: Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials: QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel incontinence was assessed using the modified Fecal Incontinence Severity Index questionnaire. Results: Compared to baseline, QoL scores during preoperative treatment were better for symptoms associated with the primary tumor in the rectum (blood and mucus in stool, constipation, diarrhea, stool frequency, buttock pain) but worse for global health status, role functioning, and symptoms related to the specific safety profile of each treatment modality. During follow-up, improved emotional functioning and lessened anxiety and insomnia were observed, but deterioration of body image, increased urinary incontinence, less sexual interest (men), and increased impotence and dyspareunia were observed. Cetuximab was associated with a deterioration of global health status during neoadjuvant chemotherapy but did not have any long-term detrimental effect. An improvement in bowel continence was observed after preoperative treatment and 3 years after sphincter-sparing surgery. Conclusions: Intensifying neoadjuvant treatment by administering induction systemic chemotherapy before chemoradiation therapy improves tumor-related symptoms and does not appear to have a significantly detrimental effect on QoL and BF, in both the short and the long term

  11. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    International Nuclear Information System (INIS)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner; Brunner, Thomas B.; Witzigmann, Helmut; Marti, Lukas; Bechstein, Wolf-Otto; Bruns, Christiane; Jungnickel, Henry; Schreiber, Stefan; Grabenbauer, Gerhard G.; Meyer, Thomas; Fietkau, Rainer

    2015-01-01

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [de

  12. CORRELATION BETWEEN CHEMOTHERAPY RESPONSE AND EXPRESSION PROFILES OF TRANSMEMBRANE PROTEINS: P-GLYCOPROTEIN (ABCB1, MRP2 (ABCC2, BCRP (ABCG2 IN PATIENTS WITH INVASIVE BREAST CANCER

    Directory of Open Access Journals (Sweden)

    К. Yu. Khristenko

    2016-01-01

    Full Text Available Overexpression of ABC drug transporters can cause multidrug resistance (MDR in cancer cells, which is a major obstacle in the success of cancer chemotherapy. Our study revealed a correlation between the expression of invasive breast cancer resistance-associated proteins, such as P-glycoprotein (ABCB1, MRP2 (ABCC2, BCRP (ABCG2 in tumor cells and pathologic response to neoadjuvant chemotherapy. The response to neoadjuvant chemotherapy was shown to be associated with a lack of BCRP expression in tumor cells. The pathologic tumor response was correlated with the presence of positive MRP2 expression and the expression level of P-glycoprotein in cells of invasive breast cancer. 

  13. Benefit of neoadjuvant chemotherapy for Siewert type II esophagogastric junction adenocarcinoma.

    Science.gov (United States)

    Hosoda, Kei; Yamashita, Keishi; Katada, Natsuya; Moriya, Hiromitsu; Mieno, Hiroaki; Sakuramoto, Shinichi; Kikuchi, Shiro; Watanabe, Masahiko

    2015-01-01

    Our objective was to clarify if preoperative chemotherapy was associated with improved survival in Japanese patients with Siewert type II adenocarcinoma of the esophagogastric junction. We retrospectively reviewed the medical records of 86 patients with Siewert type II adenocarcinoma who underwent R0 resection at the Kitasato University between 1997 and 2013. Cox regression analysis using a backward stepwise selection method was performed to identify independent prognostic factors for relapse-free survival (RFS). The median age was 67 years. The male:female ratio was 74:12. Right thoracic, left thoracic and transhiatal approaches were performed in 10, 10 and 66 patients, respectively, and perioperative transfusion in 16 patients. Preoperative chemotherapy was administered to 19 patients; out of these, 13 received chemotherapy using the DCS regimen (docetaxel 40 mg/m(2), day 1; cisplatin 60 mg/m(2), day 1; S-1 80-120 mg/body, days 1-14; every 28 days). A median of three cycles of preoperative DCS chemotherapy were used. Histological responses of 1b, 2, 3 and unknown grades were obtained in three, three, four and three patients, respectively. The 5-year RFS rate was 55%, and the median follow-up period was 36 months. Cox regression analysis regarding RFS identified (y)pN1-3 [hazard ratio (HR)=4.44; 95% confidence interval (CI)=1.98-11.27], performance of perioperative transfusion (HR=4.71; 95% CI=1.69-11.88) and no preoperative chemotherapy (HR=3.75; 95% CI=1.22-14.26) as significant and independent indicators of poor prognosis. Preoperative chemotherapy using DCS is potentially beneficial for Japanese patients with Siewert type II adenocarcinoma. Further prospective clinical studies are required to confirm our findings. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Non-randomized clinical study comparing chemotherapy plus radiotherapy with radiotherapy alone in neoadjuvant therapy for oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kayahara, Hiroaki; Okuda, Mamiko; Terakado, Nagaaki; Shintani, Satoru; Hamakawa, Hiroyuki [Ehime Univ., Shigenobu (Japan). School of Medicine

    2002-06-01

    Neoadjuvant therapy plays an important role for organ preservation and survival rate in the treatment of oral cancer. We clinically compared the effect of neoadjuvant radiotherapy and chemoradiotherapy in patients with oral cancer. We retrospectively examined 47 patients diagnosed with oral squamous cell carcinoma who underwent neoadjuvant therapy followed by curative surgery in the oral and maxillofacial surgery department of Ehime University Hospital. We divided them into two groups: radiotherapy alone (24 cases) and chemoradiotherapy (23 cases). The patients in the radiotherapy group underwent irradiation of 32.6{+-}5.0 Gy (mean {+-}SD). The patients in the chemoradiotherapy group received a low-dose fraction of cisplatin (8 mg/mm{sup 2}/day, 5 days a week; total dose: 139.4{+-}67.1 mg) and 5-fluorouracil (300 mg/mm{sup 2}/day, 5 days a week; total dose: 5,900{+-}1,839.8 mg) combined with simultaneous irradiation of 31.0{+-}3.2 Gy. None of the 24 patients had a complete response to radiotherapy alone and 12 (50%) had a partial response. Six (26%) of the 23 patients had a complete response to chemoradiotherapy and 12 (52%) had a partial response. The primary control rate (82.6%) to chemoradiotherapy was higher than that (67.5%) to radiotherapy alone although no significant difference was found. The 5-year survival rate was 64.3% in the radiotherapy group and 62.8% in the chemoradiotherapy group. The findings of the present study suggest that while the combination of radiation and cisplatin/5-fluorouracil in neoadjuvant therapy for oral cancer may not bring a significant benefit to improve survival rate, the primary local control rate is improved in comparison with radiotherapy alone. (author)

  15. Pattern of Tumor Shrinkage during Neoadjuvant Chemotherapy Is Associated with Prognosis in Low-Grade Luminal Early Breast Cancer.

    Science.gov (United States)

    Fukada, Ippei; Araki, Kazuhiro; Kobayashi, Kokoro; Shibayama, Tomoko; Takahashi, Shunji; Gomi, Naoya; Kokubu, Yumi; Oikado, Katsunori; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji; Ohno, Shinji; Hatake, Kiyohiko; Sata, Naohiro; Ito, Yoshinori

    2018-01-01

    Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion

  16. SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

    Directory of Open Access Journals (Sweden)

    Christine S. Higham

    2017-01-01

    Full Text Available Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1- associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST has been reported. Methods. We evaluated the objective response (OR rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%. Results. 34 NF1 (median age 33 years and 14 sporadic (median age 40 years MPNST patients enrolled. Five of 28 (17.9% evaluable NF1 MPNST patients had a partial response (PR, as did 4 of 9 (44.4% patients with sporadic MPNST. Stable disease (SD was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

  17. Clinicopathologic Comparison of High-Dose-Rate Endorectal Brachytherapy versus Conventional Chemoradiotherapy in the Neoadjuvant Setting for Resectable Stages II and III Low Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Jessica A. Smith

    2012-01-01

    Full Text Available Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT or intensity-modulated radiotherapy (IMRT versus high-dose-rate endorectal brachytherapy (EBT. Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls. Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P<0.001. There was a trend towards higher rate of pathologic CR for EBT (P=0.06. Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P=0.025. Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions. Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.

  18. Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women.

    Science.gov (United States)

    Martinelli, F; Signorelli, M; Bogani, G; Ditto, A; Chiappa, V; Perotto, S; Scaffa, C; Lorusso, D; Raspagliesi, F

    2016-10-01

    The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  19. Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

    Science.gov (United States)

    Bidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J; Lucci, Anthony; Naume, Bjørn; Horiguchi, Jun; Gisbert-Criado, Rafael; Sleijfer, Stefan; Toi, Masakazu; Garcia-Saenz, Jose A; Hartkopf, Andreas; Generali, Daniele; Rothé, Françoise; Smerage, Jeffrey; Muinelo-Romay, Laura; Stebbing, Justin; Viens, Patrice; Magbanua, Mark Jesus M; Hall, Carolyn S; Engebraaten, Olav; Takata, Daisuke; Vidal-Martínez, José; Onstenk, Wendy; Fujisawa, Noriyoshi; Diaz-Rubio, Eduardo; Taran, Florin-Andrei; Cappelletti, Maria Rosa; Ignatiadis, Michail; Proudhon, Charlotte; Wolf, Denise M; Bauldry, Jessica B; Borgen, Elin; Nagaoka, Rin; Carañana, Vicente; Kraan, Jaco; Maestro, Marisa; Brucker, Sara Yvonne; Weber, Karsten; Reyal, Fabien; Amara, Dominic; Karhade, Mandar G; Mathiesen, Randi R; Tokiniwa, Hideaki; Llombart-Cussac, Antonio; Meddis, Alessandra; Blanche, Paul; d'Hollander, Koenraad; Cottu, Paul; Park, John W; Loibl, Sibylle; Latouche, Aurélien; Pierga, Jean-Yves; Pantel, Klaus

    2018-04-12

    We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

  20. Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Riva, Francesca; Bidard, Francois-Clement; Houy, Alexandre; Saliou, Adrien; Madic, Jordan; Rampanou, Aurore; Hego, Caroline; Milder, Maud; Cottu, Paul; Sablin, Marie-Paule; Vincent-Salomon, Anne; Lantz, Olivier; Stern, Marc-Henri; Proudhon, Charlotte; Pierga, Jean-Yves

    2017-03-01

    In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 ( TP53 ) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS ( r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index ( P = 0.003), tumor grade ( P = 0.003), and stage ( P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free ( P < 0.001) and overall ( P = 0.006) survival. Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival. © 2016 American Association for Clinical Chemistry.

  1. Prognostic value of FDG-PET indices for the assessment of histological response to neoadjuvant chemotherapy and outcome in pediatric patients with Ewing sarcoma and osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Clement Bailly

    Full Text Available The objective of this retrospective work was to evaluate the prognostic value on histological response and survival of quantitative indices derived from FDG-PET performed before and after chemotherapy (CHT, in a homogeneous pediatric Ewing sarcoma (EWS and Osteosarcoma (OST population.Thirty-one patients with EWS and 31 with OST were included. All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had FDG-PET at diagnosis and after CHT, prior to surgery. Several parameters were evaluated: SUVmax, SUVpeak, SUVmean, metabolic tumor volume, total lesion glycolysis, 7 textural features and 3 shape features (SF. The segmentation was performed using an adaptive approach. Results were compared to histopathological regression of the resected tumor and to clinical follow-up for survival evaluation.For EWS, univariate analysis did not highlight any prognostic value on histological response, or survival regardless of all the considered metrics. For OST, only one of the SF, namely elongation, was significantly associated with PFS and OS on both univariate and multivariate analysis (PFS: p = 0.019, HR = 5.583; OS: p = 0.0062, HR = 7.113.Only elongation determined on initial FDG-PET has a potential interest as a prognostic factor of PFS and OS in pediatric OST patients. Unlike recent studies of the literature realized in adult population, all the metrics reveal limited additional prognostic value in pediatric EWS patients. This seems to reinforce the question of whether children experience different subtypes of the same pathologies than older patients, with different outcomes.

  2. Emphasis on neoadjuvant therapy for “resectable” pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Chang

    2015-05-01

    Full Text Available The treatment concept for pancreatic cancer is being transferred from “surgery first” to MDT model. The postoperative adjuvant treatment of pancreatic cancer can significantly improve the prognosis of patients and has become the standardized diagnostic and treatment practice; the value and significance of neoadjuvant therapy remains unclear. Limited clinical studies of “borderline resectable” pancreatic cancer have shown that neoadjuvant therapy can improve the R0 resection rate and improve the prognosis of patients, and it is recommended for clinical application. But the significance of neoadjuvant therapy in “resectable” pancreatic cancer is still controversial. There is a lack of consensus on indications, cycles, and regimens. It is necessary to carry out a series of prospective control studies to objectively evaluate the value of neoadjuvant therapy in improving the prognosis of “resectable” pancreatic cancer.

  3. Simple measurements on diffusion-weighted MR imaging for assessment of complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Pei-Qiang; Wu, Yao-Pan; Xie, Chuan-Miao; Wu, Pei-Hong [Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Imaging and Interventional Radiology, Guangzhou (China); An, Xin [Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Oncology, Guangzhou (China); Qiu, Xue; Kong, Ling-Heng; Liu, Guo-Chen; Pan, Zhi-Zhong; Ding, Pei-Rong [Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Colorectal Surgery, Guangzhou (China)

    2014-11-15

    To determine diagnostic performance of simple measurements on diffusion-weighted MR imaging (DWI) for assessment of complete tumour response (CR) after neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by signal intensity (SI) and apparent diffusion coefficient (ADC) measurements. Sixty-five patients with LARC who underwent neoadjuvant CRT and subsequent surgery were included. Patients underwent pre-CRT and post-CRT 3.0 T MRI. Regions of interest of the highest brightness SI were included in the tumour volume on post-CRT DWI to calculate the SI{sub lesion}, rSI, ADC{sub lesion} and rADC; diagnostic performance was compared by using the receiver operating characteristic (ROC) curves. In order to validate the accuracy and reproducibility of the current strategy, the same procedure was reproduced in 80 patients with LARC at 1.5 T MRI. Areas under the ROC curve for identification of a CR, based on SI{sub lesion}, rSI, ADC{sub lesion}, and rADC, respectively, were 0.86, 0.94, 0.66, and 0.71 at 3.0 T MRI, and 0.92, 0.91, 0.64, and 0.61 at 1.5 T MRI. Post-CRT DWI SI{sub lesion} and rSI provided high diagnostic performance in assessing CR and were significantly more accurate than ADC{sub lesion}, and rADC at 3.0 T MRI and 1.5 T MRI. (orig.)

  4. The role of neoadjuvant chemotherapy in the surgical management of women with breast cancer in a middle-income country

    Directory of Open Access Journals (Sweden)

    Cheng-Har Yip

    2017-03-01

    Full Text Available Neoadjuvant chemotherapy (NAC in women with large breast tumours can downsize tumours to allow for breast conservation surgery (BCS. The aim of this study is to compare the BCS rate between those who had NAC versus those who underwent surgery first and to determine the factors affecting response rate. 1,183 patients, who had surgery for breast cancer in a single institution from December 2012 to December 2015, were included in this study. 80 (6.8% patients had NAC. Patient and tumours characteristics, and type of surgery were compared between those who had surgery first or surgery after NAC. Variables affecting the response rate were analyzed. The BCS rate between the surgery first and the NAC group were similar (34.2% versus 35%. The pathological complete response (PCR rate, partial response rate and stable disease rate was 22.5%, 65% and 12.5%, respectively. PCR rate was not significantly affected by subtype of breast cancer, although there was a tendency for PCR to be higher in ER-negative (32.4%, PR-negative (26.1% HER2-positive (28.6%, HER2 overexpressing (37.5% and TNBC (22.7% tumours. NAC is able to downsize tumour to achieve BCS rate that is similar to those without NAC.

  5. Exploratory Cost-Effectiveness Analysis of Response-Guided Neoadjuvant Chemotherapy for Hormone Positive Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Anna Miquel-Cases

    Full Text Available Guiding response to neoadjuvant chemotherapy (guided-NACT allows for an adaptative treatment approach likely to improve breast cancer survival. In this study, our primary aim is to explore the expected cost-effectiveness of guided-NACT using as a case study the first randomized controlled trial that demonstrated effectiveness (GeparTrio trial.As effectiveness was shown in hormone-receptor positive (HR+ early breast cancers (EBC, our decision model compared the health-economic outcomes of treating a cohort of such women with guided-NACT to conventional-NACT using clinical input data from the GeparTrio trial. The expected cost-effectiveness and the uncertainty around this estimate were estimated via probabilistic cost-effectiveness analysis (CEA, from a Dutch societal perspective over a 5-year time-horizon.Our exploratory CEA predicted that guided-NACT as proposed by the GeparTrio, costs additional €110, but results in 0.014 QALYs gained per patient. This scenario of guided-NACT was considered cost-effective at any willingness to pay per additional QALY. At the prevailing Dutch willingness to pay threshold (€80.000/QALY cost-effectiveness was expected with 78% certainty.This exploratory CEA indicated that guided-NACT (as proposed by the GeparTrio trial is likely cost-effective in treating HR+ EBC women. While prospective validation of the GeparTrio findings is advisable from a clinical perspective, early CEAs can be used to prioritize further research from a broader health economic perspective, by identifying which parameters contribute most to current decision uncertainty. Furthermore, their use can be extended to explore the expected cost-effectiveness of alternative guided-NACT scenarios that combine the use of promising imaging techniques together with personalized treatments.

  6. Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

    Science.gov (United States)

    Nakatani, M; Migita, K; Matsumoto, S; Wakatsuki, K; Ito, M; Nakade, H; Kunishige, T; Kitano, M; Kanehiro, H

    2017-08-01

    Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients' nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients

  7. Retrospective analysis on prognostic impact of adjuvant chemotherapy in the patients with advanced and resectable oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Koike, Takeshi; Miyazawa, Hideki; Uehara, Shinobu; Kobayashi, Hiroichi; Kurashina, Kenji

    2006-01-01

    The effect of adjuvant chemotherapy on oral squamous cell carcinoma (SCC) is unclear mainly because there have been a few studies which evaluate the efficacy of adjuvant chemotherapy. The purpose of this retrospective study was to analyze the efficacy of adjuvant chemotherapy in the patients with advanced and resectable oral SCC. Forty-one patients in whom advanced SCC (stage III and IV) was completely removed were included in this study. The impact of multiple variables including T-classification, degree of differentiation, mode of invasion, number and level of cervical metastatic node, pre- and post-operative radiation therapy, neoadjuvant chemotherapy, and adjuvant chemotherapy on survival and control of local relapse or distant metastasis was assessed using the stepwise Cox proportional hazards model. The level of neck node metastasis (p<0.02) was a significant independent predictor for cause-specific survival and adjuvant chemotherapy was of borderline significance (p=0.07). The number of neck node metastasis (p<0.01) and adjuvant chemotherapy (p<0.01) were significantly related with disease free survival. The results of this retrospective study suggested that adjuvant chemotherapy had a significant benefit in improving disease free survival. (author)

  8. Accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC).

    Science.gov (United States)

    Mazzei, Maria Antonietta; Khader, Leila; Cirigliano, Alfredo; Cioffi Squitieri, Nevada; Guerrini, Susanna; Forzoni, Beatrice; Marrelli, Daniele; Roviello, Franco; Mazzei, Francesco Giuseppe; Volterrani, Luca

    2013-12-01

    To evaluate the accuracy of MDCT in the preoperative definition of Peritoneal Cancer Index (PCI) in patients with advanced ovarian cancer who underwent a peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant chemotherapy to obtain a pre-surgery prognostic evaluation and a prediction of optimal cytoreduction surgery. Pre-HIPEC CT examinations of 43 patients with advanced ovarian cancer after neoadjuvant chemotherapy were analyzed by two radiologists. The PCI was scored according to the Sugarbaker classification, based on lesion size and distribution. The results were compared with macroscopic and histologic data after peritonectomy and HIPEC. To evaluate the accuracy of MDCT to detect and localize peritoneal carcinomatosis, both patient-level and regional-level analyses were conducted. A correlation between PCI CT and histologic values for each patient was searched according to the PCI grading. Considering the patient-level analysis, CT shows a sensitivity, specificity, PPV, NPV, and an accuracy in detecting the peritoneal carcinomatosis of 100 %, 40 %, 93 % 100 %, and 93 %, respectively. Considering the regional level analysis, a sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 72 %, 80 %, 66 %, 84 %, and 77 %, respectively were obtained for the correlation between CT and histology. Our results encourage the use of MDCT as the only technique sufficient to select patients with peritoneal carcinomatosis for cytoreductive surgery and HIPEC on the condition that a CT examination will be performed using a dedicated protocol optimized to detect minimal peritoneal disease and CT images will be analyzed by an experienced reader.

  9. How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

    Science.gov (United States)

    Martinelli, F; Bogani, G; Ditto, A; Carcangiu, M; Papadia, A; Lecce, F; Chiappa, V; Lorusso, D; Raspagliesi, F

    2015-08-01

    Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

    Science.gov (United States)

    Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

    2018-05-03

    BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

  11. Nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy of breast cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Zong, Yu; Wu, Jiayi; Shen, Kunwei

    2017-03-07

    The value of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in neoadjuvant systemic therapy for breast cancer remains uncertain. Both electronic databases and proceedings of oncologic meetings were included in systematic literature search. Pooled rates of pathological complete response (pCR), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model to determine the effect of neoadjuvant nab-paclitaxel. Twenty-one studies with 2357 patients were included, 3 of which were randomized clinical trials. The aggregate pCR(ypT0/is ypN0) rate was 32% (95% CI 25-38%) in unselected breast cancer patients and variated in different subtypes. Within randomized clinical trials, the probability of achieving pCR was significantly higher in the nab-paclitaxel group than in the conventional taxanes group (OR = 1.383, 95%CI 1.141-1.676, p = 0.001). For non-hematological toxic effect, any grade and grade 3-4 peripheral sensory neuropathy occurred more frequently with nab-paclitaxel compared to paclitaxel (any grade, OR = 2.090, 95%CI 1.016-4.302, p = 0.045; grade3-4, OR = 3.766, 95%CI 2.324-6.100, p < 0.001). Hypersensitivity was more common with paclitaxel than nab-paclitaxel at any grade and grade 3-4. nab-paclitaxel is an effective cytotoxic drug in neoadjuvant treatment of breast cancer, especially for aggressive tumors in terms of pCR. Exchange of nab-paclitaxel for conventional taxanes could significantly improve pCR rate with reasonable toxicities.

  12. FLEEOX新辅助化疗对进展期胃癌患者营养状况的影响%Impact of Neoadjuvant FLEEOX Chemotherapy on Nutritional Status in Patients with Advanced Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    张才华; 李国立; 范朝刚; 王新颖; 李宁; 黎介寿

    2012-01-01

    Objective To investigate the effect of FLEEOX regiment on nutritional status of advanced gastric cancer patients after neoadjuvant chemotherapy. Methods Forty-eight cases of advanced gastric cancer patients from December 2010 to October 2011 in this hospital were included into. The indexes of body composition and the blood related nutritional indicators before and after neoadjuvant chemotherapy were determined. Results After neoadjuvant chemotherapy, the body weight, intracellular fluid, body mass index, protein, body fat, body cell mass, and arm circumference mildly decreased; extracellular fluid, body water content, inorganic salts, bone mineral content, non-fat group, skeletal muscle, and arm muscle circumference mildly increased, but the differences were not statistically significant (P>0. 05) . The blood albumin, prealbumin, total protein, transferrin, and lymphocytes decreased at different degrees down, but the differences were not statistically significant (P>0. 05) . Conclusion Patients have no obvious changes in nutritional status during chemotherapy of FLEEOX regiment.%目的 研究FLEEOX新辅助化疗方案对进展期胃癌患者营养状况的影响.方法 根据纳入和排除标准,共选择2010年12月至2011年10月期间我科收治的难以手术切除并进行了新辅助化疗的48例胃癌患者,利用机体组成分析仪测定化疗前、后机体组成成分的变化,同时检测血液相关营养学指标.结果 患者化疗后,体重、细胞内液、体重指数、蛋白质、体脂肪、体细胞群及上臂周长均较化疗前表现为略下降,而细胞外液、身体水分含量、无机盐、骨骼矿物质含量、非脂群、骨骼肌及上臂无脂肪周长较化疗前均表现为略轻度上升,但各项指标差异均无统计学意义(P>0.05);血液中白蛋白、前白蛋白、总蛋白、转铁蛋白及淋巴细胞均较化疗前出现不同程度下降,但差异均无统计学意义(P>0.05).结论 进展期胃癌患者接受化疗期间营养状况无明显变化,FLEEOX新辅助化疗未加重患者营养不良的状况.

  13. Chemotherapy dosing in achondroplastic dwarfism: a case report and review of literature.

    Science.gov (United States)

    Elsoueidi, R; Gresham, C; Michael, L; Chaney, D; Mourad, H

    2016-12-01

    CASE DESCRIPTION: A 74-year-old female with achondroplastic dwarfism was diagnosed with ER-, BR- and HER2- breast cancer. No guideline currently exists to direct chemotherapy dosing in this population. She received neoadjuvant chemotherapy based on body surface area utilizing actual height and weight with dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with the use of granulocyte colony-stimulating factor. Satisfactory clinical response and remission were achieved, and treatment proceeded without any significant toxicity or delays. In the absence of guideline recommendations, dosing chemotherapy based on actual height and weight in patients with achondroplastic dwarfism may be safe and appropriate. © 2016 John Wiley & Sons Ltd.

  14. Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

    Science.gov (United States)

    Noh, J M; Park, W; Suh, C-O; Keum, K C; Kim, Y B; Shin, K H; Kim, K; Chie, E K; Ha, S W; Kim, S S; Ahn, S D; Shin, H S; Kim, J H; Lee, H-S; Lee, N K; Huh, S J; Choi, D H

    2014-03-18

    To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

  15. Concurrent chemotherapy, accelerated hyperfractionated split course radiation therapy and surgery for esophageal cancer

    International Nuclear Information System (INIS)

    Becker, M.; Adelstein, D.J.; Rice, T.W.; Kirk, M.A. van; Kirby, T.J.; Koka, A.; Tefft, M.; Zuccaro, G.

    1996-01-01

    Purpose/Objectives: A prospective single arm trial was undertaken to determine the toxicity, the clinical and pathologic response rates and survival for patients with esophageal cancer treated with concurrent chemotherapy(CC) and accelerated hyperfractionated split course radiotherapy(AHFSCRT) followed by surgical resection. Materials and Methods: A prospective single arm trial was conducted between 1991 and 1995 for patients with T1-4, N0-1, M1(celiac or supraclavicular) adenocarcinoma or squamous cell carcinoma of the esophagus. A total of 74 patients entered onto the protocol, and 72 are eligible and evaluable. Neoadjuvant chemotherapy consisting of two cycles of Cisplatin(20mg/m2/day) and 5-fluorouracil (1000mg/m2/day) given concurrently with AHSCRT 1.5Gy BID (at least 6 hour between fractions) to 2400cGy and 2100cGy, with cycles 1 and 2 of chemotherapy respectively. Patients were staged/restaged with barium esophagram(BS), computerized tomograph of the chest(CAT), upper endoscopy(EGD) with ultrasound (EUS) and evaluated for surgical resection. A single adjuvant course of concurrent chemotherapy and AHSCRT was delivered for those patients who were pathologic partial responders(pPR). Results: Initial clinical staging revealed one patient stage I, 24 patients' stage IIA, 2 patients' with stage IIB, 34 patients' with stage III and 6 patients' with stage IV disease. Five patients could not be staged adequately. The toxicity to neoadjuvant therapy included nausea in 85% (grade 3 in 1%), esophagitis 90% (grade 3 in 18%), neutropenia grade 3 of 43% (with fever 17%), thrombocytopenia grade 4 in 10% and nephrotoxicity in 8%. There was one death due to neoadjuvant therapy. Of the 72 evaluable patients, 67 underwent surgery, and 65(90%) had a complete resection. Twenty-seven percent were pathologic complete responders, including 22% with adenocarcinoma and 36% with squamous cell carcinoma. Complete pathologic response after neoadjuvant therapy was accurately predicted by

  16. Oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy

    DEFF Research Database (Denmark)

    Klit, Anders; Tvedskov, Tove Filtenborg; Kroman, Niels

    2017-01-01

    BACKGROUND: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison...... to lumpectomy and mastectomy. MATERIAL AND METHODS: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early...... and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded. RESULTS: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively...

  17. The efficiency and safety of trastuzumab and lapatinib added to neoadjuvant chemotherapy in Her2-positive breast cancer patients: a randomized meta-analysis

    Directory of Open Access Journals (Sweden)

    Chen ZL

    2016-05-01

    Full Text Available Zhe-Ling Chen, Yan-Wei Shen, Shu-Ting Li, Chun-Li Li, Ling-Xiao Zhang, Jiao Yang, Meng Lv, Ya-Yun Lin, Xin Wang, Jin Yang Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China Background: The addition of human epidermal growth factor receptor 2 (Her2 therapies to neoadjuvant chemotherapy (NAC during treatment of Her2-positive breast cancer has been proposed as an effective way to improve the prognosis. However, the treatment outcomes of adding trastuzumab, lapatinib, or both to NAC were not unequivocal in randomized clinical trials. Based on these data, a meta-analysis was performed. Objective: The main objective was to evaluate the efficiency and safety of trastuzumab and lapatinib added to NAC for treatment of Her2-positive breast cancer. Methods: ClinicalTrials.gov and PubMed were searched for randomized clinical trials that compared trastuzumab, lapatinib, or both, added to NAC. The main endpoint was a pathologically complete response (pCR rate, in breast only or in breast and lymph nodes. The drug safety and the influence of hormone-receptor status, comparing the clinical response and the rate of breast conservation, were evaluated. Results: A total of eight publications were included in the primary analysis, designed as two or three subgroups. The cumulative cases were 2,349 and the analyses of all the clinical trials showed that the pCR rate was significantly higher in the group receiving trastuzumab than that in the group with lapatinib, either in breast only (P=0.001 or in breast and lymph nodes (P=0.0001. Similar results could be seen in comparisons of the combination versus trastuzumab group. Further studies of subgroups divided into hormone receptor-positive or-negative patients showed that the addition of trastuzumab or dual Her2-targeted therapy significantly improved the pCR rate in patients who were hormone-insensitive. Regarding the toxic

  18. PET/CT和CT在局部晚期肺癌新辅助化疗后淋巴结再分期中的比较研究%Evaluation of PET/CT versus CT in the mediastinal lymph node restaging of locally advanced lung cancer after neo-adjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    武雅琴; 冯冬杰; 许林; 蒋峰

    2011-01-01

    目的 评价PET/CT和CT在局部晚期(N2)非小细胞肺癌(NSCLC)新辅助化疗后淋巴结再分期中的敏感性、特异性和准确性.方法 将2005年11月至2010年5月118例经细胞学或病理学确诊的N2期NSCLC患者随机分为PET/CT组和CT组,每组59例,在新辅助化疗后分别行PET/CT和CT检查,对评价为缓解或稳定的病例根据显像结果评判纵隔淋巴结的转移情况,并与术后病理诊断相比较,从而对患者进行再分期.结果 CT组45例患者和PET/CT组51例患者评价为缓解或稳定.PET/CT组对N2期NSCLC新辅助化疗后淋巴结再分期的敏感性和特异性分别为87.5%、88.2%,明显高于CT组的56.0%和68.9%;PET/CT和CT的诊断准确性分别为85.0%和69.5%.CT组纵隔淋巴结分期的诊断相符率为66.7%,低于PET/CT组的85.7%.结论 PET/CT对于N2期NSCLC新辅助化疗后淋巴结的准确再分期有重要价值,其敏感性、特异性、准确性及纵隔淋巴结分期的诊断相符率均高于CT.%Objective To evaluate the sensitivity, specificity and accuracy of PET/CT versus CT in the restating of locally advanced (N2) non-small cell lung cancer (NSCLC) after neo-adjuvant chemotherapy. Methods One hundred and eighteen patients with cytology or pathology confirmed N2 stage NSCLC enrolled in this study were randomly divided into 2 groups (PET/CT and CT group) with 59 cases in each group. After the completion of neo-adjuvant chemotherapy, we used the PET/CT or CT to restage the mediastinal nodal lesions by comparing the corresponding pathologic staging for those whom confirmed with response or stable disease. Results Forty-five cases in CT group and fifty-one in PET/CT group achieved response or stable disease. The sensitivity, specificity and accuracy of mediastinal lymph node staging by PET/CT were 87. 5% , 88. 2% and 85. 0% , higher than 56.0% , 68.9% and 69. 5% in CT group. The diagnostic coincidence of mediastinal lymph node staging in PET/CT group was 85

  19. Sixteen years follow-up results of a randomized phase II trial of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast cancer: GOCS experience.

    Science.gov (United States)

    Leone, José Pablo; Leone, Julieta; Vallejo, Carlos Teodoro; Pérez, Juan Eduardo; Romero, Alberto Omar; Machiavelli, Mario Raul; Romero Acuña, Luis; Domínguez, María Ester; Langui, Mario; Fasce, Hebe Margot; Leone, Bernardo Amadeo; Ortiz, Eduardo; Iturbe, Julián; Zwenger, Ariel Osvaldo

    2014-01-01

    Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival.

  20. Targeted intraoperative radiotherapy tumour bed boost during breast-conserving surgery after neoadjuvant chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kolberg, Hans-Christian; Akpolat-Basci, Leyla; Stephanou, Miltiades [Marienhospital Bottrop gGmbH, Department of Gynecology and Obstetrics, Bottrop (Germany); Loevey, Gyoergy [BORAD, Bottrop (Germany); Fasching, Peter A. [University of Erlangen, Erlangen (Germany); Untch, Michael [Helios Klinikum Berlin-Buch, Berlin (Germany); Liedtke, Cornelia [University Hospital Schleswig-Holstein/Campus Luebeck, Luebeck (Germany); Bulsara, Max [University of Notre Dame, Fremantle (Australia); University College, London (United Kingdom); Vaidya, Jayant S. [University College, London (United Kingdom)

    2017-01-15

    The use of targeted intraoperative radiotherapy (TARGIT-IORT) as a tumour bed boost during breast-conserving surgery (BCS) for breast cancer has been reported since 1998. We present its use in patients undergoing breast conservation following neoadjuvant therapy (NACT). In this retrospective study involving 116 patients after NACT we compared outcomes of 61 patients who received a tumour bed boost with IORT during lumpectomy versus 55 patients treated in the previous 13 months with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence-free survival (LRFS), disease-free survival (DFS), distant disease-free survival (DDFS), breast cancer mortality (BCM), non-breast cancer mortality (NBCM) and overall mortality (OS) were compared. Median follow up was 49 months. The differences in LRFS, DFS and BCM were not statistically significant. The 5-year Kaplan-Meier estimate of OS was significantly better by 15% with IORT: IORT 2 events (96.7%, 95%CI 87.5-99.2), EBRT 9 events (81.7%, 95%CI 67.6-90.1), hazard ratio (HR) 0.19 (0.04-0.87), log rank p = 0.016, mainly due to a reduction of 10.1% in NBCM: IORT 100%, EBRT 89.9% (77.3-95.7), HR (not calculable), log rank p = 0.015. The DDFS was as follows: IORT 3 events (95.1%, 85.5-98.4), EBRT 12 events (69.0%, 49.1-82.4), HR 0.23 (0.06-0.80), log rank p = 0.012. IORT during lumpectomy after neoadjuvant chemotherapy as a tumour bed boost appears to give results that are not worse than external beam radiotherapy boost. These data give further support to the inclusion of such patients in the TARGIT-B (boost) randomised trial that is testing whether IORT boost is superior to EBRT boost. (orig.) [German] Die intraoperative Radiotherapie (TARGIT-IORT) als vorgezogener Boost im Rahmen der brusterhaltenden Therapie (BET) ist seit 1998 Gegenstand der wissenschaftlichen Diskussion. Wir praesentieren Daten zum Einsatz der IORT bei der BET nach neoadjuvanter Therapie (NACT). In diese retrospektive Analyse