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

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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.

Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

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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.

Neoadjuvant therapy for esophageal cancer. Indication and efficacy

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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)

Neoadjuvant chemotherapy in locally advanced colon cancer

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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....

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

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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)

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

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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.

Phase II study of gemcitabine plus cisplatin chemotherapy combined with intensity modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

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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)

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer

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Galsky, Matthew D; Pal, Sumanta K; Chowdhury, Simon

2015-01-01

). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved......BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had...... clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients...

Pediatric and Young Adult Nasopharyngeal Carcinoma Patients Treated With Preradiation Cisplatin and Docetaxel Chemotherapy

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Varan, Ali; Ozyar, Enis; Corapcioglu, Funda; Koeksal, Yavuz; Aydin, Burca; Yazici, Nalan; Akyuez, Canan; Bueyuekpamukcu, Muenevver

2009-01-01

Purpose: To evaluate treatment results for pediatric and young adult (aged 2 + docetaxel 75 mg/m 2 on Day 1 with premedication every 3 weeks. All patients were treated with fractionated external beam radiotherapy after chemotherapy to a median dose of 59.4 Gy (range, 54-59.4 Gy) to the primary disease and 40 Gy to the supraclavicular field with the clavicles shielded. Five children were monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy, and at follow-up. Results: The median age of the patients was 14 years (range, 9-20 years), with a male:female ratio of 6:4. Stage distribution was as follows: 2 patients had Stage IIb disease, 2 had Stage III, 4 had Stage IVa, and 2 had Stage IVb disease. After cisplatin+docetaxel chemotherapy 1 patient had a complete response, 5 had a partial response, 3 had stable disease, and 1 had disease progression. The 2-year overall survival rate in our series was 90% and the event-free survival rate was 70%. No major chemotherapy toxicity was observed. The EBV DNA titers were higher in 2 of the 5 monitored patients at the time of diagnosis. Conclusion: As neoadjuvant chemotherapy before radiotherapy, the cisplatin+docetaxel combination is safe for use in the treatment of childhood nasopharyngeal carcinoma

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

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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.

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

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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

Cisplatin, Gemcitabine, and Lapatinib as Neoadjuvant Therapy for Muscle-Invasive Bladder Cancer.

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Narayan, Vivek; Mamtani, Ronac; Keefe, Stephen; Guzzo, Thomas; Malkowicz, S Bruce; Vaughn, David J

2016-07-01

We sought to investigate the safety and efficacy of gemcitabine, cisplatin, and lapatinib (GCL) as neoadjuvant therapy in patients with muscle-invasive bladder cancer (MIBC) planned for radical cystectomy. Four cycles of GCL were administered as neoadjuvant therapy for patients with MIBC. Although initially designed as a phase II efficacy study with a primary endpoint of pathologic complete response at the time of radical cystectomy, the dose selected for investigation proved excessively toxic. A total of six patients were enrolled. The initial four patients received gemcitabine 1,000 mg/m(2) intravenously on days 1 and 8 and cisplatin 70 mg/m(2) intravenously on day 1 of each 21-day treatment cycle. Lapatinib was administered as 1,000 mg orally daily starting one week prior to the initiation of cycle 1 of gemcitabine and cisplatin (GC) and continuing until the completion of cycle 4 of GC. These initial doses were poorly tolerated, and the final two enrolled patients received a reduced lapatinib dose of 750 mg orally daily. However, reduction of the lapatinib dose did not result in improved tolerance or drug-delivery, and the trial was terminated early due to excessive toxicity. Grade 3/4 toxicities included diarrhea (33%), nausea/vomiting (33%), and thrombocytopenia (33%). The addition of lapatinib to GC as neoadjuvant therapy for MIBC was limited by excessive treatment-related toxicity. These findings highlight the importance of thorough dose-escalation investigation of combination therapies prior to evaluation in the neoadjuvant setting, as well as the limitations of determination of maximum tolerated dose for novel targeted combination regimens.

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

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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.

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

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

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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.

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

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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

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

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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.

Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

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

2000-10-01

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

The role of cisplatin in chemotherapy of advanced breast cancer

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Jurga, L; Misurova, E; Kovac, V [Department of Radiotherapy and Oncology, University Teaching Hospital, 04190 Kosice (Slovak Republic); Sevcikova, L [Department of Radiotherapy, Postgraduate School of Medicine, 81259 Bratislava (Slovak Republic)

1994-12-31

Cisplatin containing regimes as first-time, second-time or as third-line chemotherapy were administered in 26 and 36 patients, respectively. The overall response rate in patients on first-line chemotherapy was 53.9 %, in patients on on second or third-line chemotherapy 30.6 %. The differences both in overall and disease-free survival between patients on first-line and on second/third-line chemotherapy were statistically significant in favor of women treated with first-line chemotherapy (p = 0.05). Hematologic and non-hematologic toxicities were mild to moderate and were more pronounced in patients on second and third-line chemotherapy. The overall response date, disease-free survival and overall survival were significantly better and longer in the group of patients treated with `bolus` cisplatin in comparison to the group of patients treated with continuous venous infusion cisplatin. Our results confirm the activity of cisplatin-containing regimes (mainly CAP schedules) in patients with advanced breast cancer not only as first-line therapy but also in heavily pretreated patients by chemotherapy and/or radiation therapy and endocrine manipulation. (author) 10 tabs., 21 refs.

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,

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

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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.

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.

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)

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

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.

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

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...

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

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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.

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

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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.

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 ...

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 ...

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

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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.

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

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

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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

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.

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial

OpenAIRE

Crabb, Simon; Caddy, Joshua; Dunkley, Denise; Rajaram, Jessica; Ellis, Deborah; Hill, Stephanie; Whitehead, Amy; Huddart, Robert; Griffiths, Gareth; Kalevras, Michail

2018-01-01

Background: urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder...

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

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.

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

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.

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

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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.

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)

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.

Predictive Factors for Developing Venous Thrombosis during Cisplatin-Based Chemotherapy in Testicular Cancer.

Science.gov (United States)

Heidegger, Isabel; Porres, Daniel; Veek, Nica; Heidenreich, Axel; Pfister, David

2017-01-01

Malignancies and cisplatin-based chemotherapy are both known to correlate with a high risk of venous thrombotic events (VTT). In testicular cancer, the information regarding the incidence and reason of VTT in patients undergoing cisplatin-based chemotherapy is still discussed controversially. Moreover, no risk factors for developing a VTT during cisplatin-based chemotherapy have been elucidated so far. We retrospectively analyzed 153 patients with testicular cancer undergoing cisplatin-based chemotherapy at our institution for the development of a VTT during or after chemotherapy. Clinical and pathological parameters for identifying possible risk factors for VTT were analyzed. The Khorana risk score was used to calculate the risk of VTT. Student t test was applied for calculating the statistical significance of differences between the treatment groups. Twenty-six out of 153 patients (17%) developed a VTT during chemotherapy. When we analyzed the risk factors for developing a VTT, we found that Lugano stage ≥IIc was significantly (p = 0.0006) correlated with the risk of developing a VTT during chemotherapy. On calculating the VTT risk using the Khorana risk score model, we found that only 2 out of 26 patients (7.7%) were in the high-risk Khorana group (≥3). Patients with testicular cancer with a high tumor volume have a significant risk of developing a VTT with cisplatin-based chemotherapy. The Khorana risk score is not an accurate tool for predicting VTT in testicular cancer. © 2017 S. Karger AG, Basel.

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...

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

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Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

2013-09-01

Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH2 and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was 11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC50 values in ovarian cancer cells when compared with carboxylate surface dendrimers ( p cisplatin complexes resulted in a 7.0-fold increase ( p cisplatin chemotherapy of ovarian cancer.

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

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

Treatment results of nasopharyngeal carcinoma with chemotherapy (cisplatin and 5-fluorouracil) and radiation therapy

International Nuclear Information System (INIS)

Fuwa, Nobukazu; Kato, Eriko; Ito, Yosiyuki; Kikuti, Yuzo

1995-01-01

Sixteen patients with nasopharyngeal cancer were treated with a combination chemotherapy consisting of cisplatin and 5-fluorouracil and radiation therapy. Systemic chemotherapy with cisplatin (50 mg/m 2 , 2 days) and 5-fluorouracil (700 mg/m 2 , 5 days) was given successively with radiation therapy. The complications of chemotherapy were generally acceptable except one patient who was shocked by cisplatin. The survival rate was significantly improved compared with historical control cases. The main reason for this effectiveness was the improvement of localized control. The suppression of distant metastasis is the subject of future research. (author)

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.

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

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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

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...

Effect of neoadjuvant chemotherapy in hepatic steatosis.

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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.

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

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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

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...

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.

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

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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.

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

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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

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

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.

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...

Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

Science.gov (United States)

Ecke, Thorsten H

2015-01-01

The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

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.

An oncofetal glycosaminoglycan modification provides therapeutic access to Cisplatin-resistant bladder cancer

DEFF Research Database (Denmark)

Seiler, Roland; Oo, Htoo Zarni; Tortora, Davide

2017-01-01

the malaria parasite Plasmodium falciparum, we can target these sugar chains, and our results showed a significant antitumor effect in cisplatin-resistant bladder cancer. This novel treatment paradigm provides therapeutic access to bladder cancers not responding to cisplatin.......BACKGROUND: Although cisplatin-based neoadjuvant chemotherapy (NAC) improves survival of unselected patients with muscle-invasive bladder cancer (MIBC), only a minority responds to therapy and chemoresistance remains a major challenge in this disease setting. OBJECTIVE: To investigate the clinical...... significance of oncofetal chondroitin sulfate (ofCS) glycosaminoglycan chains in cisplatin-resistant MIBC and to evaluate these as targets for second-line therapy. DESIGN, SETTING, AND PARTICIPANTS: An ofCS-binding recombinant VAR2CSA protein derived from the malaria parasite Plasmodium falciparum (rVAR2...

Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

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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.

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

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

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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.

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

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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.

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

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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.

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

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.

Poly(amido)amine (PAMAM) dendrimer–cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

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Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath

2013-01-01

Dendrimer–cisplatin complexes were prepared using PAMAM dendrimers with terminal –NH 2 and –COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer–cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was ∼11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC 50 values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum–DNA adduct formation. Treatment with dendrimer–cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer

Poly(amido)amine (PAMAM) dendrimer-cisplatin complexes for chemotherapy of cisplatin-resistant ovarian cancer cells

Energy Technology Data Exchange (ETDEWEB)

Yellepeddi, Venkata Kashyap; Vangara, Kiran Kumar; Palakurthi, Srinath, E-mail: palakurthi@tamhsc.edu [Texas A and M Health Science Center, Irma Lerma Rangel College of Pharmacy (United States)

2013-09-15

Dendrimer-cisplatin complexes were prepared using PAMAM dendrimers with terminal -NH{sub 2} and -COOH groups as well as biotin-conjugated dendrimers. Preformulation parameters of dendrimer-cisplatin complexes were studied using differential scanning calorimetry (DSC) and inductively coupled plasma-mass spectrometry (ICP-MS). Cytotoxicity and mechanism of cytotoxicity of dendrimer-cisplatin complexes was investigated in OVCAR-3, SKOV, A2780 and cisplatin-resistant CP70 human ovarian cancer cell lines. The loading of cisplatin in dendrimers was {approx}11 % (w/w). PAMAM G4 dendrimers with amine surface groups (biotinylated and native) have shown 2.5- to 3.0-fold reduction in IC{sub 50} values in ovarian cancer cells when compared with carboxylate surface dendrimers (p < 0.05). A correlation was observed among cytotoxicity of the complexes, cellular uptake, and platinum-DNA adduct formation. Treatment with dendrimer-cisplatin complexes resulted in a 7.0-fold increase (p < 0.05) in expression of apoptotic genes (Bcl2, Bax, p53) and 13.2- to 27.1-fold increase (p < 0.05) in the activity of caspases 3, 8, and 9 in vitro. Results suggest that PAMAM dendrimers can be used as potential carrier for cisplatin chemotherapy of ovarian cancer.

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

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)

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.

Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy

NARCIS (Netherlands)

Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert

2017-01-01

Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore

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

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

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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.

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

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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

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.

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

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.

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

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

Statistical model for prediction of hearing loss in patients receiving cisplatin chemotherapy.

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Johnson, Andrew; Tarima, Sergey; Wong, Stuart; Friedland, David R; Runge, Christina L

2013-03-01

This statistical model might be used to predict cisplatin-induced hearing loss, particularly in patients undergoing concomitant radiotherapy. To create a statistical model based on pretreatment hearing thresholds to provide an individual probability for hearing loss from cisplatin therapy and, secondarily, to investigate the use of hearing classification schemes as predictive tools for hearing loss. Retrospective case-control study. Tertiary care medical center. A total of 112 subjects receiving chemotherapy and audiometric evaluation were evaluated for the study. Of these subjects, 31 met inclusion criteria for analysis. The primary outcome measurement was a statistical model providing the probability of hearing loss following the use of cisplatin chemotherapy. Fifteen of the 31 subjects had significant hearing loss following cisplatin chemotherapy. American Academy of Otolaryngology-Head and Neck Society and Gardner-Robertson hearing classification schemes revealed little change in hearing grades between pretreatment and posttreatment evaluations for subjects with or without hearing loss. The Chang hearing classification scheme could effectively be used as a predictive tool in determining hearing loss with a sensitivity of 73.33%. Pretreatment hearing thresholds were used to generate a statistical model, based on quadratic approximation, to predict hearing loss (C statistic = 0.842, cross-validated = 0.835). The validity of the model improved when only subjects who received concurrent head and neck irradiation were included in the analysis (C statistic = 0.91). A calculated cutoff of 0.45 for predicted probability has a cross-validated sensitivity and specificity of 80%. Pretreatment hearing thresholds can be used as a predictive tool for cisplatin-induced hearing loss, particularly with concomitant radiotherapy.

Expression of CD147 in advanced non-small cell lung cancer correlated with cisplatin-based chemotherapy resistance.

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Zeng, H Z; Qu, Y Q; Liang, A B; Deng, A M; Zhang, W J; Xiu, B; Wang, H; Wang, H

2011-01-01

CD147, a widely expressed cell surface glycoprotein in cancer, is associated with tumor invasiveness and chemotherapy resistance. Recently, CD147 is also regarded as a potential therapeutic target for cancer therapy. The aim of the study was to investigate CD147 expression in non-small cell lung cancer (NSCLC), and evaluate its correlation with cisplatin-based chemotherapy resistance. In this study, we examined immunohistochemically the expression of CD147 in 118 advanced NSCLC cases treated with cisplatin-based chemotherapy, and then the association of CD147 expression with clinicopathological characteristics was analyzed. Furthermore, RNA interference approach was used to silence CD147 expression in a cisplatin-resistant human lung cancer cell line A549/DDP, and the inhibition effect of cisplatin on tumor cells was assayed by MTT. In the overall series, positive CD147 expression was observed in 101/118 (85.6%) cases. A membranous CD147 pattern was identified in 76/101 (75.2%) of CD147 positive tumors. CD147 membranous expression,but not the overall CD147 expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced NSCLC patients. In vitro results showed that silencing CD147 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, our study indicated that membranous CD147 expression is a predictive factor of the response to cisplatin-based chemotherapies, and the use of CD147-targeted therapeutic adjuvants might be considered in the treatment of advanced NSCLC patients.

Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma

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Bang Soo-Mee

2006-01-01

Full Text Available Abstract Background Although numerous chemotherapeutic agents have been tested, the role of systemic chemotherapy for hepatocellular carcinoma (HCC has not been clarified. New therapeutic strategies are thus needed to improve outcomes, and we designed this study with new effective drug combination. Methods Twenty-nine patients with histologically-confirmed, metastatic HCC received a combination chemotherapy with doxorubicin 60 mg/m2 and cisplatin 60 mg/m2 on day 1, plus capecitabine 2000 mg/m2/day as an intermittent regimen of 2 weeks of treatment followed by a 1-week rest. Results The median age was 49 years (range, 32–64 and 19 patients were hepatitis B virus seropositive. Child-Pugh class was A in all patients and 4 had Zubrod performance status of 2. The objective response rate was 24% (95% CI 9–40 with 6 stable diseases. The chemotherapy was generally well tolerated despite one treatment-related death. Conclusion Combination chemotherapy with doxorubicin, cisplatin and capecitabine produced modest antitumor activity with tolerable adverse effects in patients with metastatic HCC.

The effects of multidisciplinary therapies, surgery plus gemcitabine, cisplatin and paclitaxel (GCP) chemotherapy, against advanced urothelial carcinoma

International Nuclear Information System (INIS)

Tanimoto, Ryuta; Saika, Takashi; Fujio, Kei

2008-01-01

Combination chemotherapy with Gemcitabine, Cisplatin and Paclitaxel (GCP) is an active and well-tolerated combination for the treatment of advanced urothelial carcinoma. There is no evidence that multidisciplinary therapy, surgery plus GCP chemotherapy, can improve survival for patients with advanced urothelial carcinoma. We retrospectively analyzed the tolerability and efficacy of multidisciplinary therapy, surgery plus GCP chemotherapy, against advanced urothelial carcinoma. In this institution, patients (pts) with histologically verified advanced urothelial carcinoma received 2-4 cycles of gemcitabine 1,200 mg/m 2 on days 1 and 8, cisplatin 70 mg/m 2 on day 1, and paclitaxel 80 mg/m 2 on days 1 and 8 prior or subsequent to surgery. Radiologic response was evaluated with computed tomography and magnetic resonance imaging. Between May 2003 and Oct 2007, 19 pts (8 pts as neoadjuvant therapy (group A) and 11 as adjuvant therapy (group B)) were analyzed. Median age was 57 years. All pts had Performance Status 0 or 1. Initial tumor, nodes and metastasis (TNM) stage was T3-4 N0 M0 in 5, T any N1-2 M0 in 9 and T any N any M1 in 5 pts. The chemotherapy was well tolerated with infrequent grade III/IV toxicity (neutropenia in 6 and anemia in 2, thrombocytopenia in 4 patients). Median follow-up was 18 months (4-47). By Oct 2007, 18 pts had undergone radical surgery (9 pts radical cystectomy, 8 pts nephroureterectomy, and 1 pt retroperitoneal lymph node dissection). In group A, the radiologic response rate was documented in 6 out of 8 accessible pts (75%), including 1 complete response (CR) and 1 pathological CR. Two out of 8 pts (25%) relapsed and died. In group B, 6 pts out 11 (55%) relapsed and 2 (18%) died of the cancer. Median estimated progression-free survival and median overall survival were 15.4 months and 19.9 months respectively. Multidisciplinary therapy, surgery plus GCP chemotherapy, is effective and tolerable even in cases of metastatic urothelial carcinoma. A

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...

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

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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

Thrombosis of abdominal aorta during cisplatin-based chemotherapy of testicular seminoma - a case report

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Gehrckens Ralf

2009-12-01

Full Text Available Abstract Background Vascular complications occurring during cisplatin-based chemotherapy of germ cell tumours are inadequately recognized to date. Case Presentation A 49 year old man with advanced seminoma underwent two courses of chemotherapy according to the PEB regimen. Upon restaging, two thrombotic deposits were noted in the descending part of the thoracic aorta and in the infrarenal abdominal aorta, respectively. Although thrombotic plaques caused aortic occlusion of about 30%, no clinical signs of malperfusion of limbs were registered. The patient was placed on anticoagulant therapy. Six months after completion of chemotherapy, thrombotic deposits had completely resolved. In the absence of other predisposing factors, it must be assumed that cisplatin-based chemotherapy represented a strong stimulus for arterial thrombosis in the aorta. Conclusions This is the first case of endo-aortic thrombosis during chemotherapy for testicular germ cell cancer. Providers of chemotherapy must be aware of arterial thrombosis even in young patients with testicular cancer.

Cisplatin-based chemotherapy changes the incidence of bilateral testicular cancer

NARCIS (Netherlands)

vanBasten, JPA; Hoekstra, HJ; vanDriel, MF; Sleijfer, DT; Droste, JHJ; Schraffordt Koops, H.

Background: The introduction of cisplatin-based chemotherapy has remarkably increased the survival of testicular cancer patients. With this success, the concern for a contraIateral testicular tumor has increased. The aim of this study was to investigate whether the risk for contralateral testicular

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

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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

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

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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.

Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

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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.

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

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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.

Amisulpride in the prevention of nausea and vomiting induced by cisplatin-based chemotherapy

DEFF Research Database (Denmark)

Herrstedt, Jørn; Summers, Yvonne; Daugaard, Gedske

2018-01-01

PURPOSE: The purpose of this study was to investigate the antiemetic effect of the dopamine D2- and dopamine D3-receptor antagonist, amisulpride, in patients receiving cisplatin-based chemotherapy. METHODS: This dose-finding, non-comparative study investigated the antiemetic effect and safety...... of increasing doses (2.5, 7.5 and 20 mg) of amisulpride against acute nausea and vomiting in the period 0-24 h after initiation of cisplatin-based chemotherapy. The 20 mg dose was also investigated in combination with the 5-HT3-receptor antagonist, ondansetron. The primary parameter was complete response (0...... interval: 65-94%) had a CR and 14/23 (61%) had no nausea at all. CONCLUSIONS: Amisulpride has antiemetic effect against cisplatin-induced acute nausea and vomiting. The effect against nausea is of particular interest. Randomised studies are warranted to further explore the effect and safety of amisulpride....

A randomized, double-blind, multicentre study comparing daily 2 and 5 mg of tropisetron for the control of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy

NARCIS (Netherlands)

Wymenga, ANM; vanderGraaf, WTA; Wils, JA; vanHeukelom, LS; vanderLinden, GHM; DullemondWestland, AC; Nooy, M; vanderHeul, C; deBruijn, KM; deVries, EGE

Background: This study compares efficacy safety and tolerability of 2 and 5 mg tropisetron in prevention of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy. Patients and methods: 152 chemotherapy-naive cancer patients were randomized in a double-blind

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

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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.

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 ...

Effects of Neoadjuvant Intraperitoneal/Systemic Chemotherapy (Bidirectional Chemotherapy for the Treatment of Patients with Peritoneal Metastasis from Gastric Cancer

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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.

Emmprin Expression Predicts Response and Survival following Cisplatin Containing Chemotherapy for Bladder Cancer: A Validation Study.

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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.

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

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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.

Non-randomized clinical study comparing chemotherapy plus radiotherapy with radiotherapy alone in neoadjuvant therapy for oral cancer

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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)

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

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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.

Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

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Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

2015-01-01

OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study.

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Wolfgang Hilbe

Full Text Available Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles.Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2 and docetaxel (75 mg/m2 d1 q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly. The primary endpoint was radiological response according to RECIST.40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95% underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months.Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected.EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.

Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy

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Timothy J. Pianta

2017-03-01

Full Text Available Background/Aims: Plasma cystatin C (pCysC may be superior to serum creatinine (sCr as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. Methods: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1, and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague–Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. Results: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16–34%], relative increases were ≥ 50% in 9 patients (35% for pCysC compared with 2 (8% for sCr (p = 0.04 and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC, but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. Conclusions: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

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

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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.

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

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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)

Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Randomized Phase 2 Trial of Neoadjuvant Preoperative Paclitaxel/Cisplatin/Radiation Therapy (RT) or Irinotecan/Cisplatin/RT in Esophageal Adenocarcinoma: Long-Term Outcome and Implications for Trial Design

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Kleinberg, Lawrence R., E-mail: kleinla@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Harvard T.H. Chan School of Public Health, Boston, Massachusetts (United States); Forastiere, Arlene A. [Department of Oncology, Johns Hopkins University, Baltimore, Maryland (United States); Keller, Steven M. [Department of Cardiovascular and Thoracic Surgery, Montefiore Medical Center, Bronx, NY (United States); Mitchel, Edith P. [Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Anne, Pramila Rani [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Benson, Al B. [Department of Medicine-Hematology/Oncology, Lurie Cancer Center, Northwestern University, Chicago, Illinois (United States)

2016-03-15

Purpose: Toxicity, pathologic complete response, and long-term outcomes are reported for the neoadjuvant therapies assessed in a randomized phase 2 Eastern Cooperative Oncology Group and American College of Radiology Imaging Network trial for operable esophageal adenocarcinoma, staged as II-IVa by endoscopy/ultrasonography (EUS). Methods and Materials: A total of 86 eligible patients began treatment. For arm A, preoperative chemotherapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 50 mg/m{sup 2}, on day 1, 8, 22, 29 during 45 Gy radiation therapy (RT), 1.8 Gy per day over 5 weeks. Adjuvant therapy was cisplatin, 30 mg/m{sup 2}, and irinotecan, 65 mg/m{sup 2} day 1, 8 every 21 days for 3 cycles. Arm B therapy was cisplatin, 30 mg/m{sup 2}, and paclitaxel, 50 mg/m{sup 2}, day 1, 8, 15, 22, 29 with RT, followed by adjuvant cisplatin, 75 mg/m{sup 2}, and paclitaxel, 175 mg/m{sup 2}, day 1 every 21 days for 3 cycles. Stratification included EUS stage and performance status. Results: In arm A, median overall survival was 35 months, and 5-, 6-, and 7-year survival rates were 46%, 39%, and 35%, respectively, whereas for arm B, they were 21 months and 27%, 27%, and 23%, respectively. Median progression- or recurrence-free survival (PFS) was 39.8 months with a 3-year PFS of 50% for arm A and 12.4 months (P=.046) with 3-year PFS of 28% for arm B. Eighty percent of the observed incidents of progression occurred within 19 months. Survival did not differ significantly by EUS and performance status strata. Conclusions: Long-term survival was similar for both arms and did not appear superior to results achieved with other standard regimens.

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

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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 �

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

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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.

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

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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

Relative Contributions of Radiation and Cisplatin-Based Chemotherapy to Sensorineural Hearing Loss in Head-and-Neck Cancer Patients

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Hitchcock, Ying J.; Tward, Jonathan D.; Szabo, Aniko; Bentz, Brandon G.; Shrieve, Dennis C.

2009-01-01

Purpose: To investigate the risk of sensorineural hearing loss (SNHL) in patients with head-and-neck cancer and treated with radiation therapy (RT) or concomitant cisplatin-based chemoradiation, the relationship among SNHL and radiation dose to the cochlea, the use of two common cisplatin dose regimens. Methods and Materials: A total of 62 head-and-neck cancer patients treated with curative intent were included in this prospective study. Of the patients, 21 received RT alone, 27 received 40 mg/m 2 weekly cisplatin, 13 received 100 mg/m 2 every 3 weeks during RT, and 1 received RT with weekly epidermal growth factor receptor inhibitor antibody. The effect of chemotherapy and RT dose on hearing was determined using a model that accounted for the age and variability between each ear for each patient. Results: We constructed a model to predict dose-dependent hearing loss for RT or cisplatin-based chemotherapy either alone or in combination. For patients only receiving RT, no significant hearing loss was found at doses to the cochlea of less than 40 Gy. Patients receiving 100 mg/m 2 or 40 mg/m 2 of cisplatin chemotherapy had an estimated +21.5 dB and +9.5 dB hearing loss at 8,000 Hz with low radiation doses (10 Gy), which rose to +38.4 dB and +18.9 dB for high radiation doses (40 Gy). Conclusions: Use of RT alone with doses of less than 40 Gy did not result in clinically significant hearing loss. High-frequency SNHL was profoundly damaged in patients who received concomitant cisplatin when doses of 100 mg/m 2 were used. The threshold cochlear dose for hearing loss with cisplatin-based chemotherapy and RT was predicted to be 10 Gy. The inner ear radiation dose constraints and cisplatin dose intensity should be considered in the treatment of advanced head-and-neck cancer

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

Usefulness of antiemetic therapy with aprepitant, palonosetron, and dexamethasone for lung cancer patients on cisplatin-based or carboplatin-based chemotherapy.

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Kitazaki, Takeshi; Fukuda, Yuichi; Fukahori, Susumu; Oyanagi, Kazuhiko; Soda, Hiroshi; Nakamura, Yoichi; Kohno, Shigeru

2015-01-01

The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy-induced nausea and vomiting (CINV) and the use of salvage treatment were assessed. The primary endpoints were the percentage of patients with a complete response (CR: no nausea and no salvage treatment) during the entire study period (5 days) after chemotherapy, during the acute phase (day 1), and during the delayed phase (days 2-5). CR rates for the entire period were 86 and 71% in patients receiving carboplatin-based and cisplatin-based chemotherapy, respectively. CR rates were respectively 98 and 100% in the acute phase versus 87 and 71% in the delayed phase. Most of the patients could ingest food throughout the entire period after chemotherapy. Assessment of various risk factors for acute and delayed CINV (gender, age, prior vomiting due to antineoplastic therapy, prior experience of motion sickness, and history of drinking) revealed no significant influence of these factors on the CR rate for the entire period in patients receiving either carboplatin-based or cisplatin-based chemotherapy. The present triple therapy can be recommended for supporting both carboplatin-based and cisplatin-based chemotherapy regimens.

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

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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.

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

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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.)

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

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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.

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

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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

Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.

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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

subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Neo-adjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08).

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Ruhstaller, T; Thuss-Patience, P; Hayoz, S; Schacher, S; Knorrenschild, J R; Schnider, A; Plasswilm, L; Budach, W; Eisterer, W; Hawle, H; Mariette, C; Hess, V; Mingrone, W; Montemurro, M; Girschikofsky, M; Schmidt, S C; Bitzer, M; Bedenne, L; Brauchli, P; Stahl, M

2018-04-04

This open-label, phase lll trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients were randomly assigned (1:1) to 2 cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary endpoint was progression-free survival (PFS). In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years (95% CI, 2.0 to not reached) with cetuximab and 2.0 years (95% CI, 1.5 to 2.8) with control (HR, 0.79; 95% CI, 0.58 to 1.07; P = .13). Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2 to 4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52 to 1.01; P = .055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31 to 0.90; P = .017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64 to 1.59, P = .97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. NCT01107639.

Induction Cisplatin and Fluorouracil-Based Chemotherapy Followed by Concurrent Chemoradiation for Muscle-Invasive Bladder Cancer

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Lin, C.-C.; Hsu, C.-H.; Cheng, Jason C.; Huang, C.-Y.; Tsai, Y.-C.; Hsu, F.-M.; Huang, K.-H.; Cheng, A.-L.; Pu, Y.-S.

2009-01-01

Purpose: To evaluate a multimodality bladder-preserving therapy in patients with muscle-invasive bladder cancer. Methods and Materials: Patients with stages T2-4aN0M0 bladder cancer suitable for cystectomy underwent radical transurethral resection and induction chemotherapy, followed by concurrent chemoradiotherapy (CCRT). Patients with a Karnofsky performance status (KPS) <80 or age ≥70 years underwent Protocol A: induction chemotherapy with three cycles of the cisplatin and 5-fluorouracil (CF) regimen, and CCRT with six doses of weekly cisplatin and 64.8 Gy radiotherapy given with the shrinking-field technique. Patients with KPS ≥80 and age <70 years underwent Protocol B: induction chemotherapy with three cycles of weekly paclitaxel plus the CF regimen, and CCRT with six doses of weekly paclitaxel and cisplatin plus 64.8 Gy radiotherapy. Interval cystoscopy was employed after induction chemotherapy and when radiotherapy reached 43.2 Gy. Patients without a complete response (CR) were referred for salvage cystectomy. Results: Among 30 patients (median, 66 years) enrolled, 17 and 13 patients underwent Protocol A and B, respectively. After induction chemotherapy, 23 patients achieved CR. Five (17%) of 7 patients without CR underwent salvage cystectomy. Overall, 28 patients (93%) completed the protocol treatment. Of 22 patients who completed CCRT, 1 had recurrence with carcinoma in situ and 3 had distant metastases. After a median follow-up of 47 months, overall and progression-free survival rate for all patients were 77% and 54% at 3 years, respectively. Of 19 surviving patients, 15 (79%) retained functioning bladders. Conclusions: Our protocols may be alternatives to cystectomy for selected patients who wish to preserve the bladder.

Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

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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.

Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.

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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.

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

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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

Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

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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

Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

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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

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

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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)

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

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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

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

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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

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

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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.

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

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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

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

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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.

The Benefit of Chemotherapy in Esophageal Cancer Patients With Residual Disease After Trimodality Therapy.

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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.

Chemoradiotherapy with or without consolidation chemotherapy using cisplatin and 5-fluorouracil in anal squamous cell carcinoma: long-term results in 31 patients

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Roh Jae

2008-01-01

Full Text Available Abstract Background The objectives of this study were to evaluate long-term results of concurrent chemoradiotherapy (CRT with 5-fluorouracil and cisplatin and the potential benefit of consolidation chemotherapy in patients with anal squamous cell carcinoma (ASCC. Methods Between January 1995 and February 2006, 31 patients with ASCC were treated with CRT. Radiotherapy was administered at 45 Gy over 5 weeks, followed by a boost of 9 Gy to complete or partial responders. Chemotherapy consisted of 5-fluorouracil (750 or 1,000 mg/m2 daily on days 1 to 5 and days 29 to 33; and, cisplatin (75 or 100 mg/m2 on day 2 and day 30. Twelve patients had T3–4 disease, whereas 18 patients presented with lymphadenopathy. Twenty-one (67.7% received consolidation chemotherapy with the same doses of 5-fluorouracil and cisplatin, repeated every 4 weeks for maximum 4 cycles. Results Nineteen patients (90.5% completed all four courses of consolidation chemotherapy. After CRT, 28 patients showed complete responses, while 3 showed partial responses. After a median follow-up period of 72 months, the 5-year overall, disease-free, and colostomy-free survival rates were 84.7%, 82.9% and 96.6%, demonstrating that CRT with 5-fluorouracil and cisplatin yields a good outcome in terms of survival and sphincter preservation. No differences in 5-year OS and DFS rates between patients treated with CRT alone and CRT with consolidation chemotherapy was observed. Conclusion our study shows that CRT with 5-FU and cisplatin, with or without consolidation chemotherapy, was well tolerated and proved highly encouraging in terms of long-term survival and the preservation of anal function in ASCC. Further trials with a larger patient population are warranted in order to evaluate the potential role of consolidation chemotherapy.

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

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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.)

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

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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.)

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

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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.

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

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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

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

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Lu, Hsueh-Ju; Yang, Chao-Chun; Wang, Ling-Wei; Chu, Pen-Yuan; Tai, Shyh-Kuan; Chen, Ming-Huang; Yang, Muh-Hwa; Chang, Peter Mu-Hsin

2015-01-01

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC. PMID:25793192

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

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Hsueh-Ju Lu

2015-01-01

Full Text Available Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC. We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0 months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%. Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%. No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC.

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

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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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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

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

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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

Systematic overview of preoperative (neoadjuvant) chemoradiotherapy trials in oesophageal cancer: Evidence of a radiation and chemotherapy dose response

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Geh, J. Ian; Bond, Simon J.; Bentzen, Soren M.; Glynne-Jones, Robert

2006-01-01

Background and purpose: Numerous trials have shown that pathological complete response (pCR) following preoperative chemoradiotherapy (CRT) and surgery for oesophageal cancer is associated with improved survival. However, different radiotherapy doses and fractionations and chemotherapy drugs, doses and scheduling were used, which may account for the differences in observed pCR and survival rates. A dose-response relationship may exist between radiotherapy and chemotherapy dose and pCR. Patients and methods: Trials using a single radiotherapy and chemotherapy regimen (5FU, cisplatin or mitomycin C-based) and providing information on patient numbers, age, resection and pCR rates were eligible. The endpoint used was pCR and the covariates analysed were prescribed radiotherapy dose, radiotherapy dosexdose per fraction, radiotherapy treatment time, prescribed chemotherapy (5FU, cisplatin and mitomycin C) dose and median age of patients within the trial. The model used was a multivariate logistic regression. Results: Twenty-six trials were included (1335 patients) in which 311 patients (24%) achieved pCR. The probability of pCR improved with increasing dose of radiotherapy (P=0.006), 5FU (P=0.003) and cisplatin (P=0.018). Increasing radiotherapy treatment time (P=0.035) and increasing median age (P=0.019) reduced the probability of pCR. The estimated α/β ratio of oesophageal cancer was 4.9 Gy (95% confidence interval (CI) 1.5-17 Gy) and the estimated radiotherapy dose lost per day was 0.59 Gy (95% CI 0.18-0.99 Gy). One gram per square metre of 5FU was estimated to be equivalent to 1.9 Gy (95% CI 0.8-5.2 Gy) of radiation and 100 mg/m 2 of cisplatin was estimated to be equivalent to 7.2 Gy (95% CI 2.1-28 Gy). Mitomycin C dose did not appear to influence pCR rates (P=0.60). Conclusions: There was evidence of a dose-response relationship between increasing protocol prescribed radiotherapy, 5FU and cisplatin dose and pCR. Additional significant factors were radiotherapy

Significant renoprotective effect of telbivudine during preemptive antiviral therapy in advanced liver cancer patients receiving cisplatin-based chemotherapy: a case-control study.

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Lin, Chih-Lang; Chien, Rong-Nan; Yeh, Charisse; Hsu, Chao-Wei; Chang, Ming-Ling; Chen, Yi-Cheng; Yeh, Chau-Ting

2014-12-01

Cisplatin is a known nephrotoxic agent requiring vigorous hydration before use. However, aggressive hydration could be life-threatening. Therefore, in cirrhotic patients with advanced hepatocellular carcinoma (HCC) under cisplatin-based chemotherapy, the risk of nephrotoxicity increased. Because previous studies showed that long-term telbivudine treatment improved renal function in chronic hepatitis B virus (HBV) infected patients, we conducted a case-control study to evaluate the clinical outcome of telbivudine preemptive therapy in HBV-related advanced HCC patients treated by combination chemotherapy comprising 5-fluorouracil, mitoxantrone and cisplatin (FMP). From June 2007 to March 2012, 60 patients with HBV-related advanced HCC, all receiving the same FMP chemotherapy protocol, were enrolled. Of them, 20 did not receive any antiviral therapy, whereas the remaining 40 patients (sex and age matched) received telbivudine preemptive therapy. Progressive decrease of aminotransferase levels (p 100 ml/min (n = 34), the median overall survival was significantly longer in the telbivudine-treated group (12.1 vs. 4.9 months; p = 0.042). Preemptive use of telbivudine significantly prevented eGFR deterioration caused by cisplatin-based chemotherapy in HBV-related advanced HCC. In patients with initially sufficient eGFR level, telbivudine treatment was associated with a longer overall survival.

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

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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.

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.

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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.

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

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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)

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

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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.

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

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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

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

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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.

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.

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

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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

Randomized Clinical Trial of Weekly vs. Triweekly Cisplatin-Based Chemotherapy Concurrent With Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

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Ryu, Sang-Young, E-mail: ryu@kcch.re.kr [Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Won-Moo; Kim, Kidong [Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Park, Sang-Il [Department of Gynecologic Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol [Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Cho, Chul-Koo [Department of Radiation Oncology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Nam, Byung-Ho [Cancer Biostatistics Branch, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Lee, Eui-Don [Department of Gynecologic Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of)

2011-11-15

Purpose: To compare compliance, toxicity, and outcome of weekly and triweekly cisplatin administration concurrent with radiotherapy in locally advanced cervical cancer. Methods and Materials: In this open-label, randomized trial, 104 patients with histologically proven Stage IIB-IVA cervical cancer were randomly assigned by a computer-generated procedure to weekly (weekly cisplatin 40 mg/m{sup 2}, six cycles) and triweekly (cisplatin 75 mg/m{sup 2} every 3 weeks, three cycles) chemotherapy arms during concurrent radiotherapy. The difference of compliance and the toxicity profiles between the two arms were investigated, and the overall survival rate was analyzed after 5 years. Results: All patients tolerated both treatments very well, with a high completion rate of scheduled chemotherapy cycles. There was no statistically significant difference in compliance between the two arms (86.3% in the weekly arm, 92.5% in the triweekly arm, p > 0.05). Grade 3-4 neutropenia was more frequent in the weekly arm (39.2%) than in the triweekly arm (22.6%) (p = 0.03). The overall 5-year survival rate was significantly higher in the triweekly arm (88.7%) than in the weekly arm (66.5%) (hazard ratio 0.375; 95% confidence interval 0.154-0.914; p = 0.03). Conclusions: Triweekly cisplatin 75-mg/m{sup 2} chemotherapy concurrent with radiotherapy is more effective and feasible than the conventional weekly cisplatin 40-mg/m{sup 2} regimen and may be a strong candidate for the optimal cisplatin dose and dosing schedule in the treatment of locally advanced cervical cancer.

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

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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

Adjuvant chemotherapy for osteosarcoma.

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Eilber, F R; Rosen, G

1989-08-01

present to minimally include high-dose methotrexate, Adriamycin, and cisplatin. It would also appear from several of these reports that not only is the adjuvant use of these chemotherapeutic agents indicated, but that the preoperative use of these agents has had significant advantages. The neoadjuvant chemotherapy begins the essential systemic chemotherapy at a very early stage, allows histologic assessment of treatment effect, permits altering drug regimens postoperative, and in many reported trials has allowed less than amputative surgery (limb salvage) to be performed. Finally, close follow-up of patients with osteosarcoma has therapeutic value.(ABSTRACT TRUNCATED AT 400 WORDS)

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

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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.

Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

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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

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

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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.

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

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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.

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

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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

Two cycles of cisplatin-based chemotherapy for low-volume stage II seminoma: results of a retrospective, single-center case series.

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Pichler, Renate; Leonhartsberger, Nicolai; Stöhr, Brigitte; Horninger, Wolfgang; Steiner, Hannes

2012-01-01

To report on the oncological outcome and toxicity of patients treated with 2 cycles of cisplatin-based chemotherapy for low-volume metastatic stage II seminoma. We retrospectively identified a case series of 15 patients with seminoma stage IIA (26.7%) and IIB (73.3%) who underwent chemotherapy consisting of 2 cycles of cisplatin, etoposide and bleomycin (PEB) (cisplatin 20 mg/m(2) on days 1-5, etoposide 100 mg/m(2) on days 1-5, bleomycin 30 mg on days 1, 8 and 15) according to patient preference (refusing a 3rd cycle of PEB) or institutional practice in the last decades. Complete staging before chemotherapy was available in all patients. Patient age, the side and diameter of the primary tumor, the size of the lymph nodes before and after chemotherapy, acute and late toxicity of chemotherapy, the incidence of second malignancies, the relapse-free rate and cancer-specific mortality were recorded. Chemotherapy was well tolerated and no episode of febrile neutropenia occurred. Thrombocytopenia grade 4 was not seen in any patient, while leukopenia grade 4 was observed in 4 (26.6%) patients. The mean (range) lymph node size decreased significantly from 2.54 cm (1.1-4.0) before chemotherapy to 0.75 cm (0.4-2.2) after chemotherapy (p < 0.001). After a median (range) follow-up of 60 (13-185) months, no patient had relapsed, no patient had died as a result of seminoma and second malignancy was seen in only 1 (6.6%) patient. These excellent long-term results from a retrospective case series of 2 cycles of PEB in stage IIA/IIB seminoma patients represent a hint for further research with a view to reducing treatment burden. However, these incidental findings should be studied in prospective trials prior to drawing any conclusions. Copyright © 2013 S. Karger AG, Basel.

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

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

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

Epirubicin, oxaliplatin, and capectabine is just as "MAGIC"al as epirubicin, cisplatin, and fluorouracil perioperative chemotherapy for resectable locally advanced gastro-oesophageal cancer

Directory of Open Access Journals (Sweden)

Bhawna Sirohi

2014-01-01

Full Text Available Background: The perioperative use of epirubicin, cisplatin, and fluorouracil (ECF significantly improves outcomes in patients with gastric and gastro-oesophageal (GO cancers but is cumbersome to administer. Given the equivalence of epirubicin, oxaliplatin, and capectabine (EOX with ECF in advanced setting, we analyzed the compliance, efficacy, and toxicity of perioperative EOX in resectable but locally advanced cancers. Methods: This is a retrospective analysis of prospectively maintained database of patients treated between January 2012 and September 2013 at Tata Memorial Centre. Patients were planned to receive 3# of neoadjuvant (NA and 3# of adjuvant EOX (intravenous epirubicin 50 mg/m 2 D1, oxaliplatin 130 mg/m 2 , on D1, capecitabiine 1250 mg/m 2 D1-21 every 21 days. On completion of NA therapy, patients were planned to undergo gastrectomy and D2 lymphadenectomy. Results: A total of 99 patients (76% males, median age 51 years were treated with perioperative EOX. Preoperatively, 93% patients completed EOX. Post-NA chemotherapy, 4 patients progressed, 1 patient died and 94 were taken up for surgery. Of these, 9 were inoperable and 85 patients underwent radical surgery. Of these, 71% (60/85 were able to complete three cycles of adjuvant EOX. The compliance to complete all 6 cycles of perioperative chemotherapy was 64%. Grade 3 and 4 toxicities were comparable to the MAGIC dataset apart from higher number of diarrhea in our patients. Conclusions: In patients with resectable GO adenocarcinoma, it is possible to deliver the MAGIC-type perioperative chemotherapy with EOX with better compliance, toxicity, and efficacy rates.

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

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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

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

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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.

[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.

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

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

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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)

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.

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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.

Superior mesenteric artery syndrome following initiation of cisplatin-containing chemotherapy: a case report

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Ushiki Atsuhito

2012-01-01

Full Text Available Abstract Introduction Superior mesenteric artery syndrome is a rare cause of upper intestinal obstruction resulting from compression of the duodenum by the superior mesenteric artery and abdominal aorta. Case presentation We describe a case of superior mesenteric artery syndrome in a 61-year-old Japanese man with non-small cell lung cancer who had been treated with cisplatin-containing chemotherapy and had lost 7 kg in weight. The diagnosis was confirmed by the typical findings of abdominal computed tomography showing distended stomach resulting from compression of the third portion of the duodenum and reduction of an aortomesenteric distance and aortomesenteric angle. Conclusions This case highlights the importance of considering the possibility of superior mesenteric artery syndrome in patients treated with chemotherapy, especially those presenting with a low body mass index and showing weight loss during chemotherapy.

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

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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.

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

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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.

Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

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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

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer: Intraperitoneal chemotherapy with taxanes.

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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.

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

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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

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

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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.

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

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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)

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

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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).

Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

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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

Benefit of neoadjuvant chemotherapy for Siewert type II esophagogastric junction adenocarcinoma.

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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.

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

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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

Arterial occlusion precipitated by cisplatinbased chemotherapy

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Joseph, D.; Dubashi, B.; Karthikeyan, B.; Jain, A.

2010-01-01

Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

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

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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

[Influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin].

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Shen, Congxiang; Liu, Yanhui; Wen, Zhong; Yang, Keke; Li, Guanxue; Zhang, Shenhua; Zhang, Xinyu

2015-06-23

To explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. Transfected nasopharyngeal carcinoma 5-8F cell lines with pCDH-CMV-PinX1-copGFP vector constructed by lentivirus to generate Lenti-PinX1-5-8F cells containing PinX1 gene, using Lenti-Ctrl-5-8F cell (blank vector without PinX1 gene was used to transfect 5-8F cell lines) and 5-8F cell as controls. Expression of PinX1 gene, telomerase activity, the inhibition of cancer cells proliferation, combined anticancer effect with Cisplatin and the expression of lung resistance protein (LRP) and Bcl-2 were detected with fluorescent quantitation polymerase chain reaction (PCR), flow cytometry, thiazolyl blue (MTT) method, areole test, Western blot and drug sensitivity test, respectively, in four groups (Lenti-PinX1-5-8F cell + Cisplatin, Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell) so as to explore the influence and mechanism of PinX1 gene on the chemotherapy sensitivity of nasopharyngeal carcinoma cells in response to Cisplatin. The telomerase activity in Lenti-PinX1-5-8F cell (0.146 ± 0.004) was lower than those in the other two control cells (Lenti-Ctrl-5-8F cell: 0.967 ± 0.016, 5-8F cell: 1.000 ± 0.034, both P Cisplatin after lower level telomerase activity induced by PinX1 gene. Proliferation index (PI) (%) in Lenti-PinX1-5-8F cell + Cisplatin (14.39 ± 3.66) was also less than the other groups (Lenti-PinX1-5-8F cell, Cisplatin and 5-8F cell groups, 32.97 ± 3.00, 31.18 ± 4.24 and 47.19 ± 4.19, all P Cisplatin, which may be mediated by the down-regulation of telomerase activity and the inhibition of LRP and Bcl-2 gene in nasopharyngeal carcinoma cells.

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

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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

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.

A Multinational Study to Measure the Value that Patients with Cancer Place on Improved Emesis Control Following Cisplatin Chemotherapy

OpenAIRE

George Dranitsaris; Pauline Leung; Renoto Ciotti; Ana Ortega; Maria Spinthouri; Lycurgus Liaropoulos; Roberto Labianca; Antonello Quadri

2001-01-01

Background: The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively. Objective: To measure the value that patients with cancer place on improved emesis control and quality of life. Design: ...

Results of the conservative treatment associating radiotherapy and concomitant chemotherapy in the bladder filtering cancers

International Nuclear Information System (INIS)

Salem, N.; Bladou, F.; Gravis, G.; Karsenty, G.; Tallet, A.; Lopez, L.; Alzieu, C.; Serment, G.

2004-01-01

Full text of publication follows: purpose: to describe outcome of patients with muscle-invasive bladder carcinoma treated with multimodality therapy in our institution from 1993 to 2002. Patients and methods: the charts of sixty patients with T2-4, N0-1, M0 treated with TURBT followed by a chemo-radiotherapy combination were retrospectively reviewed: 22 received neo-adjuvant chemotherapy (CMV/MVAC) followed by concomitant chemo-radiotherapy (weakly cisplatin/carbo-platin or a cisplatin and 5-fluorouracil association) and the other 38 concomitant chemo-radiotherapy alone. Radiotherapy delivered a median dose of 45 Gy to the pelvis and 65 Gy to the bladder in a mono-fractionated or twice a day fractionation scheme. Follow-up evaluations included cystoscopy with biopsies at regular intervals. Salvage cystectomy was recommended in case of local persistent tumor or bladder relapse. Results: median follow-up was 48.5 months (10-126 months). 82% (18/22) of the patients receiving neo-adjuvant chemotherapy had 2 or more cycles and 85% (51/60) got the concomitant chemotherapy as planned. Radiotherapy was completed in 56 patients. Twenty-eight patients relapsed either locally (14 did not achieve local complete response after chemo-radiation and 6 had true local relapse during follow-up) or at distant sites. Actuarial 5-year disease-specific survival and freedom from local and distant relapse rate are respectively 54% and 42%. Actuarial local control rate with intact bladder was 56% at 5-year. When separated according to stage and grade, patients with T2/3 grade 2 tumors had significantly better chance of remaining relapse-free than the others (p = 0.045). Salvage cystectomy (n = 11) for isolated local failure in this population achieved limited results. Conclusion: our experience shows that a significant number of patients will achieve long survival with their bladder intact after multimodality therapy. (authors)

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

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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.

New developments in cisplatin chemotherapy for cancer

OpenAIRE

力石, 秀実

2005-01-01

Cisplatin is one of the most potent and widely used anticancer agents for the treatment of various solid cancers. Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, thereby activating apoptosis. However, the development of resistance (acquired or intrinsic) to cisplatin is a major clinical problem. Several mechanisms are implicated in cisplatin resistance, including decreased intracellular drug accumulation, increased levels of cellular thiols, increased...

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.

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

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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.

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

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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

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

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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).

A multinational study to measure the value that patients with cancer place on improved emesis control following cisplatin chemotherapy.

Science.gov (United States)

Dranitsaris, G; Leung, P; Ciotti, R; Ortega, A; Spinthouri, M; Liaropoulos, L; Labianca, R; Quadri, A

2001-01-01

The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively. To measure the value that patients with cancer place on improved emesis control and quality of life. Willingness-to-pay analysis. Five study sites in Canada, Italy, Spain and Greece. 245 patients with cancer either receiving chemotherapy with cisplatin or who had received cisplatin-based chemotherapy within the previous 6 months. After background information had been presented, patients were asked to define the maximum that they would pay per day for a drug that reduced their risk of acute and delayed (days 2 to 5) emesis by 20 and 30%, respectively. Costs were converted to US dollars ($US) using year 2000 exchange rates. For a 20% improvement in acute emesis, Canadian, Italian and Spanish patients with cancer were willing to pay $US46, $US34 and $US63 per day, respectively, compared with $US8 for patients from Greece (p < 0.001). For a 30% improvement in delayed emesis, Canadian, Italian and Spanish patients with cancer were also willing to pay more than their Greek counterparts (SUS41, $US31, $US50 and $US9 daily for 4 days, respectively; p < 0.001). These significant differences in patient value between countries remained, even after adjusting for socioeconomic variables and previous history of emesis. There are substantial cultural differences in how patients with cancer value benefit and improved quality of life. Since the majority of the world's population resides outside North America and Western Europe, there may be a need to re-evaluate perceived levels of patient benefit and measures of quality of life.

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.

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

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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

Clinical Significance of POU5F1P1 rs10505477 Polymorphism in Chinese Gastric Cancer Patients Receving Cisplatin-Based Chemotherapy after Surgical Resection

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Lili Shen

2014-07-01

Full Text Available This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1 rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023. Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations.

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.

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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

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.

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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

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

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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.

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.

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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

Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

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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.

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

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Ruff P

2018-02-01

Full Text Available Paul Ruff,1,2 Herbert Cubasch,2,3 Maureen Joffe,2,4 Evan Rosenbaum,5 Nivashni Murugan,2,3 Ming-Chih Tsai,2,3 Oluwatosin Ayeni,2 Katherine D Crew,5–7 Judith S Jacobson,6,7 Alfred I Neugut5–7 1Division of Medical Oncology, Department of Internal Medicine, University of the Witwatersrand, Faculty of Health Sciences, 2Noncommunicable Diseases Research Division, Wits Health Consortium, University of the Witwatersrand, Faculty of Health Sciences, 3Department of Surgery, Chris Hani Baragwanath Academic Hospital and University of the Witwatersrand, Faculty of Health Sciences, 4MRC Developmental Pathways of Health Research Unit, Department of Paediatrics, University of Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; 5Department of Medicine, College of Physicians and Surgeons, Columbia University, 6Herbert Irving Comprehensive Cancer Center, Columbia University, 7Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA Background: 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. Methods: 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

Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

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Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

2010-01-01

PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...... samples were evaluated for selected biomarkers. Results Six (22%) of 28 patients achieved pathologic complete responses, including both patients with BRCA1 germline mutations;18 (64%) patients had a clinical complete or partial response. Fourteen (50%) patients showed good pathologic responses (Miller...

GTSE1 expression represses apoptotic signaling and confers cisplatin resistance in gastric cancer cells

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Subhash, Vinod Vijay; Tan, Shi Hui; Tan, Woei Loon; Yeo, Mei Shi; Xie, Chen; Wong, Foong Ying; Kiat, Zee Ying; Lim, Robert; Yong, Wei Peng

2015-01-01

Platinum based therapy is commonly used in the treatment of advanced gastric cancer. However, resistance to chemotherapy is a major challenge that causes marked variation in individual response rate and survival rate. In this study, we aimed to identify the expression of GTSE1 and its correlation with cisplatin resistance in gastric cancer cells. Methylation profiling was carried out in tissue samples from gastric cancer patients before undergoing neoadjuvent therapy using docetaxel, cisplatin and 5FU (DCX) and in gastric cancer cell lines. The correlation between GTSE1 expression and methylation in gastric cancer cells was determined by RT-PCR and MSP respectively. GTSE1 expression was knocked-down using shRNA’s and its effects on cisplatin cytotoxicity and cell survival were detected by MTS, proliferation and clonogenic survival assays. Additionally, the effect of GTSE1 knock down in drug induced apoptosis was determined by western blotting and apoptosis assays. GTSE1 exhibited a differential methylation index in gastric cancer patients and in cell lines that correlated with DCX treatment response and cisplatin sensitivity, respectively. In-vitro, GTSE1 expression showed a direct correlation with hypomethylation. Interestingly, Cisplatin treatment induced a dose dependent up regulation as well as nuclear translocation of GTSE1 expression in gastric cancer cells. Knock down of GTSE1 enhanced cisplatin cytotoxity and led to a significant reduction in cell proliferation and clonogenic survival. Also, loss of GTSE1 expression caused a significant increase in P53 mediated apoptosis in cisplatin treated cells. Our study identifies GTSE1 as a biomarker for cisplatin resistance in gastric cancer cells. This study also suggests the repressive role of GTSE1 in cisplatin induced apoptosis and signifies its potential utility as a therapeutic target for better clinical management of gastric cancer patients. The online version of this article (doi:10.1186/s12885

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

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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.

A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy.

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Nakashima, Kazuhisa; Murakami, Haruyasu; Yokoyama, Kouichi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Nishiyama, Fumie; Kikugawa, Mami; Kaneko, Masayo; Iwamoto, Yumiko; Koizumi, Satomi; Mori, Keita; Isobe, Takeshi; Takahashi, Toshiaki

2017-09-01

The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Simultaneous radiochemotherapy in cervical cancer: recommendations for chemotherapy

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Dunst, J.; Haensgen, G.

2001-01-01

Background: Simultaneous radiochemotherapy has recently been demonstrated to be superior to radiation alone in the treatment of cervical cancer. The objective of this article is to summarize the data of major randomized trials and to derive recommendations for daily clinical practice. Materials and Methods: We have analyzed the data from seven randomized trials in the recent literature in which radiotherapy alone as standard treatment has been compared to simultaneous radiochemotherapy. Four trials used cisplatin-based chemotherapy regimens, 5-FU, mitomycin C and epirubicin were used each in one trial. Results: All trials demonstrated some improvement in survival which was significant in the studies with cisplatin-based chemotherapy regimens. The survival benefit resulted mainly from an improvement in local control whereas chemotherapy had only a small and insignificant effect on distant metastases. Thus, the main action of chemotherapy is ''radiosensitization''. Cisplatin as single drug yielded comparable results as compared to combined regimens although the cisplatin dose was lower in the studies with combination chemotherapy. For the definitive treatment of locally advanced cancers, monotherapy with cisplatin can be recommended. Mitomycin C offers an attractive alternative to cisplatin in patients with contraindications for cisplatin. For postoperative radiochemotherapy, a combination of cisplatin/5-FU should be used because data with cisplatin alone are lacking so far. Simultaneous radiochemotherapy should also be considered for the curative treatment of local recurrences. Conclusions: The addition of simultaneous chemotherapy to radiotherapy is indicated in the vast majority of patients with cervical cancers who are treated with curative intent. (orig.) [de

Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study.

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Croitoru, Adina; Gramaticu, Iulia; Dinu, Ioana; Gheorghe, Liana; Alexandrescu, Sorin; Buica, Florina; Luca, Ioana; Becheanu, Gabriel; Herlea, Vlad; Simionov, Iulia; Hrehoret, Doina; Lupescu, Ioana; Popescu, Irinel; Diculescu, Mircea

2012-09-01

This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.

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)

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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

Intensity-modulated radiotherapy with simultaneous modulated accelerated boost technique and chemotherapy in patients with nasopharyngeal carcinoma

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Fareed, Muhammad M; AlAmro, Abdullah S; Bayoumi, Yasser; Tunio, Mutahir A; Ismail, Abdul S; Akasha, Rashad; Mubasher, Mohamed; Al Asiri, Mushabbab

2013-01-01

To present our experience of intensity-modulated radiotherapy (IMRT) with simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Sixty eight patients of NPC were treated between April 2006 and December 2011 including 45 males and 23 females with mean age of 46 (range 15–78). Stage distribution was; stage I 3, stage II 7, stage III 26 and stage IV 32. Among 45 (66.2%) evaluated patients for presence of Epstein-Barr virus (EBV), 40 (88.8%) were positive for EBV. Median radiation doses delivered to gross tumor volume (GTV) and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume (CTV) and 50.4 Gy to clinically negative neck. In addition 56 (82.4%) patients with bulky tumors (T4/N2+) received neoadjuvant chemotherapy 2–3 cycles (Cisplatin/Docetaxel or Cisplatin/Epirubicin or Cisplatin/5 Flourouracil). Concurrent chemotherapy with radiation was weekly Cisplatin 40 mg/m 2 (40 patients) or Cisplatin 100 mg/m 2 (28 patients). With a median follow up of 20 months (range 3–43), one patient developed local recurrence, two experienced regional recurrences and distant failure was seen in 3 patients. Estimated 3 year disease free survival (DFS) was 94%. Three year DFS for patients with EBV was 100% as compared to 60% without EBV (p = 0.0009). Three year DFS for patients with undifferentiated histology was 98% as compared to 82% with other histologies (p = 0.02). Acute grade 3 toxicity was seen as 21 (30.9%) having G-III mucositis and 6 (8.8%) with G-III skin reactions. Late toxicity was minimal and loss of taste was seen in 3 patients (7.5%) at time of analysis. IMRT with SMART in combination with chemotherapy is feasible and effective in terms of both the clinical response and safety profile. EBV, histopathology and nodal involvement were found important prognostic factors for locoregional recurrence

Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

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Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Brunner, Thomas B. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); University Hospital Freiburg, Department of Radiation Oncology, Freiburg (Germany); Witzigmann, Helmut [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Marti, Lukas [Hospital of Kanton St. Gallen, General Surgery, St. Gallen (Switzerland); Bechstein, Wolf-Otto [University Hospital Frankfurt, Department of Surgery, Frankfurt/Main (Germany); Bruns, Christiane [University Hospital Munich, Department of Surgery - Hospital Campus Grosshadern, Munich (Germany); University Hospital Magdeburg, Department of Surgery, Magdeburg (Germany); Jungnickel, Henry [Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Schreiber, Stefan [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Grabenbauer, Gerhard G. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Coburg, Department of Radiation Oncology, Coburg (Germany); Meyer, Thomas [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Hospital Ansbach, General Surgery, Ansbach (Germany); Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

2014-09-25

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.) [German] Mehrere nichtrandomisierte Studien zeigten, dass eine neoadjuvante Therapie das Ueberleben bei Patienten mit Pankreaskarzinom verlaengert. Beim lokal fortgeschrittenen Rektumkarzinom gehoert die

Prevention of cisplatin nephrotoxicity

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Hayati Fatemeh

2016-01-01

Full Text Available Cisplatin has a well-established role in the treatment of broad spectrum of malignancies; however its use is limited because of cisplatin-induced nephrotoxicity (CIN which can be progressive in more than 50% of cases. The most important risk factors for CIN include higher doses of cisplatin, previous cisplatin chemotherapy, underlying kidney damage and concurrent treatment with other potential nephrotoxin agents, such as aminoglycosides, nonsteroidal anti-inflammatory agents, or iodinated contrast media. Different strategies have been offered to diminish or prevent nephrotoxicity of cisplatin. The standard approach for prevention of CIN is the administration of lower doses of cisplatin in combination with full intravenous hydration prior and after cisplatin administration. Cisplatin-induced oxidative stress in the kidney may be prevented by natural antioxidant compounds. The results of this review show that many strategies for prevention of CIN exist, however, attention to the administration of these agent for CIN is necessary.

Protein kinase C β inhibits autophagy and sensitizes cervical cancer Hela cells to cisplatin.

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Li, Na; Zhang, Wei

2017-04-28

Recently, autophagy has been indicated to play an essential role in various biological events, such as the response of cervical cancer cells to chemotherapy. However, the exact signalling mechanism that regulates autophagy during chemotherapy remains unclear. In the present study, we investigated the regulation by cisplatin on protein kinase C β (PKC β), on B-cell lymphoma 2 (Bcl-2) and on apoptosis in cervical cancer Hela cells. And then we examined the regulation by cisplatin on autophagy and the role of autophagy on the chemotherapy in Hela cells. In addition, the regulation of the PKC β on the autophagy was also investigated. Our results indicated that cisplatin promoted PKC β in Hela cells. The PKC β inhibitor reduced the cisplatin-induced apoptosis, whereas increased the cisplatin-induced autophagy in Hela cells. On the other side, the PKC β overexpression aggravated the cisplatin-induced apoptosis, whereas down-regulated the cisplatin-induced autophagy. Taken together, our study firstly recognized the involvement of PKC β in the cytotoxicity of cisplatin via inhibiting autophagy in cervical cancer cells. We propose that PKC β would sensitize cervical cancer cells to chemotherapy via reducing the chemotherapy induced autophagy in cancer cells. © 2017 The Author(s).

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

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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.

Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy.

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Benkafadar, Nesrine; Menardo, Julien; Bourien, Jérôme; Nouvian, Régis; François, Florence; Decaudin, Didier; Maiorano, Domenico; Puel, Jean-Luc; Wang, Jing

2017-01-01

Cisplatin is a widely used chemotherapy drug, despite its significant ototoxic side effects. To date, the mechanism of cisplatin-induced ototoxicity remains unclear, and hearing preservation during cisplatin-based chemotherapy in patients is lacking. We found activation of the ATM-Chk2-p53 pathway to be a major determinant of cisplatin ototoxicity. However, prevention of cisplatin-induced ototoxicity is hampered by opposite effects of ATM activation upon sensory hair cells: promoting both outer hair cell death and inner hair cell survival. Encouragingly, however, genetic or pharmacological ablation of p53 substantially attenuated cochlear cell apoptosis, thus preserving hearing. Importantly, systemic administration of a p53 inhibitor in mice bearing patient-derived triple-negative breast cancer protected auditory function, without compromising the anti-tumor efficacy of cisplatin. Altogether, these findings highlight a novel and effective strategy for hearing protection in cisplatin-based chemotherapy. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

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

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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)

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

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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

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

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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

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

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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

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

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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

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

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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

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

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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

Risk factors associated with ineligibility of adjuvant cisplatin-based chemotherapy after nephroureterectomy

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Shao IH

2014-10-01

Full Text Available I-Hung Shao,1,2,* Yu-Hsiang Lin,1,* Chen-Pang Hou,1 Horng-Heng Juang,3,4 Chien-Lun Chen,1 Phei-Lang Chang,1,4 Ke-Hung Tsui, 1,41Department of Urology, Chang Gung Memorial Hospital at Linkou, Chang Gung University, 2Department of Urology, Lotung Poh-Ai Hospital, 3Department of Anatomy, Chang Gung University, 4Bioinformation Center, Chang Gung Memory Hospital, Kwei-Shan, Tao-Yuan, Taiwan, Republic of China*These authors contributed equally to this workPurpose: Radical nephroureterectomy (RNU is a standard treatment for upper urinary tract urothelial carcinoma. However, RNU can result in decreased renal function and cannot be treated with adjuvant chemotherapy. We performed a risk group stratification analysis to determine the preoperative factors that are predictive of diminished renal function after RNU.Materials and methods: We retrospectively evaluated the medical records of all patients who underwent nephroureterectomy for upper urinary tract urothelial carcinoma at the Chang Gung Memorial Hospital from 2001 to 2008. We analyzed the association between perioperative glomerular filtration rate and preoperative parameters including cancer characteristics, serum creatinine level, and kidney size measured on computed tomographic images.Results: A total of 242 patients fulfilled the inclusion criteria. The average decrease in renal function 1 month after RNU was 19.7%. Using 60 mL/min/1.73 m2 as the eligibility cutoff for cisplatin-based chemotherapy, 42.1% of the population was eligible prior to nephroureterectomy, whereas following surgery only 15.2% remained eligible. Using a cutoff of 45 mL/min/1.73 m2, 59.9% of the cohort was eligible for fractionated cisplatin dosing preoperatively, whereas only 32.6% remained above the cutoff postoperatively. The most significant predictors of poor postoperative renal function were body mass index >25 kg/m2, age >65 years, contralateral kidney length less than 10 cm, and absence of ipsilateral hydronephrosis

A phase II study of VP-16-ifosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer

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Woo, In Sook; Park, Young Suk; Kwon, Sung Hee

2000-01-01

At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell ling cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m 2 (on day 1-3), ifosfamide 1000 mg/m 2 (on days 1 and 2) and cisplatin 100 mg/m 2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity. (author)

Feasibility Study of Moderately Accelerated Intensity-Modulated Radiotherapy Plus Concurrent Weekly Cisplatin After Induction Chemotherapy in Locally Advanced Head-and Neck Cancer

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Morganti, Alessio G.; Mignogna, Samantha; Deodato, Francesco; Massaccesi, Mariangela; Cilla, Savino; Calista, Franco; Serafini, Giovanni; Digesu, Cinzia; Macchia, Gabriella; Picardi, Vincenzo; Caravatta, Luciana; Di Lullo, Liberato; Giglio, Gianfranco; Sallustio, Giuseppina; Piermattei, Angelo

2011-01-01

Purpose: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). Methods and Materials: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m 2 plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. Results: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. Conclusions: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

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

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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.

Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma

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Federico, Rea; Matteo, Ceccarelli; Gbenga, Kazeem; Paolo, Marchi; Francesco, Facciolo; Adolfo, Favaretto; Giuseppe, Marulli; Lorenzo, Spaggiari; Martino, DePas Tommaso; Anna, Ceribelli; Adriano, Paccagnella; Gino, Crivellari; Francesca, Russo

2013-01-01

Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results. Phase II, open-label study of the combination of chemotherapy (pemetrexed 500 mg/m 2 +cisplatin 75 mg/m 2 IV every 21 days × 3 cycles), followed by surgery (en-bloc extrapleural pneumonectomy, 3–8 weeks after chemotherapy) and hemithoracic radiation (total radiation beam 54 Gy, received 4–8 weeks post-surgery). The primary endpoint was event-free survival, defined as the time from enrollment to time of first observation of disease progression, death due to any cause, or early treatment discontinuation. Fifty-four treatment-naïve patients with T1-3 N0-2 malignant pleural mesothelioma were enrolled, 52 (96.3%) completed chemotherapy, 45 (83.3%) underwent surgery, 22 (40.7%) completed the whole treatment including 90-day post-radiation follow-up. The median event-free survival was 6.9 months (95%CI: 5.0-10.5), median overall survival was 15.5 months (95%CI 11.0-NA) while median time-to-tumor response was 4.8 months (95%CI: 2.5-8.0). Eighteen (33.3%) and 13 (24.1%) patients were still event-free after 1 and 2 years, respectively. The most common treatment-emergent adverse events were nausea (63.0%), anemia (51.9%) and hypertension (42.6%). Following two cardiopulmonary radiation-related deaths the protocol was amended (21 [38.9%] patients were already enrolled in the study): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended. The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients. It may be worthy of further investigation. Clinicaltrial.com registrationID #NCT00087698

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

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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

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

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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.

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

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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

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

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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

Adjuvant Bidirectional Chemotherapy with Intraperitoneal Pemetrexed Combined with Intravenous Cisplatin for Diffuse Malignant Peritoneal Mesothelioma

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Lana Bijelic

2012-01-01

Full Text Available Cytoreductive surgery (CRS with heated intraoperative intraperitoneal chemotherapy (HIPEC has emerged as optimal treatment for diffuse malignant peritoneal mesothelioma (DMPM showing median survivals of 36–92 months. However, recurrences occur frequently even in patients undergoing optimal cytreduction and are often confined to the abdomen. We initiated a Phase II study of adjuvant intraperitoneal pemetrexed combined with intravenous cisplatin for patients undergoing CRS and HIPEC for DMPM. The treatment consisted of pemetrexed 500 mg/m2 intraperitoneally and cisplatin 50 mg/m2 intravenously given simultaneously on day 1 of every 21 day cycle for 6 cycles. The primary endpoint of the study was treatment related toxicity. From July 2007 until July 2009 ten patients were enrolled. Nine of 10 completed all 6 cycles of adjuvant treatment per protocol. The most common toxicities were fatigue, nausea and abdominal pain grade 1 or 2. There was one grade 3 toxicity consisting of a catheter infection. The median survival for all 10 patients was 33.5 months. Pharmacokinetic analysis of intraperitoneal pemetrexed showed a peritoneal to plasma area under the curve ratio of 70. Our study shows that adjuvant intravenous cisplatin and intraperitoneal pemetrexed can be used following CRS and HIPEC for DMPM with low morbidity.

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

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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

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

Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Kawaoka, Tomokazu; Aikata, Hiroshi; Takaki, Shintaro; Katamura, Yoshio; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Hieda, Masashi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

2009-01-01

We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% at 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.

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

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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.

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

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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.

Amelioration of Cisplatin-Induced Nephrotoxicity in Rats by Curcumin

African Journals Online (AJOL)

Keywords: Cisplatin, Oxidative stress, Curcumin, α-Tocopherol, Nephrotoxicity. Tropical ... exerts various side effects in several organs particularly in ... Previous study provides evidence which ..... chemotherapy by cisplatin but further in vivo.

Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy

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Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya; Amarasiriwardena, Chitra J; Lupoli, Nicola

2011-01-01

The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC 50 = 0.77 ± 0.11 μM comparable to that of free cisplatin (IC 50 = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.

GAS5 modulated autophagy is a mechanism modulating cisplatin sensitivity in NSCLC cells.

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Zhang, N; Yang, G-Q; Shao, X-M; Wei, L

2016-06-01

In this study, we investigated the association between lncRNA GAS5 and cisplatin (DDP) resistance in NSCLC and further studied the regulative effect of GAS5 on autophagy and DDP resistance. GAS5 expression in cancerous and adjacent normal tissues from 15 NSCLC patients received neoadjuvant chemotherapy and the following surgery were measured using qRT-PCR analysis. GAS5 gain-and-loss study was performed using A549 and A549/DDP cells as an in-vitro model to investigate the effect of GAS5 on autophagy and cisplatin sensitivity. NSCLC tissues had a substantially lower expression of GAS5 than adjacent normal tissues. The NSCLC tissues from patients with progressive disease (PD) had even lower GAS5 expression. GAS5 knockdown increased DDP IC50 of A549 cells, while GAS5 overexpression decreased DDP IC50 of A549/DDP cells. A549/DDP cells had significantly higher basal autophagy than A549 cells. GAS5 knockdown resulted in decreased autophagy in A549 cells, while GAS5 overexpression led to increased autophagy in A549/DDP cells. Treatment with 3-MA, an autophagy inhibitor, significantly decreased DDP IC50 and promoted DDP-induced cell apoptosis in A549 cells. In addition, 3-MA also partly reversed the effect of GAS5 knockdown. In A549/DDP cells, GAS5 showed the similar effect as 3-MA in reducing DPP IC50 and promoting DDP-induced apoptosis and also presented synergic effect with 3-MA. GAS5 downregulation is associated with cisplatin resistance in NSCLC. GAS5 can inhibit autophagy and therefore enhance cisplatin sensitivity in NSCLC cells.

COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.

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Crabb, Simon J; Martin, Karen; Abab, Julia; Ratcliffe, Ian; Thornton, Roger; Lineton, Ben; Ellis, Mary; Moody, Ronald; Stanton, Louise; Galanopoulou, Angeliki; Maishman, Tom; Geldart, Thomas; Bayne, Mike; Davies, Joe; Lamb, Carolynn; Popat, Sanjay; Joffe, Johnathan K; Nutting, Chris; Chester, John; Hartley, Andrew; Thomas, Gareth; Ottensmeier, Christian; Huddart, Robert; King, Emma

2017-12-01

Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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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

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

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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.

Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin.

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Oyama, Katsunobu; Fushida, Sachio; Kaji, Masahide; Takeda, Toshiya; Kinami, Shinichi; Hirono, Yasuo; Yoshimoto, Katsuhiro; Yabushita, Kazuhisa; Hirosawa, Hisashi; Takai, Yuki; Nakano, Tatsuo; Kimura, Hironobu; Yasui, Toshiaki; Tsuneda, Atsushi; Tsukada, Tomoya; Kinoshita, Jun; Fujimura, Takashi; Ohta, Tetsuo

2013-11-01

We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life". Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

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

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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.

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.)

Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

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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.

[Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

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Ohta, M; Hara, N; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

1988-06-01

We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

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

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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

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)

Sclerosing Epithelioid Fibrosarcoma of the Bone: A Case Report of High Resistance to Chemotherapy and a Survey of the Literature

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Thomas G. P. Grunewald

2010-01-01

Full Text Available Sclerosing epithelioid fibrosarcoma (SEF is a rare soft tissue sarcoma mostly occurring in extraosseous sites. SEF represents a clinically challenging entity especially because no standardized treatment regimens are available. Intraosseous localization is an additional challenge with respect to the therapeutical approach. We report on a 16-year-old patient with SEF of the right proximal tibia. The patient underwent standardized neoadjuvant chemotherapy analogous to the EURAMOS-1 protocol for the treatment of osteosarcoma followed by tumor resection and endoprosthetic reconstruction. Histopathological analysis of the resected tumor showed >90% vital tumor cells suggesting no response to chemotherapy. Therefore, therapy was reassigned to the CWS 2002 High-Risk protocol for the treatment of soft tissue sarcoma. To date (22 months after diagnosis, there is no evidence of relapse or metastasis. Our data suggest that SEF may be resistant to a chemotherapy regimen containing Cisplatin, Doxorubicin, and Methotrexate, which should be considered in planning treatment for patients with SEF.

Tumour resistance to cisplatin: a modelling approach

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Marcu, L [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Bezak, E [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Olver, I [Faculty of Medicine, University of Adelaide, North Terrace, SA 5000 (Australia); Doorn, T van [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia)

2005-01-07

Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

Tumour resistance to cisplatin: a modelling approach

International Nuclear Information System (INIS)

Marcu, L; Bezak, E; Olver, I; Doorn, T van

2005-01-01

Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

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

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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

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

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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

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...

Synthesis of [13N]cisplatin

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Haber, M.T.; Risenspire, K.C.

1985-01-01

A method for the ''carrier-added'' synthesis of [ 13 N]cisplatin is described. Yields were approx.1-4 mCi from 20-40 mCi of [ 13 N]ammonia with a total synthesis time of 19-28 minutes. The product was approx.96% radiochemically pure as judged by HPLC analysis and had a specific activity of approx.100 mCi/mmole in 1.0 ml of saline. [ 13 N)Cisplatin was administered intraperitoneally to mice. Of the tissues investigated, concentration of label was highest in kidneys. At 10 min, considerable label in the blood, liver, and kidney was in a form other than cisplatin. However, no evidence was obtained that [ 13 N]ammonia was released from [ 13 N]cisplatin in vivo. [ 13 N]Cisplatin may be used to assess drug delivery to primary and metastatic brain tumors in patients receiving intravenous or intraarterial cisplatin chemotherapy. (author)

Clinical Initial Response of Neoadjuvant Chemotheraphy in Triple Negative, HER-2, and Luminal Types of Breast Cancer in Denpasar (A Preliminary Study

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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.

Risk Factors of anemia in head and neck cancer patients undergoing chemotherapy with high-dose cisplatin

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Johan Kurnianda

2008-12-01

Full Text Available Cisplatin is well-known for its effectiveness against cancer, as well as its toxicity to human tissues. Of several documented side effects, anemia was reported to have significant association with decreased quality of life. This study was conducted to investigate development of cisplatin-induced anemia, and to identify independent factors contributing to anemia. Clinical data from head and neck cancer patients treated with high-dose cisplatin between December 2002 and December 2005 were obtained in this study. Incidence and risk factors of anemia were assessed in a model including age, sex, baseline hemoglobin level, baseline creatinine clearance, and occurrence of distant metastases. Multivariate logistic regression was used to define independent predictors of anemia. Among 86 eligible patients, 26 (30.2% developed anemia, defined as Hb level lower than 11 g/dL. Age > 55 years old (RR = 2.2, 95% CI, 1.2-4.0, female sex (RR = 2.0, 95% CI, 1.2-3.8, baseline Hb ≤ 13 g/dL (RR = 4.2, 95% CI, 1.9-9.4 and baseline CrCl < 50 mL/min (RR = 2.9, 95% CI, 1.7-5.1 were significantly correlated with incidence of anemia (P < 0.05. In multivariate analysis, baseline Hb and baseline CrCl were identified as independent risk factors for anemia. However, considerable confounding was observed in baseline CrCl after stratified by age (aRR = 2.2, 95% CI, 1.1-4.7. Thus, baseline Hb level was the strongest predictor of anemia. The findings suggested that baseline Hb and CrCl were useful to recognize cisplatin-treated patients at risk for anemia who might benefits from preventive measures. (Med J Indones 2008; 17: 248-54Keywords: anemia, cisplatin, chemotherapy, hemoglobin, creatinine clearance

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

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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.)

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.)

Neoadjuvant intra-arterial chemotherapy combined with radiotherapy and surgery in patients with advanced maxillary sinus cancer

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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.

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.

Long-term survival benefit of upfront chemotherapy in patients with newly diagnosed borderline resectable pancreatic cancer.

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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.

Ototoxicity After Intensity-Modulated Radiation Therapy and Cisplatin-Based Chemotherapy in Children With Medulloblastoma

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Paulino, Arnold C.; Lobo, Mark; Teh, Bin S.; Okcu, M. Fatih; South, Michael; Butler, E. Brian; Su, Jack; Chintagumpala, Murali

2010-01-01

Purpose: To report the incidence of Pediatric Oncology Group (POG) Grade 3 or 4 ototoxicity in a cohort of patients treated with craniospinal irradiation (CSI) followed by posterior fossa (PF) and/or tumor bed (TB) boost using intensity-modulated radiation therapy (IMRT). Methods and Materials: From 1998 to 2006, 44 patients with medulloblastoma were treated with CSI followed by IMRT to the PF and/or TB and cisplatin-based chemotherapy. Patients with standard-risk disease were treated with 18 to 23.4 Gy CSI followed by either a (1) PF boost to 36 Gy and TB boost to 54 to 55.8 Gy or (2) TB boost to 55.8 Gy. Patients with high-risk disease received 36 to 39.6 Gy CSI followed by a (1) PF boost to 54 to 55.8 Gy, (2) PF boost to 45 Gy and TB boost to 55.8 Gy, or (3) TB boost to 55.8 Gy. Median audiogram follow-up was 41 months (range, 11-92.4 months). Results: POG Grade Ototoxicity 0, 1, 2, 3. and 4 was found in 29, 32, 11, 13. and 3 ears. respectively, with POG Grade 3 or 4 accounting for 18.2% of cases. There was a statistically significant difference in mean radiation dose (D mean ) cochlea according to degree of ototoxicity, with D mean cochlea increasing with severity of hearing loss (p = 0.027). Conclusions: Severe ototoxicity was seen in 18.2% of ears in children treated with IMRT boost and cisplatin-based chemotherapy. Increasing dose to the cochlea was associated with increasing severity of hearing loss.

Multicenter safety study on cetuximab combined with intensity modulated radiotherapy and concurrent chemotherapy of cisplatin in locoregionally advanced nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Chen Chunyan; Zhao Chong; Gao Li

2012-01-01

Objective: To evaluate the safety of cetuximab combined with intensity-modulated radiotherapy (IMRT) plus concurrent cisplatin chemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC) in a Chinese multicenter clinical study. Methods: From July 2008 to April 2009, 100 Patients with primary stage III- IV b non-keratinizing NPC were enrolled. The planned dose of IMRT to gross tumor volume and positive cervical lymph nodes was 66.0-75.9 Gy and 60-70 Gy in 30-33 fractions. Cisplatin (80 mg/m 2 , q3 week (w)) and cetuximab (400 mg/m 2 one w before radiation, and then 250 mg/m 2 per w) were given concurrently. The adverse events (AEs) were graded according to common terminology criteria for adverse events v3.0. Results: The compliance of the entire group of patient was satisfactory. Actual median dose to gross tumor volume was 69.96 Gy, and the median dose to positive cervical lymph nodes was 68 Gy. Median dose of cisplatin was 133 mg, median first-dose of cetuximab was 690 mg, and median weekly dose was 410 mg. AEs were well tolerated and manageable, mainly consisting of acneiform skin eruptions,dermatitis and mucositis. Grade 4 mucositis was observed in 2% of the patients and no other grade 4 AEs were observed. Conclusions: The combined treatment modality of IMRT + concurrent chemotherapy + cetuximab in loco-regionally advanced NPC is well tolerated. (authors)

Experimental study on combination of chemotherapy and radiotherapy

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Tanaka, Juichi

1986-01-01

Recently, by applying multidrug therapy using cisplatin and bleomycin to the treatment of head and neck cancer, the response rate of chemotherapy has been markedly increased and thus, chemotherapy has taken an important part in the treatment of head and neck cancer. In this paper a clinical application of chemotherapy in combination with radiotherapy was evaluated from the point of the cure rate and also preservation of the structures and the functions of the head and neck region. In order to test the advantage or usefulness of initial chemotherapy followed by radiotherapy (= pre-radiation chemotherapy), the experimental study on combination of chemotherapy and radiotherapy was designed by using ICR mice and Ehrlich solid carcinoma. Cisplatin and peplomycin, a newly developed derivative of bleomycin, were used as chemotherapeutic agents. Tumor growth delay rate was chosen as a parameter to indicate the effectiveness. Results obtained are as follows. 1. Combination chemotherapy of cisplatin and peplomycin was more effective than each single agent on Ehrlich solid carcinoma. Synergistic effect was obtained by higher dose. So, the combination of cisplatin and peplomycin was proved to be eligible for pre-radiation chemotherapy. 2. Synergistic effect of chemotherapy and radiotherapy was observed when chemotherapy was used prior to radiotherapy on Ehrlich solid carcinoma. 3. Even their additional effect was not recognized when radiotherapy preceded to chemotherapy on Ehrlich solid carcinoma. 4. No severe toxic effect was seen in the mice. The experimental results made it clear that pre-radiation chemotherapy is beneficial to the treatment of head and neck cancer. (author)

Cisplatin nephrotoxicity: mechanisms and renoprotective strategies.

Science.gov (United States)

Pabla, N; Dong, Z

2008-05-01

Cisplatin is one of the most widely used and most potent chemotherapy drugs. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinum-based therapeutics. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death and inflammation. Renoprotective approaches are being discovered, but the protective effects are mostly partial, suggesting the need for combinatorial strategies. Importantly, it is unclear whether these approaches would limit the anticancer effects of cisplatin in tumors. Examination of tumor-bearing animals and identification of novel renoprotective strategies that do not diminish the anticancer efficacy of cisplatin are essential to the development of clinically applicable interventions.

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.

Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors.

Science.gov (United States)

Bagrodia, Aditya; Lee, Byron H; Lee, William; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Pietzak, Eugene J; Gao, Sizhi Paul; Zabor, Emily C; Ostrovnaya, Irina; Kaffenberger, Samuel D; Syed, Aijazuddin; Arcila, Maria E; Chaganti, Raju S; Kundra, Ritika; Eng, Jana; Hreiki, Joseph; Vacic, Vladimir; Arora, Kanika; Oschwald, Dayna M; Berger, Michael F; Bajorin, Dean F; Bains, Manjit S; Schultz, Nikolaus; Reuter, Victor E; Sheinfeld, Joel; Bosl, George J; Al-Ahmadie, Hikmat A; Solit, David B; Feldman, Darren R

2016-11-20

Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture-based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic

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.

Results of the Tremplin trial proposing an induction chemotherapy followed by concomitant radiotherapy with cisplatin ou cetuximab in order to protect the larynx

International Nuclear Information System (INIS)

Pointreau, Y.; Calais, G.; Pointreau, Y.; Calais, G.; Pointreau, Y.; Rolland, F.; Bardet, E.; Alfonsi, M.; Baudoux, A.; Sire, G.; De Raucourt, D.; Tuchais, C.; Lefebvre, J.L.

2010-01-01

The authors report a randomized phase II trial which aimed at comparing over three months the laryngeal protection after a TPF-based induction chemotherapy followed by radiotherapy in combination with cisplatin or cetuximab. Over two years, 153 patients have been concerned. The TPF-based induction chemotherapy followed by radiotherapy with cetuximab seems to be the less toxic. A longer monitoring is needed to get better information in terms of laryngeal protection rate, life quality, and laryngeal functionality. Short communication

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.

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.

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

Radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for N2-3 nasopharyngeal cancer. A multicenter trial of the Forum for Nuclear Cooperation in Asia

International Nuclear Information System (INIS)

Ohno, Tatsuya; Thinh, D.H.Q.; Kato, Shingo

2013-01-01

The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2-3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1-4 N2-3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m 2 ), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m 2 on Day 1) and fluorouracil (800 mg/m 2 on Days 1-5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of radiotherapy (RT). The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3-4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities. (author)

Emblica extract prevents cisplatin-induced apoptosis in dermal papilla fibroblasts

OpenAIRE

Sudjit Luanpitpong; Varisa Pongrakhananon; Ubonthip Nimmannit; Pithi Chanvorachote

2008-01-01

Cisplatin is a widely prescribed anticancer agent that causes hair loss in patients. Since the dermal papilla (DP) fibroblasts are known to be a key mediator in controlling hair growth and loss, understanding the effect and underlying mechanism of cisplatin on these cells may lead to new strategy for hair loss protection in chemotherapy patients. Less is known regarding the effect of cisplatin on DP fibroblasts. We thus treated DP cells with cisplatin (0-250 mmol/L) and found that cisplatin i...

Re-irradiation with cetuximab or cisplatin-based chemotherapy for recurrent squamous cell carcinoma of the head and neck

Energy Technology Data Exchange (ETDEWEB)

Dornoff, Nicolas; Weiss, Christian; Roedel, Franz [J. W. Goethe University, Department of Radiotherapy and Oncology, Frankfurt a. M. (Germany); Wagenblast, Jens [J. W. Goethe University, Department of Otorhinolaryngology, Frankfurt a. M. (Germany); Ghanaati, Shahram [J. W. Goethe University, Department of Maxillofacial Surgery, Frankfurt a. M. (Germany); Atefeh, Nateghian; Roedel, Claus; Balermpas, Panagiotis [J. W. Goethe University, Department of Radiotherapy and Oncology, Frankfurt a. M. (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); German Cancer Consortium (DKTK) partner site: Frankfurt, Frankfurt a. M. (Germany)

2015-08-15

Locoregional recurrence remains the main pattern of failure after primary combined modality treatment of squamous cell carcinoma of the head and neck (SCCHN). We compared the efficacy and toxicity of either cisplatin or cetuximab in combination with re-irradiation (ReRT) for recurrent unresectable SCCHN. Various clinicopathological factors were investigated to establish a prognostic score. Between 2007 and 2014, 66 patients with recurrent SCCHN originating in a previously irradiated area received cetuximab (n = 33) or cisplatin-based chemotherapy (n = 33) concomitant with ReRT. Toxicity was evaluated weekly and at every follow-up visit. Physical examination, endoscopy, CT or MRI scans were used to evaluate response and disease control. With a mean follow-up of 18.3 months, the 1-year overall survival (OS) rates for Re-RT with cetuximab and cisplatin-based chemotherapy were 44.4 and 45.5 % (p = 0.352), respectively. At 1 year, local control rates (LCR) were 46.4 and 54.2 % (p = 0.625), freedom from metastases (FFM) rates 73.6 and 81 % (p = 0.842), respectively. Haematological toxicity ≥ grade 3 occurred more often in the cisplatin group (p < 0.001), pain ≥ grade 3 was increased in the cetuximab group (p = 0.034). A physiological haemoglobin level and a longer interval between primary RT and ReRT, proved to be significant prognostic factors for OS (multivariate: p = 0.003, p = 0.002, respectively). Site of the recurrence and gross target volume (GTV) did not show a significant impact on OS in multivariate analysis (p = 0.160, p = 0.167, respectively). A prognostic-score (1-4 points) based on these four variables identified significantly different subgroups: 1-year OS for 0/1/2/3/4 prognostic points: 10, 38, 76, 80 and 100 %, respectively (p < 0.001). Both cetuximab- and cisplatin-based ReRT of SCCHN recurrences are feasible and effective treatment options with comparable results in terms of tumour control and survival. Acute adverse events may differ slightly

Chemotherapy or radio-chemotherapy for advanced adenocarcinoma of the oesophagus and cardiac orifice

International Nuclear Information System (INIS)

Seitz, J.F.; Duffaud, F.; Dahan, L.; Ries, P.; Ville, E.; Laugier, R.

2001-01-01

Adenocarcinomas of esophagus and cardia represent in France approximately 20 to 40% of the esophagus cancers. They have a high risk to develop lymph nodes metastases and liver metastases. Currently, only 50 to 70% of patients may benefit from surgical curative resection at diagnosis, but more than 50% of them will recur. The standard of treatment of these metastatic adenocarcinomas is chemotherapy. Three large randomized comparative studies, between chemotherapy and supportive care, showed that chemotherapy significantly extends the median of survival (from 3-4 months to 10-12 months) and improves the quality of life. Currently, the combination of epirubicin-cisplatin-continuous 5FU (ECF) is the most effective regimen but it is difficult to administer and tolerate because of the long continuous 5FU infusion. In France, the most commonly used combination regimen still associates 5FU and cisplatin. New drugs (such as docetaxel, CPT11, oxaliplatin) used alone or in combination, especially with 5U, are very promising. Radio-chemotherapy is the preferred treatment for locoregional recurrences, because it improves dysphagia and enables to obtain complete tumor responses. Current results from concomitant radio-chemotherapy studies for esophagus cancer, based on 5FU alone, 5FU-cisplatin or 5FU-mitomycin, given as preoperative treatment or as exclusive treatment, support to use radio-chemotherapy for the treatment of loco-regional recurrences after surgical resection. Nevertheless, the optimal radio-chemotherapy schedule still remain to be defined (dose, duration, splitting of radiotherapy, choice of anticancer drugs). (authors)

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.

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.

Molecular mechanisms of cisplatin resistance in cervical cancer.

Science.gov (United States)

Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

2016-01-01

Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%-20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer.

Survival benefit from chemotherapy with mitomycin-c vinblastine and cisplatin in advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Joaquin, C.F.

1992-01-01

Between January 1989 and May 1991 a prospective trial was conducted among the patients in the Lung Center of the Philippines who were diagnosed to have unresectable and metastatic non-small cell lung cancer (NSCLC). There were two groups of patients: those who consented to chemotherapy with the mitomycin, vinblastine and cisplatin regimen (n=31) and those who refused any form of chemotherapy or radiation (n=15). These groups were followed up and compared as to patient characteristics and duration of survival. The results show no identifiable features in the responders and non-responders to chemotherapy which could predict tumor response. The median survival of the untreated group was 15 weeks and that of the treated group was 34 weeks. This was statistically significant. No significant difference in survival between the responders and the non-responders was observed. The objective tumor response rate to the MVP regimen was 25.8%. The most common toxic effects were emesis and hematologic abnormalities. The study recommends the option of chemotherapy with the MVP regimen rather than no treatment at all after considering the risks and benefits for the patient with advanced stage NSCLC. (auth.). 19 refs.; 2 figs.; 4 tabs

Cisplatin Therapy Does Not Worsen Renal Function in Severe Antenatal Bartter Syndrome.

Science.gov (United States)

Welch, Thomas R; Shaffer, David R; Feldman, Darren R

2017-01-01

A 30-year-old man with severe antenatal Bartter syndrome, diagnosed and treated in infancy, developed testicular carcinoma. Despite the known renal complications of cisplatin, this drug was used for his chemotherapy because of its superior antineoplastic effect. Nonsteroidal anti-inflammatory drug administration was continued during cisplatin therapy. Despite an increase in his oral potassium requirement, renal function was maintained following completion of chemotherapy. In spite of its significant associated nephrotoxicity, cisplatin can be used in patients with severe antenatal Bartter syndrome if required for therapy of malignancy.

Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).

Science.gov (United States)

Ferrari, Stefano; Meazza, Cristina; Palmerini, Emanuela; Tamburini, Angela; Fagioli, Franca; Cozza, Raffaele; Ferraresi, Virginia; Bisogno, Gianni; Mascarin, Maurizio; Cefalo, Graziella; Manfrini, Marco; Capanna, Rodolfo; Biagini, Roberto; Donati, Davide; Picci, Piero

2014-01-01

Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study). Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity. From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered. The limb salvage rate was 94% and the good pathologic response rate 51% (these figures were 92% and 48%, respectively, in the ISG/OS-1 study). At a median follow-up of 39 months (range, 4-80), the 5-year overall survival rate was 80% (95% CI, 73%-87%) and the event-free survival was 50% (95% CI, 39%-59%). For comparison, the 5-year overall and event-free survival rates in ISG/OS-1 were 73% (95% CI, 65%-81%) and 64% (95% CI, 56%-73%), respectively. This study confirms that in nonmetastatic osteosarcoma of the extremity, conservative surgery in more than 90% and a good pathologic response rate of 50% can be expected with primary chemotherapy based on the MAP regimen. The response and resection rates in the ISG/OS-Oss study are in the same range as those of the previous study, whereas the event-free survival is lower than that previously achieved. Since the only difference between the two studies was the cumulative dose of postoperatively given MTX, our data support the importance of the cumulative dose of MTX in the MAP regimen.

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.

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.

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

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).

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.

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

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...

Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma

International Nuclear Information System (INIS)

Rajkumar, S. Vincent; Buckner, Jan C.; Schomberg, Paula J.; Reid, Joel M.; Bagniewski, Pamela J.; Ames, Matthew M.; Cascino, Terrence L.; Marks, Randolph S.

1998-01-01

Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done. Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m 2 days 1-3, cisplatin 30 mg/m 2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29-42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m 2 every 8 weeks x 4 cycles was given after radiation therapy. Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m 2 days 1-3, cisplatin 20 mg/m 2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m 2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 μg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean ± SD 2 hr and 6 hr plasma concentrations were 0.92 ± 0.43 μg/ml and 0.36 ± 0.12 μg/ml, respectively. Estimated duration of exposure to >0.1 μg/ml etoposide was 10-17 hr. Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained

Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Platinum Chemotherapy in Muscle Invasive Urothelial Carcinoma.

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Alexander S Baras

Full Text Available The 5-year cancer specific survival (CSS for patients with muscle invasive urothelial carcinoma of the bladder (MIBC treated with cystectomy alone is approximately 50%. Platinum based neoadjuvant chemotherapy (NAC plus cystectomy results in a marginal 5-10% increase in 5-year CSS in MIBC. Interestingly, responders to NAC (neoadjuvant gemcitabine cisplatin NAC and subsequent cystectomy. The clinical parameters that have been previously associated with NAC response were also examined in our cohort.Our analyses of the available mRNA gene expression data in a discovery cohort (n = 33 and the HPA resulted in 8 candidate protein biomarkers. The combination of GDPD3 and SPRED1 resulted in a multivariate classification tree that was significantly associated with NAC response status (Goodman-Kruskal γ = 0.85 p<0.0001 in our independent NAC treated MIBC cohort. This model was independent of the clinical factors of age and clinical tumor stage, which have been previously associated with NAC response by our group. The combination

The Role of Redox-Regulating Enzymes in Inoperable Breast Cancers Treated with Neoadjuvant Chemotherapy

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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.

Radiochemotherapy with gemcitabine and cisplatin in pancreatic cancer - feasible and effective

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Wilkowski, R.; Thoma, M.; Duehmke, E.; Heinemann, V.; Rau, H.G.; Wagner, A.; Stoffregen, C.

2003-01-01

Background: Concomittant radiotherapy and chemotherapy with gemcitabine appears to be a promising tool for the treatment of pancreatic cancer since gemcitabine - applied as single or combination therapy - proved to have better efficacy in pancreatic cancer than 5-FU containing schemes and furthermore offers radiosensitizing potential. In the present paper our pilot data of concomittant and sequential chemoradiation with gemcitabine and cisplatin are presented. Patients and Methods: A total of 57 patients (f/m 23/34) with pancreatic cancer was treated, of whom 33 patients had irresectable tumors, 19 patients following resection (R1 and/or pN+) and five patients with local recurrent disease. Radiotherapy was delivered in 25 fractions up to a total dose of 45.0 Gy specified according to ICRU reference point (50 patients, 1.8 Gy/fraction) respectively 50.0 Gy to gross tumor volume (seven patients; 45.0 Gy in locoregional lymphatic pathways; 2.0/ 1.8 Gy/fraction). Concomittant with radiotherapy cisplatin (30 mg/m 2 ) and gemcitabine (300 mg/m 2 ) were applied on days 1, 8, 22 and 29. After simultaneous chemoradiation two sequential cycles gemcitabine and cisplatin (1000 mg/m 2 and 50 mg/m 2 d 1, 15) were applied. Results: With a median follow-up of 8.2 months the median survival time was 14.8 months (irresectable patients: 10.3 months, postoperative patients 15.1 months). Within 33 irresectable patients 19 and four partial and complete remissions, respectively, were observed. In 14 patients a secondary resection was possible. Using leveled antiemetics with ondansetron and dexamethasone no gastrointestinal toxicities grade III or IV were observed. Hematologic toxicities were the most grave side effects (leukocytopenia III/IV in 29/Five patients and thrombocytopenia III/IV in 21/eight patients), however with minor clinical relevancy (one neutropenic infection, one thrombopenic epistaxis). Conclusion: The presented treatment scheme using concomittant and sequential

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC

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Nikaedo Sueli M

2004-09-01

Full Text Available Abstract Background Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC can be achieved with cisplatin-based chemotherapy (CT, its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. Methods In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years, younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2, and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2. We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Results Analysis was by intention to treat. Main toxicities (grade 3–4 was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP and overall survival (OS were 27.0 (95% CI: 10.1 to 43.7 weeks and 30.1 (95% CI: 24.4 to 35.8 weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%, with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Conclusion Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions.

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

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Pereira, José Rodrigues; Martins, Sandro J; Nikaedo, Sueli M; Ikari, Flora K

2004-01-01

Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m 2 , on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m 2 or 90 mg/m 2 ), and older patients were allocated to lower cisplatin doses (60 mg/m 2 or 70 mg/m 2 ). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Analysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions

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

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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.

Discovery – Cisplatin and The Treatment of Testicular and Other Cancers

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Prior to the discovery of cisplatin in 1965, men with testicular cancer had few medical options. Now, thanks to NCI research, cisplatin and similar chemotherapy drugs are known for curing testicular and other forms of cancer.

Results of chemoradiotherapyfor muscle-invasive bladder cancer

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Yu. V. Gumenetskaya

2013-01-01

Full Text Available This study presents the results of chemoradiotherapy (CRT in 108 patients with muscle-invasive bladder cancer in whom surgery was contraindicated. The efficacies and toxicities of three variants of CRT were evaluated. Group 1 (neoadjuvant chemotherapy: 2–3 cycles of cisplatin-containing combination chemotherapy followed by a continuous course of external beam radiation therapy (EBRT. Group 2: concurrent CRT – cisplatin i.v., 70–100 mg/m 2 during the first and last weeks of continuous-course EBRT. Group 3: sequential neoadjuvant chemotherapy, 2–3 cycles and concurrent CRT. The comparative analysis of long-term outcomes following CRT indicated an improvement in survival rates in group 3 in which the 5-and 10-year cancer-specific survival rates were 42,3 ± 8,8 % and 31,3 ± 9,4 %, respectively, compared with 28,6 ± 9,7 % and 28,6 ± 9,7 % in group 1, and 29,5 ± 8,5 % and 14,8 ± 7,4 % in group 2, respectively (р=0,093. Acute toxicity (GU Grade 1 or 2 arose more often from concurrent radiation and chemotherapy: in 40,0 % and 40,5 % of cases in groups 2 and 3, respectively, whereas in group 1 it occurred in 25,9 % of cases (р<0,2. Late radiation toxicity (GU Grade 2 occurred more often in the concurrent CRT groups: 11,4 % and 11,9 % versus 3,2 % in the neoadjuvant chemotherapy group; Grade 3 was noted in 5,7 % and 2,4 % of patients in groups 2 and 3, respectively. The results indicated that chemoradiotherapy including neoadjuvant and concomitant chemotherapy improved the outcomes in patients with muscle-invasive bladder cancer in whom surgery was contraindicated. There was an acceptable rate of clinically significant complications.

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

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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.

Stages III and IV squamous cell carcinoma of the mouth: Three-year experience with superselective intraarterial chemotherapy using cisplatin prior to definitive treatment

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Hirai, Toshinori; Korogi, Yukunori; Hamatake, Satoshi; Nishimura, Ryuichi; Baba, Yuji; Takahashi, Mutsumasa; Uji, Yasuyoshi; Taen, Akira

1999-01-01

Purpose: This study was designed to assess the 3-year experience with superselective intraarterial chemotherapy prior to definitive treatment for stages III and IV squamous cell carcinomas of the mouth.Methods: Twenty-two patients prospectively received superselective intraarterial chemotherapy using relatively low-dose cisplatin via a transfemoral approach. The locations of the tumors were the tongue (n=12), gingiva (n=5), buccal mucosa (n=2), hard palate (n=1), floor of the mouth (n=1), and lip (n=1). After intraarterial chemotherapy, 21 patients underwent surgery (n=14), radiation therapy (n=6), or both (n=1). The survival rate of 25 patients who underwent surgery with/without radiationtherapy until 1992 at Kumamoto University Hospital was also evaluated as a historical control. The survival curve was calculated with the Kaplan-Meier method, and the statistical difference between survival curves was determined with the generalized Wilcoxon test.Results: The overall response rate was 95% [complete response (tumor completely resolved), 24%; partial response (tumor reduction ≥50%), 71%]. Fifty-two intraarterial infusions were performed without any catheter-related complications. Mild and transient local toxicity such as edema or mucositis of the infused area was relatively common. One patient died of renal failure from cisplatin. After a median follow-up of 20 months (range 2-41 months), the estimated 3-year survival rate for patients who underwent intraarterial chemotherapy plus surgery was 91%. The survival of the patients who underwent intraarterial chemotherapy plus surgery tended to be longer than that of the historical control.Conclusions: Early tumor reduction without delay of subsequent treatments can be obtained by intraarterial chemotherapy while minimizing complications and possibly improving survival. Further investigations of long-term survival with larger series need to be performed.

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

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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.

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

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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

Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.

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De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R

2016-01-01

While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation with cisplatin or carboplatin for locally advanced cervix cancer: the experience of a tertiary cancer centre

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Au-Yeung, George; Mileshkin, Linda; Rischin, Danny; Bernshaw, David M.; Kondalsamy-Chennakesavan, Srinivas; Narayan, Kailash

2013-01-01

Definitive treatment with concurrent cisplatin and radiation is the standard of care for locally advanced cervix cancer. The optimal management of patients with a contraindication to cisplatin has not been established. We conducted a retrospective audit of concurrent chemotherapy in a cohort of patients with locally advanced cervix cancer. All patients with locally advanced cervix cancer treated with definitive radiation were entered into a prospective database. Information regarding their demographics, stage, histology, recurrence and survival were recorded. Pharmacy records were reviewed to determine concurrent chemotherapy use. A total of 442 patients were included in the audit. Two hundred sixty-nine patients received cisplatin, 59 received carboplatin and 114 received no concurrent chemotherapy. Overall survival was significantly improved with the use of concurrent cisplatin compared with radiation alone (adjusted hazard ratio 0.53, P=0.001), as was disease-free survival and rate of distant failure. The use of carboplatin was not associated with any significant benefit in terms of overall survival or disease-free survival. The results of this audit are consistent with the known significant survival benefit with concurrent cisplatin chemotherapy. However, there did not appear to be any significant benefit with carboplatin although there were potential confounding factors. The available evidence in the literature would favour the use of non-platinum chemotherapy rather than carboplatin in patients with contraindications to cisplatin.

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

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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

Leukocytoclastic vasculitis complicating cisplatin + radiation treatment for laryngeal cancer: a case report.

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Quintanilha, Júlia Coelho França; Visacri, Marília Berlofa; Amaral, Laís Sampaio; Lima, Carmen Silvia Passos; Cintra, Maria Letícia; Moriel, Patricia

2017-12-06

Leukocytoclastic vasculitis is typically mediated by deposition of immune complexes and is related to many causes, including medication. To the best of our knowledge, leukocytoclastic vasculitis related to cisplatin has not yet been described in the scientific literature. We report a rare case of leukocytoclastic vasculitis after the first cycle of high-dose cisplatin chemotherapy in a patient with larynx carcinoma. A 48-year-old Caucasian man with larynx carcinoma received a high-dose of cisplatin monochemotherapy (100 mg/m 2 every 21 days), along with 70 Gy of radiotherapy divided into 35 sessions, as a therapeutic schedule. Twelve days after the first chemotherapy administration and after 8 sessions of radiotherapy (total of 16 Gy), the patient presented with acute onset of palpable purpura in the lower limbs. The patient was hospitalized for 10 days, and during this period, he underwent several examinations to rule out infectious, autoimmune, and neoplastic disorders. A skin biopsy showed leukocytoclastic vasculitis with a positive pattern for IgM and C3, as detected through direct immunofluorescence. Twenty-five days after cisplatin administration, the chemotherapy regimen was changed to carboplatin AUC 5, and the episodes of purpura ceased, reinforcing the hypothesis of an adverse reaction to cisplatin. Cisplatin can induce leukocytoclastic vasculitis and clinicians should be aware of this potential effect for better case management and diagnosis.

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

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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.

Cisplatin-induced hypokalemic paralysis.

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Mohammadianpanah, Mohammad; Omidvari, Shapour; Mosalaei, Ahmad; Ahmadloo, Niloofar

2004-08-01

Profound hypokalemic conditions resulting from cisplatin therapy have been known to produce hypokalemic paralysis in rare cases. We describe such a case of cisplatin-induced hypokalemic paralysis. A 15-year-old Persian girl with ovarian dysgerminoma presented with severe generalized weakness and paraplegia 1 week after the fourth course of cisplatin-based chemotherapy. On physical examination, there was symmetric flaccid paralysis and areflexia in all of the extremities and particularly in the lower limbs. Her serum potassium concentration was 1.7 mmol/L. Metastatic disease was excluded by a comprehensive systemic evaluation. Complete clinical and paraclinical recovery was achieved after short-term administration of potassium supplement. Adverse drug reactions are common with cisplatin, but the drug is only rarely associated with hypokalemic paralysis. Based on the Naranjo causality algorithm, an objective assessment revealed cisplatin to be a probable cause of hypokalemic paralysis in this case. This adverse drug event--whether isolated or secondary to hypomagnesemia--may be deceptive, leading to a fatal mistake in the oncology setting, and should therefore be precisely differentiated from cancer-related complications. This case suggests that cisplatin should be added to the list of agents causing hypokalemic paralysis. Regular serum electrolyte measurement, the early detection of cation deficiency, and appropriate replacement of cations are all recommended.

Type III radical hysterectomy after induction chemotherapy for patients with locally advanced cervical carcinoma.

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Lopez-Graniel, C; Reyes, M; Chanona, G; Gonzalez, A; Robles, E; Mohar, A; Lopez-Basave, H; De La Garza, J G; Dueñas-Gonzalez, A

2001-01-01

Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical carcinoma. The aim of this study was to evaluate the feasibility, technical aspects, and clinical results of surgery after induction chemotherapy in this patient population. Forty-one untreated cervical carcinoma patients staged as IB2 to IIIB received three 21-day courses of cisplatin 100mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 followed by surgery or concomitant chemoradiation. The response to chemotherapy, operability, surgical/pathological findings, disease-free period, and survival of the surgically treated patients were evaluated. All 41 patients were evaluated for toxicity and 40 were evaluated for response. The overall objective response rate was 95% (95% confidence interval 88%-100%), and was complete in three patients (7.5%) and partial in 35 (87.5%). Granulocytopenia grades 3/4 occurred in 13.8% and 3.4% of the courses, respectively, whereas nonhematological toxicity was mild. Twenty-three patients underwent type III radical hysterectomy. Mean duration of surgery was 3.8 h (range 2:30-5:20), median estimated blood loss was 670 ml and median hospital stay was 5.2 days. Intraoperative complications occurred in one case (venous injury). In all but one case the resection margins were negative. Four patients (17%) had positive nodes (one node each); six (26%) had complete pathologic response, three (13%) had microscopic; and 14 (60%) macroscopic residual disease. At 24 months of maximum follow-up (median 20), the disease-free and overall survival rates were 59% and 91%, respectively. Induction chemotherapy with cisplatin/gemcitabine produced a high response rate and did not increase the difficulty of surgery. Operating time, blood loss, intraoperative complications, and hospital stay were all within the range observed for type III hysterectomy in early stage patients. We therefore conclude that type III radical hysterectomy is feasible in locally

Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

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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

[A Case of Resected Gastric Cancer Invading the Esophagus with Esophageal Recurrence That Responded to Weekly Docetaxel／Cisplatin Chemotherapy].

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Maezawa, Yukio; Hayashi, Tsutomu; Yamamoto, Jun; Ohnishi, Hiroshi; Horii, Nobutoshi; Inoue, Hirohide; Kimura, Jun; Takagawa, Ryo; Makino, Hirochika; Suzuki, Yoshihiro; Ohshima, Takashi; Tsuburaya, Akira; Rino, Yasushi; Kunisaki, Chikara; Masuda, Munetaka

2015-10-01

A 77-year-old man underwent total gastrectomy with D1+ lymph node dissection after being diagnosed with cT4aN2M0, cStage ⅢB gastric cancer. Peritoneal dissemination was detected in the bursa omentalis. The pathological diagnosis after surgery was pT4aN3b (21/41) M1 (P1). He was treated with 6 courses of S-1 chemotherapy. Two years after surgery, upper gastrointestinal endoscopy revealed the presence of a tumor in the mid-thoracic esophagus. It was diagnosed to as metastatic esophageal cancer and treated with combination chemotherapy consisting of docetaxel (25 mg/m2, days 1, 8, 15) and cisplatin (25 mg/m2, days 1, 8, 15) in a 28-day cycle. A clinically complete response was observed after 5 courses of chemotherapy. Currently, the patient is alive with no signs of recurrence 12 months after the initial recurrence.

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

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Choi, Il Jung; Park, Eunku Seul; Han, Myung Seok; Choi, Youngmin; Je, Goo Hwa; Kim, Hyun Ho

2008-01-01

Objective To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer. Methods We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m2 cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m2/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin. Results Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease. Conclusion CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated. PMID:19471554

Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma

Directory of Open Access Journals (Sweden)

Ming-Chun Ma

2014-01-01

Full Text Available Advanced hepatocellular carcinoma (HCC remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m2 and cisplatin (50 mg/m2 infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I and those who received several cycles (group II. The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P<0.0001. The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P<0.0001. The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT.

Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

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Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

2012-10-01

This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

Science.gov (United States)

Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

2011-01-01

Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer

International Nuclear Information System (INIS)

Wang, Yuxia; Gao, Ying; Cheng, Hairong; Yang, Guichun; Tan, Wenhua

2015-01-01

Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. - Highlights: • STC2 was upregulated in cervical cancer and promoted cervical cancer cell proliferation. • Cisplatin resistant cells had elevated STC2 levels and enhanced proliferation. • STC2 regulated cisplatin chemosensitivity in cervical cancer cells. • STC2 regulated the activity of the MAPK signaling pathway.

Intraperitoneal chemotherapy for advanced ovarian and peritoneal cancers in patients following interval debulking surgery or primary cytoreductive surgery: Tom Baker Cancer Centre experience from 2006 to 2009.

Science.gov (United States)

Nelson, Gregory; Lucero, Carlos Aspe; Chu, Pamela; Nation, Jill; Ghatage, Prafull

2010-03-01

To describe our experience with cisplatin- and paclitaxel-based IP chemotherapy in patients treated initially with either neoadjuvant chemotherapy and interval debulking surgery (IDS) or primary cytoreductive surgery (PCRS). We performed a retrospective review of the records of 67 patients (38 IDS, 29 PCRS) enrolled in the intraperitoneal (IP) chemotherapy program at the Tom Baker Cancer Centre between 2006 and 2009. Information pertaining to patient demographics, IP chemotherapy toxicity, and catheter complications was extracted, and the median time to recurrence was calculated. Most patients in the study were aged 50 to 70 years and had a diagnosis of stage III serous ovarian cancer. Overall, 295/393 IP cycles (75%) were successfully administered. The proportion of patients completing six cycles of chemotherapy in the IDS and PCRS groups was 53% and 59%, respectively. Frequent (> 25%) Grade 1 to 2 chemotherapy toxicities included fatigue, peripheral neuropathy, and nausea. Catheter complications were observed in 34% of patients (23/67). The recurrence rates for patients completing four or more cycles of IP chemotherapy in the IDS and PCRS groups were 58% and 35%, respectively, with the median time to recurrence approximately one year. Although IP chemotherapy is well tolerated in both IDS and PCRS patients, the median time to recurrence is shorter than expected.

Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer

International Nuclear Information System (INIS)

Tedesco, Karen L.; Berlin, Jordan; Blanke, Charles D.; Teng Ming; Choy, Hak; Roberts, John; Beauchamp, R. Daniel; Leach, Steve; Wyman, Ken; Tarpley, John; Shyr, Yu; Caillouette, Carol; Chakravarthy, Bapsi

2005-01-01

Purpose: Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer. Methods: Chemotherapy consisted of i.v. cisplatin 80 mg/m 2 (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m 2 increments, starting at 200 mg/m 2 /d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy. Results: Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m 2 /d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery. Conclusion: The recommended UFT dose for Phase II studies is 200 mg/m 2 /d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy

Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

International Nuclear Information System (INIS)

Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng; Xia, Qiang

2012-01-01

Highlights: ► miR-199a-5p levels were significantly decreased after cisplatin treatment. ► Cisplatin treatment induced autophagy activation. ► Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell

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Xu, Ning; Zhang, Jianjun; Shen, Conghuan; Luo, Yi; Xia, Lei; Xue, Feng [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China); Xia, Qiang, E-mail: xiaqiang1@yahoo.com.cn [Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, 1630 Dongfang Road, Shanghai 200127, People' s Republic of China (China)

2012-07-13

Highlights: Black-Right-Pointing-Pointer miR-199a-5p levels were significantly decreased after cisplatin treatment. Black-Right-Pointing-Pointer Cisplatin treatment induced autophagy activation. Black-Right-Pointing-Pointer Cisplatin-induced downregulation of miR-199a-5p increases drug resistance by activating autophagy in HCC cell. -- Abstract: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Systemic chemotherapy plays an important role in the treatment of patients with advanced liver cancer. However, chemoresistance to cisplatin is a major limitation of cisplatin-based chemotherapy in the clinic, and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-199a-5p levels were significantly reduced in HCC patients treated with cisplatin-based chemotherapy. Cisplatin treatment also resulted in decreased miR-199a-5p levels in human HCC cell lines. Forced expression of miR-199a-5p promoted cisplatin-induced inhibition of cell proliferation. Cisplatin treatment activated autophagy in Huh7 and HepG2 cells, which increased cell proliferation. We further demonstrated that downregulated miR-199a-5p enhanced autophagy activation by targeting autophagy-associated gene 7 (ATG7). More important, autophagy inhibition abrogated miR-199a-5p downregulation-induced cell proliferation. These data demonstrated that miR-199a-5p/autophagy signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

A case of Esophageal small cell carcinoma with multiple liver metastases responding to chemotherapy with Irinotecan plus Cisplatin

International Nuclear Information System (INIS)

Endo, K.; Kohnoe, S.; Toh, Y.; Haraguchi, M.; Okamura, T.; Nishiyama, K.; Baba, H.; Maehara, Y.

2005-01-01

We report a case of small cell esophageal carcinoma (SCEC) with multiple liver metastases treated with some success by chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP). Radiologic and endoscopic examination of a 75-year-old man with multiple liver tumors disclosed a 4.0-cm type 2 tumor in the middle third of the esophagus. An endoscopically obtained biopsy specimen was diagnosed as undifferentiated small cell carcinoma. Multiple liver metastases were confirmed but lymph node metastases and distant metastases other than those in the liver were not detected. After six courses of chemotherapy with CPT-11 plus CDDP, the primary lesion showed complete response and liver metastases showed partial response. However, because all lesions almost immediately relapsed or progressed, arterial infusion chemotherapy for liver metastases and radiation for the primary lesion were given as second-line treatment. The primary lesion showed complete response with radiation. Arterial infusion chemotherapy prevented the progression of liver metastases once, but the patient died of liver failure at last. No distant lesions including metastatic lymph nodes were confirmed over the course of his illness, and the patient survived for a year after first diagnosis. Although the prognosis of SCEC is quite unfavorable due to highly aggressive behavior, a better prognosis is possible with effective chemotherapy and second-line treatment is important in improving prognosis

Biodistribution and dosimetry of 195mPt-cisplatin in normal volunteers

OpenAIRE

Sathekge, M.; Wagener, J.; Smith, S.V.; Soni, N.; Zeevaart, J.R.

2013-01-01

195mPt-cisplatin is regarded as a promising imaging agent for optimizing dosage in patients receiving cisplatin chemotherapy. We investigated the whole-body distribution and radiation dosimetry of 195mPt-cisplatin in humans. Methods: Whole-body scans were obtained up to 144 h after intravenous injection of 112.4 MBq 195mPt-cisplatin in each of five subjects. Blood samples were taken at various times up to 144 h after injection. Urine was collected up to 114 h aft...

Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck

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Tribius, Silke; Kilic, Yasemin [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Kronemann, Stefanie [Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schroeder, Ursula [Dept. of Head and Neck Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Hakim, Samer [Dept. of Oro-Maxillo-Facial Surgery, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Rades, Dirk [Dept. of Radiation Oncology, Univ. Medical Center Hamburg-Eppendorf, Hamburg (Germany); Dept. of Radiation Oncology, Univ. Hospital Schleswig-Holstein, Campus Luebeck (Germany)

2009-10-15

Background and purpose: the optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33; n = 54) or two courses cisplatin (20 mg/m{sup 2}/d1-5 + 29-33) + 5-fluorouracil (5-FU; 600 mg/m{sup 2}/d1-5 + 29-33; n = 74). Results: at least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: two courses of fractionated cisplatin (20 mg/m{sup 2}/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. (orig.)

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

Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line

OpenAIRE

Zhang Ping; Zhang Zhiyuan; Zhou Xiaojian; Qiu Weiliu; Chen Fangan; Chen Wantao

2006-01-01

Abstract Background Cisplatin is widely used for chemotherapy of head and neck squamous cell carcinoma. However, details of the molecular mechanism responsible for cisplatin resistance are still unclear. The aim of this study was to identify the expression of genes related to cisplatin resistance in oral squamous cell carcinoma cells. Methods A cisplatin-resistant cell line, Tca/cisplatin, was established from a cisplatin-sensitive cell line, Tca8113, which was derived from moderately-differe...

Molecular mechanisms of cisplatin resistance in cervical cancer

Directory of Open Access Journals (Sweden)

Zhu H

2016-06-01

Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance

Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

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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)

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)

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.

Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial.

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Hale, Matthew D; Nankivell, Matthew; Hutchins, Gordon G; Stenning, Sally P; Langley, Ruth E; Mueller, Wolfram; West, Nicholas P; Wright, Alexander I; Treanor, Darren; Hewitt, Lindsay C; Allum, William H; Cunningham, David; Hayden, Jeremy D; Grabsch, Heike I

2016-11-22

Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated. PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0.006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1.94 (1.39-2.71), unlike those with lower or higher PoT (PoT70% (N=28, HR:0.65 (0.36-1.18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0.0402. This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial that the proportion of tumour in the pre-chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification.Proportion of tumour is a novel biomarker which can be measured in the pre-treatment diagnostic biopsy and which may enable the identification of chemotherapy responders and non-responders among patients with oesophageal carcinoma. Proportion of tumour could easily become part of the routine reporting of oesophageal cancer biopsies and may aid in managing patients with borderline resectable cancer.

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

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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.)

The renoprotective activity of hesperetin in cisplatin induced nephrotoxicity in rats: Molecular and biochemical evidence.

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Kumar, Mukesh; Dahiya, Vicky; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Lahkar, Mangala

2017-05-01

Nephrotoxicity remain a major life-threatening complication in cancer patients on cisplatin chemotherapy. In this study, we investigated the protective effect and possible cellular mechanism of the hesperetin, a naturally-occurring bioflavonoid against cisplatin-induced renal injury in rats. Hesperetin was administered at a dose of 50mg/kg and 100mg/kg orally for 10days and cisplatin (7.5mg/kg, ip) was administered on the 5th day of experiment. Cisplatin induced nephrotoxicity was evidenced by alteration in the level of markers such as blood urea nitrogen, creatinine, serum albumin and severe histopathological changes in kidney. Cisplatin administration also resulted in significant increase in the tissue oxidative stress and inflammatory cytokines. The level of antioxidants enzymes were decreased significantly in the cisplatin administered rats. Hesperetin treatment (50mg/kg and 100mg/kg) normalized the renal function by attenuation of the cisplatin-induced oxidative stress, lipid peroxidation, and inflammatory cytokines and histopathological alterations. On the basis of these experimental findings our present study postulate that co-administration of hesperetin with cisplatin chemotherapy may be promising preventive approach to limit the major mortal side effect of cisplatin. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

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Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

2010-08-01

Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

Case report: An unusual case of cisplatin induced paralytic ileus

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Rosdiana Abd Rahim

2017-12-01

Full Text Available Background: Ileus is a failure of normal intestinal motility in the absence of mechanical obstruction. Ileus is thought to result from an imbalance between sympathetic and parasympathetic motor activity, resulting in intestinal atony. Few anti-cancer therapies reported to be associated with paralytic ileus, such as vincristine, vinblastine and paclitaxel. It is thought as a consequences of autonomic neuropathy. Here we present a paralytic ileus experience during cisplatin therapy. Case presentation: We present a case of 57 years old gentleman with diagnosis of metastatic nasopharyngeal carcinoma to lung and multiple bones who develop paralytic ileus following chemotherapy cisplatin and fluorouracil. The patient complained of abdominal discomfort with bloating and not tolerating Ryle tube feeding started 3 days after completion of cycle 2 cisplatin & fluorouracil infusion chemotherapy. No vomiting and still passing out small amount of stool everyday. Physical examination revealed abdominal distension, lower abdominal tenderness, sluggish bowel sound and empty rectum. The blood investigations for electrolyte, renal and hepatic function, and amylase were normal. Abdominal computerized tomography showed diffuse dilatation of small and large bowels extending to the rectum, without any obstructive pathology which was consistent with paralytic ileus. He was hospitalized and treated with nasogastric decompression and partial parenteral nutrition started. The symptoms improved after few days of decompression. Conclusion: Peripheral neuropathy due to cisplatin has been well described, however paralytic ileus has not previously been reported in medical literature. From patient self-reported outcome study, however, this complication was not that uncommon, and was reported by 0.76% of patients receiving cisplatin, especially people who are male, 60 years old and more, have been taking the drug for more than 1 month, also take medication dexamethasone. The

Rapidly Growing Esophageal Carcinosarcoma Reduced by Neoadjuvant Radiotherapy Alone

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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.

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

Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

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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.

Multiparametric analysis of cisplatin-induced changes in cancer cells using FLIM

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Shirmanova, Marina V.; Sergeeva, Tatiana F.; Gavrina, Alena I.; Dudenkova, Varvara V.; Lukyanov, Konstantin A.; Zagaynova, Elena V.

2018-02-01

Cisplatin is an effective anticancer drug commonly used in the treatment of solid tumors. Although DNA is considered as the primary target, the cisplatin action at the cellular level remains unknown. Advanced fluorescence microscopy techniques allow probing various physiological and physicochemical parameters in living cells and tissues with unsurpassed sensitivity in real time. This study was focused on the investigation of cellular bioenergetics and cytosolic pH in colorectal cancer cells during chemotherapy with cisplatin. Special attention was given to the changes in cisplatininduced apoptosis that was identified using genetically encoded FLIM/FRET sensor of caspase-3 activity. Metabolic measurements using FLIM of the metabolic cofactor NAD(P)H showed decreased contribution from free NAD(P)H (a1, %) in all treated cells with more pronounced alterations in the cells undergoing apoptosis. Analysis of cytosolic pH using genetically encoded fluorescent sensor SypHer1 revealed a rapid increase of the pH value upon cisplatin exposure irrespective of the induction of apoptosis. To the best of our knowledge, a simultaneous assessment of metabolic state, cytosolic pH and caspase-3 activity after treatment with cisplatin was performed for the first time. These findings improve our understanding of the cell response to chemotherapy and mechanisms of cisplatin action.

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

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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

Enhancing the efficacy of cisplatin in ovarian cancer treatment – could arsenic have a role

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Helm C William

2009-01-01

Full Text Available Abstract Ovarian cancer affects more than 200,000 women each year around the world. Most women are not diagnosed until the disease has already metastasized from the ovaries with a resultant poor prognosis. Ovarian cancer is associated with an overall 5 year survival of little more than 50%. The mainstay of front-line therapy is cytoreductive surgery followed by chemotherapy. Traditionally, this has been by the intravenous route only but there is more interest in the delivery of intraperitoneal chemotherapy utilizing the pharmaco-therapeutic advantage of the peritoneal barrier. Despite three large, randomized clinical trials comparing intravenous with intraperitoneal chemotherapy showing improved outcomes for those receiving at least part of their chemotherapy by the intraperitoneal route. Cisplatin has been the most active drug for the treatment of ovarian cancer for the last 4 decades and the prognosis for women with ovarian cancer can be defined by the tumor response to cisplatin. Those whose tumors are innately platinum-resistant at the time of initial treatment have a very poor prognosis. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin and will ultimately succumb to the disease. Improving the efficacy of cisplatin could have a major impact in the fight against this disease. Arsenite is an exciting agent that not only has inherent single-agent tumoricidal activity against ovarian cancer cell lines but also multiple biochemical interactions that may enhance the cytotoxicity of cisplatin including inhibition of deoxyribose nucleic acid (DNA repair. In vitro studies suggest that arsenite may enhance the activity of cisplatin in other cell types. Arsenic trioxide is already used clinically to treat acute promyelocytic leukemia demonstrating its safety profile. Further research in ovarian cancer is warranted to define

Predictive factors for response and prognostic factors for long-term survival in consecutive, single institution patients with locally advanced and/or metastatic transitional cell carcinoma following cisplatin-based chemotherapy

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Jessen, Christian; Agerbaek, Mads; Von Der Maase, Hans

2009-01-01

PURPOSE: The study was undertaken to identify pre-treatment clinical and histopathological factors of importance for response and survival after cisplatin-based combination chemotherapy, in patients with locally advanced or metastatic transitional cell carcinoma of the urothelium. PATIENTS...

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

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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

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

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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

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

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Chien Chih-Yen

2011-03-01

Full Text Available Abstract Background This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1 expression on response to cisplatin-based induction chemotherapy (IC followed by concurrent chemoradiation (CCRT in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC patients. Methods Fifty-seven patients with locally advanced unresectable HNSCC who received cisplatin-based IC followed by CCRT from January 1, 2006 through January 1, 2008. Eligibility criteria included presence of biopsy-proven HNSCC without a prior history of chemotherapy or radiotherapy. Immunohistochemistry was used to assess ERCC1 expression in pretreatment biopsy specimens from paraffin blocks. Clinical parameters, including smoking, alcohol consumption and betel nuts chewing, were obtained from the medical records. Results The 12-month progression-free survival (PFS and 2-year overall survival (OS rates of fifty-seven patients were 61.1% and 61.0%, respectively. Among these patients, thirty-one patients had low ERCC1 expression and forty-one patients responded to IC followed by CCRT. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 12-month PFS rates (73.3% vs. 42.3%, p Conclusions Our study suggest that a high expression of ERCC1 predict a poor response and survival to cisplatin-based IC followed by CCRT in patients with locally advanced unresectable HNSCC in betel nut chewing area.

A prospective and randomized study of radiotherapy, sequential chemotherapy radiotherapy and concomitant chemo therapy-radiotherapy in unresectable non small cell carcinoma of the lung

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Dasgupta Anirban

2006-01-01

Full Text Available Purpose: Treatment of advanced Non small cell lung cancer (NSCLC often produces dismal results. Combination of available treatment modalities has reportedly improved the outcome. A prospectively randomized trial was conducted, comparing combined treatment modalities versus radiotherapy alone, in treatment of unresectable NSCLC. Materials and Methods: A total of 103 patients were randomized to three groups. In group ′A′, 32 patients received radiotherapy alone (6500 cGy/30 fraction. In group ′B′, 35 patients received neoadjuvant chemotherapy (Cisplatin 80 mg/m2 on day 1 and Etoposide 100 mg/m day 1-3 intravenously q3 weeks for 3 cycles, followed by radiotherapy (6000 cGy/30 fractions and 3 more cycles of Chemotherapy, with the same regimen. In group ′C′, 36 patients received radiotherapy (5000 cGy/25 fractions with concurrent chemotherapy (ciplatin 20 mg/m2 + Etoposide 75 mg/m2 intravenously on day 1-5 and day 22-26, followed by 2 more cycles of chemotherapy,q3 weeks with the same regimen. Results: Initial treatment responses were significantly higher in group ′B′ ( P P Conclusion: Addition of chemotherapy with radiation in unresectable NSCLC improves response rates, time to tumour progression and disease free survival, though the same effect is not translated in overall survival.

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

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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.

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

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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.

Vinorelbine as neoadjuvant chemotherapy in advanced cervical carcinoma.

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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

Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients

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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

[Conversion Therapy Using Etoposide and Cisplatin Chemotherapy for Liver Metastases from Advanced Gastric Mixed Adenoneuroendocrine Carcinoma - A Case Report].

Science.gov (United States)

Inaba, Yoko; Fujita, Maiko; Ninomiya, Riki; Hashimoto, Daijo

2017-11-01

Gastric mixed adenoneuroendocrine carcinoma(MANEC)with multiple liver metastases is a rare condition with most data being derived from case reports. We present a case with liver metastases from gastric MANEC that respond remarkably to chemotherapy. Sixty-one-year-old male with severe anemia referred to surgical consultation due to advanced gastric cancer with multiple liver metastases. To relieve uncontrollable tumor bleeding, simple distal gastrectomy for symptom palliation was performed. Based on the tentative diagnosis with gastric poorly differentiated adenocarcinoma, a course of TS-1 and oxaliplatin therapy was administrated. Thereafter final diagnosis with neuroendocrine carcinoma with tubular adenocarcinoma was made, and the chemotherapy was switched to etoposide and cisplatin. Follow up abdominal CT scan after the third course of the therapy showed remarkable tumor shrinkages(PR). In anticipation of the chemotherapy effects in the adjuvant setting, we performed liver metastasectomy for curative intent. Two of 6 resected liver specimens showed no viable cancer cells at all (pCR). However, immediately after the surgery, multiple liver metastases developed, and the recurrent masses had kept growing up rapidly. The third line carboplatin and etoposide chemotherapy was given once but was withdrawn because of bone marrow suppression. At the present, the patient is alive with recurrent diseases for 18 months after initial diagnosis.

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.

[50th anniversary of cisplatin].