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Sample records for survival locoregional control

  1. Locoregional control and survival after breast conserving therapy

    International Nuclear Information System (INIS)

    Rajer, M.; Majdic, E.

    2006-01-01

    Background. The purpose of our study was to present a 5-year survival and locoregional control rates in breast cancer patients and to establish eventual impact of the treatment and patient characteristics on locoregional control and survival. Methods. From January 1998 to December 1999 564 stage 1 and 2 breast cancer patients were treated with breast conserving therapy. We evaluated the following characteristics: age, histological diagnosis, grade, size, number of metastatic lymph nodes, hormonal receptor status, extensive intraductal component (EIDC), vascular invasion, pathologic tumour margins, type of surgery and use of adjuvant therapy. Results. The mean age of our patients was 54.2 years. Invasive ductal carcinoma was the most common diagnosis (82.4%), followed by invasive lobular carcinoma (10.6%). Most of the tumours were grade 2. Seventy-two % of patients had T1 tumours, 24% T2 and 3% T is tumours. Metastatic lymph nodes were present in 44% of patients. All patients were treated with breast conserving surgery followed by radiotherapy (RT). Fifty % of patients received adjuvant chemotherapy and/ or hormonal therapy. The 5-year survival rate was 88.5%. Tumour size, number of metastatic lymph nodes, grade, hormonal receptors and vascular invasion proved to be statistically significant prognostic factors for the survival, while age and histological diagnosis were not. Local recurrence developed in 4.3% of our patients, while in 3.4% regional recurrence developed. Conclusions. Breast conserving surgery followed by RT was associated with good rates of locoregional control and survival, comparable to those reported in the literature. (author)

  2. Influence of locoregional irradiation on local control and survival in breast cancer

    International Nuclear Information System (INIS)

    Cutuli, B.

    1998-01-01

    Locoregional control is a crucial step in the achievement of breast cancer cure. In ductal carcinoma in situ, breast irradiation significantly reduces the rates of local recurrence whatever the histological subtypes, as demonstrated by the NSABP-B17 trial (25.8 % of local recurrences without radiotherapy vs. 11.4 % with radiotherapy). In infiltrating breast carcinomas, complementary breast irradiation has been shown to significantly improve the local control and slightly the overall survival in five randomized trials. Following mastectomy, locoregional irradiation clearly reduces the chest wall and nodal relapse rates, especially in case of lesions more than 5 cm or with nodal involvement and/or large lymphatic or vascular emboli. Two recent randomized trials confirmed the benefit of well-adapted locoregional irradiation in all subgroups, especially in patients with one to three axillary involves nodes. In the Danish trial (including pre-menopausal high-risk women), radiotherapy reduced locoregional relapses from 32 to 9 % (p<0.001) and increased the 10-year survival rate from 45 to 54% (p<0.001). In the Canadian trial, locoregional relapse rate decreased from 25 to 13 % and the 10-year survival rate increased from 56 to 65 %. The meta-analysis published in 1995 by the EBCTCG showed only a modest benefit due to locoregional irradiation in breast cancer. However, when small or old trials were excluded due to imperfect methodology or inadequate irradiation techniques, the benefit of modern radiotherapy became much more evident in a population of 7,840 patients. Locoregional irradiation appears to be able to reduce the risk of metastatic evolution occurring after local or nodal relapse and must be integrated in a multidisciplinary strategy. Treatment toxicity (especially toxicity due to irradiation of internal mammary nodes) is of special concern, as anthracycline-based chemotherapy is prescribed more often. The use of a direct field, with at least 60 % of the dose

  3. The impact of locoregional control and the survival of patient with cancer tried with radiotherapy

    International Nuclear Information System (INIS)

    Perez, Carlos

    1999-01-01

    The cost of the treatment of the fault of locoregional control of a neoplasia is bigger 5 at 10 that the initial treatment, when this it is successful. In the last 10 years every time it is spoken more of the treatment of the locoregional cancer. The surgery and the radiotherapy (intermediate dose 4500 to 5000 cGy) they are used to remove the primary tumor, the ganglion and the extensions of locoregional micro metastases. The chemotherapy is used to supplement the locoregional control and to give systemic treatment of distal micro metastases, it is spoken of the advantages of using the surgery, the chemotherapy and the radiotherapy and the kindness of each one inside this investigation

  4. Radiotherapy in supraglottic carcinoma -with respect to locoregional control and survival-

    International Nuclear Information System (INIS)

    Nam, Taek Keun; Oh, Yoon Kyeong; Chung, Woong Ki; Cho, Jae Shik; Ahn, Sung Ja; Nah, Byung Sik

    2002-01-01

    A retrospective study was undertaken to determine the role of conventional radiotherapy with or without surgery for treating a supraglottic carcinoma in terms of the local control and survival. From Jan. 1986 to Oct. 1996, a total of 134 patients were treated for a supraglottic carcinoma by radiotherapy with or without surgery. Of them, 117 patients who had completed the radiotherapy formed the base of this study. The patients were redistributed according to the revised AJCC staging system (1997). The number of patients of stage I, II, III, IVA, IVB were 6 (5%), 16 (14%), 53 (45%), 32 (27%), 10 (9%), respectively. Eighty patients were treated by radical radiotherapy in the range of 61.2 ∼ 79.2 Gy (mean:69.2 Gy) to the primary tumor and 45.0 ∼ 93.6 Gy (mean:54.0 Gy) to regional lymphatics. All patients with stage I and IVB were treated by radiotherapy alone. Thirty-seven patients underwent surgery plus postoperative radiotherapy in the range of 45.0 ∼ 68.4 Gy (mean:56.1 Gy) to the primary tumor bed and 45.0 ∼ 59.4 Gy (mean:47.2 Gy) to the regional lymphatics. Of them, 33 patients received a total laryngectomy (± lymph node dissection), three had a supraglottic horizontal laryngectomy (± lymph node dissection), and one had a primary excision alone. The 5-year survival rate (5YSR) of all patients was 43%. The 5YSR of the patients with stage I + II, III + IV were 49.9%, 41.2%, respectively (ρ = 0.27). However, the disease-specific survival rate of the patients with stage I (n=6) was 100%. The 5YSRs of patients who underwent surgery plus radiotherapy (S + RT) vs radiotherapy alone (RT) in stage II, III, IVA were 100% vs 43% (ρ = 0.17), 62% vs 52% (ρ =0.32), 58% vs 6% (ρ < 0.001), respectively. The 5-year actuarial locoregional control rate (5YLCR) of all the patients was 57%. The 5YLCR of the patients with stage I, II, III, IVA, IVB was 100%, 74%, 60%, 44%, 30%, respectively (ρ = 0.008). The 5YLCR of the patients with S + RT vs RT in stage II, III, IVA

  5. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-01-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p 70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of ≥12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of ≥12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells was an independent prognostic factor for locoregional control and survival in patients irradiated for NSCLC. EPO-R expression showed a trend

  6. Anemia: friend or foe? Low hemoglobin is associated with decreased survival, loco-regional control and late complications: a secondary analysis of RTOG 85-27

    International Nuclear Information System (INIS)

    Lee, W. Robert; Berkey, B.; Marcial, V.; Fu, K.K.; Cooper, J. S.; Vikram, B.; Coia, L.R.; Rotman, M.; Ortiz, H.

    1997-01-01

    Purpose: Classical teaching holds that hypoxia reduces the lethal effects of ionizing radiation. Many reports have correlated low hemoglobin (Hgb) levels with reduced loco-regional control (LRC) following radiotherapy (RT) suggesting that anemia may be associated with tumor hypoxia. If hypoxia protects tumors from the lethal effects of ionizing radiation then it might protect normal tissues in a similar fashion. The purpose of the present study was to examine the effect of Hgb level on the LRC, survival and late complications in patients with advanced head and neck cancer treated with conventional radiotherapy with or without a hypoxic cell sensitizer. Methods: From March 1988 to September 1991, 521 patients with Stage III or IV squamous cell carcinoma of the head and neck were entered onto a randomized trial examining the addition of etanidazole (SR 2508) to conventional RT (66 Gy in 33 fractions to 74 Gy in 37 fractions, 5 days a week). Hgb levels were stratified as high (≥ 14.5 grams-percent for men, ≥ 13.0 grams-percent for women) or low (<14.5 for men, <13.0 for women). Loco-regional failure rates were calculated using the cumulative incidence approach. Overall survival was estimated according to the Kaplan-Meier method. Late RT toxicity was scored according to the RTOG morbidity scale. Differences in rates of LRC, survival and late complications were tested by the Cox proportional hazard model. The median follow-up of surviving patients was 57 months with a range of 1-7.5 years. Results: Of 504 eligible patients, 451 had Hgb measured prior to the second week of RT. One hundred and sixty-two patients (35.9%) were classified as having a high Hgb (HH) and 289 (64.1%) patients were classified as having a low Hgb (LH). Patients in the LH group had significantly lower survival and a trend towards lower LRC and late RT complications (see Table). Conclusion: Low Hgb levels are associated with a statistically significant reduction in survival and a trend towards

  7. Adding concurrent chemotherapy to postoperative radiotherapy improves locoregional control but Not overall survival in patients with salivary gland adenoid cystic carcinoma—a propensity score matched study

    International Nuclear Information System (INIS)

    Hsieh, Cheng-En; Lin, Chien-Yu; Lee, Li-Yu; Yang, Lan-Yan; Wang, Chun-Chieh; Wang, Hung-Ming; Chang, Joseph Tung-Chieh; Fan, Kang-Hsing; Liao, Chun-Ta; Yen, Tzu-Chen; Fang, Ku-Hao; Tsang, Yan-Ming

    2016-01-01

    To compare the long-term outcomes in patients with salivary gland adenoid cystic carcinoma (SGACC) treated with post-operative chemoradiotherapy (POCRT) versus post-operative radiotherapy (PORT). We retrospectively reviewed the records of 91 SGACC patients treated with surgery followed by PORT (n = 58) or POCRT (n = 33) between 2000 and 2013. Treatment outcomes between groups were compared using propensity score matching (1:1 nearest neighbor). The median radiation dose was 66 Gy, and patients were followed up for a median of 71 months. Cisplatin-based concurrent regimens were the most commonly used chemotherapy schedules. In the entire study cohort, patients undergoing POCRT showed a trend toward higher locoregional control (LRC) rates than those treated with PORT alone at both 5 and 8 years (97 and 97 % versus 84 and 79 %, respectively; P = .066). Distant metastases were the most common form of treatment failure and occurred in 31 (34 %) patients (PORT, n = 17; POCRT, n = 14). After propensity score matching (33 pairs), patients receiving POCRT had 5- and 8 year LRC rates of 97 and 97 %, respectively, compared with 79 and 67 % for patients treated with PORT alone (P = .017). The two groups did not differ significantly in terms of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). However, a significantly better opioid-requiring pain-free survival (ORPFS) was achieved in POCRT group (P = .038). Subgroup analyses revealed that patients with stage III − IV disease (P = .040 and .017), positive surgical margins (P = .011 and .050), or perineural invasion (P = .013 and .035) had significantly higher 5- and 8 year LRC and ORPFS when treated with POCRT, respectively. In SGACC patients, adding concurrent chemotherapy to PORT may increase LRC and ORPFS rates, particularly in presence of stage III − IV disease, positive surgical margins, or perineural invasion. However, no significant differences in DMFS, DFS, and OS were

  8. Adjuvant Medications That Improve Survival after Locoregional Therapy.

    Science.gov (United States)

    Boas, F Edward; Ziv, Etay; Yarmohammadi, Hooman; Brown, Karen T; Erinjeri, Joseph P; Sofocleous, Constantinos T; Harding, James J; Solomon, Stephen B

    2017-07-01

    To determine if outpatient medications taken at the time of liver tumor embolization or ablation affect survival. A retrospective review was done of 2,032 liver tumor embolization, radioembolization, and ablation procedures performed in 1,092 patients from June 2009 to April 2016. Pathology, hepatocellular carcinoma (HCC) stage (American Joint Committee on Cancer), neuroendocrine tumor (NET) grade, initial locoregional therapy, overall survival after initial locoregional therapy, Child-Pugh score, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index, and outpatient medications taken at the time of locoregional therapy were analyzed for each patient. Kaplan-Meier survival curves were calculated for patients taking 29 medications or medication classes (including prescription and nonprescription medications) for reasons unrelated to their primary cancer diagnosis. Kaplan-Meier curves were compared using the log-rank test. For patients with HCC initially treated with embolization (n = 304 patients), the following medications were associated with improved survival when taken at the time of embolization: beta-blockers (P = .0007), aspirin (P = .0008) and other nonsteroidal antiinflammatory drugs (P = .009), proton pump inhibitors (P = .004), and antivirals for hepatitis B or C (P = .01). For colorectal liver metastases initially treated with ablation (n = 172 patients), beta-blockers were associated with improved survival when taken at the time of ablation (P = .02). Aspirin and beta-blockers are associated with significantly improved survival when taken at the time of embolization for HCC. Aspirin was not associated with survival differences after locoregional therapy for NET or colorectal liver metastases, suggesting an HCC-specific effect. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  9. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    International Nuclear Information System (INIS)

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-01-01

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

  10. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer

    International Nuclear Information System (INIS)

    Hentschel, Maria; Appold, Steffen; Baumann, Michael; Schreiber, Andreas; Abolmaali, Nasreddin; Abramyuk, Andrij; Doerr, Wolfgang; Kotzerke, Joerg; Zoephel, Klaus

    2011-01-01

    Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV max ), the average SUV (SUV mean ) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV max of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT (ΔSUV max10/20 ≥ 50%) than for patients with ΔSUV max20 max from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV max , especially ΔSUV max10/20 , for an early estimation of therapy outcome. Confirmatory studies are warranted. (orig.)

  11. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hentschel, Maria [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Appold, Steffen; Baumann, Michael [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Schreiber, Andreas [Hospital Dresden-Friedrichstadt, Department of Radiotherapy, Dresden (Germany); Abolmaali, Nasreddin [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Institute and Polyclinic of Diagnostic Radiology, Dresden (Germany); Abramyuk, Andrij [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany); Doerr, Wolfgang [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Radiotherapy and Radiation Oncology, Dresden (Germany); Kotzerke, Joerg; Zoephel, Klaus [Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, Clinic and Polyclinic of Nuclear Medicine, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology, OncoRay, National Center for Radiation Research in Oncology Dresden, Dresden (Germany)

    2011-07-15

    Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV{sub max}), the average SUV (SUV{sub mean}) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV{sub max} of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT ({delta}SUV{sub max10/20} {>=} 50%) than for patients with {delta}SUV{sub max20} < 50% (2-year OS = 38%; p = 0.02; 2-year LRC 40%; p = 0.06). A pretreatment GTV PET below the median of 10.2 ml predicted a better 2-year OS (34% for GTV PET {>=} 10.2 ml vs 83% for GTV PET < 10.2 ml; p = 0.02). The decrease of SUV{sub max} from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV{sub max}, especially {delta}SUV{sub max10/20}, for an early estimation of therapy outcome. Confirmatory studies are warranted. (orig.)

  12. Surgical resection of solitary distant metastasis from locoregionally controlled advanced hypopharyngeal malignancy: A ray of hope

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    Chelakkot G Prameela

    2018-01-01

    Full Text Available Head and neck malignancies have always been challenging for the clinician, both with regards to locoregional control and distant metastasis. Aggressive approaches translate to an acceptable locoregional control, but distant failures pose a dilemma. Newer, sophisticated, imaging modalities have helped in early diagnosis of solitary metastasis, and in turn have opened up an array of interventional procedures, which to some extent improve the disease-free survival and quality of life, as was seen in the present case of locoregionally controlled advanced hypopharyngeal malignancy who presented with solitary distant metastasis. Still, diligent care needs to be taken not to aggravate the scenario with these interventions.

  13. The effect of external beam radiotherapy volume on locoregional control in patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer

    International Nuclear Information System (INIS)

    Kim, Tae Hyun; Kim, Sang Soo; Cho, Kwan Ho; Shin, Kyung Hwan; Chung, Ki-Wook; Lee, You Jin; Park, Chan Sung; Lee, Eun Kyung; Kim, Tae Sung; Kim, Seok Ki; Jung, Yoo Seok; Ryu, Jun Sun

    2010-01-01

    We evaluated outcomes of patients treated with external beam radiotherapy (EBRT) for locoregionally advanced or recurrent nonanaplastic thyroid cancer and analyzed the effect of EBRT volume on locoregional control. This study included 23 patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer who were treated with EBRT. Two different EBRT target volumes were executed as follows: 1) limited field (LF, n = 11) included the primary (involved lobe) or recurrent tumor bed and the positive nodal area; 2) elective field (EF, n = 12) included the primary (involved lobe) or recurrent tumor bed and the regional nodal areas in the cervical neck and upper mediastinum. Clinical parameters, such as gender, age, histologic type, recurrence, stage, thyroglobulin level, postoperative residuum, radioiodine treatment, and EBRT volume were analyzed to identify prognostic factors associated with locoregional control. There were no significant differences in the clinical parameter distributions between the LF and EF groups. In the LF group, six (55%) patients developed locoregional recurrence and three (27%) developed distant metastasis. In the EF group, one (8%) patient developed locoregional recurrence and one (8%) developed a distant metastasis. There was a significant difference in locoregional control rate at 5 years in the LF and EF groups (40% vs. 89%, p = 0.041). There were no significant differences in incidences of acute and late toxicities between two groups (p >0.05). EBRT with EF provided significantly better locoregional control than that of LF; however, further larger scaled studies are warranted

  14. Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

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    Merrell, Kenneth W.; Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Quevedo, J. Fernando [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Harmsen, William S. [Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States); Kendrick, Michael L. [Department of General Surgery, Mayo Clinic, Rochester, Minnesota (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Hallemeier, Christopher L., E-mail: hallemeier.christopher@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2016-03-01

    Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as

  15. Locoregional control in infants with neuroblastoma: role of radiation therapy and late toxicity

    International Nuclear Information System (INIS)

    Paulino, Arnold C.; Mayr, Nina A.; Simon, James H.; Buatti, John M.

    2002-01-01

    Purpose: To review patterns of failure in infants with neuroblastoma and determine late toxicity and efficacy of radiotherapy (RT) on locoregional control. Methods and Materials: From 1955 to 1998, 53 children (35 males and 18 females) 1 month), and primary site were not found to impact on survival or progression. None of the Stage 1, 2A, or 2B patients recurred. One of 15 Stage 3 and 5 of 6 Stage 4 children recurred (6 distant metastases, 4 local failure). Four of 6 (67%) LN+ patients treated with locoregional RT and 8 of 10 (80%) LN+ patients treated without RT were locally controlled. There was no isolated locoregional relapse. Two Stage 4S patients died of respiratory compromise secondary to hepatomegaly. RT toxicity: For the 20 infants who received RT, 13 are alive with long-term follow-up ranging from 9.3 to 41 years, median 23 years. The 10 and 15-year musculoskeletal toxicity rates were 38.5% and 47.3% for those receiving RT and 3.3% for no RT (p=0.02, log-rank test). Five of 6 infants <6 months of age and 1 of 7 ≥6 months developed musculoskeletal toxicity. Musculoskeletal effects were seen in 6 RT patients and included bony hypoplasia in 6, scoliosis in 5, soft tissue hypoplasia in 3, slipped capital femoral epiphysis in 2, kyphosis in 1, and osteochondroma in 1. Three required orthopedic intervention, all receiving ≥20 Gy. One child developed bowel obstruction at 21 months and another developed a leiomyosarcoma in the treatment field 34 years after RT. Conclusions: Our study shows that most LN+ infants achieve locoregional control without RT. Infants <6 months receiving RT were the most susceptible to musculoskeletal abnormalities. Further studies are needed to determine if cardiovascular anomalies are more frequently seen in children with neuroblastoma

  16. The effects of postoperative irradiation on loco-regional tumor control and survival in patients with head and neck carcinomas by tumor subsites and relative risk factors for recurrence

    International Nuclear Information System (INIS)

    Schmidt-Ullrich, Rupert K.; Johnson, Christopher R.; Payne, Cheryl; Lu Jiandong; Han, Daniel

    1997-01-01

    Purpose/Objective: This study reports on a unique experience in the management of patients with advanced head and neck squamous cell carcinomas (HNSCC) in which, between 1982 and 1990, patients with varied risk for recurrence were either referred for immediate postoperative irradiation by one surgical group or offered radiotherapy after surgical failure by the other. We have previously demonstrated in patients with high risk for recurrence that combined surgery and postoperative radiotherapy (S/RT) resulted in improved loco-regional tumor control (LRC) and overall patient survival (OS) for the entire patient cohort. This updated and expanded analysis describes the benefit of postoperative irradiation for patients with HNSCC depending upon relative risk factors for recurrence and different subsites of primary tumors. Materials and Methods: Of 219 patients, 190 were evaluable because of tumor locations in the major subsites analyzed, i.e. oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (L). Depending upon the philosophy of the two surgical groups, 79 patients were treated with combined S/RT and 111 with S alone with a >90% compliance. Minimum 2-year follow-up applies to all data reported. The two patient groups were well balanced with respect to tumor stages (AJCC 1983) and other patient characteristics. Histopathological review revealed 88 cases with one risk factor for recurrence, 49 patients with positive resection margin (PRM) and 39 with extracapsular extension (ECE); an additional 22 patients presented with both risk factors and 80 patients were found to have no risk factors. S, consisting of wide local excisions or radical resections including neck dissections, and postoperative RT with doses between 50 and 70 Gy were similar for both groups. Statistical evaluations consisted of Kaplan-Meier analyses to calculate LRC and OS rates and of multivariate Cox's proportional hazard models to estimate significance of treatment effects including S vs. S

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

    Directory of Open Access Journals (Sweden)

    Xuemei Ji

    Full Text Available BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC treated by intensity modulated radiotherapy (IMRT and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS, metastasis-free survival (MFS, relapse-free survival (RFS, and disease-free survival (DFS were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03, patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03, neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.

  18. Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Xing, Minzhi; Sakaria, Sonali; Dhanasekaran, Renumathy; Parekh, Samir; Spivey, James; Knechtle, Stuart J.; Zhang, Di; Kim, Hyun S.

    2017-01-01

    Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

  19. Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Minzhi [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Sakaria, Sonali [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Dhanasekaran, Renumathy [Stanford University School of Medicine, Division of Gastroenterology and Hepatology (United States); Parekh, Samir; Spivey, James [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Knechtle, Stuart J. [Duke University School of Medicine, Division of Transplant Surgery, Department of Surgery (United States); Zhang, Di [University of Pittsburgh, Department of Biostatistics, Graduate School of Public Health (United States); Kim, Hyun S., E-mail: kevin.kim@yale.edu [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States)

    2017-03-15

    Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

  20. Tumor Hypoxia is Independent of Hemoglobin and Prognostic for Loco-regional Tumor Control after Primary Radiotherapy in Advanced Head and Neck Cancer

    International Nuclear Information System (INIS)

    Nordsmark, Marianne; Overgaard, Jens

    2004-01-01

    There is evidence that tumor hypoxia adversely affects loco-regional tumor control and survival in head and neck cancer. The aim of the current study was to compare pretreatment tumor oxygenation measured by Eppendorf pO2 electrodes with known prognostic factors in advanced head and neck tumors after definitive radiotherapy, and to evaluate the prognostic significance of these parameters on loco-regional tumor control. Sixty-seven patients, median age 56 years (22-82), all with primary stage III-IV squamous cell carcinoma were available for survival analysis. Tumor oxygenation was described as the fraction of pO2 values=2.5 mmHg (HP2.5) and the median tumor pO2. By regression analysis HP2.5 was independent of known prognostic factors including stage, pretreatment hemoglobin (Hb) and the largest tumor diameter at the site of pO2 measurement. By Kaplan-Meier analysis loco-regional tumor control at 5 years was in favor of less hypoxic tumors using either HP2.5 or median tumor pO2 as descriptors and stratifying by the median values. Also, Hb was prognostic of loco-regional tumor control at 5 years using the median value as cut off. HP2.5 as continuous parameter was highly significant for loco-regional tumor control in a multivariate analysis. In conclusion both HP2.5 and total Hb were prognostic for loco-regional tumor control, but HP2.5 as continuous variable was independently the strongest prognostic indicator for loco-regional tumor control after definitive primary radiotherapy in advanced head and neck tumors

  1. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Kim, Jin Hee; Kim, Yong Hoon [Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of); Byun, Sang Jun [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2016-12-15

    To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.

  2. A prognostic scoring model for survival after locoregional therapy in de novo stage IV breast cancer.

    Science.gov (United States)

    Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ganti, Apar Kishor; Krishnamurthy, Jairam; Tandra, Pavan Kumar

    2018-05-02

    The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two "groups" [group 1 (0-7 points) and group 2 (7-17 points)]. Kaplan-Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p < 0.0001). The group 1 and group 2 in the training cohort showed a significant difference in the 3-year OS (p < 0.0001) (68 vs. 26%). On internal validation, comparable OS was seen between the respective groups in each cohort (p = 0.77). Our prognostic scoring system will help oncologists to predict the prognosis in de novo stage IV BC patients treated with LRT. Although firm treatment-related conclusions cannot be made due to the retrospective nature of the study, LRT appears to be associated with a better OS in specific subgroups.

  3. 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...

  4. Genetic variations in radiation and chemotherapy drug action pathways and survival in locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

    Directory of Open Access Journals (Sweden)

    Huai Liu

    Full Text Available BACKGROUND AND PURPOSE: Treatment outcomes vary greatly in patients with nasopharyngeal carcinoma (NPC. The purpose of this study is to evaluate the influence of radiation and chemotherapy drug action pathway gene polymorphisms on the survival of patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. MATERIAL AND METHODS: Four hundred twenty-one consecutive patients with locoregionally advanced NPC were prospectively recruited. We utilized a pathway approach and examined 18 polymorphisms in 13 major genes. Polymorphisms were detected using the LDR-PCR technique. Multifactor dimensionality reduction (MDR analysis was performed to detect potential gene-gene interaction. RESULTS: After adjustment for clinicopathological characteristics, overall survival was significantly decreased in patients with the MPO rs2243828 CT/CC genotype (HR=2.453, 95% CI, 1.687-3.566, P<0.001. The ERCC1 rs3212986 CC (HR=1.711, 95% CI, 1.135-2.579, P=0.010, MDM2 rs2279744 GT/GG (HR=1.743, 95% CI, 1.086-2.798, P=0.021, MPO rs2243828 CT/CC (HR=3.184, 95% CI, 2.261-4.483, P<0.001 and ABCB1 rs2032582 AT/AA (HR=1.997, 95% CI, 1.086-3.670, P=0.026 genotypes were associated with poor progression-free survival. Prognostic score models based on independent prognostic factors successfully classified patients into low-, intermediate-, and high-risk groups. Furthermore, MDR analysis showed no significant interaction between polymorphisms. CONCLUSIONS: Four single nucleotide polymorphisms were associated with survival in patients with locoregionally advanced NPC treated with cisplatin- and fluorouracil-based chemoradiotherapy. Combining clinical prognostic factors with genetic information was valuable in identifying patients with different risk.

  5. Elective Inguinal Node Irradiation in Early-Stage T2N0 Anal Cancer: Prognostic Impact on Locoregional Control

    Energy Technology Data Exchange (ETDEWEB)

    Zilli, Thomas, E-mail: Thomas.Zilli@hcuge.ch [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Betz, Michael [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Radiation Oncology Institute, Hirslanden Lausanne, Lausanne (Switzerland); Bieri, Sabine [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Ris, Frederic; Roche, Bruno [Department of Surgery, Geneva University Hospital, Geneva (Switzerland); Roth, Arnaud D. [Oncosurgery Unit, Geneva University Hospital, Geneva (Switzerland); Allal, Abdelkarim S. [Department of Radiation Oncology, Geneva University Hospital, Geneva (Switzerland); Department of Radiation Oncology,Hôpital Fribourgeois, Fribourg (Switzerland)

    2013-09-01

    Purpose: To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. Methods and Materials: Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. Results: Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC, cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). Conclusions: In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.

  6. Combining polyamine depletion with radiation therapy for rapidly dividing head and neck tumors: Strategies for improved locoregional control

    International Nuclear Information System (INIS)

    Petereit, D.G.; Harari, P.M.; Contreras, L.; Pickart, M.A.; Verma, A.K.; Kinsella, T.J.; Gerner, E.W.

    1994-01-01

    Locoregional control is adversely affected as clonogens from rapidly proliferating tumors repopulate during a course of radiation therapy. The cytostatic agent α-difluoromethylornithine (DFMO) was investigated for its capacity to slow proliferation kinetics in human squamous cell carcinomas (SSC) of the head and neck (H ampersand N), with the ultimate objective of improving locoregional control in rapidly dividing tumors treated with radiation therapy. Three human SSC cell lines established from primary H ampersand N tumors were evaluated in vitro (cell culture) and in vivo (SSC tumor xenografts in athymic mice) for the capacity of DFMO to induce growth inhibition. Flow cytometry analysis of SCC tumor growth kinetics and quantitative assessment of polyamine biosynthesis inhibition was performed to verify DFMO activity. DFMO effects on in vitro SSC radiosensitivity using clonogenic survival were also studied. A noncytotoxic exposure to DFMO (5mM x 72 hours) induced pronounced growth inhibition in all three SSC cell lines (70-90% at 7 days), and induced a 2-3 fold delay in volume doubling time for SCC tumor xenografts when administered orally in the drinking water (1.5%) to athymic mice. Kinetic analysis via flow cytometry confirmed that DFMO produced a lengthening of SCC cell cycle times, but did not alter in vitro radiosensitivity. Inhibition of ornithine decarboxylase (ODC) activity and depletion of endogenous polyamines (putrescine and spermidine), were confirmed in normal tissue (mouse skin) and in human SSC tumor xenografts of athymic mice receiving continuous oral DFMO. These data indicate that antiproliferative agents, such as DFMO, are capable of altering human SSC growth kinetics without altering intrinsic radiosensitivity. Such kinetic modulation may therefore provide a strategy to reduce the adverse impact of tumor cell proliferation during a radiotherapy treatment course for rapidly dividing tumors such as those in the H ampersand N. 33 refs., 5 figs

  7. Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition

    International Nuclear Information System (INIS)

    Kawashima, Mitsuhiko; Ariji, Takaki; Kameoka, Satoru

    2013-01-01

    The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n=21) and/or N2/3 (n=24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤ Grade 1. The overall survival rate at 3 years was 87%. Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer. (author)

  8. Comprehensive Locoregional Treatment and Systemic Therapy for Postmastectomy Isolated Locoregional Recurrence

    International Nuclear Information System (INIS)

    Kuo, S.-H.; Huang, C.-S.; Kuo, W.-H.; Cheng, A.-L.; Chang, K.-J.; Chia-Hsien Cheng, Jason

    2008-01-01

    Purpose: To assess the impact of comprehensive locoregional therapy and systemic therapy on disease control and survival for postmastectomy patients with isolated locoregional recurrence (ILRR). Methods and Materials: A total of 115 postmastectomy breast cancer patients treated for ILRR were included. Of the patients, 98 underwent comprehensive locoregional treatment (local tumor excision plus postoperative radiotherapy), and 17 received definitive radiotherapy alone. Involved-field radiotherapy was given to 69 patients, whereas entire-field radiotherapy (both involved-field and elective-field, involving the chest wall and regional lymphatics) was given to 46 patients. Systemic therapy consisting of hormone therapy, chemotherapy, or both was given to 69% of patients. Results: Patients treated with comprehensive locoregional treatment had a significantly better 5-year invasive disease-free survival (IDFS) and overall survival (OS) after ILRR than patients treated with definitive radiotherapy alone (IDFS rate, 51% vs. 16%, p = 0.006; OS rate, 62% vs. 37%, p = 0.017). Patients with the most comprehensive locoregional treatment (recurrent tumor excision and entire-field radiotherapy) and systemic therapy had a significantly better 5-year IDFS and OS than patients given either treatment or neither treatment (IDFS rate, 52% vs. 39%, p = 0.011; OS rate, 63% vs. 50%, p = 0.026). Multivariate analysis revealed that positive axillary lymph nodes, Grade III tumor, negative estrogen and progesterone receptor status at primary diagnosis, disease-free interval of less than 2 years, and less comprehensive locoregional treatment were significantly associated with worse IDFS and OS. Conclusions: Use of comprehensive locoregional therapy and systemic therapy can achieve good survival outcome in a substantial proportion of postmastectomy patients with ILRR

  9. Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

    Directory of Open Access Journals (Sweden)

    Zhen-Yu He

    Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

  10. HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: Results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

    International Nuclear Information System (INIS)

    Lohaus, Fabian; Linge, Annett; Tinhofer, Inge; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Avlar, Melanie; Grosu, Anca-Ligia

    2014-01-01

    Objective: To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. Materials and methods: For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. Results: In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p = 0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p < 0.01) but not with distant metastases. Conclusions: HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial

  11. Efficacy of hypofractionated radiotherapy in loco-regional tumor control in breast

    International Nuclear Information System (INIS)

    Riaz, O.; Mahmood, A.; Rasul, S.; Haider, N.; Gul, S.

    2017-01-01

    Objective: To evaluate the efficacy of hypofractionated radiotherapy (HFRT) in locoregional control (LRC) in breast cancer. Study Design: Descriptive case series. Place and Duration of Study: Oncology Department of CMH Rawalpindi, from Jan 2014 to Oct 2014. Material and Methods: Fifty three female patients with histopathologically confirmed breast cancer and Eastern Cooperative Oncology Group performance status (ECOG-PS) greater than equal to 2 were enrolled in the study. These patients required post-operative radio-therapy to intact breast/ chest wall / residual breast tissue were treated using linear accelerator. Lateral/medial tangential and ipsilateral supraclavicular fields were employed to a dose of 39 Gy in 13 fractions with 6 MV photon beam. The ipsilateral axilla was also radiated if required to same dose with postero-anterior field. Scar boost was administered using 6 MeV electron beam to a dose of 7.5 Gy in 3 fractions in patients with high risk features for local recurrence like high grade, positive axillary nodes, lymphovascular invasion and close or positive surgical resection margins. Patients were followed up weekly during radio-therapy (RT) and three monthly after completion of RT for a period of 6 months. Any suspicious lesion was subjected to biopsy. Data analysis was done with the help of the Statistical Package for the Social Sciences (SPSS) version 19 software, which included descriptive analysis. Loco-regional control (LRC) and loco-regional recurrence (LRR) rates were calculated. LRC was no recurrence of tumor/tumor control in chest wall, axilla, residual breast tissue, and/or infraclavicular/supraclavicular lymph nodes. LRR was appearance of nodules / leison at local site which was biopsied and confirmed histopathologically. Results: Fifty three female patients with histopathologically confirmed breast cancer and ECOG-PS greater than equal to 2 requiring post-operative radio-therapy to intact breast/chest wall/ residual breast tissue were

  12. Pretreatment Quality of Life Predicts for Locoregional Control in Head and Neck Cancer Patients: A Radiation Therapy Oncology Group Analysis

    International Nuclear Information System (INIS)

    Siddiqui, Farzan; Pajak, Thomas F.; Watkins-Bruner, Deborah; Konski, Andre A.; Coyne, James C.; Gwede, Clement K.; Garden, Adam S.; Spencer, Sharon A.; Jones, Christopher; Movsas, Benjamin

    2008-01-01

    Purpose: To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional control (LRC) and/or overall survival (OS). Methods and Materials: HRQOL questionnaires, using a validated instrument, the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H and N), version 2, were completed by patients before the start of treatment. OS and LRC were the outcome measures analyzed using a multivariate Cox proportional hazard model. Results: Baseline FACT-H and N data were available for 1,093 patients and missing for 417 patients. No significant difference in outcome was found between the patients with and without baseline FACT-H and N data (p = 0.58). The median follow-up time was 27.2 months for all patients and 49 months for surviving patients. Multivariate analyses were performed for both OS and LRC. Beyond tumor and nodal stage, Karnofsky performance status, primary site, cigarette use, use of concurrent chemotherapy, and altered fractionation schedules, the FACT-H and N score was independently predictive of LRC (but not OS), with p = 0.0038. The functional well-being component of the FACT-H and N predicted most significantly for LRC (p = 0.0004). Conclusions: This study represents, to our knowledge, the largest analysis of HRQOL as a prognostic factor in locally advanced head and neck cancer patients. The results of this study have demonstrated the importance of baseline HRQOL as a significant and independent predictor of LRC in patients with locally advanced head and neck cancer

  13. Locoregional Treatment Outcomes After Multimodality Management of Inflammatory Breast Cancer

    International Nuclear Information System (INIS)

    Bristol, Ian J.; Woodward, Wendy A.; Strom, Eric A.; Cristofanilli, Massimo; Domain, Delora; Singletary, S. Eva; Perkins, George H.; Oh, Julia L.; Yu, T.-K.; Terrefe, Welela; Sahin, Aysegul A.; Hunt, Kelly K.; Hortobagyi, Gabriel N.; Buchholz, Thomas A.

    2008-01-01

    Purpose: The aims of this study were to determine outcomes for patients with inflammatory breast cancer (IBC) treated with multimodality therapy, to identify factors associated with locoregional recurrence, and to determine which patients may benefit from radiation dose escalation. Methods and Materials: We retrospectively reviewed 256 consecutive patients with nonmetastatic IBC treated at our institution between 1977 and 2004. Results: The 192 patients who were able to complete the planned course of chemotherapy, mastectomy, and postmastectomy radiation had significantly better outcomes than the 64 patients who did not. The respective 5-year outcome rates were: locoregional control (84% vs. 51%), distant metastasis-free survival (47% vs. 20%), and overall survival (51% vs. 24%) (p < 0.0001 for all comparisons). Univariate factors significantly associated with locoregional control in the patients who completed plan treatment were response to neoadjuvant chemotherapy, surgical margin status, number of involved lymph nodes, and use of taxanes. Increasing the total chest-wall dose of postmastectomy radiation from 60 Gy to 66 Gy significantly improved locoregional control for patients who experienced less than a partial response to chemotherapy, patients with positive, close, or unknown margins, and patients <45 years of age. Conclusions: Patients with IBC who are able to complete treatment with chemotherapy, mastectomy, and postmastectomy radiation have a high probability of locoregional control. Escalation of postmastectomy radiation dose to 66 Gy appears to benefit patients with disease that responds poorly to chemotherapy, those with positive, close, or unknown margin status, and those <45 years of age

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

    Directory of Open Access Journals (Sweden)

    Victor E. Chen, BS

    2017-04-01

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

  15. The relationship between HPV status and chemoradiotherapy in the locoregional control of penile cancer.

    Science.gov (United States)

    Yuan, Zhigang; Naghavi, Arash O; Tang, Dominic; Kim, Youngchul; Ahmed, Kamran A; Dhillon, Jasreman; Giuliano, Anna R; Spiess, Philippe E; Johnstone, Peter A

    2018-03-27

    Penile cancer (PeCa) is a rare, aggressive malignancy often associated with the human papillomavirus (HPV). The practice of a personalized risk-adapted approach is not yet established. This study is to assess the relationship between HPV tumor status and chemoradiotherapy (CRT) in PeCa locoregional control (LRC). We retrospectively identified patients with HPV status who were diagnosed with squamous cell carcinoma of the penis and treated with surgical resection between 1999 and 2016. The relationship between tumor/treatment characteristics and LRC were analyzed with univariate and multivariate Cox proportional hazard regression analysis (UVA and MVA, respectively). Time-to-event outcomes were estimated with Kaplan-Meier curves and compared via log-rank tests. Fifty-one patients were identified. The median follow-up was 36.6 months. Patients were primarily HPV-negative (HPV-) (n = 28, 55%), and pathologic node positive (pN+) (55%). The 2 year LRC rate was 54%. pN+ patients had a significantly lower 2 year LRC (37 vs. 81%, p = 0.002). In the subgroup analysis of pN+ patients (n = 28), there was a LRC benefit associated with the addition of CRT (HR 0.19; 95% CI 0.05-0.70, p = 0.012) and HPV-positive (HPV+) disease (HR 0.18; 95% CI 0.039-0.80, p = 0.024) using MVA. HPV+ patients treated with CRT had improved 2 year LRC compared to HPV- patients (83 vs. 38%, p = 0.038). Adjuvant CRT and HPV+ disease independently predicted for improved LRC in pN+ PeCa. In HPV+ PeCa, the LRC benefit was primarily observed in patients treated with adjuvant CRT. Prospective investigation of HPV+ and CRT is required to further delineate their roles in optimizing PeCa treatment.

  16. Survivability via Control Objectives

    Energy Technology Data Exchange (ETDEWEB)

    CAMPBELL,PHILIP L.

    2000-08-11

    Control objectives open an additional front in the survivability battle. A given set of control objectives is valuable if it represents good practices, it is complete (it covers all the necessary areas), and it is auditable. CobiT and BS 7799 are two examples of control objective sets.

  17. Dose-response relationship in locoregional control for patients with stage II-III esophageal cancer treated with concurrent chemotherapy and radiotherapy

    International Nuclear Information System (INIS)

    Zhang Zhen; Liao Zhongxing; Jin Jing; Ajani, Jaffer; Chang, Joe Y.; Jeter, Melenda; Guerrero, Thomas; Stevens, Craig W.; Swisher, Stephen; Ho, Linus; Yao, James; Allen, Pamela; Cox, James D.; Komaki, Ritsuko

    2005-01-01

    Purpose: To evaluate the correlation between radiation dose and locoregional control (LRC) for patients with Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy. Methods and materials: The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received ≤51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30-51 Gy) and 59.4 Gy (range, 54-64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering ≥45 Gy at 1.8-2 Gy/fraction daily. Total doses of 5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year local control rate (36% vs. 19%, p = 0.011), disease-free survival rate (25% vs. 10%, p = 0.004), and overall survival rate (13% vs. 3%, p = 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p = 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p = 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p = 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although

  18. Radiotherapy for Locoregional Recurrent Cervix Cancer after Surgery

    International Nuclear Information System (INIS)

    Yang, Mi Gyoung

    1994-01-01

    Purpose: The role of radiotherapy in the management of patients with locoregional recurrent cervix cancer after radical surgery were retrospectively analyzed. Methods and materials: Twenty-eight patients treated with radiotherapy for locoregional recurrence after primary surgery for carcinoma of the cervix between 1989 and 1993 were analyzed. The median follow-up of survivors was 15 months (ranged 7-43 months). Eight patients had their disease confined to the vagina and 19 patients(68%) had pelvic mass as part of their locoregional recurrent disease. Within 24 months after the initial surgery, 82% of recurrences manifested themselves. All patients had whole pelvic irradiation with or without intracavitary radiotherapy(ICR). Results: Complete response(CR) was achieved in 18 patients(64%). Five of eighteen patients(28%) with initial CR developed second locoregional recurrence. Response to radiotherapy correlated strongly with tumor volume, site of recurrence and total radiation dose. The overall 2 year survival rate was 43% and the disease free survival was 31%. Survival rate was significantly influenced by the factors of interval from operation to recurrence, size and site of recurrent tumor, radiation dose, response of radiotherapy, lymph node status as initial presentation. The principal cause of death was lung metastasis(36%). Conclusion: Radiotherapy is an excellent modality for control of locoregional recurrent cervix cancer. To improve local control and survival rate, whole pelvic external radiotherapy in addition to ICR with more than 75.0Gy at the depth of 1.0cm from vaginal mucosa is needed and frequent follow up and early detection of recurrence is suggested as well

  19. A comparative study of survival rates after treatment with induction chemotherapy or concurrent chemoradiotherapy in locoregionally advanced head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Hiraga, Yukihiro; Kou, Junichi

    2012-01-01

    Since 1989 our treatment approach for head and neck squamous cell carcinoma (HNSCC) has involved comprehensive treatment with chemotherapy, radiation followed by surgery, if needed. Between 1989 and 2005 chemotherapy using fluorouracil and carboplatin div was administered as induction chemotherapy (ICT), and concurrent chemoradiotherapy (CCRT) was administered more recently between 2006 and 2011. In this study we compared the statistical difference in 3-year survival rates between the ICT group and CCRT group. The number of target patients was 137, all of which were previously untreated and suffered from locoregionally advanced HNSCC: 52 with Stage III, 78 with Stage IVA, 7 with Stage IVB. In the ICT and CCRT groups, 3-year cause-specific survival rates were 68.2% and 76.3% respectively, both of which were statistically not recessive compared to those in the other issues. Furthermore, the rate between the two groups was identified as significant for Stage III and not significant for Stage IV. In conclusion, the addition of new modalities for the treatment of far-advanced HNSCC should be mandatory. (author)

  20. Dose-escalated intensity-modulated radiotherapy is feasible and may improve locoregional control and laryngeal preservation in laryngo-hypopharyngeal cancers.

    Science.gov (United States)

    Miah, Aisha B; Bhide, Shreerang A; Guerrero-Urbano, M Teresa; Clark, Catharine; Bidmead, A Margaret; St Rose, Suzanne; Barbachano, Yolanda; A'hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L; Harrington, Kevin J; Nutting, Christopher M

    2012-02-01

    To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study. Copyright © 2012 Elsevier Inc. All rights

  1. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    International Nuclear Information System (INIS)

    Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa; Clark, Catharine; Bidmead, A. Margaret; St Rose, Suzanne; Barbachano, Yolanda; A’Hern, Roger; Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L.; Harrington, Kevin J.; Nutting, Christopher M.

    2012-01-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1–77.3) months and for DL2 was 36.2 (4.2–63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5–78.9%) in DL1 and 78.4% (58.1–89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5–96.3%) in DL1 and 96.4% (77.7–99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy–IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK

  2. Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Miah, Aisha B; Bhide, Shreerang A; Guerrero-Urbano, M Teresa [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Clark, Catharine; Bidmead, A Margaret [Institute of Cancer Research, London (United Kingdom); Department of Physics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); St Rose, Suzanne; Barbachano, Yolanda; A' Hern, Roger [Department of Statistics, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Tanay, Mary; Hickey, Jennifer; Nicol, Robyn; Newbold, Kate L [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Harrington, Kevin J [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom); Nutting, Christopher M., E-mail: chris.nutting@rmh.nhs.uk [Head and Neck Unit, The Royal Marsden National Health Service (NHS) Foundation Trust, London (United Kingdom); Institute of Cancer Research, London (United Kingdom)

    2012-02-01

    Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III

  3. Buccal mucosa carcinoma: surgical margin less than 3 mm, not 5 mm, predicts locoregional recurrence

    Directory of Open Access Journals (Sweden)

    Chiou Wen-Yen

    2010-09-01

    Full Text Available Abstract Background Most treatment failure of buccal mucosal cancer post surgery is locoregional recurrence. We tried to figure out how close the surgical margin being unsafe and needed further adjuvant treatment. Methods Between August 2000 and June 2008, a total of 110 patients with buccal mucosa carcinoma (25 with stage I, 31 with stage II, 11 with stage III, and 43 with Stage IV classified according to the American Joint Committee on Cancer 6th edition were treated with surgery alone (n = 32, surgery plus postoperative radiotherapy (n = 38 or surgery plus adjuvant concurrent chemoradiotherapy (n = 40. Main outcome measures: The primary endpoint was locoregional disease control. Results The median follow-up time at analysis was 25 months (range, 4-104 months. The 3-year locoregional control rates were significantly different when a 3-mm surgical margin (≤3 versus >3 mm, 71% versus 95%, p = 0.04 but not a 5-mm margin (75% versus 92%, p = 0.22 was used as the cut-off level. We also found a quantitative correlation between surgical margin and locoregional failure (hazard ratio, 2.16; 95% confidence interval, 1.14 - 4.11; p = 0.019. Multivariate analysis identified pN classification and surgical margin as independent factors affecting disease-free survival and locoregional control. Conclusions Narrow surgical margin ≤3 mm, but not 5 mm, is associated with high risk for locoregional recurrence of buccal mucosa carcinoma. More aggressive treatment after surgery is suggested.

  4. Buccal mucosa carcinoma: surgical margin less than 3 mm, not 5 mm, predicts locoregional recurrence

    International Nuclear Information System (INIS)

    Chiou, Wen-Yen; Hung, Shih-Kai; Lin, Hon-Yi; Hsu, Feng-Chun; Lee, Moon-Sing; Ho, Hsu-Chueh; Su, Yu-Chieh; Lee, Ching-Chih; Hsieh, Chen-Hsi; Wang, Yao-Ching

    2010-01-01

    Most treatment failure of buccal mucosal cancer post surgery is locoregional recurrence. We tried to figure out how close the surgical margin being unsafe and needed further adjuvant treatment. Between August 2000 and June 2008, a total of 110 patients with buccal mucosa carcinoma (25 with stage I, 31 with stage II, 11 with stage III, and 43 with Stage IV classified according to the American Joint Committee on Cancer 6 th edition) were treated with surgery alone (n = 32), surgery plus postoperative radiotherapy (n = 38) or surgery plus adjuvant concurrent chemoradiotherapy (n = 40). Main outcome measures: The primary endpoint was locoregional disease control. The median follow-up time at analysis was 25 months (range, 4-104 months). The 3-year locoregional control rates were significantly different when a 3-mm surgical margin (≤3 versus >3 mm, 71% versus 95%, p = 0.04) but not a 5-mm margin (75% versus 92%, p = 0.22) was used as the cut-off level. We also found a quantitative correlation between surgical margin and locoregional failure (hazard ratio, 2.16; 95% confidence interval, 1.14 - 4.11; p = 0.019). Multivariate analysis identified pN classification and surgical margin as independent factors affecting disease-free survival and locoregional control. Narrow surgical margin ≤3 mm, but not 5 mm, is associated with high risk for locoregional recurrence of buccal mucosa carcinoma. More aggressive treatment after surgery is suggested

  5. Combined heavy smoking and drinking predicts overall but not disease-free survival after curative resection of locoregional esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sun P

    2016-07-01

    Full Text Available Peng Sun,1,2,* Cui Chen,3,* Fei Zhang,1,2,* Hang Yang,1,2 Xi-Wen Bi,1,2 Xin An,1,2 Feng-Hua Wang,1,2 Wen-Qi Jiang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 3Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Introduction: The prognostic impact of smoking and drinking on esophageal squamous cell carcinoma (ESCC was scarcely discussed. We investigated the prognostic value of smoking and drinking and their relationships with clinicopathological characteristics in a large cohort of patients with locoregional ESCC.Patients and methods: We retrospectively analyzed 488 patients who underwent curative treatment at a single institution between January 2007 and December 2008. A chi-square test was used to evaluate the relationships between smoking and drinking and clinicopathological variables, the Kaplan–Meier method was used for 5-year overall survival (OS and disease-free survival, and Cox proportional hazards models were applied for univariate and multivariate analyses of variables with respect to OS and disease-free survival.Results: Heavy smokers were more likely to have advanced Tumor-Node-Metastases (TNM stage and higher neutrophil/lymphocyte ratio at diagnosis (P<0.05. Drinkers were more likely to have advanced TNM stage, to present with a larger tumor, and to undergo multidisciplinary treatment (P<0.05. For patients who used neither heavy tobacco nor alcohol, used either tobacco or alcohol, and used both, the 5-year OS rates and OS times were 57.4%, 46.4%, and 39.1% (P<0.05 and not reached, 55.2 months, and 41.2 months (P<0.05, respectively. On multivariate analysis, patients who both heavily smoked and drank had 1.392 times the risk of dying during follow-up compared with

  6. Radiotherapy in Locoregional Recurrent Breast Carcinoma

    International Nuclear Information System (INIS)

    Ha, Sung Whan; Yang, Mi Gyoung; Chung, Woong Ki; Park, Charn Il; Bang, Yung Jue; Kim, Noe Kyung; Choe, Kuk Jin

    1988-01-01

    Thirty eight women with recurrent breast carcinoma involving chest wall and/or regional lymph nodes after surgery with or without systemic therapy were treated with radiation between 1979 and 1986. Among them, 5 patients were excluded from analysis because of incomplete treatment. The median follow up of survivors was 30 months (ranged 1-79 months). Fifteen (45%) patients had their disease confined to the chest wall and eighteen patients had lymph node involvement as some of their locoregional recurrent disease. Within 36 months after the initial treatment, 87% of recurrences manifested themselves. All patients had radiotherapy to at least the site of involvement. In 8 patients, recurrent tumors were treated with complete excision followed by radiation. Of the remaining 25 patients, 18(72%) had complete response (CR) following radiotherapy. The actuarial 3-year survival of all patients following locoregional recurrence was 50%. Three year survival was 24% in those 25 patients who had recurrences within 24 months of the initial treatment. For those 8 patients whose recurrences occurred after more than 24 month disease free interval, the 3-year survival was 100%. For those patients with recurrences confined to chest wall alone, 3-year survival was 57%. The patients who had lymph node involvement as part of their locoregional recurrences had a 43% 3-year survival. The majority of them developed distant metastases. Those patients who had a CR showed 63% 3-year survival. On the other hand, 1 year survival was only 33% for those patients who had a less than CR. Three patients developed carcinoma of the contralateral breast following radiotherapy. Three year survival following locoregional recurrence was 40% for patients whose initial treatment for their primary breast carcinoma was surgery and adjuvant systemic therapy. For those patients whose primary breast carcinoma was treated by surgery alone, the 3-year survival following locoregional recurrence was 71%. In

  7. Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study.

    Science.gov (United States)

    George, Daniel J; Martini, Jean-François; Staehler, Michael; Motzer, Robert J; Magheli, Ahmed; Escudier, Bernard; Gerletti, Paola; Li, Sherry; Casey, Michelle; Laguerre, Brigitte; Pandha, Hardev S; Pantuck, Allan J; Patel, Anup; Lechuga, Maria J; Ravaud, Alain

    2018-04-01

    Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit. Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between < versus ≥ median IHC parameter using the Kaplan-Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated. Results: Baseline characteristics were similar in patients with ( n = 191) and without ( n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8 + T-cell density ≥ versus < median [median (95% CI), not reached (6.83-not reached) versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81); P = 0.009] treated with sunitinib ( n = 101), but not with placebo ( n = 90). The sensitivity and specificity for CD8 + T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1 + versus PD-L1 - tumors (HR 1.75; P = 0.103). Among all patients with PD-L1 + tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175). Conclusions: Greater CD8 + T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554-61. ©2018 AACR . ©2018 American Association for Cancer Research.

  8. Pretreatment quality of life predicts for locoregional control in head and neck cancer patients : A radiation therapy oncology group analysis

    NARCIS (Netherlands)

    Siddiqui, Farzan; Pajak, Thomas F.; Watkins-Bruner, Deborah; Konski, Andre A.; Coyne, James C.; Gwede, Clement K.; Garden, Adam S.; Spencer, Sharon A.; Jones, Christopher; Movsas, Benjamin

    2008-01-01

    Purpose: To analyze the prospectively collected health-related quality-of-life (HRQOL) data from patients enrolled in two Radiation Therapy Oncology Group randomized Phase III head and neck cancer trials (90-03 and 91-11) to assess their value as an independent prognostic factor for locoregional

  9. Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

    2014-11-15

    Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

  10. Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

    International Nuclear Information System (INIS)

    Bergom, Carmen; Kelly, Tracy; Bedi, Meena; Saeed, Hina; Prior, Phillip; Rein, Lisa E.; Szabo, Aniko; Wilson, J. Frank; Currey, Adam D.; White, Julia

    2016-01-01

    Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m 2 ; 91% of the patients were overweight (BMI ≥25 kg/m 2 ) and 69% of the patients were clinically obese (BMI ≥30 kg/m 2 ). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m 2 (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with breast conservation

  11. Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bergom, Carmen; Kelly, Tracy; Bedi, Meena; Saeed, Hina; Prior, Phillip [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Rein, Lisa E.; Szabo, Aniko [Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wilson, J. Frank; Currey, Adam D. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); White, Julia, E-mail: Julia.White@osumc.edu [Department of Radiation Oncology, James Cancer Hospital, Ohio State University Comprehensive Cancer Center, Columbus, Ohio (United States)

    2016-09-01

    Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m{sup 2}; 91% of the patients were overweight (BMI ≥25 kg/m{sup 2}) and 69% of the patients were clinically obese (BMI ≥30 kg/m{sup 2}). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m{sup 2} (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with

  12. Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and 18F-FDG PET/CT scan correlation

    International Nuclear Information System (INIS)

    Feigen, Malcolm; Lawford, Catherine; Churcher, Katheryn; Zupan, Eddy; Hamilton, Chris; Lee, Sze Ting; Scott, Andrew M.

    2011-01-01

    The management of malignant pleural mesothelioma represents one of the most challenging issues in oncology, as there is no proven long-term benefit from surgery, radiotherapy or chemotherapy alone or in combination. Locoregional progression remains the major cause of death, but radical surgical resection may produce major postoperative morbidity. While radical or postoperative radiotherapy using conventional techniques has resulted in severe toxicity with no impact on survival, recent advances in radiotherapy delivery may be more effective. We treated patients with locally advanced mesothelioma whose tumours had been sub optimally resected with high-dose three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) to large volumes of one hemithorax, using CT and positron emission tomography (PET) scan-based treatment planning. Clinical outcomes were assessed by determining patterns of failure and metabolic changes in total glycolytic volume (TGV) between pre- and post-irradiation 18 F-FDG PET/CT scans and by recording acute and late toxicity grades. Fourteen patients were analysed with 40 PET scans performed before and up to 4.5 years after radiotherapy. Eleven patients had pleurectomy/decortications, one had an extrapleural pneumonectomy and two had no surgery. Four patients who received chemotherapy had all progressed prior to radiotherapy. After radiotherapy, the in-field local control rate was 71%. No progression occurred in two patients, one was salvaged with further radiotherapy to a new site, four recurred inside the irradiated volume all with concurrent distant metastases and the other seven had distant metastases only. The TGVs were reduced by an average of 67% (range 12–100%) after doses of 45 to 60 Gy to part or all of one hemithorax. There were no serious treatment-related toxicities. Median survival was 25 months from diagnosis and 17 months after starting radiotherapy. We have established that mesothelioma can be

  13. Survivability of SCADA Control Loop

    NARCIS (Netherlands)

    Camacho, José; de Boer, Pieter-Tjerk; Remke, Anne Katharina Ingrid

    2009-01-01

    The endorsement of information technologies for critical infrastructures control introduces new threats in their security and surveillance. Along with certain level of protection against attacks, it is desirable for critical processes to survive even if they succeed. A stochastic Petri Nets-based

  14. Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional

    Energy Technology Data Exchange (ETDEWEB)

    Chen, J.L.Y.; Tsai, C.L.; Chen, W.Y.; Wang, C.W. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; Huang, Y.S.; Chen, Y.F. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Medical Imaging; Kuo, S.H. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; National Taiwan Univ. College of Medicine, Taipei (China). Graduate Inst. of Clinical Medicine; Hong, R.L. [National Taiwan Univ. Hospital, Taipei (China). Div. of Medical Oncology; Ko, J.Y.; Lou, P.J. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Otolaryngology

    2013-12-15

    Purpose: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and materials: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97 % of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. Results: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1 %, respectively. A total of 27 patients had locoregional recurrence: 85.2 % in-field failures, 11.1 % marginal failures, and 3.7 % out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9 %) compared to those receiving conservative treatment (32.0 %, p = 0.051). In patients treated with 1 course of radiotherapy, grade {>=} 3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6 % of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. Conclusion: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome. (orig.)

  15. Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional

    International Nuclear Information System (INIS)

    Chen, J.L.Y.; Tsai, C.L.; Chen, W.Y.; Wang, C.W.; Huang, Y.S.; Chen, Y.F.; Kuo, S.H.; National Taiwan Univ. College of Medicine, Taipei; Hong, R.L.; Ko, J.Y.; Lou, P.J.

    2013-01-01

    Purpose: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and materials: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97 % of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. Results: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1 %, respectively. A total of 27 patients had locoregional recurrence: 85.2 % in-field failures, 11.1 % marginal failures, and 3.7 % out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9 %) compared to those receiving conservative treatment (32.0 %, p = 0.051). In patients treated with 1 course of radiotherapy, grade ≥ 3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6 % of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. Conclusion: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome. (orig.)

  16. Pregnancy associated nasopharyngeal carcinoma: A retrospective case-control analysis of maternal survival outcomes

    International Nuclear Information System (INIS)

    Cheng, Yi-Kan; Zhang, Fan; Tang, Ling-Long; Chen, Lei; Zhou, Guan-Qun; Zeng, Mu-Sheng; Kang, Tie-Bang; Jia, Wei-Hua; Shao, Jian-Yong; Mai, Hai-Qiang; Guo, Ying; Ma, Jun

    2015-01-01

    Background: Pregnancy-associated nasopharyngeal carcinoma (PANPC) has been associated with poor survival. Recent advances in radiation technology and imaging techniques, and the introduction of chemotherapy have improved survival in nasopharyngeal carcinoma (NPC); however, it is not clear whether these changes have improved survival in PANPC. Therefore, the purpose of this study was to compare five-year maternal survival in patients with PANPC and non-pregnant patients with NPC. Methods: After adjusting for age, stage and chemotherapy mode, we conducted a retrospective case-control study among 36 non-metastatic PANPC patients and 36 non-pregnant NPC patients (control group) who were treated at our institution between 2000 and 2010. Results: The median age of both groups was 30 years (range, 23–35 years); median follow-up for all patients was 70 months. Locoregionally-advanced disease accounted for 83.3% of all patients with PANPC and 92.9% of patients who developed NPC during pregnancy. In both the PANPC and control groups, 31 patients (86.1%) received chemotherapy and all patients received definitive radiotherapy. The five-year rates for overall survival (70% vs. 78%, p = 0.72), distant metastasis-free survival (79% vs. 76%, p = 0.77), loco-regional relapse-free survival (97% vs. 91%, p = 0.69) and disease-free survival (69% vs. 74%, p = 0.98) were not significantly different between the PANPC and control groups. Multivariate analysis using a Cox proportional hazards model revealed that only N-classification was significantly associated with five-year OS. Conclusion: This study demonstrates that, in the modern treatment era, pregnancy itself may not negatively influence survival outcomes in patients with NPC; however, pregnancy may delay the diagnosis of NPC

  17. Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy

    International Nuclear Information System (INIS)

    Haylock, Brian J.; Coppin, Chris M.L.; Jackson, Jeremy; Basco, Vivien E.; Wilson, Kenneth S.

    2000-01-01

    Purpose: To evaluate prospectively the impact of combination chemotherapy in the combined modality treatment of isolated first locoregional recurrence (LRR) following mastectomy for breast cancer. Methods and Materials: Between 1979 and 1989, 120 chemotherapy-naive women with isolated LRR as first failure after mastectomy were prospectively identified, uniformly staged, and systematically followed. Treatment consisted of excision if feasible, radical locoregional radiotherapy, and a hormonal maneuver (unless estrogen receptor negative). The initial chemotherapy cohort also received 8 cycles of doxorubicin and cyclophosphamide. This was compared to a subsequent control cohort. Results: For all patients, the 10-year actuarial relapse-free survival ± 95% confidence interval was 42.1 ± 9.2%, and overall survival was 56.8 ± 9.1%. No difference was seen in locoregional control between cohorts. At 5 years, distant recurrence-free survival for chemotherapy and control cohort respectively was 75.4 ± 10.8% and 60.7 ±12.5% (p = 0.33) and overall survival was 81.9% ± 9.6 and 74.3% ± 11.2 (p = 0.24). Univariate analysis showed no prognostic importance for any imbalance between cohorts. Cox modeling confirmed that complete resection was strongly associated with fewer LRR (hazard ratio [HR] 0.32, p = 0.001) and also with better overall survival (HR 1.82, p = 0.019). Chemotherapy produced a substantial reduction in risk of death (HR 0.72 CI 0.421-1.235, p = 0.23). Conclusions: In this prospective but nonrandomized study of treatment for first LRR, the risk of death in the later control cohort was 1.39 times the risk in the chemotherapy cohort but failed to reach statistical significance. The results justify further study

  18. Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC.

    Science.gov (United States)

    Linge, Annett; Schötz, Ulrike; Löck, Steffen; Lohaus, Fabian; von Neubeck, Cläre; Gudziol, Volker; Nowak, Alexander; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Bunea, Hatice; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Lauber, Kirsten; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Baretton, Gustavo B; Buchholz, Frank; Krause, Mechthild; Belka, Claus; Baumann, Michael

    2018-04-01

    To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy. HPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression. Correlation between the HPV detection methods was high (chi-squared test, p HPV positive tumours irrespective of the detection method. The most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Comparative Long-term Study of a Large Series of Patients with Invasive Ductal Carcinoma and Invasive Lobular Carcinoma. Loco-Regional Recurrence, Metastasis, and Survival.

    Science.gov (United States)

    García-Fernández, Antonio; Lain, Josep María; Chabrera, Carol; García Font, Marc; Fraile, Manel; Barco, Israel; Torras, Merçe; Reñe, Asumpta; González, Sonia; González, Clarissa; Piqueras, Mercedes; Veloso, Enrique; Cirera, Lluís; Pessarrodona, Antoni; Giménez, Nuria

    2015-01-01

    Our aim was to compare histologic and immunohistochemical features, surgical treatment and clinical course, including disease recurrence, distant metastases, and mortality between patients with invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC). We included 1,745 patients operated for 1,789 breast tumors, with 1,639 IDC (1,600 patients) and 145 patients with ILC and 150 breast tumors. The median follow-up was 76 months. ILC was significantly more likely to be associated with a favorable phenotype. Prevalence of contralateral breast cancer was slightly higher for ILC patients than for IDC patients (4.0% versus 3.2%; p = n.s). ILC was more likely multifocal, estrogen receptor positive, Human Epidermal Growth Factor Receptor-2 (HER2) negative, and with lower proliferative index compared to IDC. Considering conservative surgery, ILC patients required more frequently re-excision and/or mastectomy. Prevalence of stage IIB and III stages were significantly more frequent in ILC patients than in IDC patients (37.4% versus 25.3%, p = 0.006). Positive nodes were significantly more frequent in the ILC patients (44.6% versus 37.0%, p = 0.04). After adjustment for tumor size and nodal status, frequencies of recurrence/metastasis, disease-free and specific survival were similar among patients with IDC and patients with ILC. In conclusion, women with ILC do not have worse clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics rather than on lobular versus ductal histology. © 2015 Wiley Periodicals, Inc.

  20. Effective treatment of the brachial plexus syndrome in breast cancer patients by early detection and control of loco-regional metastases with radiation or systemic therapy

    International Nuclear Information System (INIS)

    Kamenova, B.; Braverman, A.S.; Schwartz, M.; Sohn, C.; Lange, C.; Efiom-Ekaha, D.; Rotman, M.; Yoon, H.

    2009-01-01

    In breast cancer (BC) patients the brachial plexus syndrome (BPS) has been reported to be due to loco-regional metastases or radiation plexopathy. Associated arm edema is considered more suggestive of the latter. Radiation therapy is the only effective treatment for BPS reported. The charts of all BC patients who presented to our clinic from 1982 to 2006 with homolateral arm pain and neurological deficits, without humerus, cervical spine, or brain metastases, were reviewed. There were 28 patients fulfilling these criteria for BPS. Supraclavicular, axillary or chest wall metastases developed synchronously with the BPS in 26 patients; in 21 they were recurrences, found 6-94 months (median 34 months) after primary BC treatment, while in 5 others they were progressing inoperable primary tumors and nodes. Arm edema first occurred at the same time as loco-regional metastases in 19 patients. Treatment for the BPS was administered to 22 patients; it was directed at their loco-regional metastases. The BPS was initially treated with radiation (8 patients) or chemo- or endocrine therapy (14 patients); 19 (86%) had partial or complete remission of pain and neurologic deficits, with an 8-month median duration. The BPS in BC patients is due to loco-regional metastases and is often associated with arm edema. Chemo- or endocrine therapy induced the remission of pain and deficits as frequently as radiation therapy. (author)

  1. Effect of continued tobacco smoking during radiotherapy on loco-regional control for carcinoma of the larynx

    DEFF Research Database (Denmark)

    Møller, P.; Primdahl, H.; C, A. Kristensen

    2015-01-01

    Purpose/Objective: Tobacco smoking impose a poor prognosis on cancer patients either from reduced treatment response, new primary cancers, or other tobacco-related diseases. The effect of tobacco cessation in smokers commencing radiation treatment for head and neck cancer has only been investigated...... in small, selected cohortes. We evaluated the impact of continuous smoking on local tumor control in a large, national cohort of a classical tobaccorelated laryngeal cancer. Materials and Methods: From our national database, we identified 1,455 patients diagnosed with laryngeal cancer between 2000-2010 who...... were all active smokers at the date of diagnosis. Patients treated with primary radiotherapy > 60 Gy were included. No surgery was allowed. Tobacco consumption was recorded weekly during radiotherapy, and two and six weeks after, and any smoking during RT was considered active smoking. Follow-up data...

  2. Photochemical Internalization of Bleomycin Before External-Beam Radiotherapy Improves Locoregional Control in a Human Sarcoma Model

    International Nuclear Information System (INIS)

    Norum, Ole-Jacob; Bruland, Oyvind Sverre; Gorunova, Ludmila; Berg, Kristian

    2009-01-01

    Purpose: The aim of this study was to explore the tumor growth response of the combination photochemical internalization and external-beam radiotherapy. Photochemical internalization is a technology to improve the utilization of therapeutic macromolecules in cancer therapy by photochemical release of endocytosed macromolecules into the cytosol. Methods and Materials: A human sarcoma xenograft TAX-1 was inoculated subcutaneously into nude mice. The photosensitizer AlPcS 2a and bleomycin were intraperitoneally administrated 48 h and 30 min, respectively, before diode laser light exposure at 670 nm (20 J/cm 2 ). Thirty minutes or 7 days after photochemical treatment, the animals were subjected to 4 Gy of ionizing radiation. Results: Using photochemical internalization of bleomycin as an adjunct to ionizing radiation increased the time to progression for the tumors from 17 to 33 days as compared with that observed with photodynamic therapy combined with ionizing radiation as well as for radiochemotherapy with bleomycin. The side effects observed when photochemical internalization of bleomycin was given shortly before ionizing radiation were eliminated by separating the treatment modalities in time. Conclusion: Photochemical internalization of bleomycin combined with ionizing radiation increased the time to progression and showed minimal toxicity and may therefore reduce the total radiation dose necessary to obtain local tumor control while avoiding long-term sequelae from radiotherapy.

  3. Locoregional treatment outcomes for breast cancer patients with ipsilateral supraclavicular metastases at diagnosis

    International Nuclear Information System (INIS)

    Huang, Eugene H.; Strom, Eric A.; Valero, Vicente; Fornage, Bruno; Perkins, George H.; Oh, Julia L.; Yu, T.-K.; Tereffe, Welela; Woodward, Wendy A.; Hunt, Kelly K.; Meric-Bernstam, Funda; Sahin, Aysegul A.; Bedrosian, Isabelle; Hortobagyi, Gabriel N.; Buchholz, Thomas A.

    2007-01-01

    Purpose: To evaluate the locoregional efficacy of multimodality treatment for breast cancer patients who present with ipsilateral supraclavicular (SCV) disease without systemic metastases. Methods: We retrospectively reviewed the data from 71 patients with ipsilateral SCV involvement at presentation. SCV involvement in 16 patients (23%) was diagnosed by ultrasound examination only, without palpable disease. All patients were treated with curative intent using neoadjuvant chemotherapy, mastectomy or breast-conserving surgery (BCT), and radiotherapy. Results: The 5-year SCV control, locoregional control (LRC), disease-free survival, and overall survival rate was 90%, 77%, 30%, and 47%, respectively. Patients with persistent SCV disease after neoadjuvant chemotherapy by physical examination had a lower rate of LRC (64% vs. 86%, p = 0.026), as did those with persistent SCV disease by ultrasound examination (66% vs. 96%, p = 0.007). Of those with a complete response of SCV disease by physical examination after neoadjuvant chemotherapy, those with persistently abnormal ultrasound findings had significantly worse disease-free survival (0% vs. 55%, p = 0.03). BCT was not associated with lower rates of LRC (82% for BCT vs. 76% for mastectomy, p = 0.80). Conclusion: Radiotherapy achieved excellent LRC after surgery for patients with ipsilateral SCV metastases who achieved a complete response of the SCV disease after neoadjuvant chemotherapy. For patients who achieved a complete response of the SCV disease by physical examination, ultrasonography of the SCV fossa may help assess the risk of disease recurrence. SCV involvement should not be considered a contraindication for BCT

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  6. Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical Cancer: 4-Year Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Tinkle, Christopher L.; Weinberg, Vivian [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chen, Lee-May [Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California (United States); Littell, Ramey [Gynecologic Oncology, The Permanente Medical Group, San Francisco, California (United States); Cunha, J. Adam M.; Sethi, Rajni A. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Chan, John K. [Gynecologic Oncology, California Pacific Medical Center, San Francisco, California (United States); Hsu, I-Chow, E-mail: ichow.hsu@ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, California (United States)

    2015-08-01

    Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgical staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall

  7. Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Treatment outcomes of a prospective, multicentric clinical study

    International Nuclear Information System (INIS)

    Wu, Fang; Wang, Rensheng; Lu, Heming; Wei, Bo; Feng, Guosheng; Li, Guisheng; Liu, Meilian; Yan, Haolin; Zhu, Jinxian; Zhang, Yong; Hu, Kai

    2014-01-01

    Background and purpose: To evaluate long-term outcome in locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. Material and methods: Between January 2006 and August 2008, 249 patients with stage III–IVb NPC were treated by IMRT plus concurrent chemotherapy in this multicenter prospective study. Results: With a mean follow-up of 54.1 months, the 5-year actuarial rates of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 78.4%, 86.8%, 88.4%, 78.0%, respectively. There were 29 local recurrences, 25 regional recurrences and 52 distant metastases, respectively. Distant metastasis is the main cause of treatment failure. N-stage was an independent prognostic factor for LRFS, RRFS, DMFS and OS. Acute toxicity ⩾grade III mainly consisted of mucositis (34.9%), neutropenia (11.2%), xerostomia (5.6%), and dermatitis (5.2%). The main documented late toxicity was xerostomia, and the severity of xerostomia decreased over time. At 24 months after treatment, 13.2% of patients had grade 2 xerostomia, and none had grade 3 or 4 xerostomia. Conclusions: IMRT with concurrent cisplatin chemotherapy resulted in encouraging rates of local and distant control and overall survival with acceptable rates of acute and limited rates of late toxicity in patients with locoregionally advanced NPC. Distant metastasis remained the main cause of failure. More effective systemic therapy should be explored for patients with advanced N-stage

  8. Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

    Science.gov (United States)

    Kimoto, Takuya; Yamazaki, Hideya; Suzuki, Gen; Aibe, Norihiro; Masui, Koji; Tatekawa, Kotoha; Sasaki, Naomi; Fujiwara, Hitoshi; Shiozaki, Atsushi; Konishi, Hirotaka; Nakamura, Satoaki; Yamada, Kei

    2017-09-01

    Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer. We retrospectively investigated 35 patients treated for a postoperative loco-regional recurrence of esophageal cancer with local field radiotherapy between December 2008 and March 2016. The median irradiation dose was 60 Gy (range: 50-67.5 Gy). Thirty-one (88.6%) patients received concurrent chemotherapy. The median follow-up period was 18 months (range: 5-94 months). The 2-year overall survival was 55.7%, with a median survival time of 29.9 months. In the univariate analysis, the maximal diameter ≤20 mm (P = 0.0383), solitary lesion (P = 0.0352), and the complete remission after treatment (P = 0.00411) had a significantly better prognosis. A total of 27 of 35 patients (77.1%) had progressive disease (loco-regional failure [n = 9], distant metastasis [n = 7], and both loco-regional failure and distant metastasis [n = 11]). No patients had Grade 3 or greater mucositis. Local field radiotherapy is a considerable treatment option for postoperative loco-regional recurrence of esophageal cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  9. Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience

    International Nuclear Information System (INIS)

    Chua, Daniel T.T.; Sham, Jonathan S.T.; Choy, Damon; Kwong, Dora L.W.; Au, Gordon K.H.; Kwong, Philip W.K.; Yau, C.-C.; Cheng, Ashley C.K.; Wan, K.Y.

    2001-01-01

    Purpose: Our center contributed 183 patients to the Asian-Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available. Methods and Materials: Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Ho's T3 disease, N2-N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (≤3 cm, >3-6 cm, > 6 cm). Patients were randomized to receive 2-3 cycles of CT with cisplatin 60 mg/m 2 and epirubicin 110 mg/m 2 D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan-Meier method and significance of survival curve differences calculated using log-rank test. Analysis was performed based on the intent-to-treat. Results: The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease

  10. Outcome following radiotherapy for loco-regionally recurrent non-small cell lung cancer

    International Nuclear Information System (INIS)

    Foo, K.; Yeghiaian-Alvandi, R.; Foroudi, F.

    2005-01-01

    Local and regional recurrence of non-small cell lung cancer is reported to occur in 13-20% of treatment failures after resection. Reported post-recurrent median survival following radiotherapy ranges from 9 to 14 months. This study examines survival following radiotherapy alone for patients with loco-regionally recurring non-small cell lung cancer after initial surgery. Fifty-five patients, receiving radiotherapy at Westmead Hospital between 1979 and 1997, were eligible for study. Data were collected retrospectively by reviewing patient records. The end-point was overall survival. Symptom control was also recorded. Prognostic factors for analysis included age, sex, original presenting stage, disease-free interval (DFI), performance status, site of recurrence, treatment intent and dose. The median overall survival was 11.5 months (95% confidence interval: 8.1-13.0). Survival following treatment with radical intent was 26 months compared to 10.5 months for patients treated with palliative intent (P = 0.025). There was no significant difference in survival for short (<2 years) or long DFI, performance status, radiation dose, age, sex, site of recurrence or stage. Most patients (55%) had partial or complete resolution of symptoms. Radiotherapy results in overall post-recurrence median survival of nearly 1 year, consistent with previous published data. Radical treatment intent predicts better prognosis as a result of patient selection and higher dose. Radiotherapy is effective at palliating symptoms of this disease Copyright (2005) Blackwell Publishing Asia Pty Ltd

  11. Radiation Field Design and Patterns of Locoregional Recurrence Following Definitive Radiotherapy for Breast Cancer

    International Nuclear Information System (INIS)

    Chen, Susie A.; Schuster, David M.; Mister, Donna; Liu Tian; Godette, Karen; Torres, Mylin A.

    2013-01-01

    Purpose: Locoregional control is associated with breast cancer-specific and overall survival in select women with breast cancer. Although several patient, tumor, and treatment characteristics have been shown to contribute to locoregional recurrence (LRR), studies evaluating factors related to radiotherapy (XRT) technique have been limited. We investigated the relationship between LRR location and XRT fields and dose delivered to the primary breast cancer in women experiencing subsequent locoregional relapse. Methods and Materials: We identified 21 women who were previously treated definitively with surgery and XRT for breast cancer. All patients developed biopsy-result proven LRR and presented to Emory University Hospital between 2004 and 2010 for treatment. Computed tomography (CT) simulation scans with XRT dose files for the initial breast cancer were fused with 18 F-labeled fluorodeoxyglucose positron emission tomography (FDG PET)/CT images in DICOM (Digital Imaging and Communications in Medicine) format identifying the LRR. Each LRR was categorized as in-field, defined as ≥95% of the LRR volume receiving ≥95% of the prescribed whole-breast dose; marginal, defined as LRR at the field edge and/or not receiving ≥95% of the prescribed dose to ≥95% of the volume; or out-of-field, that is, LRR intentionally not treated with the original XRT plan. Results: Of the 24 identified LRRs (3 patients experienced two LRRs), 3 were in-field, 9 were marginal, and 12 were out-of-field. Two of the 3 in-field LRRs were marginal misses of the additional boost XRT dose. Out-of-field LRRs consisted of six supraclavicular and six internal mammary nodal recurrences. Conclusions: Most LRRs in our study occurred in areas not fully covered by the prescribed XRT dose or were purposely excluded from the original XRT fields. Our data suggest that XRT technique, field design, and dose play a critical role in preventing LRR in women with breast cancer.

  12. Breast conserving surgery in locoregional treatment of breast carcinoma after Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Haberer, S.; Le Scodan, R.; Kirova, Y.M.; Moisson, P.; Campana, F.; Fourquet, A.; Bollet, M.A.; Belin, L.; Savignoni, A.; Stevens, D.; Decaudin, D.; Pierga, J.Y.; Reyal, F.

    2012-01-01

    Purpose. - To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. Patients and methods. - Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. Results. - Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). Conclusions. - Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position. (authors)

  13. Long-term bresults of radiotherapy combined with nedaplatin and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer: update on a phase II study

    Directory of Open Access Journals (Sweden)

    Jingu Keiichi

    2012-11-01

    Full Text Available Abstract Background In 2006, we reported the effectiveness of chemoradiotherapy for postoperative recurrent esophageal cancer with a median observation period of 18 months. The purpose of the present study was to update the results of radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU for postoperative loco-regional recurrent esophageal cancer. Methods Between 2000 and 2004, we performed a phase II study on treatment of postoperative loco-regional recurrent esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h and 5-FU (500 mg/m2/24 h for 5 days. The primary endpoint was overall survival rate, and the secondary endpoints were progression-free survival rate, irradiated-field control rate and chronic toxicity. Results A total of 30 patients were enrolled in this study. The regimen was completed in 76.7% of the patients. The median observation period for survivors was 72.0 months. The 5-year overall survival rate was 27.0% with a median survival period of 21.0 months. The 5-year progression-free survival rate and irradiated-field control rate were 25.1% and 71.5%, respectively. Grade 3 or higher late toxicity was observed in only one patient. Two long-term survivors had gastric tube cancer more than 5 years after chemoradiotherapy. Pretreatment performance status, pattern of recurrence (worse for patients with anastomotic recurrence and number of recurrent lesions (worse for patients with multiple recurrent lesions were statistically significant prognostic factors for overall survival. Conclusions Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. However, the prognosis of patients with multiple regional recurrence or anastomotic recurrence is very poor.

  14. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    International Nuclear Information System (INIS)

    Franckena, Martine; Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-01-01

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research

  15. Locoregional post-mastectomy radiotherapy for breast cancer: literature review

    International Nuclear Information System (INIS)

    Noel, G.; Mazeron, J.J.

    2000-01-01

    Postoperative radiotherapy is controversial after radical mastectomy. Recent clinical trials have shown an increase in survival with this irradiation and conclusions of previous meta-analyses should be reconsidered and conclusions of previous meta-analyses should be reconsidered. The results of a large number of randomized clinical trials in which women received post-mastectomy radiotherapy or not have been renewed. These trials showed a decrease in locoregional failure with the use of postoperative radiotherapy but survival advantages have not been clearly identified. A large number of randomized clinical trials compared postoperative radiotherapy alone, chemotherapy alone and the association of the two treatments. They showed that chemotherapy was less active locally than radiotherapy and that radiotherapy and chemotherapy significantly increased both disease-free and overall survival rates in the groups which received postoperative radiotherapy. These favourable results were, however, obtained with optimal radiotherapy techniques and a relative sparing of lung tissue and cardiac muscle. Many retrospective clinical analyses concluded that results obtained in locoregional failure rate were poor and that these failures led to an increase in future risks. Both radiotherapy and systemic treatment should be delivered after mastectomy, reserved for patients with a high risk of with a diameter ≥ 5 cm. However, radiotherapy could produce secondary effects, and techniques of radiotherapy should be optimal. (author)

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

    International Nuclear Information System (INIS)

    Ou Dan; He Xiayun; Hu Chaosu; Ying Hongmei; Zhu Guopei

    2012-01-01

    Objective: To evaluate the efficacy and toxicity of gemcitabine plus cisplatin (GP) chemotherapy combined with intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: 71 patients (Stage III: 41, Stage IV A : 30) with locoregionally advanced NPC were entered this study. Neoadjuvant chemotherapy was consisted of cisplatin 25 mg/m 2 intravenously on d1-3 and gemcitabine 1000 mg/m 2 in 30 minutes intravenous infusion on days 1 and 8, every 3 weeks for 2 cycles. Adjuvant chemotherapy consisted of 2 cycles of the same GP regimen was given at 28 days after the end of radiotherapy. The prescription doses was 66.0-70.4 Gy to the gross tumor volume, 66 Gy to positive neck nodes, 60 Gy to the high-risk clinical target volume, 54 Gy to the low-risk clinical target volume. Results: The overall response rate to neoadjuvant chemotherapy was 91.2%, acute toxicity was mainly grade 1-2 myleosuppression. All patients completed IMRT. The median follow-up duration was 38 months. The 3-year nasopharyngeal local control, regional control, distant metastasis-free survival rate and overall survival rate were 93%, 99%, 91%, 90%, respectively. Severe late toxicities included grade 3 trismus in 1 patient, grade 3 hearing impairment in 2 patients and cranial nerve palsy in 2 patients, respectively. No grade 4 late toxicities were observed. Conclusions: The combination of GP chemotherapy and IMRT for locoregionally advanced nasopharyngeal carcinoma is well-tolerated, convenient, effective, and warrants further studies of more proper cycles of GP regimen. (authors)

  17. Therapeutic results and prognostic factors after irradiation of loco-regional prostate cancer

    International Nuclear Information System (INIS)

    Debrigode, C.; Dubois, J.; Hay, H.M.; Astre, C.; Savu, N.M.

    1994-01-01

    The present study concerns 140 patients with loco-regional prostatic cancer, treated with external beam irradiation at the CRLC Val-d'Aurelle in Montpellier, France, between 1982 and 1988, with a minimum of 54 months follow-up. The local control after radiotherapy is 78.6%, all stages and histological grades combined. The median overall survival is 114 months and the median disease-free survival 59 months. The most frequent modality of treatment failure is metastatic disease, isolated (32.8%) or combined to local relapse (10%). The rate of urinary intolerance symptoms during treatment was 87.1 and 80.6% for the digestive ones. The late urinary complications and sequellae rate was 21.4% for the cystitis-type and 12.9% for post-radiotherapy urethral structures; the latter has imposed in 2/3 of cases one or more trans-urethral resections that never showed pathological signs of recurrence. Digestive complications and sequellae occurred in 31.3% of the patients; in the latter group there were two internal digestive fistulae which needed surgical treatment and three postradiotherapeutic stenosis of the anal canal. The prognostic factors revealed by statistical analysis are clinical stage, pathological grade for overall and disease-free survival, age for overall survival and trans-urethral resection for disease-free survival, the latter being equally a risk factor for cystitis-type complications and urethral structures. (authors). 26 refs., 8 figs., 7 tabs

  18. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    International Nuclear Information System (INIS)

    Wasserman, Todd H.; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-01-01

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m 2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade ≥2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival

  19. Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome.

    Science.gov (United States)

    Patrikidou, Anna; Brureau, Laurent; Casenave, Julien; Albiges, Laurence; Di Palma, Mario; Patard, Jean-Jacques; Baumert, Hervé; Blanchard, Pierre; Bossi, Alberto; Kitikidou, Kyriaki; Massard, Christophe; Fizazi, Karim; Blanchet, Pascal; Loriot, Yohann

    2015-05-01

    The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Controlling chaotic transients: Yorke's game of survival

    DEFF Research Database (Denmark)

    Aguirre, Jacobo; D'ovidio, Francesco; Sanjuán, Miguel A. F.

    2004-01-01

    . This problem is focused as a two-person, mathematical game between two players called "the protagonist" and "the adversary." The protagonist's goal is to survive. He can lose but cannot win; the best he can do is survive to play another round, struggling ad infinitum. In the absence of actions by either player...... knows the action of the adversary in choosing his response and is permitted to choose the initial point x(0) of the game. We use the "slope 3" tent map in an example of this problem. We show that it is possible for the protagonist to survive....

  1. Concurrent Chemotherapy and Intensity-Modulated Radiotherapy for Locoregionally Advanced Laryngeal and Hypopharyngeal Cancers

    International Nuclear Information System (INIS)

    Lee, Nancy Y.; O'Meara, William; Chan, Kelvin; Della-Bianca, Cesar; Mechalakos, James G.; Zhung, Joanne; Wolden, Suzanne L.; Narayana, Ashwatha; Kraus, Dennis; Shah, Jatin P.; Pfister, David G.

    2007-01-01

    Purpose: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. Conclusion: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser

  2. Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial.

    Science.gov (United States)

    Giuliano, Armando E; Ballman, Karla; McCall, Linda; Beitsch, Peter; Whitworth, Pat W; Blumencranz, Peter; Leitch, A Marilyn; Saha, Sukamal; Morrow, Monica; Hunt, Kelly K

    2016-09-01

    The early results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in locoregional recurrence for patients with positive sentinel lymph nodes (SLNs) randomized either to axillary lymph node dissection (ALND) or sentinel lymph node dissection (SLND) alone. We now report long-term locoregional recurrence results. ACOSOG Z0011 prospectively examined overall survival of patients with SLN metastases undergoing breast-conserving therapy randomized to undergo ALND after SLND or no further axillary specific treatment. Locoregional recurrence was prospectively evaluated and compared between the groups. Four hundred forty-six patients were randomized to SLND alone and 445 to SLND and ALND. Both groups were similar with respect to age, Bloom-Richardson score, Estrogen Receptor status, adjuvant systemic therapy, histology, and tumor size. Patients randomized to ALND had a median of 17 axillary nodes removed compared with a median of only 2 SLNs removed with SLND alone (P alone arm (P = 0.28). Ten-year cumulative locoregional recurrence was 6.2% with ALND and 5.3% with SLND alone (P = 0.36). Despite the potential for residual axillary disease after SLND, SLND without ALND offers excellent regional control for selected patients with early metastatic breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

  3. Loco-regional therapy for liver cancer

    Directory of Open Access Journals (Sweden)

    YE Shenglong

    2013-01-01

    Full Text Available Loco-regional therapy, which uses imaging technologies to facilitate targeted delivery of therapeutic agents to cancers, has emerged as the most commonly used non-surgical treatment for primary liver cancer. Since the theory of loco-regional therapy was introduced, various strategies have been developed and successfully applied in clinic, including interventional radiology methods (mainly transarterial chemoembolization and local ablative methods (such as intratumoral ethanol injection, radiofrequency ablation, microwave coagulation, laser-induced thermal therapy, high-intensity focused ultrasound, and cryotherapy. TACE has been widely applied to treat inoperable liver cancers at intermediate and advanced stages, while the local ablative therapies have proven more suitable for small (<5 cm liver cancers. However, choosing the appropriate loco-regional therapy strategy should be carried out on an individual basis, considering the patient's particular disease condition and characteristics. To help guide such treatment decisions, this review highlights the principal indications, theory, techniques, and reported efficacies of the various loco-regional therapy strategies.

  4. Long term outcomes after salvage radiotherapy for postoperative locoregionally recurrent non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ji; Song, Chang Hoon; Kim, Jae Sung [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Mi Young [Dept. of Radiation Oncology, Kyungpook National University Medical Center, Daegu (Korea, Republic of)

    2017-03-15

    The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

  5. Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

    Science.gov (United States)

    Brockley, L K; Cooper, M A; Bennett, P F

    2013-01-01

    The aim of the study was to compare the effect of carboplatin chemotherapy on the survival of canine patients diagnosed with malignant melanoma after loco-regional control or as a sole therapy. A retrospective study of 63 dogs with oral, digital or cutaneous malignant melanoma treated with surgery and/or chemotherapy was undertaken. Dogs were grouped based on the anatomical site of melanoma development. For oral melanoma, dogs were subclassified into two groups: loco-regional control and gross disease. All patients in the digital and cutaneous groups had achieved loco-regional control with surgery. Comparisons between survival data for each group at each anatomical site were then made. Within the loco-regional control groups survival time was compared between those treated with and without chemotherapy post surgery. For the oral melanoma patients with gross disease survival was compared between those treated with chemotherapy and palliative therapy. The toxicity of carboplatin chemotherapy was evaluated overall. The overall median survival times for patients with oral, digital and cutaneous melanoma were 389, 1,350 days and not reached (with a median follow-up of 776 days) respectively. Median survival time was defined as "not reached" when less than 50% of the subjects died of the disease at the end of the follow-up period, or at the time they were lost to follow-up. The addition of chemotherapy to surgery did not confer a survival benefit in the loco-regional control setting when assessing survival for each anatomical site. For oral melanoma patients with gross disease there was no difference between survival of patients treated with chemotherapy and palliative intent therapy. There was however an improvement in survival in the three dogs that responded to chemotherapy (978 days; p=0.039) compared to the eight non-responders (147 days). On univariate and multivariate analysis, anatomic location was the only variable that was significantly related to survival (p=0

  6. Larynx preservation with primary non-surgical treatment for loco-regionally advanced larynx cancer

    International Nuclear Information System (INIS)

    Corry, June; Peters, Lester; D'Costa, Leta; Chua, Margaret; Peters, Lester J.; Vallance, Neil; Lyons, Bernard; Kleid, Stephen; Sizeland, Andrew

    2011-01-01

    Full text: The objective of this paper was to review the results of primary non-surgical treatment with the aim of larynx preservation for loco-regionally advanced larynx cancer (LALC). Methods: All patients with LALC presenti:lg between January 2002 and Decem ber 2006 who were selected for primary non-surgical treatment were included in this study. Results: There were 60 patients, 48% with stage III and 52% with stage IV disease. The median follow-up of living patients was 41 months. Larynx preservation with local disease control was achieved in 83% and 77% of patients at 3 and 5 years, respectively. Failure-free survival at 3 and 5 years was 66% and 59%, respectively, and overall survival was 67% and 45%, respectively. All patients with larynx preservation had a functional voice. Two patients became feeding tube dependant. Thirty-nine percent of all deaths were unrelated to LALC. Conclusions: Primary non-surgical treatment achieves high rates of larynx preservation with a low rate of severe complications but overall survival remains disappointing.

  7. A comparative evaluation of pain and anxiety levels in 2 different anesthesia techniques: locoregional anesthesia using conventional syringe versus intraosseous anesthesia using a computer-controlled system (Quicksleeper).

    Science.gov (United States)

    Özer, Senem; Yaltirik, Mehmet; Kirli, Irem; Yargic, Ilhan

    2012-11-01

    The aim of this study was to compare anxiety and pain levels during anesthesia and efficacy of Quicksleeper intraosseous (IO) injection system, which delivers computer-controlled IO anesthesia and conventional inferior alveolar nerve block (IANB) in impacted mandibular third molars. Forty subjects with bilateral impacted mandibular third molars randomly received IO injection or conventional IANB at 2 successive appointments. The subjects received 1.8 mL 2% articaine. IO injection has many advantages, such as enabling painless anesthesia with less soft tissue numbness and quick onset of anesthesia as well as lingual and palatal anesthesia with single needle penetration. Although IO injection is a useful technique commonly used during various treatments in dentistry, the duration of injection takes longer than conventional techniques, there is a possibility of obstruction at the needle tip, and, the duration of the anesthetic effect is inadequate for prolonged surgical procedures. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Radiation Therapy for Loco-Regional Recurrence of Adenocarcinoma of the Rectum

    International Nuclear Information System (INIS)

    Cho, K. H.; Seong, J. S.; Suh, C. O.; Kim, G. E.

    1984-01-01

    Thirty patients with loco-regional recurrence following curative surgery for adenocarcinoma of the rectum were retrospectively. Evaluated to determine factors influencing survival and the efficacy of radiation therapy. In this review of 30 patients undergoing radiation therapy, more than 50 percent (17/30) had definite symptomatic and objective response. Ninety percent of patients (27/30) received significant palliation. Over all 2-year survival rate was 7.4% and their median was 13.0 months. Grade of response and Sex were statistically related to survival

  9. TEN-YEAR RECURRENCE RATES IN YOUNG WOMEN WITH BREAST CANCER BY LOCOREGIONAL TREATMENT APPROACH

    Science.gov (United States)

    Beadle, Beth M.; Woodward, Wendy A.; Tucker, Susan L.; Outlaw, Elesyia D.; Allen, Pamela K.; Oh, Julia L.; Strom, Eric A.; Perkins, George H.; Tereffe, Welela; Yu, Tse-Kuan; Meric-Bernstam, Funda; Litton, Jennifer K.; Buchholz, Thomas A.

    2011-01-01

    Purpose Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35 years or younger. Methods and Materials Data for 668 breast cancers in 652 young patients with breast cancer were retrospectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. Results Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT (p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT (p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04). Conclusions Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemotherapy provided a significant benefit to either approach. PMID:18707822

  10. Ten-Year Recurrence Rates in Young Women With Breast Cancer by Locoregional Treatment Approach

    International Nuclear Information System (INIS)

    Beadle, Beth M.; Woodward, Wendy A.; Tucker, Susan L.; Outlaw, Elesyia D.; Allen, Pamela K.; Oh, Julia L.; Strom, Eric A.; Perkins, George H.; Tereffe, Welela; Yu, T.-K.; Meric-Bernstam, Funda; Litton, Jennifer K.; Buchholz, Thomas A.

    2009-01-01

    Purpose: Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35 years or younger. Methods and Materials: Data for 668 breast cancers in 652 young patients with breast cancer were retrospectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. Results: Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT (p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT (p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04). Conclusions: Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemotherapy provided a significant benefit to either approach

  11. The impact of young age on locoregional recurrence after doxorubicin-based breast conservation therapy in patients 40 years old or younger: How young is 'young'?

    International Nuclear Information System (INIS)

    Oh, Julia L.; Bonnen, Mark; Outlaw, Elesyia D.; Schechter, Naomi R.; Perkins, George H.; Strom, Eric A.; Babiera, Gildy; Oswald, Mary Jane; Allen, Pamela K.; Thames, Howard D.; Buchholz, Thomas A.

    2006-01-01

    Purpose: The aim of this study was to investigate whether patients <35 years old have similar risk of locoregional recurrence after breast conservation therapy compared with patients 35 to 40 years old. Methods and materials: We retrospectively reviewed records of 196 consecutive patients ≤40 years old who received breast conservation therapy (BCT) from 1987 to 2000 for breast cancer and compared outcomes between patients <35 years old with patients 35 to 40 years old. The majority of patients received neoadjuvant chemotherapy as part of their treatment. Multivariate analysis was performed to assess risk factors for locoregional recurrence. Results: After a median follow-up of 64 months, 22 locoregional recurrences (LRR) were observed. Twenty patients developed locoregional recurrence as their first site of relapse. Two patients had bone-only metastases before their locoregional recurrence. On multivariate analysis, age <35 years was associated with a statistically significant increased risk of locoregional recurrence. The 5-year rate of locoregional control was 87.9% in patients <35 years old compared with 91.7% in patients 35 to 40 years old (p = 0.042). Conclusions: Our finding supports an increased risk of locoregional recurrence as a function of younger age after breast conservation therapy, even among young patients 40 years old and younger

  12. Role of nuclear medicine in the treatment of malignant gliomas: the locoregional radioimmunotherapy approach

    International Nuclear Information System (INIS)

    Riva, P.; Franceschi, G.; Riva, N.; Casi, M.; Santimaria, M.; Adamo, M.

    2000-01-01

    The high-grade malignant gliomas (anaplastic astrocytomas and glioblastoma) have a very bad prognosis since the available methods of treatment (surgery, radiotherapy and chemotherapy) are unable to control the progression of the disease for long. The use of specific monoclonal antibodies labelled with a suitable isotope (iodine-131 or yttrium-90) represents an effective approach to hamper tumour regrowth. Some authors have injected the antibodies intravenously, or have tried to increase the tumour/background ratio with the avidin/ biotin system. In many cases the labelled monoclonal antibodies were injected directly into the tumoral bed after the operation. The authors' experiences concern a quite large locoregional radioimmunotherapy study which was performed by using antitenascin antibodies labelled initially with 131 I and more recently with 90 Y. The clinical results demonstrate the ability of this technique to control, for a long time, the growth of these tumours. The glioblastoma median survival was prolonged to 25 months ( 131 I group) or 31 months ( 90 Y group). The response rate (which comprises PR, CR and NED) was 47.1% (glioblastoma 131 I group) or 40% (glioblastoma 90 Y group). In many cases a significant tumour shrinking effect was radiologically demonstrated. The use of 90 Y proved more favourable in bulky lesions, and reduced the radioprotection problems. (orig.)

  13. Surviving Hypopharynx-Larynx Carcinoma in the Era of IMRT

    International Nuclear Information System (INIS)

    Studer, Gabriela; Peponi, Evangelia; Kloeck, Stephan; Dossenbach, Thomas; Huber, Gerhard; Glanzmann, Christoph

    2010-01-01

    Purpose: Outcome in locoregionally advanced laryngeal carcinoma and hypopharyngeal carcinoma after conventional radiation techniques is known for modest disease control and considerable late toxicity. Considering the lack of standardization in prescription dose for intensity-modulated radiotherapy (IMRT), we aimed to compare the results after our methods of simultaneously integrated boost IMRT with published results. Methods and Materials: Between March 2002 and December 2008, 65 hypopharyngeal, 31 supraglottic, and 27 locoregionally advanced glottic tumor patients underwent definitive IMRT (with simultaneous chemotherapy in 86%). Of these, 64% presented with locoregionally advanced disease. Mean follow-up was 26 months (range, 3-83 months), with a median of 21 months. Treatment (2.0-2.2Gy per fraction, 66-72.6Gy) followed a prospectively defined protocol. If the boost volume included more than half of the larynx or a substantial part of the pharynx, dose was limited to 2.0Gy per fraction. Results: The 2-year local, nodal, and locoregional control (LRC) rates for the entire cohort were 82%, 90%, and 77%, respectively; the disease-free and overall survival rates were 75% and 83%, respectively. The ultimate 2-year LRC rate, including salvage surgery, was 86%. Laryngectomy was required in 2 LRC patients needing tracheostoma already before; 2 further LRC patients needed tracheostomy before IMRT and remained tracheostoma dependent, and 3 patients remained feeding tube dependent after IMRT. Salvage laryngectomy was successful in 8 of 11. Of all 123 patients, 91 patients (74%) are locoregionally controlled and live with a functional laryngopharynx. Conclusions: Simultaneously integrated boost IMRT with limited acceptance of dose inhomogeneity resulted in very satisfactory disease control despite a slight left shift of planning target volume curves on the dose-volume histogram. Considering the treatment tolerance, a careful increase in dose in our patients seems possible

  14. Definitive chemoradiation for locoregional recurrences of esophageal cancer after primary curative treatment.

    Science.gov (United States)

    Jeene, P M; Versteijne, E; van Berge Henegouwen, M I; Bergmann, J J G H M; Geijsen, E D; Muller, K; van Laarhoven, H W M; Hulshof, M C C M

    2017-02-01

    The aim of this study was to determine the outcome of salvage definitive chemoradiation (dCRT) for a locoregional recurrence after any prior curative treatment outside previously irradiated areas. Thirty-nine patients treated between January 2005 and December 2014 were reviewed for locoregional recurrent esophageal cancer outside previously irradiated areas. All patients received salvage treatment with external beam radiotherapy (50.4 Gy in 28 fractions) combined with weekly concurrent paclitaxel and carboplatin. The median follow-up period was 15 months (range 1.7-120). The median overall survival (OS) for all patients after salvage dCRT was 22 months (95% CI 6.2-37.6). The 1-, 3-, and 5-year OS was 72%, 31%, and 28%, respectively. Median survival after salvage dCRT for a regional lymph node recurrence was 33 months (95% CI 5.8-60.3) versus 14 months (95% CI 6.8-21.6) for a recurrence at the anastomosis (P = 0.022, logrank). Median OS was 35 months for the squamous cell carcinoma group and 19 months for the adenocarcinoma group (P = 0.67). Sixteen of 39 patients developed a locoregional recurrence after salvaged dCRT. The median locoregional recurrence-free survival (LRFS) was 24 months. The 1-, 3-, and 5-year LRFS was 79%, 36%, and 36%, respectively. Median disease-free survival (DFS) was 15 months. The 1-, 3-, and 5-year DFS was 66%, 27%, and 27%, respectively. Of 16 patients, 8 (50%) with a primary failure at the site of the anastomosis developed a local recurrence after salvaged dCRT compared to 7 of 22 patients (32%) with a primary recurrence in a lymph node. Definitive chemoradiation is a feasible and effective treatment for locoregional recurrent esophageal cancer outside a previously irradiated area, and should be given with a curative intent. This holds true for recurrence of both squamous cell carcinoma and adenocarcinoma. Lymph node recurrences have a markedly better prognosis than recurrences at the site of the anastomosis. © 2016

  15. Locoregional recurrence following maxillectomy: implications for microvascular reconstruction.

    Science.gov (United States)

    Likhterov, Ilya; Fritz, Michael A; El-Sayed, Ivan H; Rahul Seth; Rayess, Hani M; Knott, P Daniel

    2017-11-01

    Reconstruction of maxillectomy defects offers potential quality-of-life improvement, although cavity coverage may impact surveillance of recurrent malignancy. We describe the pattern of postmaxillectomy locoregional recurrence. Retrospective review. Patients from 2001 to 2011 at the University of California, San Francisco and the Cleveland Clinic. Among 75 patients with malignancy resulting in partial or total maxillectomy, 57 were treated with obturators and 18 underwent reconstructive surgery. Disease recurrence occurred primarily locally (19 of 22 cases of recurrence, 25% of the cohort) at a mean of 17 months postoperatively. Recurrence was associated with T4 disease, positive margins, and surveillance imaging. Four (5.3%) patients required flap mobilization/obturator removal to obtain biopsy. Salvage surgery was attempted in 13 of the 19 cases with recurrent disease (68%) and was successful in six (46%) patients. Of these, five patients initially had Brown type 1 or type 2 defects. The free flap had to be revised in one (1.3%) patient to achieve successful salvage. Maxillectomy provides good long-term locoregional oncologic control, with cure being correlated to disease stage at presentation and negative margins after initial surgery. Patients with recurrent disease whose initial resection resulted in a Brown class 3 defect or greater were rarely successfully salvaged. Surveillance is best performed with a combination of physical exam and imaging. Obturator removal/flap mobilization rarely impedes the diagnosis of recurrent disease, and either modality should be offered to appropriate patients in the primary setting if significant quality-of-life improvement is likely. 4. Laryngoscope, 127:2534-2538, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  16. The Effect of Adjuvant Trastuzumab on Locoregional Recurrence of Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Treated with Mastectomy.

    Science.gov (United States)

    Lanning, Ryan M; Morrow, Monica; Riaz, Nadeem; McArthur, Heather L; Dang, Chau; Moo, Tracy-Ann; El-Tamer, Mahmoud; Krause, Kate; Siu, Chun; Hsu, Meier; Zhang, Zhigang; Pei, Xin; McCormick, Beryl; Powell, Simon N; Ho, Alice

    2015-08-01

    Human epidermal growth factor receptor 2 (HER2) overexpression was associated with locoregional recurrence (LRR) in the preadjuvant trastuzumab era. This study aimed to examine the effect of trastuzumab on LRR in mastectomy patients and whether it varied with postmastectomy radiation (PMRT). From the authors' institutional database, 501 women with stages I-III HER2-positive breast cancer who underwent mastectomy from 1998 to 2007 were identified. A landmark analysis was performed to compare two cohorts: 170 women who received trastuzumab and 281 who did not. Kaplan-Meier methods were used to estimate locoregional recurrence-free survival (LRRFS). A propensity score analysis was used to balance the treatment groups with respect to multiple covariates. Analogous methods were used to study the effect of PMRT. The women in the trastuzumab group were more likely to be node positive and to receive systemic therapy or PMRT (p < 0.01). The 5-year LRRFS was 98 % in the trastuzumab troup versus 94 % in the no trastuzumab group [hazard ratio (HR) 0.31; 95 % confidence interval (CI) 0.09-1.09; p = 0.07]. After adjustment for multiple covariates, including receipt of chemotherapy and PMRT, trastuzumab decreased LRR rates (HR 0.21; 95 % CI 0.04-0.94; p = 0.04). Among the women who received PMRT, trastuzumab reduced the 5-year LRR rate (0 vs 5 %; p = 0.06). Among those who did not receive PMRT, trastuzumab did not significantly decrease LRR (3 vs 6 %; p = 0.26). High rates of locoregional control (5-year rate, 98 %) were observed among patients who received trastuzumab and mastectomy ± PMRT. Trastuzumab decreased LRR in HER2-positive women who received mastectomy and PMRT, suggesting that the largest benefit is seen in a higher-risk subset of patients.

  17. Locoregional injection of F-18 radiopharmaceuticals suppresses tumor xenograft growth in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wong, C -L [The Univ. of Texas M.D. Anderson Cancer Center, Texas (United States)

    2004-07-01

    The energetic positrons (0.633 Mev) from F-18 dissipate kinetic energies before annihilation to produce two 0.511 Mev photons which also contribute to the radiation absorbed dose to the surroundings. In living organism, the contribution from the positron itself to the surrounding tissues (up to 2 mm) is larger than from the 2 photons. Apoptosis has been reported in rat tumors after systemic injection of F-18 FDG although no growth retardation was noted. This study is designed to exploit the pharmacokinetic advantages of locoregional injection of positron emitters in the suppression of tumor growth in rats. Methods: Groups of Fisher 344 adult female rats were inoculated with rat mammary tumors (100,000 cells) intramuscularly (IM) in the thigh. Locoregional injection with F-18 NaF or F-18 FDG was accomplished in days 3 or 7 with single doses of increasing strengths (0.2 to 3 mCi). Tumor growth rates were noted and compared to control (sham injection with saline). The locoregional distribution and clearance of F-18 were estimated from serial tomograms using a Concord MicroPET (R4) after intramuscular injection of 0.1-0.2 mCi of F-18 NaF or F-18 FDG in groups of triplicate rats. Results: A dose-related pattern of tumor suppression is noted with F-18 FDG, whether treatment occurs in day 3 or 7 after inoculation. Additional experiment of injection of 5 mci of F-18 FDG at day 14 also suppressed the growth of a well-formed tumor. Tumor suppression by F-18 NaF is less obvious and only occurs with high dose (2 mCi). MicroPET images demonstrate that F-18 FDG is retained in the injection site while F-18 NaF dissipates rapidly. Conclusion: Locoregional injection of positron-emitters may be sufficient to suppress tumor growth. The mechanism is likely related to the pharmacokinetic profile of the compound within the tissue. Discussion: Locoregional application of radionuclides may provide feasible alternatives to slow tumor growth or prevent tumor recurrence. The use of

  18. The Place of Extensive Surgery in Locoregional Recurrence and Limited Metastatic Disease of Breast Cancer: Preliminary Results

    Directory of Open Access Journals (Sweden)

    M. Berlière

    2015-01-01

    Full Text Available The aims of this study were first to clearly define two different entities: locoregional recurrences and limited metastatic disease and secondly to evaluate the place of extensive surgery in these two types of recurrence. Material and Methods. Twenty-four patients were followed from June 2004 until May 2014. All patients underwent surgery but for 1 patient this surgery was stopped because the tumour was unresectable. Results. The median interval between surgery for the primary tumour and the locoregional recurrence or metastatic evolution was 129 months. Eight patients had pure nodal recurrences, 4 had nodal and muscular recurrences, 5 had muscular + skin recurrences, and 8 had metastatic evolution. Currently, all patients are still alive but 2 have liver metastases. Disease free survival was measured at 2 years and extrapolated at 5 years and was 92% at these two time points. No difference was observed for young or older women; limited metastatic evolution and locoregional recurrence exhibited the same disease free survival. Conclusion. Extensive surgery has a place in locoregional and limited metastatic breast cancer recurrences but this option must absolutely be integrated in the multidisciplinary strategy of therapeutic options and needs to be planned with a curative intent.

  19. Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer

    DEFF Research Database (Denmark)

    Tramm, Trine; Kyndi, Marianne; Myhre, Simen

    2014-01-01

    , and has shown prognostic impact in terms of loco-regional failure and predictive impact for PMRT. Reports have also shown predictive value in terms of benefit of PMRT from intrinsic subtypes and derived approximations. The aim of this study was to examine: 1) the agreement between various methods...... for determining the intrinsic subtypes; and 2) the relationship between the prognostic and predictive impact of the DBCG-RT profile and the intrinsic subtypes. MATERIAL AND METHODS: Intrinsic subtypes and the DBCG-RT profile was determined from microarray analysis based on fresh frozen tissue from 191 patients...... and predictive information obtained from the DBCG-RT profile cannot be substituted by any approximation of the tumors intrinsic subtype. The predictive value of the intrinsic subtypes in terms of PMRT was influenced by the method used for assignment to the intrinsic subtypes....

  20. Cerebral control and survival after stereotactic radiotherapy of brain metastases

    International Nuclear Information System (INIS)

    Arnold, Elmar Till

    2014-01-01

    This retrospective study, including 275 patients who underwent stereotactic radiotherapy due to brain metastases between 2003 and 2008, investigates influencing factors regarding cerebral control and survival, symptomatic effects and a potential benefit for patients older than 70 years. We were able to identify risk factors for remote brain failure which leads to a therapeutic recommendation. Furthermore we confirm a positive symptomatic effect and a benefit of stereotactic readiotherapy for patients over 70 years.

  1. The impact of smoking on the clinical outcome of locoregionally advanced nasopharyngeal carcinoma after chemoradiotherapy

    International Nuclear Information System (INIS)

    Guo, Shan-Shan; Huang, Pei-Yu; Chen, Qiu-Yan; Liu, Huai; Tang, Lin-Quan; Zhang, Lu; Liu, Li-Ting; Cao, Ka-Jia; Guo, Ling; Mo, Hao-Yuan; Guo, Xiang; Hong, Ming-Huang; Mai, Hai-Qiang

    2014-01-01

    Cigarette smoking is a common risk factor for developing nasopharyngeal carcinoma. However, the relationship between smoking and clinical outcomes remains uncertain. The patients who participated in this study were drawn from a randomized clinical trial, for which the purpose was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy with that of induction chemotherapy plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. The patients who ever smoked were divided into the following categories of cumulative smoking exposure based on the duration of smoking and the quantity of cigarettes smoked: light, short-term smokers; light, long-term smokers; heavy, short-term smokers; and heavy, long-term smokers. A log-rank test and Cox models were used to assess the association between smoking and the clinical outcomes of overall survival (OS), failure-free survival (FFS), locoregional recurrence failure-free survival (LRFFS) and distant failure-free survival (DFFS). We found that ever-smokers experienced significantly shorter LRFFS times than never-smokers (5-year LRFFS rates: 85.8% vs. 88.5%, P = 0.022). The amount of smoking was significantly associated with FFS (P = 0.046) and LRFFS (P = 0.001) in the different ever-smoker groups. The amount of smoking was associated with LRFFS [P = 0.002, HR = 2.069 (95% confident interval (CI), 1.298-3.299)] even after a multivariable adjustment. Smoking increases the risk of locoregional recurrence. Furthermore, the amount of smoking influences the prognosis of smokers, and these effects are dose-dependent

  2. Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer. Effects on local control, control of metastases, and overall survival

    International Nuclear Information System (INIS)

    Kurita, Hiroshi; Ohtsuka, Akiko; Kobayashi, Hiroichi; Kurashina, Kenji; Shikama, Naoto; Oguchi, Masahiko

    2000-01-01

    Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer. (author)

  3. Feasibility of carbon-ion radiotherapy for re-irradiation of locoregionally recurrent, metastatic, or secondary lung tumors.

    Science.gov (United States)

    Hayashi, Kazuhiko; Yamamoto, Naoyoshi; Karube, Masataka; Nakajima, Mio; Tsuji, Hiroshi; Ogawa, Kazuhiko; Kamada, Tadashi

    2018-03-02

    Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  4. Pattern of loco-regional failure after definitive radiotherapy for non-small cell lung cancer

    DEFF Research Database (Denmark)

    Schytte, Tine; Nielsen, Tine Bjørn; Brink, Carsten

    2014-01-01

    , and occurrence of distant metastasis. It is challenging to evaluate loco-regional control after definitive radiotherapy for NSCLC since it is difficult to distinguish between radiation-induced damage to the lung tissue and tumour progression/recurrence. In addition it may be useful to distinguish between...... intrapulmonary failure and mediastinal failure to be able to optimize radiotherapy in order to improve loco-regional control even though it is not easy to discriminate between the two sites of failure. Material and methods. This study is a retrospective analysis of 331 NSCLC patients treated with definitive...... with mediastinal relapse. Conclusion. We conclude that focus should be on increasing doses to intrapulmonary tumour volume, when dose escalation is applied to improve local tumour control in NSCLC patients treated with definitive radiotherapy, since most recurrences are located here....

  5. Novel Approaches to Locoregional and Systemic Immunotherapy for Ovarian Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0298 TITLE: Novel approaches to locoregional and systemic immunotherapy for ovarian cancer PRINCIPAL INVESTIGATOR...Dmitriy Zamarin CONTRACTING ORGANIZATION: Memorial Sloan Kettering Cancer Center New York, NY 10017 REPORT DATE: October 2017 TYPE OF REPORT...TITLE AND SUBTITLE Novel approaches to locoregional and systemic immunotherapy for ovarian cancer 5a. CONTRACT NUMBER vel ap roaches to l c regional

  6. DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences

    Energy Technology Data Exchange (ETDEWEB)

    Harms, Wolfgang [St. Claraspital, Abteilung fuer Radioonkologie, Basel (Switzerland); Budach, W. [Heinrich-Heine-University, Duesseldorf (Germany); Dunst, J. [University Hospital Schleswig-Holstein, Kiel (Germany); Feyer, P. [Vivantes Hospital Neukoelln, Berlin (Germany); Fietkau, R.; Sauer, R. [University Hospital Erlangen, Erlangen (Germany); Krug, D. [University Hospital Heidelberg, Heidelberg (Germany); Piroth, M.D. [Witten/Herdecke University, HELIOS-Hospital Wuppertal, Wuppertal (Germany); Sautter-Bihl, M.L. [Municipal Hospital, Karlsruhe (Germany); Sedlmayer, F. [Paracelsus Medical University Hospital, Salzburg (Austria); Wenz, F. [University of Heidelberg, University Medical Center Mannheim, Medical Faculty Mannheim, Mannheim (Germany); Haase, W.; Souchon, R.; Collaboration: Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

    2016-04-15

    To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012. A comprehensive survey of the literature using the search phrases ''locoregional breast cancer recurrence'', ''chest wall recurrence'', ''local recurrence'', ''regional recurrence'', and ''breast cancer'' was performed, using the limits ''clinical trials'', ''randomized trials'', ''meta-analysis'', ''systematic review'', and ''guidelines''. Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts

  7. Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET).

    Science.gov (United States)

    Rossi, C R; Vecchiato, A; Mastrangelo, G; Montesco, M C; Russano, F; Mocellin, S; Pasquali, S; Scarzello, G; Basso, U; Frasson, A; Pilati, P; Nitti, D; Lurkin, A; Ray-Coquard, I

    2013-06-01

    The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto). The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

  8. Locoregional Confinement and Major Clinical Benefit of 188Re-Loaded CXCR4-Targeted Nanocarriers in an Orthotopic Human to Mouse Model of Glioblastoma.

    Science.gov (United States)

    Séhédic, Delphine; Chourpa, Igor; Tétaud, Clément; Griveau, Audrey; Loussouarn, Claire; Avril, Sylvie; Legendre, Claire; Lepareur, Nicolas; Wion, Didier; Hindré, François; Davodeau, François; Garcion, Emmanuel

    2017-01-01

    Gold standard beam radiation for glioblastoma (GBM) treatment is challenged by resistance phenomena occurring in cellular populations well prepared to survive or to repair damage caused by radiation. Among signals that have been linked with radio-resistance, the SDF1/CXCR4 axis, associated with cancer stem-like cell, may be an opportune target. To avoid the problem of systemic toxicity and blood-brain barrier crossing, the relevance and efficacy of an original system of local brain internal radiation therapy combining a radiopharmaceutical with an immuno-nanoparticle was investigated. The nanocarrier combined lipophilic thiobenzoate complexes of rhenium-188 loaded in the core of a lipid nanocapsule (LNC 188 Re) with a function-blocking antibody, 12G5 directed at the CXCR4, on its surface. The efficiency of 12G5-LNC 188 Re was investigated in an orthotopic and xenogenic GBM model of CXCR4-positive U87MG cells implanted in the striatum of Scid mice. We demonstrated that 12G5-LNC 188 Re single infusion treatment by convection-enhanced delivery resulted in a major clinical improvement in median survival that was accompanied by locoregional effects on tumor development including hypovascularization and stimulation of the recruitment of bone marrow derived CD11b- or CD68-positive cells as confirmed by immunohistochemistry analysis. Interestingly, thorough analysis by spectral imaging in a chimeric U87MG GBM model containing CXCR4-positive/red fluorescent protein (RFP)-positive- and CXCR4-negative/RFP-negative-GBM cells revealed greater confinement of DiD-labeled 12G5-LNCs than control IgG2a-LNCs in RFP compartments. Main conclusion: These findings on locoregional impact and targeting of disseminated cancer cells in tumor margins suggest that intracerebral active targeting of nanocarriers loaded with radiopharmaceuticals may have considerable benefits in clinical applications.

  9. Low locoregional recurrence rates in patients treated after 2000 with doxorubicin based chemotherapy, modified radical mastectomy, and post-mastectomy radiation

    International Nuclear Information System (INIS)

    Greenbaum, Michael P.; Strom, Eric A.; Allen, Pamela K.; Perkins, George H.; Oh, Julia L.; Tereffe, Welela; Yu, Tse-Kuan; Buchholz, Thomas A.; Woodward, Wendy A.

    2010-01-01

    Purpose: To determine the rate of locoregional recurrence (LRR) associated with modern tri-modality therapy. Methods: We retrospectively reviewed data from 291 consecutive PMRT patients treated from 1999 to 2001. These patients were compared to an historical group of 313 patients treated from 1979 to 1988 who had fluoroscopic simulation and contour-generated 2D planning. 1999-2001 spans the adoption of CT simulators for breast radiation therapy and a comparison was made between patients simulated before and after the implementation of CT simulation. Five-year actuarial rates for LRR, distal metastasis (DM), and overall survival (OS) between the pre and post CT simulation cohorts were compared as well. Results: Compared to a 2D planned historic control, the combined contemporary patients had improved outcomes at 5 years for all endpoints studied; LRR 3.0% vs. 11.5%, DM 29.2% vs. 39.2%, and OS 79.2% vs. 70.6% (p = 0.0004, 0.0052, 0.0012, respectively). Significant factors in a multivariate analysis for LRR were: advanced T-stage (RR = 2.14, CI = 1.11-4.11, p = 0.023), and percent positive nodes (RR = 1.01, CI = 1.00-1.02, p = 0.012). The comparison of the pre and post CT-simulated PMRT patients (1999-2001) found no significant difference in any endpoint. Conclusions: The rate of locoregional control for PMRT patients treated with modern radiotherapy is outstanding and has improved significantly compared to historical controls.

  10. Control of neural stem cell survival by electroactive polymer substrates.

    Directory of Open Access Journals (Sweden)

    Vanessa Lundin

    Full Text Available Stem cell function is regulated by intrinsic as well as microenvironmental factors, including chemical and mechanical signals. Conducting polymer-based cell culture substrates provide a powerful tool to control both chemical and physical stimuli sensed by stem cells. Here we show that polypyrrole (PPy, a commonly used conducting polymer, can be tailored to modulate survival and maintenance of rat fetal neural stem cells (NSCs. NSCs cultured on PPy substrates containing different counter ions, dodecylbenzenesulfonate (DBS, tosylate (TsO, perchlorate (ClO(4 and chloride (Cl, showed a distinct correlation between PPy counter ion and cell viability. Specifically, NSC viability was high on PPy(DBS but low on PPy containing TsO, ClO(4 and Cl. On PPy(DBS, NSC proliferation and differentiation was comparable to standard NSC culture on tissue culture polystyrene. Electrical reduction of PPy(DBS created a switch for neural stem cell viability, with widespread cell death upon polymer reduction. Coating the PPy(DBS films with a gel layer composed of a basement membrane matrix efficiently prevented loss of cell viability upon polymer reduction. Here we have defined conditions for the biocompatibility of PPy substrates with NSC culture, critical for the development of devices based on conducting polymers interfacing with NSCs.

  11. Surgical resection of late solitary locoregional gastric cancer recurrence in stomach bed.

    Science.gov (United States)

    Watanabe, Masanori; Suzuki, Hideyuki; Maejima, Kentaro; Komine, Osamu; Mizutani, Satoshi; Yoshino, Masanori; Bo, Hideki; Kitayama, Yasuhiko; Uchida, Eiji

    2012-07-01

    Late-onset and solitary recurrence of gastric signet ring cell (SRC) carcinoma is rare. We report a successful surgical resection of late solitary locoregional recurrence after curative gastrectomy for gastric SRC carcinoma. The patient underwent total gastrectomy for advanced gastric carcinoma at age 52. Seven years after the primary operation, he visited us again with sudden onset of abdominal pain and vomiting. We finally decided to perform an operation, based on a diagnosis of colon obstruction due to the recurrence of gastric cancer by clinical findings and instrumental examinations. The laparotomic intra-abdominal findings showed that the recurrent tumor existed in the region surrounded by the left diaphragm, colon of splenic flexure, and pancreas tail. There was no evidence of peritoneal dissemination, and peritoneal lavage fluid cytology was negative. We performed complete resection of the recurrent tumor with partial colectomy, distal pancreatectomy, and partial diaphragmectomy. Histological examination of the resected specimen revealed SRC carcinoma, identical in appearance to the previously resected gastric cancer. We confirmed that the intra-abdominal tumor was a locoregional gastric cancer recurrence in the stomach bed. The patient showed a long-term survival of 27 months after the second operation. In the absence of effective alternative treatment for recurrent gastric carcinoma, surgical options should be pursued, especially for late and solitary recurrence.

  12. Cancer of Oral Cavity Abutting the Mandible; Predictors of Loco-regional Failure

    International Nuclear Information System (INIS)

    Saber, T.K.; Hussein, H.A.; Mebeed, A.H.; El Sebai, H.I.; Sami, I.; Farahat, I.G.

    2009-01-01

    The purpose of this study is to analyze the causes of Loco-regional failure in 51 patients with tumors of the oral cavity abutting the mandible. Patients and Methods: This cross-sectional study (27 patients were operated upon in the retrospective section and 24 patients in the prospective section of the study) was done in the department of Surgical Oncology, National Cancer Institute, Cairo University, from January 2003 to January 2008. Fifty-one patients, with oral cavity cancerous lesions abutting the mandible, were operated upon by segmental mandibulectomy en-bloc with primary tumor resection in addition to modified radical or selective neck dissection according to the status of the cervical lymph nodes. Results: During a median follow-up of 2 years, 29 patients (56.8%) had local recurrences, the incidence of nodal recurrence after neck dissection was detected in 4 patients (7.8%). On multivariate analysis, tumor depth, tumor grade, oral mucosa, soft tissue and bone surgical margins in addition to metastatic lymphadenopathy were independent prognostic factors of loco-regional failure and disease-free survival. Conclusion: Oral cavity cancers abutting the mandible should be treated with great caution by a multidisciplinary oncology team (resection and reconstruction surgeons) as it has a very aggressive biologic behavior. Negative intraoperative pathological margins should be attempted since this is the critical point for patients with cancers abutting the mandible? Further research on the biologic margin and genetic study is required

  13. Coyote removal, understory cover, and survival of white-tailed deer neonates: Coyote Control and Fawn Survival

    Energy Technology Data Exchange (ETDEWEB)

    Kilgo, John C. [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Vukovich, Mark [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Ray, H. Scott [USDA Forest Service, Savannah River; New Ellenton, SC (United States); Shaw, Christopher E. [USDA Forest Service; Southern Research Station, New Ellenton, SC (United States); Ruth, Charles [South Carolina Dept. of Natural Resources, Columbia, SC (United States)

    2014-09-01

    Predation by coyotes (Canis latrans) on white-tailed deer (Odocoileus virginianus) neonates has led to reduced recruitment in many deer populations in southeastern North America. This low recruitment combined with liberal antlerless deer harvest has resulted in declines in some deer populations, and consequently, increased interest in coyote population control. We investigated whether neonate survival increased after coyote removal, whether coyote predation on neonates was additive to other mortality sources, and whether understory vegetation density affected neonate survival. We monitored neonate survival for 4 years prior to (2006–2009) and 3 years during (2010–2012) intensive coyote removal on 3 32-km2 units on the United States Department of Energy’s Savannah River Site, South Carolina. We removed 474 coyotes (1.63 coyotes/km2 per unit per year), reducing coyote abundance by 78% from pre-removal levels. The best model (wi = 0.927) describing survival probability among 216 radio-collared neonates included a within-year quadratic time trend variable, date of birth, removal treatment, and a varying removal year effect. Under this model, survival differed between pre-treatment and removal periods and it differed among years during the removal period, being >100% greater than pre-treatment survival (0.228) during the first removal year (0.513), similar to pre-treatment survival during the second removal year (0.202), and intermediate during the third removal year (0.431). Despite an initial increase, the overall effect of coyote removal on neonate survival was modest. Mortality rate attributable to coyote predation was lowest during the first removal year (0.357) when survival was greatest, but the mortality rate from all other causes did not differ between the pretreatment period and any year during removals, indicating that coyote predation acted as an additive source of mortality. Survival probability was not related to

  14. Locoregionally Advanced Head and Neck Cancer Treated With Primary Radiotherapy: A Comparison of the Addition of Cetuximab or Chemotherapy and the Impact of Protocol Treatment

    International Nuclear Information System (INIS)

    Caudell, Jimmy J.; Sawrie, Stephen M.; Spencer, Sharon A.; Desmond, Renee A.; Carroll, William R.; Peters, Glenn E.; Nabell, Lisle M.; Meredith, Ruby F.; Bonner, James A.

    2008-01-01

    Purpose: The addition of platinum-based chemotherapy (ChRT) or cetuximab (ExRT) to concurrent radiotherapy (RT) has resulted in improved survival in Phase III studies for locoregionally advanced head and neck cancer (LAHNC). However the optimal treatment regimen has not been defined. A retrospective study was performed to compare outcomes in patients who were treated definitively with ExRT or ChRT. Methods: Cetuximab with concurrent RT was used to treat 29 patients with LAHNC, all of whom had tumors of the oral cavity, oropharynx, or larynx. All patients were T2 to T4 and overall American Joint Committee on Cancer Stage III to IVB, with a Karnofsky Performance Status (KPS) score of 60 or greater. ChRT was used to treat 103 patients with similar characteristics. Patients were evaluated for locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). Median follow-up for patients alive at last contact was 83 months for those treated with ExRT and 53 months for those treated with ChRT. Cox proportional hazard models were used to assess independent prognostic factors. Results: The LRC, DMFS, and DSS were not significantly different, with 3-year rates of 70.7%, 92.4%, and 78.6% for ExRT and 74.7%, 86.6%, and 76.5% for ChRT, respectively. The OS was significantly different between the two groups (p = 0.02), with 3-year rates of 75.9% for ExRT and 61.3% for ChRT. OS was not significant when patients who were on protocol treatments of ExRT or ChRT were compared. Also, OS was not significant when multivariate analysis was used to control for potential confounding factors. Conclusion: In our single-institution retrospective review of patients treated with ExRT or ChRT, no significant differences were found in LRC, DMFS, DSS, or OS

  15. Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

    International Nuclear Information System (INIS)

    Nguyen, David H.A.; Truong, Pauline T.; Alexander, Cheryl; Walter, Caroline V.; Hayashi, Emily; Christie, Jennifer; Lesperance, Mary

    2012-01-01

    Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0–1, Stage T1–2 tumors, N0–1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0–1, estrogen receptor–positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64–0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor

  16. Postmastectomy radiotherapy reduces locoregional and disease recurrence in patients with stage II–III triple-negative breast cancer treated with neoadjuvant chemotherapy and mastectomy

    Directory of Open Access Journals (Sweden)

    Chen XX

    2018-04-01

    Full Text Available Xingxing Chen,1,2,* Fan Xia,1,2,* Jurui Luo,1,2,* Jinli Ma,1,2 Zhaozhi Yang,1,2 Li Zhang,1,2 Yan Feng,1,2 Zhimin Shao,2,3 Xiaoli Yu,1,2 Xiaomao Guo1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; 3Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China *These authors contributed equally to this work Background: This study investigated the effect of postmastectomy radiotherapy (PMRT in patients with stage II–III triple-negative breast cancer (TNBC after neoadjuvant chemotherapy (NAC and modified radical mastectomy (MRM.Patients and methods: A total of 104 women with stage II–III TNBC who received NAC and MRM at our institution between January 2000 and July 2007 were identified. Patients were divided into 2 groups (PMRT and non-PMRT for statistical analysis.Results: The median follow-up time was 64 months (range 12–123 months. The 5 year cumulative locoregional recurrence (LRR and disease recurrence (DR rates were 26.5% and 49.6%, respectively. Despite their more adverse prognostic features, patients with PMRT had lower 5 year cumulative LRR and DR rates than those without PMRT (LRR: 18.3% vs 52.2%, respectively, p=0.0005; DR: 45% vs 69.1%, p=0.0334, respectively. On multivariate analysis of the entire study cohort, forgoing PMRT was significantly associated with developing LRR and DR. Subset analysis revealed that PMRT significantly reduced the 5 year LRR rate in patients with pre-chemotherapy clinical stages IIA (8.3% vs 46.2%, p=0.019 and IIIA (16% vs 66.7%, p=0.003. PMRT also significantly reduced the 5 year DR rate in patients with pre-chemotherapy clinical stage IIA (24.5% vs 69.3%, p=0.0151 and ≥IIIB (70.8% vs 100%, p=0.0481.Conclusion: In our cohort of patients with TNBC treated with NAC and MRM, PMRT significantly improved locoregional control and disease

  17. The influence of circumferential resection margin status on loco-regional recurrence in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Park, Hae Jin; Kim, Hak Jae; Chie, Eui Kyu; Kang, Chang Hyun; Kim, Young Tae

    2013-06-01

    To analyze treatment outcomes and patterns of recurrence, and to examine the impact of adjuvant postoperative radiotherapy (PORT) after esophagectomy in esophageal squamous cell carcinoma (SqCC) regarding the status of circumferential resection margin (CRM). We performed a retrospective review of esophageal cancer patients operated in Seoul National University Hospital between 2003 and 2010. Pathologically proven T3 SqCC patients with written reports mentioning the status of CRM were selected. Fifty-nine out of 71 patients (83.1%) had CRM+. Twenty-eight patients had radiotherapy in CRM+ and CRM-, respectively. The median follow-up period was 17.1 months (range: 5.2-63.1). Median survival and 2-year overall survival were 13.8 months and 41.9% in CRM+, and 27.3 months and 74.1% in CRM-, respectively. Loco-regional relapse-free survival (LRRFS) rate at 2 years was 33.6% and 74.1% in each groups (P = 0.029). Loco-regional recurrence was the major pattern of failure in CRM+. PORT did not improve LRRFS. The esophageal SqCC patients with CRM+ after resection showed worse LRRFS. This finding validated the prognostic value of CRM status. Nevertheless, we failed to demonstrate the benefits of adjuvant PORT in CRM+. This might suggest the necessity of neoadjuvant therapy to decrease the CRM+ rate after esophagectomy. Copyright © 2012 Wiley Periodicals, Inc.

  18. High-dose radiation improved local tumor control and overall survival in patients with inoperable/unresectable non-small-cell lung cancer: Long-term results of a radiation dose escalation study

    International Nuclear Information System (INIS)

    Kong, F.-M.; Haken, Randall K. ten; Schipper, Matthew J.; Sullivan, Molly A.; Chen, Ming; Lopez, Carlos; Kalemkerian, Gregory P.; Hayman, James A.

    2005-01-01

    Purpose: To determine whether high-dose radiation leads to improved outcomes in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: This analysis included 106 patients with newly diagnosed or recurrent Stages I-III NSCLC, treated with 63-103 Gy in 2.1-Gy fractions, using three-dimensional conformal radiation therapy (3D-CRT) per a dose escalation trial. Targets included the primary tumor and any lymph nodes ≥1 cm, without intentionally including negative nodal regions. Nineteen percent of patients (20/106) received neoadjuvant chemotherapy. Patient, tumor, and treatment factors were evaluated for association with outcomes. Estimated median follow-up was 8.5 years. Results: Median survival was 19 months, and 5-year overall survival (OS) was 13%. Multivariate analysis revealed weight loss (p = 0.011) and radiation dose (p = 0.0006) were significant predictors for OS. The 5-year OS was 4%, 22%, and 28% for patients receiving 63-69, 74-84, and 92-103 Gy, respectively. Although presence of nodal disease was negatively associated with locoregional control under univariate analysis, radiation dose was the only significant predictor when multiple variables were included (p = 0.015). The 5-year control rate was 12%, 35%, and 49% for 63-69, 74-84, and 92-103 Gy, respectively. Conclusions: Higher dose radiation is associated with improved outcomes in patients with NSCLC treated in the range of 63-103 Gy

  19. Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seiwert, Tanguy Y., E-mail: tseiwert@medicine.bsd.uchicago.edu [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Melotek, James M. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Blair, Elizabeth A. [Department of Otolaryngology, University of Chicago, Chicago, Illinois (United States); Stenson, Kerstin M. [Department of Otolaryngology, Rush University, Chicago, Illinois (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Witt, Mary Ellyn [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Lingen, Mark W. [Department of Pathology, University of Chicago, Chicago, Illinois (United States); Kocherginsky, Masha [Department of Public Health Sciences, University of Chicago, Chicago, Illinois (United States); Villaflor, Victoria M. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States); Cohen, Ezra E.W. [Moores Cancer Center, University of California, San Diego, San Diego, California (United States); Haraf, Daniel J. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Vokes, Everett E. [Departments of Medicine, University of Chicago, Chicago, Illinois (United States)

    2016-09-01

    Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

  20. Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer

    International Nuclear Information System (INIS)

    Seiwert, Tanguy Y.; Melotek, James M.; Blair, Elizabeth A.; Stenson, Kerstin M.; Salama, Joseph K.; Witt, Mary Ellyn; Brisson, Ryan J.; Chawla, Apoorva; Dekker, Allison; Lingen, Mark W.; Kocherginsky, Masha; Villaflor, Victoria M.; Cohen, Ezra E.W.; Haraf, Daniel J.; Vokes, Everett E.

    2016-01-01

    Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further

  1. Effectiveness of Cetuximab in Combination with Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A 1:2 Propensity Score-matched Analysis.

    Science.gov (United States)

    Wu, Li-Rong; Zhu, Huan-Feng; Xu, Jianhua; Jiang, Xue-Song; Yin, Li; Jiang, Ning; Zong, Dan; Wang, Fei-Jiang; Huang, Sheng-Fu; Bian, Xiu-Hua; Wu, Jian-Feng; Song, Dan; Guo, Wen-Jie; Liu, Ju-Ying; He, Xia

    2018-01-01

    Background : This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods : A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results : After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

  2. Survival of egg-laying controlling neuroendocrine cells during reproductive senescence of a mollusc

    NARCIS (Netherlands)

    Janse, C.

    2004-01-01

    During brain aging neuronal degradation occurs. In some neurons this may result in degeneration and cell death, still other neurons may survive and maintain their basic properties. The present study deals with survival of the egg-laying controlling neuroendocrine caudodorsal cells (CDCs) during

  3. Sequencing chemotherapy and radiotherapy in locoregional advanced breast cancer patients after mastectomy – a retrospective analysis

    International Nuclear Information System (INIS)

    Piroth, Marc D; Pinkawa, Michael; Gagel, Bernd; Stanzel, Sven; Asadpour, Branka; Eble, Michael J

    2008-01-01

    Combined chemo- and radiotherapy are established in breast cancer treatment. Chemotherapy is recommended prior to radiotherapy but decisive data on the optimal sequence are rare. This retrospective analysis aimed to assess the role of sequencing in patients after mastectomy because of advanced locoregional disease. A total of 212 eligible patients had a stage III breast cancer and had adjuvant chemotherapy and radiotherapy after mastectomy and axillary dissection between 1996 and 2004. According to concerted multi-modality treatment strategies 86 patients were treated sequentially (chemotherapy followed by radiotherapy) (SEQgroup), 70 patients had a sandwich treatment (SW-group) and 56 patients had simultaneous chemoradiation (SIM-group) during that time period. Radiotherapy comprised the thoracic wall and/or regional lymph nodes. The total dose was 45–50.4 Gray. As simultaneous chemoradiation CMF was given in 95.4% of patients while in sequential or sandwich application in 86% and 87.1% of patients an anthracycline-based chemotherapy was given. Concerning the parameters nodal involvement, lymphovascular invasion, extracapsular spread and extension of the irradiated region the three treatment groups were significantly imbalanced. The other parameters, e.g. age, pathological tumor stage, grading and receptor status were homogeneously distributed. Looking on those two groups with an equally effective chemotherapy (EC, FEC), the SEQ- and SW-group, the sole imbalance was the extension of LVI (57.1 vs. 25.6%, p < 0.0001). 5-year overall- and disease free survival were 53.2%/56%, 38.1%/32% and 64.2%/50%, for the sequential, sandwich and simultaneous regime, respectively, which differed significantly in the univariate analysis (p = 0.04 and p = 0.03, log-rank test). Also the 5-year locoregional or distant recurrence free survival showed no significant differences according to the sequence of chemo- and radiotherapy. In the multivariate analyses the sequence had no

  4. Feasibility and efficacy of chemoradiotherapy for elderly patients with locoregionally advanced nasopharyngeal carcinoma: results from a matched cohort analysis

    International Nuclear Information System (INIS)

    Liu, Huai; Guo, Xiang; Cao, Ka-Jia; Hong, Ming-Huang; Mai, Hai-Qiang; Chen, Qiu-Yan; Guo, Ling; Tang, Lin-Quan; Mo, Hao-Yuan; Zhong, Zong-Liang; Huang, Pei-Yu; Luo, Dong-Hua; Sun, Rui

    2013-01-01

    To clarify the feasibility and efficacy of chemoradiotherapy (CRT) in elderly (age≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (NPC). From January 2000 to December 2006, 101 newly diagnosed elderly non-metastatic NPC patients (age≥65 years) who received cisplatin 3-weekly or weekly concurrent CRT with/without sequential chemotherapy were recruited. Each patient from the CRT group was matched to another patient treated with radiotherapy (RT) alone based on age, gender, pathological type, performance status, overall stage, stage method, Adult Comorbidity Evaluation-27 (ACE-27) score and RT technique, from the same institute and time period. We also recruited 101 young patients (age<65 years) as the referent group, which had been matched to the CRT group based on patient characteristics and treatment parameters. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared among groups. CRT was feasible in elderly NPC patients, while a concurrent regimen of weekly cisplatin was more tolerable. Grade≥3 acute toxicity in CRT group was similar with referent group, although it was significantly higher than the RT alone group (65.3% vs. 43.6%, P=0.002). Furthermore, patients with ACE-27 score≥2 in the CRT group had significantly higher severe acute toxicity and dose reduction. Survival was poorer in elderly patients than the referent group. Compared to RT alone, CRT significantly improved the 5-year overall survival (OS: 54.6% vs. 39.3%, P=0.009), cancer-specific survival (CSS: 56.6% vs. 42.7%, P=0.022), disease-free survival (DFS: 51.6% vs. 30.2%, P=0.028) and locoregional relapse-free survival (LRRFS: 78.4% vs. 52.2%, P=0.003), but not distant metastasis-free survival (DMFS: 69.6% vs. 63.6%, P=0.669). However, CRT did not significantly improve 5-year OS (43.6% vs. 27.3%, P=0.893) or CSS (43.6% vs. 34.1%, P=0.971) in elderly NPC patients with ACE-27 score≥2. CRT is feasible and effective in

  5. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial.

    Science.gov (United States)

    Forbes, John F; Sestak, Ivana; Howell, Anthony; Bonanni, Bernardo; Bundred, Nigel; Levy, Christelle; von Minckwitz, Gunter; Eiermann, Wolfgang; Neven, Patrick; Stierer, Michael; Holcombe, Chris; Coleman, Robert E; Jones, Louise; Ellis, Ian; Cuzick, Jack

    2016-02-27

    Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6-8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64-1·23]). The non-inferiority of anastrozole was established (upper 95% CI

  6. Chemical Weed Control Increases Survival and Growth in Hardwood Plantings

    Science.gov (United States)

    Gayne G. Erdmann

    1967-01-01

    In a plantation of four hardwood species on a silt loam soil planted to 1-0 stock, 4 pounds of active atrazine or simazine controlled weeds effectively without injuring the trees. Chemical weed control was better on plowed and disked ground than on unprepared ground. Yellow-poplar and white ash grew faster on prepared ground. Black walnut and red oak did not respond...

  7. Early restaging whole-body 18F-FDG PET during induction chemotherapy predicts clinical outcome in patients with locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Yen, Ruoh-Fang; Chen, Tony Hsiu-Hsi; Ting, Lai-Lei; Tzen, Kai-Yuan; Pan, Mei-Hsiu; Hong, Ruey-Long

    2005-01-01

    This study was undertaken to evaluate the utility of whole-body 18 F-FDG PET in monitoring therapeutic effect during induction chemotherapy (IC) and in predicting prognosis in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Fifty patients who had histologically proven, locoregionally advanced NPC without distant metastasis and had received IC were recruited in this study. The study cohort consisted of 19 females and 31 males (age 17-72 years, mean 45.9±11.9). Whole-body 18 F-FDG PET was performed in each patient after completion of one (33 patients) or two (17 patients) courses of IC. Each patient was restaged on the basis of the 18 F-FDG PET results. Patients who were downstaged to stage I or II were classified as major responders; the rest were classified as non-major responders. Only 1 of the 23 major responders subsequently developed local recurrence. At the time of data analysis, all major responders were alive; by contrast, of the 27 non-major responders, 15 had locoregional recurrence or distant metastasis and nine had died (seven of NPC and two of treatment-related complications). Kaplan-Meier survival analysis showed significantly longer recurrence-free survival and overall survival in major responders (56.4±9.2 and 58.1±2.2 months) as compared with non-major responders (33.7±23.2 and 44.7±20.0 months), with p 18 F-FDG PET scan after the first or second course of IC is useful for predicting therapeutic response and outcome in patients with locoregionally advanced NPC. (orig.)

  8. Survival benefit of adjuvant radiotherapy in stage III and IV bladder cancer: results of 170 patients

    Directory of Open Access Journals (Sweden)

    Bayoumi Y

    2014-11-01

    Full Text Available Yasser Bayoumi,1 Tarek Heikal,2 Hossam Darweish2 1Radiation Oncology, National Cancer Institute, Cairo University, Giza, Egypt; 2Medical Oncology, Damietta Cancer Institute, Ministry of Health, Damietta, Egypt Background: Radical cystectomy (RC with or without neoadjuvant chemotherapy is the standard treatment for muscle-invasive bladder cancers. However, the locoregional recurrence rate is still significantly higher for locally advanced cases post-RC. The underuse of postoperative radiotherapy (PORT in such cases after RC is related mainly to a lack of proven survival benefit. Here we are reporting our long-term Egyptian experience with bladder cancer patients treated with up-front RC with or without conformal PORT. Patients and methods: This retrospective study included 170 locally advanced bladder cancer (T3–T4, N0/N1, M0 patients who had RC performed with or without PORT at Damietta Cancer Institute during the period of 1998–2006. The treatment outcomes and toxicity profile of PORT were evaluated and compared with those of a non-PORT group of patients. Results: Ninety-two patients received PORT; 78 did not. At median follow-up of 47 months (range, 17–77 months, 33% locoregional recurrences were seen in the PORT group versus 55% in the non-PORT group (P<0.001. The overall distant metastasis rate in the whole group was 39%, with no difference between the two groups. The 5-year disease-free survival for the whole group of patients was 53%±11%, which was significantly affected by additional PORT, and 65%±13% compared with 40%±9% for the non-PORT group (P=0.04. The pathological subtypes did not affect 5-year disease-free survival significantly (P=0.9. The 5-year overall survival was 44%±10%. Using multivariate analysis, PORT, stage, and extravesical extension (positive surgical margins were found to be important prognostic factors for locoregional control. Stage and lymph node status were important prognosticators for distant metastasis

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

    Science.gov (United States)

    Alsina, Maria; Rivera, Fernando; Ramos, Francisco Javier; Galán, Maica; López, Rafael; García-Alfonso, Pilar; Alés-Martinez, José Enrique; Queralt, Bernardo; Antón, Antonio; Carrato, Alfredo; Grávalos, Cristina; Méndez-Vidal, Maria José; López, Carlos; de Mena, Inmaculada Ruiz; Tabernero, Josep; Giralt, Jordi; Aranda, Enrique

    2018-02-01

    Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

  10. Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma

    International Nuclear Information System (INIS)

    Giuliani, Meredith E.; Lindsay, Patricia E.; Sun, Alexander; Bezjak, Andrea; Le, Lisa W.; Brade, Anthony; Cho, John; Leighl, Natasha B.; Shepherd, Frances A.; Hope, Andrew J.

    2012-01-01

    Purpose: To determine the patterns of loco-regional (LR) and distant failure in patients with limited-stage small cell lung carcinoma (LS-SCLC) treated with curative intent. Methods: From 1997 to 2008, 253 LS-SCLC patients were treated with curative intent chemo-radiation at our institution. A retrospective review identified sites of failure. The cumulative LR failure (LRF) rate was calculated. Distant failure-free survival (FFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Volumetric images of LR failures were delineated and registered with the original radiation treatment plans if available. Dosimetric parameters for the delineated failure volumes were calculated from the original treatment information. Results: The median follow-up was 19 months. The site of first failure was LR in 34, distant in 80 and simultaneous LR and distant in 31 patients. The cumulative LRF rate was 29% and 38% at 2 and 5 years. OS was 44% at 2 years. Seventy patients had electronically archived treatment plans of which there were 16 LR failures (7 local and 39 regional failure volumes). Of the local and regional failure volumes 29% and 31% were in-field, respectively. Conclusions: The predominant pattern of LR failure was marginal or out-of-field. LR failures may be preventable with improved radiotherapy target definition.

  11. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Montejo, Michael E.; Shrieve, Dennis C. [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O. [Division of Otolaryngology-Head Neck Surgery, Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Agarwal, Neeraj [Department of Internal Medicine, Oncology Division, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Hitchcock, Ying J., E-mail: ying.hitchcock@hci.utah.edu [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States)

    2011-12-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  12. IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Montejo, Michael E.; Shrieve, Dennis C.; Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O.; Agarwal, Neeraj; Hitchcock, Ying J.

    2011-01-01

    Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38–55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8–78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.

  13. Novel multisensor probe for monitoring bladder temperature during locoregional chemohyperthermia for nonmuscle-invasive bladder cancer: technical feasibility study

    NARCIS (Netherlands)

    Cordeiro, Ernesto R.; Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

    2013-01-01

    The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional

  14. Patterns of Care and Locoregional Treatment Outcomes in Older Esophageal Cancer Patients: The SEER-Medicare Cohort

    International Nuclear Information System (INIS)

    Smith, Grace L.; Smith, Benjamin D.; Buchholz, Thomas A.; Liao Zhongxing; Jeter, Melenda; Swisher, Stephen G. M.D.; Hofstetter, Wayne L.; Ajani, Jaffer A.; McAleer, Mary F.; Komaki, Ritsuko; Cox, James D.

    2009-01-01

    Purpose: Optimal management of elderly patients with nonmetastatic esophageal cancer is unclear. Outcomes data after locoregional treatment are lacking for this group. Methods: We assessed outcomes associated with standard locoregional treatments in 2,626 patients (age > 65 years) from the Surveillance Epidemiology and End Results (SEER)-Medicare cohort diagnosed with nonmetastatic esophageal cancer from 1992 to 2002. In patients treated with radiotherapy alone (RT), surgery alone (S), chemoradiotherapy (CRT), or preoperative chemotherapy followed by surgery (CRT + S), overall and disease-free survival were compared using proportional hazards regression. Postoperative complications were compared using logistic regression. Results: Mean age was 76 ± 6 years. Seven percent underwent CRT + S, 39% CRT, 30% S, and 24% RT. One-year survival was 68% (CRT + S), 52% (CRT), 53% (S), and 16% (RT), respectively (p < 0.001). Patients who underwent CRT + S demonstrated improved overall survival compared with S alone (hazard ratio [HR] = 0.81; 95% confidence interval [CI], 0.66-0.98; p = 0.03) and RT (HR = 0.44; 95% CI, 0.35-0.55; p < 0.0001); and comparable survival to CRT (HR = 0.82; 95% CI, 0.67-1.01; p = 0.06). Patients who underwent CRT + S also had comparable postoperative mortality (HR = 0.96; 95% CI, 0.87-1.07; p = 0.45) and complications (OR = 0.89; 95% CI, 0.70-1.14; p = 0.36) compared with S alone. Conclusions: Preoperative chemoradiotherapy may be an acceptable treatment option in appropriately selected older esophageal cancer patients. This treatment modality did not appear to increase surgical complications and offered potential therapeutic benefit, particularly compared with surgery alone.

  15. Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study.

    Science.gov (United States)

    Tang, Xin-Ran; Li, Ying-Qin; Liang, Shao-Bo; Jiang, Wei; Liu, Fang; Ge, Wen-Xiu; Tang, Ling-Long; Mao, Yan-Ping; He, Qing-Mei; Yang, Xiao-Jing; Zhang, Yuan; Wen, Xin; Zhang, Jian; Wang, Ya-Qin; Zhang, Pan-Pan; Sun, Ying; Yun, Jing-Ping; Zeng, Jing; Li, Li; Liu, Li-Zhi; Liu, Na; Ma, Jun

    2018-03-01

    Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival. We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; padvanced nasopharyngeal carcinoma and might be able to predict which patients benefit

  16. Biochemical Control With Radiotherapy Improves Overall Survival in Intermediate and High-Risk Prostate Cancer Patients Who Have an Estimated 10-Year Overall Survival of >90%

    International Nuclear Information System (INIS)

    Herbert, Christopher; Liu, Mitchell; Tyldesley, Scott; Morris, W. James; Joffres, Michel; Khaira, Mandip; Kwan, Winkle; Moiseenko, Vitali; Pickles, Thomas

    2012-01-01

    Purpose: To identify subgroups of patients with carcinoma of the prostate treated with radical radiotherapy that have improved overall survival when disease is biochemically controlled. Methods and Materials: A cohort of 1,060 prostate cancer patients treated with radical radiotherapy was divided into nine subgroups based on National Comprehensive Cancer Network risk category and estimated 10-year overall survival (eOS 10y) derived from the age adjusted Charlson Comorbidity Index. Patients with and without biochemical control were compared with respect to overall survival. Actuarial estimates of overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of overall survival. Results: Median follow-up was 125 months (range, 51–176 months). Only the subgroups with high or intermediate risk disease and an eOS 10y of >90% had a statistically significantly improved overall survival when prostate cancer was biochemically controlled. In all other groups, biochemical control made no significant difference to overall survival. In the subgroup with high-risk disease and eOS 10y >90%, actuarial overall survival was 86.3% (95% confidence interval [CI] 78.5%–94.1%) and 62.1% (95% CI 52.9%–71.3%) for patients with biochemical control and biochemical relapse respectively (p = 0.002). In the intermediate risk group with eOS >90%, actuarial overall survival was 95.3% (95% CI 89.0%–100%) and 79.8% (95% CI 68.0%–91.6%) for biochemically controlled and biochemically relapsed patients (p = 0.033). On multivariate analysis, National Comprehensive Cancer Network risk group (p = 0.005), biochemical control (p = 0.033) and eOS 10y (p 90%.

  17. Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Nancy, E-mail: leen2@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Schoder, Heiko [Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beattie, Brad [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lanning, Ryan; Riaz, Nadeem; McBride, Sean [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katabi, Nora [Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Li, Duan [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yarusi, Brett; Chan, Susie; Mitrani, Lindsey [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Pfister, David G.; Sherman, Eric; Baxi, Shrujal [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Boyle, Jay; Morris, Luc G.T.; Ganly, Ian; Wong, Richard [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Humm, John [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2016-09-01

    Purpose: To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV{sup +}) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes. Methods and Materials: Patients with HPV{sup +} oropharyngeal carcinoma were enrolled on an institutional review board–approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment {sup 18}F-fluorodeoxyglucose and dynamic {sup 18}F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on{sup 18}F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis–free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance. Results: Thirty-three HPV{sup +} OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on {sup 18}F-FMISO PET. The 2-year distant metastasis–free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was

  18. Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Lee, Nancy; Schoder, Heiko; Beattie, Brad; Lanning, Ryan; Riaz, Nadeem; McBride, Sean; Katabi, Nora; Li, Duan; Yarusi, Brett; Chan, Susie; Mitrani, Lindsey; Zhang, Zhigang; Pfister, David G.; Sherman, Eric; Baxi, Shrujal; Boyle, Jay; Morris, Luc G.T.; Ganly, Ian; Wong, Richard; Humm, John

    2016-01-01

    Purpose: To report a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV"+) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes. Methods and Materials: Patients with HPV"+ oropharyngeal carcinoma were enrolled on an institutional review board–approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment "1"8F-fluorodeoxyglucose and dynamic "1"8F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on"1"8F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1 week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis–free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance. Results: Thirty-three HPV"+ OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32 months (range, 21-61 months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on "1"8F-FMISO PET. The 2-year distant metastasis–free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically

  19. Impact of Postmastectomy Radiation on Locoregional Recurrence in Breast Cancer Patients With 1-3 Positive Lymph Nodes Treated With Modern Systemic Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tendulkar, Rahul D., E-mail: tendulr@ccf.org [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Rehman, Sana; Shukla, Monica E.; Reddy, Chandana A. [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Moore, Halle; Budd, G. Thomas [Department of Solid Tumor Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Dietz, Jill; Crowe, Joseph P. [Department of General Surgery, Cleveland Clinic Foundation, Cleveland, Ohio (United States); Macklis, Roger [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio (United States)

    2012-08-01

    Purpose: Postmastectomy radiation therapy (PMRT) remains controversial for patients with 1-3 positive lymph nodes (LN+). Methods and Materials: We conducted a retrospective review of all 369 breast cancer patients with 1-3 LN+ who underwent mastectomy without neoadjuvant systemic therapy between 2000 and 2007 at Cleveland Clinic. Results: We identified 271 patients with 1-3 LN+ who did not receive PMRT and 98 who did receive PMRT. The median follow-up time was 5.2 years, and the median number of LN dissected was 11. Of those not treated with PMRT, 79% received adjuvant chemotherapy (of whom 70% received a taxane), 79% received hormonal therapy, and 5% had no systemic therapy. Of the Her2/neu amplified tumors, 42% received trastuzumab. The 5-year rate of locoregional recurrence (LRR) was 8.9% without PMRT vs 0% with PMRT (P=.004). For patients who did not receive PMRT, univariate analysis showed 6 risk factors significantly (P<.05) correlated with LRR: estrogen receptor/progesterone receptor negative (hazard ratio [HR] 2.6), lymphovascular invasion (HR 2.4), 2-3 LN+ (HR 2.6), nodal ratio >25% (HR 2.7), extracapsular extension (ECE) (HR 3.7), and Bloom-Richardson grade III (HR 3.1). The 5-year LRR rate was 3.4% (95% confidence interval [CI], 0.1%-6.8%] for patients with 0-1 risk factor vs 14.6% [95% CI, 8.4%-20.9%] for patients with {>=}2 risk factors (P=.0006), respectively. On multivariate analysis, ECE (HR 4.3, P=.0006) and grade III (HR 3.6, P=.004) remained significant risk factors for LRR. The 5-year LRR was 4.1% in patients with neither grade III nor ECE, 8.1% with either grade III or ECE, and 50.4% in patients with both grade III and ECE (P<.0001); the corresponding 5-year distant metastasis-free survival rates were 91.8%, 85.4%, and 59.1% (P=.0004), respectively. Conclusions: PMRT offers excellent control for patients with 1-3 LN+, with no locoregional failures to date. Patients with 1-3 LN+ who have grade III disease and/or ECE should be strongly considered

  20. Dental implant survival rate in well-controlled diabetic patients. A systematic review.

    Directory of Open Access Journals (Sweden)

    Heber Arbildo

    2015-12-01

    Full Text Available Background: Dental implants have now become one of the most popular options for replacing a missing tooth. On the other hand, diabetes mellitus is a systemic disease that affects a large part of the population and is generally considered an absolute or relative contraindication to implant therapy. Aim: To determine the survival rate of dental implants in controlled diabetic patients through a systematic review. Material and methods: A systematic search in Pubmed, SciELO and RedALyC databases was performed. The selection criteria were: studies published in the last 10 years, with at least 20 controlled diabetic patients, reporting survival rate and number of implants placed, with follow-up periods equal to or longer than 1 year, including a control group of healthy patients. Methodological quality was analyzed with the follwing scales: Jadad and Downs & Black’s CMQ. Results: Three articles with a follow-up period between 1 and 12 years were analyzed. The overall survival rate of dental implants in diabetic controlled patients was 97.43%. Conclusion: The reviewed literature suggests that survival rate of dental implants in well-controlled diabetic patients is similar to non-diabetic patients.

  1. Population-based cancer survival in the United States: Data, quality control, and statistical methods.

    Science.gov (United States)

    Allemani, Claudia; Harewood, Rhea; Johnson, Christopher J; Carreira, Helena; Spika, Devon; Bonaventure, Audrey; Ward, Kevin; Weir, Hannah K; Coleman, Michel P

    2017-12-15

    Robust comparisons of population-based cancer survival estimates require tight adherence to the study protocol, standardized quality control, appropriate life tables of background mortality, and centralized analysis. The CONCORD program established worldwide surveillance of population-based cancer survival in 2015, analyzing individual data on 26 million patients (including 10 million US patients) diagnosed between 1995 and 2009 with 1 of 10 common malignancies. In this Cancer supplement, we analyzed data from 37 state cancer registries that participated in the second cycle of the CONCORD program (CONCORD-2), covering approximately 80% of the US population. Data quality checks were performed in 3 consecutive phases: protocol adherence, exclusions, and editorial checks. One-, 3-, and 5-year age-standardized net survival was estimated using the Pohar Perme estimator and state- and race-specific life tables of all-cause mortality for each year. The cohort approach was adopted for patients diagnosed between 2001 and 2003, and the complete approach for patients diagnosed between 2004 and 2009. Articles in this supplement report population coverage, data quality indicators, and age-standardized 5-year net survival by state, race, and stage at diagnosis. Examples of tables, bar charts, and funnel plots are provided in this article. Population-based cancer survival is a key measure of the overall effectiveness of services in providing equitable health care. The high quality of US cancer registry data, 80% population coverage, and use of an unbiased net survival estimator ensure that the survival trends reported in this supplement are robustly comparable by race and state. The results can be used by policymakers to identify and address inequities in cancer survival in each state and for the United States nationally. Cancer 2017;123:4982-93. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U

  2. Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

    Directory of Open Access Journals (Sweden)

    Rui Guo

    Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

  3. The Impact of Preradiation Residual Disease Volume on Time to Locoregional Failure in Cutaneous Merkel Cell Carcinoma—A TROG Substudy

    Energy Technology Data Exchange (ETDEWEB)

    Finnigan, Renee [Division of Cancer Services, Princess Alexandra Hospital, University of Queensland, Brisbane (Australia); Hruby, George [Department of Radiation Oncology, Sydney Cancer Centre, University of Sydney, Sydney (Australia); Wratten, Chris [Calvary Mater Newcastle Hospital, Newcastle (Australia); Keller, Jacqui; Tripcony, Lee; Dickie, Graeme [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane (Australia); Rischin, Danny [Department of Medical Oncology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne (Australia); Poulsen, Michael, E-mail: michael_poulsen@health.qld.gov.au [Division of Cancer Services, Princess Alexandra Hospital, University of Queensland, Brisbane (Australia)

    2013-05-01

    Purpose: This study evaluated the impact of margin status and gross residual disease in patients treated with chemoradiation therapy for high-risk stage I and II Merkel cell cancer (MCC). Methods and Materials: Data were pooled from 3 prospective trials in which patients were treated with 50 Gy in 25 fractions to the primary lesion and draining lymph nodes and 2 schedules of carboplatin based chemotherapy. Time to locoregional failure was analyzed according to the burden of disease at the time of radiation therapy, comparing patients with negative margins, involved margins, or macroscopic disease. Results: Analysis was performed on 88 patients, of whom 9 had microscopically positive resection margins and 26 had macroscopic residual disease. The majority of gross disease was confined to nodal regions. The 5-year time to locoregional failure, time to distant failure, time to progression, and disease-specific survival rates for the whole group were 73%, 69%, 62%, and 66% respectively. The hazard ratio for macroscopic disease at the primary site or the nodes was 1.25 (95% confidence interval 0.57-2.77), P=.58. Conclusions: No statistically significant differences in time to locoregional failure were identified between patients with negative margins and those with microscopic or gross residual disease. These results must, however, be interpreted with caution because of the limited sample size.

  4. Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

    International Nuclear Information System (INIS)

    Bentzen, Anne Gry; Guren, Marianne G.; Wanderås, Eva H.; Frykholm, Gunilla; Tveit, Kjell M.; Wilsgaard, Tom; Dahl, Olav; Balteskard, Lise

    2012-01-01

    Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

  5. Chemoradiotherapy of Anal Carcinoma: Survival and Recurrence in an Unselected National Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Bentzen, Anne Gry, E-mail: anne.gry.bentzen@unn.no [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Institute of Clinical Medicine, University of Tromso, Tromso (Norway); Guren, Marianne G.; Wanderas, Eva H. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Frykholm, Gunilla [Department of Oncology, St. Olav' s University Hospital, Trondheim, Norway and The Norwegian Radiation Protection Authority (NRPA), Osteras (Norway); Tveit, Kjell M. [Department of Oncology, Oslo University Hospital, Oslo (Norway); Faculty of Medicine, University of Oslo, Oslo (Norway); Wilsgaard, Tom [Department of Community Medicine, University of Tromso, Tromso (Norway); Dahl, Olav [Section of Oncology, Institute of Medicine, University of Bergen and Department of Oncology, Haukeland University Hospital, Bergen (Norway); Balteskard, Lise [Department of Oncology, University Hospital of Northern Norway, Tromso (Norway); Centre for Clinical Documentation and Evaluation, Northern Norway Regional Health Authority, Tromso (Norway)

    2012-06-01

    Purpose: To evaluate treatment results, elucidate whether national guidelines were followed, and identify areas demanding further treatment optimization. Methods and Material: Between July 2000 and June 2007, 328 patients were treated with curatively intended chemoradiotherapy (CRT) for nonmetastatic squamous cell carcinoma of the anal region, according to national treatment guidelines based on tumor stage. Results: Complete response after CRT was obtained in 87% of patients, rising to 93% after salvage surgery. Chemotherapy, elective irradiation of the groin and salvage surgery were performed to a lesser extent in elderly patients, mainly because of frailty and comorbidity. Recurrence occurred in 24% of the patients, resulting in a 3- and 5-year recurrence-free survival (RFS) of 79% and 74%, respectively. Locoregional recurrences dominated, most commonly in the primary tumor site. Recurrence was treated with curative intent in 45% of the cases. The 3- and 5-year overall survival were 79% and 66%, and cancer-specific survival (CSS) were 84% and 75%, respectively. The risk of adverse outcome increased significantly with more locally advanced tumors and for male gender in multivariable analyses for RFS and CSS. Conclusions: The treatment results are in accordance with similar cohorts. The primary treatment control rate was high, but there was a significant risk of locoregional recurrence in advanced tumors. The loyalty to national guidelines was broad, although individual adjustments occurred. However, caution to avoid toxicity must not lead to inadequate treatment. Male gender seems to have inferior outcome.

  6. A thermal control system for long-term survival of scientific instruments on lunar surface.

    Science.gov (United States)

    Ogawa, K; Iijima, Y; Sakatani, N; Otake, H; Tanaka, S

    2014-03-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime -200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a "regolith mound". Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  7. A thermal control system for long-term survival of scientific instruments on lunar surface

    International Nuclear Information System (INIS)

    Ogawa, K.; Iijima, Y.; Tanaka, S.; Sakatani, N.; Otake, H.

    2014-01-01

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime −200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a “regolith mound”. Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system

  8. A thermal control system for long-term survival of scientific instruments on lunar surface

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, K., E-mail: ogawa@astrobio.k.u-tokyo.ac.jp [Department of Complexity Science and Engineering, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba (Japan); Iijima, Y.; Tanaka, S. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo, Sagamihara, Kanagawa (Japan); Sakatani, N. [The Graduate University for Advanced Studies, Shonan Village, Hayama, Kanagawa (Japan); Otake, H. [JAXA Space Exploration Center, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo, Sagamihara, Kanagawa (Japan)

    2014-03-15

    A thermal control system is being developed for scientific instruments placed on the lunar surface. This thermal control system, Lunar Mission Survival Module (MSM), was designed for scientific instruments that are planned to be operated for over a year in the future Japanese lunar landing mission SELENE-2. For the long-term operations, the lunar surface is a severe environment because the soil (regolith) temperature varies widely from nighttime −200 degC to daytime 100 degC approximately in which space electronics can hardly survive. The MSM has a tent of multi-layered insulators and performs a “regolith mound”. Temperature of internal devices is less variable just like in the lunar underground layers. The insulators retain heat in the regolith soil in the daylight, and it can keep the device warm in the night. We conducted the concept design of the lunar survival module, and estimated its potential by a thermal mathematical model on the assumption of using a lunar seismometer designed for SELENE-2. Thermal vacuum tests were also conducted by using a thermal evaluation model in order to estimate the validity of some thermal parameters assumed in the computed thermal model. The numerical and experimental results indicated a sufficient survivability potential of the concept of our thermal control system.

  9. Online Adaptive Hyperthermia Treatment Planning During Locoregional Heating to Suppress Treatment-Limiting Hot Spots

    NARCIS (Netherlands)

    Kok, H. Petra; Korshuize-van Straten, Linda; Bakker, Akke; de Kroon-Oldenhof, Rianne; Geijsen, Elisabeth D.; Stalpers, Lukas J. A.; Crezee, Johannes

    2017-01-01

    Adequate tumor temperatures during hyperthermia are essential for good clinical response, but excessive heating of normal tissue should be avoided. This makes locoregional heating using phased array systems technically challenging. Online application of hyperthermia treatment planning could help to

  10. Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

    Science.gov (United States)

    2010-01-01

    The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes. The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure. The patients' population comprised 65 males and 50 females. Their mean age at the 1st diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection ± neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%. Recurrence was identified in 23 males and 20 females. The mean age of 1st diagnosis of the

  11. Local control and survival in spinal cord compression from lymphoma and myeloma

    International Nuclear Information System (INIS)

    Wallington, M.; Mendis, S.; Premawardhana, U.; Sanders, P.; Shahsavar-Haghighi, K.

    1997-01-01

    Background: Between 1979 and 1989, 48 cases of extradural spinal cord and cauda equina compression in patients with lymphoma (24) and myeloma (24) received local radiation therapy for control of cord compression. Twenty five (52%) of the cases were treated by surgical decompression prior to irradiation. Thirty five (73%) of the cases received chemotherapy following the diagnosis of spinal cord compression. Post-treatment outcome was assessed at a minimum follow-up of 24 months to determine the significant clinical and treatment factors following irradiation. Results: Seventeen (71%) of the lymphoma and 15 (63%) of the myeloma patients achieved local control, here defined as improvement to, or maintenance of ambulation with minimal or no assistance for 3 months from the start of radiotherapy. At a median follow-up of 30 (2-98) for the lymphoma and 10 (1-87) months for the myeloma patients, the results showed that survival following local radiation therapy for cord compression was independently influenced by the underlying disease type in favour of lymphoma compared to myeloma (P<0.01). The median duration of local control and survival figures were 23 and 48 months for the lymphomas compared to 4.5 and 10 months for the myeloma cases. Survival was also independently influenced by preservation of sphincter function at initial presentation (P<0.02) and the achievement of local control following treatment (P<0.01). Discussion: We conclude that while disease type independently impacts on outcome following treatment of spinal cord compression in lymphoma and myeloma, within both of these disease type the achievement of local control of spinal cord compression is an important management priority, for without local control survival may be adversely affected

  12. Factors influencing local control and survival for patients undergoing stereotactic radiosurgery for intracranial metastases

    International Nuclear Information System (INIS)

    Suh, John H.; Barnett, Gene H.; Sohn, Jason W.; Fernandez-Vicioso, Eduardo; Kupelian, Patrick A.

    1996-01-01

    PURPOSE: To identify factors affecting local control and survival for patients undergoing stereotactic radiosurgery for intracranial metastases. MATERIALS AND METHODS: From 3/90-10/95, 99 patients (median age 58, range 29-83; 44 women, 55 men) with asymptomatic or mildly symptomatic intracranial metastases measuring < 4 cm in diameter and ≥ 1 cm from optic chiasm and Karnofsky Performance Status (KPS) ≥ 70 underwent modified linear accelerator-based stereotactic radiosurgery (SRS). Patients characteristics included 20 with recurrent disease, 66 with solitary lesions, and 42 with systemic disease. Forty six patients underwent surgical resection prior to SRS (16 biopsy, 3 subtotal resection (STR), and 21 gross total resection (GTR)). Eighty of 99 patients underwent whole brain radiation treatments (median 4005 cGy/15 fx, range 2200-6000 cGy). A total of 154 lesions were treated with 143 being evaluable on follow-up CT or MRI scans. Radiosurgery parameters (median) were the following: volume 2.8 cc (range 0.1-38 cc) and a peripheral dose of 1700 cGy (range 500-2400 cGy) with normalization to the 80% line (range 50-90%). Survival was measured from the date of SRS. Local control was defined as stabilization or decrease in size of the intracranial lesion(s). RESULTS: The following factors were analyzed with respect to local control and survival: 1) solitary vs. multiple lesions, 2) Age < or ≥ 60, 3) sex, 4) radiosensitive vs. radioresistant (renal cell and melanoma) histologies, 5) recurrent vs. newly diagnosed lesions, 6) KPS (70-80 vs. 90-100), 7) extent of surgery (biopsy vs. STR/GTR), 8) use of whole brain radiation treatments, 9) absence or presence of systemic disease, 10) dose (< or ≥ 1500 cGy) and 11) volume (< or ≥ 3 cc). On univariate analysis, survival was significantly influenced by female sex, presence of solitary lesion, absence of systemic disease, and extent of surgery. On multivariate analysis, female sex (p=0.0037), absence of systemic disease

  13. Bronchoscopic findings and bleeding control predict survival in patients with solid malignancies presenting with mild hemoptysis.

    Science.gov (United States)

    Grosu, Horiana B; Casal, Roberto F; Morice, Rodolfo C; Nogueras-González, Graciela M; Eapen, Georgie A; Ost, David; Sarkiss, Mona G; Jimenez, Carlos A

    2013-08-01

    Regardless of its volume, hemoptysis is a concerning symptom. Mild hemoptysis and its significance in patients with solid malignancies has not been studied. We conducted a retrospective chart review of patients with solid malignancies who presented for evaluation of mild hemoptysis. In this population, we studied the impact of bronchoscopic findings and endobronchial therapies on overall survival and bleeding recurrence. Patients were categorized into four groups on the basis of the presence or absence of active bleeding and endobronchial disease at the time of initial bronchoscopy: active bleeding with endobronchial lesion (AB/EBL), active bleeding without endobronchial lesion (AB/no-EBL), absence of active bleeding but with endobronchial lesion (no-AB/EBL), and absence of active bleeding and endobronchial lesion (no-AB/no-EBL). Ninety-five of the 112 patients with solid malignancies and mild hemoptysis underwent bronchoscopies. There was a significantly lower median survival time for patients with bronchoscopic findings of active bleeding and endobronchial lesion compared with patients with no active bleeding and/or no endobronchial lesion (3.48 mo; 95% confidence interval [CI], 2.14-6.05). On a multivariate analysis, factors independently associated with improved survival were higher hemoglobin values (hazard ratio [HR], 0.78; 95% CI, 0.67-0.91) and cessation of hemoptysis without recurrence at 48 hours (HR, 0.43; 95% CI, 0.22-0.84). Variables independently associated with worse survival were disease stage (HR, 10.8; 95% CI, 2.53-46.08) and AB/EBL (HR, 3.20; 95% CI, 1.74-5.89). In patients with solid malignancies presenting with mild hemoptysis, bronchoscopic findings of AB/EBL are associated with decreased survival. Hemoptysis control without recurrence at 48 hours after endobronchial intervention may improve survival.

  14. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

    Science.gov (United States)

    Aebi, Stefan; Gelber, Shari; Anderson, Stewart J; Láng, István; Robidoux, André; Martín, Miguel; Nortier, Johan W R; Paterson, Alexander H G; Rimawi, Mothaffar F; Cañada, José Manuel Baena; Thürlimann, Beat; Murray, Elizabeth; Mamounas, Eleftherios P; Geyer, Charles E; Price, Karen N; Coates, Alan S; Gelber, Richard D; Rastogi, Priya; Wolmark, Norman; Wapnir, Irene L

    2014-02-01

    Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who

  15. Repetitive transarterial chemoembolization (TACE) of liver metastases from gastric cancer: Local control and survival results

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, Thomas J., E-mail: T.Vogl@em.uni-frankfurt.de [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Gruber-Rouh, Tatjana; Eichler, Katrin [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Nour-Eldin, Nour-Eldin A. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Department of Radiology, Faculty of Medicine, Cairo University, Cairo (Egypt); Trojan, Jörg [Department of Internal Medicine I, Johann Wolfgang Goethe-University Frankfurt (Germany); Zangos, Stephan [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Naguib, Nagy N.N. [Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt (Germany); Radiology Department, Faculty of Medicine, Alexandria University, Alexandria (Egypt)

    2013-02-15

    Objective: To evaluate the local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of patients with liver metastases of gastric cancer. Materials and methods: The study was retrospectively performed. 56 patients (mean age, 52.4) with unresectable liver metastases of gastric cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. In total, 310 chemoembolization procedures were performed (mean, 5.5 sessions per patient). The local chemotherapy protocol consisted of mitomycin alone (30.4%), mitomycin and gemcitabine (33.9%), or mitomycin, gemcitabine and cisplatin (35.7%). Embolization was performed with lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST. Survival data from first chemoembolization were calculated according to the Kaplan–Meier method. Results: The local tumor control was: complete response in 1.8% (n = 1), partial response in 1.8% (n = 1), stable disease in 51.8% (n = 29) and progressive disease in 44.6% (n = 25) of patients. The 1-, 2-, and 3-year survival rate from the start of chemoembolization were 58%, 38%, and 23% respectively. The median and mean survival times were 13 and 27.1 months. A Statistically significant difference between patients treated with different chemotherapy protocols was noted (ρ = 0.045) with the best survival time in the mitomycin, gemcitabine and cisplatin group. Conclusion: Transarterial chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with gastric cancer.

  16. Controls on Arctic sea ice from first-year and multi-year survival rates

    Energy Technology Data Exchange (ETDEWEB)

    Hunke, Jes [Los Alamos National Laboratory

    2009-01-01

    The recent decrease in Arctic sea ice cover has transpired with a significant loss of multi year ice. The transition to an Arctic that is populated by thinner first year sea ice has important implications for future trends in area and volume. Here we develop a reduced model for Arctic sea ice with which we investigate how the survivability of first year and multi year ice control the mean state, variability, and trends in ice area and volume.

  17. A software package for patient-specific dosimetry in the locoregional RIT of gliomas using 188Re labelled NIMOTUZUMAB

    International Nuclear Information System (INIS)

    Torres, L.A.; Coca, M.A.; Sanchez, Y.; Cornejo, N.; Catasus, C.; Denaro, M. de

    2008-01-01

    Full text: The locoregional treatment of high-grade gliomas using beta emitter compounds allows delivering high radiation doses in the tumor bed and the brain adjacent tissues of patients suffering these aggressive malignancies. The main goal of this work was to implement patient-specific dosimetry procedures using a voxel-based methodology in order to compute and analyze the three-dimensional doses distributions received by the patients undergoing loco-regional treatment of gliomas with the 188 Re labeled MAb NIMOTUZUMAB. A software package called TRIDOSE has been developed to perform the image managing, volume registration, dose calculations and qualitative and quantitative analysis of the results, including dose-volume histograms and isodose curves. The dosimetric factors at voxel level for 188 Re ('S' values) were estimated using two different methods, Monte Carlo simulations of energy transport and deposition and the integration of the dose kernel functions. A quality control module was also implemented in order to test the software using well-known 3D distribution of activities or counts. The TRIDOSE outputs were compared with other commercial software showing relative differences lower than 1.10% for different sphere sizes. The established dosimetric procedures constitute a useful tool to compute the absorbed doses received by patients undergoing radioimmunotherapy of brain tumors with 188 Re-NIMOTUZUMAB. (author)

  18. Dissociation of Survival, Proliferation, and State Control in Human Hematopoietic Stem Cells.

    Science.gov (United States)

    Knapp, David J H F; Hammond, Colin A; Miller, Paul H; Rabu, Gabrielle M; Beer, Philip A; Ricicova, Marketa; Lecault, Véronique; Da Costa, Daniel; VanInsberghe, Michael; Cheung, Alice M; Pellacani, Davide; Piret, James; Hansen, Carl; Eaves, Connie J

    2017-01-10

    The role of growth factors (GFs) in controlling the biology of human hematopoietic stem cells (HSCs) remains limited by a lack of information concerning the individual and combined effects of GFs directly on the survival, Mitogenesis, and regenerative activity of highly purified human HSCs. We show that the initial input HSC activity of such a purified starting population of human cord blood cells can be fully maintained over a 21-day period in serum-free medium containing five GFs alone. HSC survival was partially supported by any one of these GFs, but none were essential, and different combinations of GFs variably stimulated HSC proliferation. However, serial transplantability was not detectably compromised by many conditions that reduced human HSC proliferation and/or survival. These results demonstrate the dissociated control of these three human HSC bio-responses, and set the stage for future improvements in strategies to modify and expand human HSCs ex vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis.

    Science.gov (United States)

    Stromberg, Paul E; Woolsey, Cheryl A; Clark, Andrew T; Clark, Jessica A; Turnbull, Isaiah R; McConnell, Kevin W; Chang, Katherine C; Chung, Chun-Shiang; Ayala, Alfred; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2009-06-01

    Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1(-/-) and wild-type (WT) mice. However, Rag-1(-/-) animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared to septic WT mice. Reconstitution of lymphocytes in Rag-1(-/-) mice via adoptive transfer decreases intestinal apoptosis to levels seen in WT animals. Subset analysis indicates that CD4(+) but not CD8(+), gammadelta, or B cells are responsible for the antiapoptotic effect of lymphocytes on the gut epithelium. Gut-specific overexpression of Bcl-2 in transgenic mice decreases mortality following CLP. This survival benefit is lymphocyte dependent since gut-specific overexpression of Bcl-2 fails to alter survival when the transgene is overexpressed in Rag-1(-/-) mice. Further, adoptively transferring lymphocytes to Rag-1(-/-) mice that simultaneously overexpress gut-specific Bcl-2 results in improved mortality following sepsis. Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality.

  20. Outcomes of Locoregional Tumor Therapy for Patients with Hepatocellular Carcinoma and Transjugular Intrahepatic Portosystemic Shunts

    Energy Technology Data Exchange (ETDEWEB)

    Padia, Siddharth A., E-mail: spadia@uw.edu; Chewning, Rush H., E-mail: rchewnin@uw.edu; Kogut, Matthew J., E-mail: kogutm@uw.edu; Ingraham, Christopher R., E-mail: cringa@uw.edu; Johnson, Guy E., E-mail: gej@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Bhattacharya, Renuka, E-mail: renuka@uw.edu [University of Washington Medical Center, Division of Gastroenterology and Hepatology, Department of Medicine (United States); Kwan, Sharon W., E-mail: shakwan@uw.edu; Monsky, Wayne L., E-mail: wmonsky@uw.edu; Vaidya, Sandeep, E-mail: svaidya@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States); Hippe, Daniel S., E-mail: dhippe@uw.edu [University of Washington Medical Center, Department of Radiology (United States); Valji, Karim, E-mail: kvalji@uw.edu [University of Washington Medical Center, Section of Interventional Radiology, Department of Radiology (United States)

    2015-08-15

    PurposeLocoregional therapy for hepatocellular carcinoma (HCC) can be challenging in patients with a transjugular intrahepatic portosystemic shunt (TIPS). This study compares safety and imaging response of ablation, chemoembolization, radioembolization, and supportive care in patients with both TIPS and HCC.MethodsThis retrospective study included 48 patients who had both a TIPS and a diagnosis of HCC. Twenty-nine of 48 (60 %) underwent treatment for HCC, and 19/48 (40 %) received best supportive care (i.e., symptomatic management only). While etiology of cirrhosis and indication for TIPS were similar between the two groups, treated patients had better baseline liver function (34 vs. 67 % Child-Pugh class C). Tumor characteristics were similar between the two groups. A total of 39 ablations, 17 chemoembolizations, and 10 yttrium-90 radioembolizations were performed on 29 patients.ResultsAblation procedures resulted in low rates of hepatotoxicity and clinical toxicity. Post-embolization/ablation syndrome occurred more frequently in patients undergoing chemoembolization than ablation (47 vs. 15 %). Significant hepatic dysfunction occurred more frequently in the chemoembolization group than the ablation group. Follow-up imaging response showed objective response in 100 % of ablation procedures, 67 % of radioembolization procedures, and 50 % of chemoembolization procedures (p = 0.001). When censored for OLT, patients undergoing treatment survived longer than patients receiving supportive care (2273 v. 439 days, p = 0.001).ConclusionsAblation appears to be safe and efficacious for HCC in patients with TIPS. Catheter-based approaches are associated with potential increased toxicity in this patient population. Chemoembolization appears to be associated with increased toxicity compared to radioembolization.

  1. Vinorelbine and paclitaxel for locoregional advanced or metastatic non-small-cell lung cancer.

    Science.gov (United States)

    Pérez, Juan E; Machiavelli, Mario R; Romero, Alberto O; Romero Acuña, Luis A; Domínguez, María E; Fasce, Hebe; Flores Acosta, Luis; Marrone, Nora; Romero Acuña, Juan M; Langhi, Mario J; Amato, Sonia; Bologna, Fabrina; Ortiz, Eduardo H; Leone, Bernardo A; Lacava, Juan A; Vallejo, Carlos T

    2002-08-01

    A phase II trial was performed to evaluate the efficacy and toxicity of the novel combination of vinorelbine and paclitaxel as first-line chemotherapy in patients with stages IIIB and IV non-small-cell lung cancer. From January 1997 to September 1999, 34 patients (9 stage IIIB and 25 stage IV) received a regimen consisting of the following: vinorelbine 30 mg/m2 20 minutes intravenous (i.v.) infusion, days 1 and 8; and paclitaxel 135 mg/m2 3-hour i.v. (starting 1 hour after vinorelbine) on day 1. Cycles were repeated every 28 days until progression of disease or unacceptable toxicity development. The median age was 57 years (range 41-70 years); median performance status was 1. Histology was as follows: squamous cell in 24 (71%), large cell in 1 (3%), and adenocarcinoma in 9 (26%). All patients are evaluable for toxicity, whereas 30 are evaluable for response (4 patients refused treatment). Objective response was recorded in 4 of 30 patients (13%, 95% CI 1-25%). No complete response was observed. Partial response was recorded in 4 patients (13%), no change in 10 patients (34%), and progressive disease in 16 patients (53%). The median time to treatment failure was 4 months and median survival was 9 months. The limiting toxicity was myelosuppression: leukopenia in 23 patients (68%), whereas neutropenia was observed in 25 patients (78%). Peripheral neurotoxicity developed in 14 patients (41%) (without G3 or G4 episodes), and constipation (G1-G2: 10 patients), myalgia (G1-G2: 11 patients), diarrhea (G1-G2: 7 patients), and stomatitis were observed in 7 patients. Vinorelbine-paclitaxel combination showed only modest activity against locoregionally advanced or metastatic NSCLC.

  2. The bifunctional autophagic flux by 2-deoxyglucose to control survival or growth of prostate cancer cells

    International Nuclear Information System (INIS)

    Jeon, Jeong Yong; Kim, Seung Won; Park, Ki Cheong; Yun, Mijin

    2015-01-01

    Recent reports using metabolism regulating drugs showed that nutrient deprivation was an efficient tool to suppress cancer progression. In addition, autophagy control is emerging to prevent cancer cell survival. Autophagy breaks down the unnecessary cytoplasmic components into anabolic units and energy sources, which are the most important sources for making the ATP that maintains homeostasis in cancer cell growth and survival. Therefore, the glucose analog 2-deoxyglucose (2DG) has been used as an anticancer reagent due to its inhibition of glycolysis. Prostate cancer cells (PC3) were treated with 2DG for 6 h or 48 h to analyze the changing of cell cycle and autophagic flux. Rapamycin and LC3B overexpressing vectors were administered to PC3 cells for autophagy induction and chloroquine and shBeclin1 plasmid were used to inhibit autophagy in PC3 cells to analyze PC3 cells growth and survival. The samples for western blotting were prepared in each culture condition to confirm the expression level of autophagy related and regulating proteins. We demonstrated that 2DG inhibits PC3 cells growth and had discriminating effects on autophagy regulation based on the different time period of 2DG treatment to control cell survival. Short-term treatment of 2DG induced autophagic flux, which increased microtubule associated protein 1 light chain 3B (LC3B) conversion rates and reduced p62 levels. However, 2DG induced autophagic flux is remarkably reduced over an extended time period of 2DG treatment for 48 h despite autophagy inducing internal signaling being maintained. The relationship between cell growth and autophagy was proved. Increased autophagic flux by rapamycin or LC3B overexpression powerfully reduced cell growth, while autophagy inhibition with shBeclin1 plasmid or chloroquine had no significant effect on regulating cell growth. Given these results, maintaining increased autophagic flux was more effective at inhibiting cancer cell progression than inhibition of

  3. Regional PET/CT after water gastric inflation for evaluating loco-regional disease of gastric cancer

    International Nuclear Information System (INIS)

    Lee, Soo Jin; Lee, Won Woo; Yoon, Hai-Jeon; Lee, Ho-Young; Lee, Kyoung Ho; Kim, Young Hoon; Park, Do Joong; Kim, Hyung-Ho; So, Young

    2013-01-01

    Objective: We aimed to improve diagnostic accuracy of 18 F-fluoro-2-deoxyglucose (FDG) PET/CT for gastric cancer with water gastric inflation. Materials and methods: 44 gastric cancer patients (M:F = 30:14, age ± std = 62.1 ± 14.5y) were enrolled before surgery. Fifty minutes after injection of FDG (0.14 mCi/kg body weight), whole body PET/CT was performed first and then regional PET/CT over gastric area was obtained 80 min post FDG injection after water gastric inflation. Diagnostic accuracies for loco-regional lesions were compared between whole body and regional PET/CT. Results: 48 primary tumors (23 EGC and 25 AGC) and 348 LN stations (61 metastatic and 287 benign) in 44 patients were investigated. Primary tumor sensitivity of whole body PET/CT (50% = 24/48) was significantly improved by regional PET/CT (75% = 36/48, p < 0.005). Sensitivity of whole body PET/CT (24.6% = 15/61) for LN metastasis was also significantly improved by regional PET/CT (36.1% = 22/61, p < 0.01), whereas specificity of whole body PET/CT (99.3% = 285/287) was not compromised by regional PET/CT (98.3% = 282/287, p > 0.05). Higher primary tumor FDG uptake in regional PET/CT indicated shorter progress-free survival (p = 0.0003). Conclusion: Diagnostic accuracy of whole body PET/CT for loco-regional disease of gastric cancer could be significantly improved by regional PET/CT after water gastric inflation and prognosis could be effectively predicted by primary tumor FDG uptake in regional PET/CT

  4. The effect of initial density and parasitoid intergenerational survival rate on classical biological control

    International Nuclear Information System (INIS)

    Xiao Yanni; Tang Sanyi

    2008-01-01

    Models of biological control have a long history of theoretical development that have focused on the interaction of a parasitoid and its host. The host-parasitoid systems have identified several important and general factors affecting the long-term dynamics of interacting populations. However, much less is known about how the initial densities of host-parasitoid populations affect the biological control as well as the stability of host-parasitoid systems. To do this, the classical Nicholson-Bailey model with host self-regulation and parasitoid intergenerational survival rate is used to uncover the effect of initial densities on the successful biological control. The results indicate that the simplest Nicholson-Bailey model has various coexistence with a wide range of parameters, including boundary attractors where the parasitoid population is absent and interior attractors where host-parasitoid coexists. The final stable states of host-parasitoid populations depend on their initial densities as well as their ratios, and those results are confirmed by basins of attraction of initial densities. The results also indicate that the parasitoid intergenerational survival rate increases the stability of the host-parasitoid systems. Therefore, the present research can help us to further understand the dynamical behavior of host-parasitoid interactions, to improve the classical biological control and to make management decisions

  5. Diagnostic accuracy of endoscopic ultrasonography (EUS) for the preoperative locoregional staging of primary gastric cancer.

    Science.gov (United States)

    Mocellin, Simone; Pasquali, Sandro

    2015-02-06

    Endoscopic ultrasound (EUS) is proposed as an accurate diagnostic device for the locoregional staging of gastric cancer, which is crucial to developing a correct therapeutic strategy and ultimately to providing patients with the best chance of cure. However, despite a number of studies addressing this issue, there is no consensus on the role of EUS in routine clinical practice. To provide both a comprehensive overview and a quantitative analysis of the published data regarding the ability of EUS to preoperatively define the locoregional disease spread (i.e., primary tumor depth (T-stage) and regional lymph node status (N-stage)) in people with primary gastric carcinoma. We performed a systematic search to identify articles that examined the diagnostic accuracy of EUS (the index test) in the evaluation of primary gastric cancer depth of invasion (T-stage, according to the AJCC/UICC TNM staging system categories T1, T2, T3 and T4) and regional lymph node status (N-stage, disease-free (N0) versus metastatic (N+)) using histopathology as the reference standard. To this end, we searched the following databases: the Cochrane Library (the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE, EMBASE, NIHR Prospero Register, MEDION, Aggressive Research Intelligence Facility (ARIF), ClinicalTrials.gov, Current Controlled Trials MetaRegister, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), from 1988 to January 2015. We included studies that met the following main inclusion criteria: 1) a minimum sample size of 10 patients with histologically-proven primary carcinoma of the stomach (target condition); 2) comparison of EUS (index test) with pathology evaluation (reference standard) in terms of primary tumor (T-stage) and regional lymph nodes (N-stage). We excluded reports with possible overlap with the selected studies. For each study, two review authors extracted a standard set of data, using a dedicated data extraction

  6. Environmental control of phase transition and polyp survival of a massive-outbreaker jellyfish.

    Directory of Open Access Journals (Sweden)

    Laura Prieto

    Full Text Available A number of causes have been proposed to account for the occurrence of gelatinous zooplankton (both jellyfish and ctenophore blooms. Jellyfish species have a complex life history involving a benthic asexual phase (polyp and a pelagic sexual phase (medusa. Strong environmental control of jellyfish life cycles is suspected, but not fully understood. This study presents a comprehensive analysis on the physicochemical conditions that control the survival and phase transition of Cotylorhiza tuberculata; a scyphozoan that generates large outbreaks in the Mediterranean Sea. Laboratory experiments indicated that the influence of temperature on strobilation and polyp survival was the critical factor controlling the capacity of this species to proliferate. Early life stages were less sensitive to other factors such as salinity variations or the competitive advantage provided by zooxanthellae in a context of coastal eutrophication. Coherently with laboratory results, the presence/absence of outbreaks of this jellyfish in a particular year seems to be driven by temperature. This is the first time the environmental forcing of the mechanism driving the life cycle of a jellyfish has been disentangled via laboratory experimentation. Projecting this understanding to a field population under climatological variability results in a pattern coherent with in situ records.

  7. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    International Nuclear Information System (INIS)

    Duprez, Fréderic; Madani, Indira; Morbée, Lieve; Bonte, Katrien; Deron, Philippe; Domján, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

    2012-01-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60–66 Gy (n = 13) at 2 Gy per fraction over 6–7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1–2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15–121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment (≥6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1–2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and

  8. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    Energy Technology Data Exchange (ETDEWEB)

    Duprez, Frederic, E-mail: frederic.duprez@ugent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Madani, Indira; Morbee, Lieve [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien; Deron, Philippe; Domjan, Vilmos [Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  9. The clinical impact of hypoxia-regulated gene expression in loco-regional gastroesophageal cancer

    DEFF Research Database (Denmark)

    Winther, M.; Alsner, J.; Tramm, T.

    2015-01-01

    Purpose/Objective: In a former study (1), the hypoxia gene expression classifier, developed in head and neck squamous cell carcinomas, was applied in 89 patients with loco-regional gastroesophageal cancer (GC). Analysis of the 15 genes was indicative of hypoxia being more profound in esophagus...... and display greater heterogeneity compared to AC. However, previous indications that the hypoxia classifier might hold prognostic significance in ESCC patients could not be confirmed. Ongoing work includes in vitro studies of esophageal cancer cell lines in order to identify alternative hypoxia induced genes...... and to further explore the prognostic value of hypoxia in patients with loco-regional gastroesophageal cancer. (Figure Presented)....

  10. Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Maklad AM

    2016-10-01

    Full Text Available Ahmed Marzouk Maklad,1,2 Yasser Bayoumi,2,3 Mohamed Abdalazez Senosy Hassan,2,4 AbuSaleh A Elawadi,5,6 Hussain AlHussain,2 Ashraf Elyamany,7,8 Saleh F Aldhahri,9 Khalid Hussain Al-Qahtani,10 Mubarak AlQahtani,11 Mutahir A Tunio12 1Clinical Oncology, Sohag University, Sohag, Egypt; 2Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 3Radiation Oncology, NCI, Cairo University, Cairo, 4Radiation Oncology, Minia Oncology Center, Minia, 5Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 6Medical Physics, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 7Medical Oncology, SECI-Assiut University, Assiut, Egypt; 8Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, 9Department of Otolaryngology, Head and Neck Surgery, King Saud University, 10Department of Otolaryngology-Head and Neck Surgery, College of Medicine, King Saud University, 11Department of ENT, King Fahad Medical City, 12Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia Background: We aimed to investigate the patterns of failure (locoregional and distant metastasis, associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT combined with chemotherapy. Patients and methods: From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results: The median follow-up time was 52.2 months (range: 11–87 months. Epstein–Barr virus infection was positive in 63.2% of

  11. Suspected survivor bias in case-control studies: stratify on survival time and use a negative control.

    Science.gov (United States)

    van Rein, Nienke; Cannegieter, Suzanne C; Rosendaal, Frits R; Reitsma, Pieter H; Lijfering, Willem M

    2014-02-01

    Selection bias in case-control studies occurs when control selection is inappropriate. However, selection bias due to improper case sampling is less well recognized. We describe how to recognize survivor bias (i.e., selection on exposed cases) and illustrate this with an example study. A case-control study was used to analyze the effect of statins on major bleedings during treatment with vitamin K antagonists. A total of 110 patients who experienced such bleedings were included 18-1,018 days after the bleeding complication and matched to 220 controls. A protective association of major bleeding for exposure to statins (odds ratio [OR]: 0.56; 95% confidence interval: 0.29-1.08) was found, which did not become stronger after adjustment for confounding factors. These observations lead us to suspect survivor bias. To identify this bias, results were stratified on time between bleeding event and inclusion, and repeated for a negative control (an exposure not related to survival): blood group non-O. The ORs for exposure to statins increased gradually to 1.37 with shorter time between outcome and inclusion, whereas ORs for the negative control remained constant, confirming our hypothesis. We recommend the presented method to check for overoptimistic results, that is, survivor bias in case-control studies. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Evaluation of Acute Locoregional Toxicity in Patients With Breast Cancer Treated With Adjuvant Radiotherapy in Combination With Bevacizumab

    International Nuclear Information System (INIS)

    Goyal, Sharad; Rao, Malay S.; Khan, Atif; Huzzy, Lien; Green, Camille; Haffty, Bruce G.

    2011-01-01

    Purpose: Preclinical studies have shown that bevacizumab combined with radiotherapy (RT) induces a radiosensitizing effect. Published reports regarding the safety of combination therapy involving bevacizumab and RT are lacking. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent bevacizumab plus RT. Methods and Materials: After institutional review board approval was obtained, patients with breast cancer who received bevacizumab were identified; these patients were then cross-referenced with patients receiving RT. Toxicity was scored by the Common Terminology Criteria for Adverse Events. Patients were matched 1:1 with those who did not receive bevacizumab. Statistical analysis was performed to analyze toxicity between the two groups. Results: Fourteen patients were identified to have received bevacizumab plus RT. All patients receivedbevacizumab during RT without delay or treatment breaks; there were no RT treatment breaks in all patients. No patient receiving bevacizumab plus RT experienced ≥Grade 3 toxicity; 3 matched control patients experienced a Grade 3 skin reaction. There was no difference in fatigue, radiation fibrosis, pneumonitis, or lymphedema between the two groups. Five patients (35%) developed reduction in ejection fraction; 2 with right-sided and 3 with left-sided treatment. Patients with left-sided treatment experienced a persistent reduction in ejection fraction compared with those receiving right-sided treatment. Conclusion: Concurrent bevacizumab and RT did not increase acute locoregional toxicity in comparison with matched control patients who did not receive RT alone. The addition of concurrent RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated.

  13. An improved technique for breast cancer irradiation including the locoregional lymph nodes

    NARCIS (Netherlands)

    Hurkmans, C. W.; Saarnak, A. E.; Pieters, B. R.; Borger, J. H.; Bruinvis, I. A.

    2000-01-01

    PURPOSE: To find an irradiation technique for locoregional irradiation of breast cancer patients which, compared with a standard technique, improves the dose distribution to the internal mammary-medial supraclavicular (IM-MS) lymph nodes. The improved technique is intended to minimize the lung dose

  14. Notch controls the survival of memory CD4+ T cells by regulating glucose uptake.

    Science.gov (United States)

    Maekawa, Yoichi; Ishifune, Chieko; Tsukumo, Shin-ichi; Hozumi, Katsuto; Yagita, Hideo; Yasutomo, Koji

    2015-01-01

    CD4+ T cells differentiate into memory T cells that protect the host from subsequent infection. In contrast, autoreactive memory CD4+ T cells harm the body by persisting in the tissues. The underlying pathways controlling the maintenance of memory CD4+ T cells remain undefined. We show here that memory CD4+ T cell survival is impaired in the absence of the Notch signaling protein known as recombination signal binding protein for immunoglobulin κ J region (Rbpj). Treatment of mice with a Notch inhibitor reduced memory CD4+ T cell numbers and prevented the recurrent induction of experimental autoimmune encephalomyelitis. Rbpj-deficient CD4+ memory T cells exhibit reduced glucose uptake due to impaired AKT phosphorylation, resulting in low Glut1 expression. Treating mice with pyruvic acid, which bypasses glucose uptake and supplies the metabolite downstream of glucose uptake, inhibited the decrease of autoimmune memory CD4+ T cells in the absence of Notch signaling, suggesting memory CD4+ T cell survival relies on glucose metabolism. Together, these data define a central role for Notch signaling in maintaining memory CD4+ T cells through the regulation of glucose uptake.

  15. Controls on Arctic sea ice from first-year and multi-year ice survival rates

    Science.gov (United States)

    Armour, K.; Bitz, C. M.; Hunke, E. C.; Thompson, L.

    2009-12-01

    The recent decrease in Arctic sea ice cover has transpired with a significant loss of multi-year (MY) ice. The transition to an Arctic that is populated by thinner first-year (FY) sea ice has important implications for future trends in area and volume. We develop a reduced model for Arctic sea ice with which we investigate how the survivability of FY and MY ice control various aspects of the sea-ice system. We demonstrate that Arctic sea-ice area and volume behave approximately as first-order autoregressive processes, which allows for a simple interpretation of September sea-ice in which its mean state, variability, and sensitivity to climate forcing can be described naturally in terms of the average survival rates of FY and MY ice. This model, used in concert with a sea-ice simulation that traces FY and MY ice areas to estimate the survival rates, reveals that small trends in the ice survival rates explain the decline in total Arctic ice area, and the relatively larger loss of MY ice area, over the period 1979-2006. Additionally, our model allows for a calculation of the persistence time scales of September area and volume anomalies. A relatively short memory time scale for ice area (~ 1 year) implies that Arctic ice area is nearly in equilibrium with long-term climate forcing at all times, and therefore observed trends in area are a clear indication of a changing climate. A longer memory time scale for ice volume (~ 5 years) suggests that volume can be out of equilibrium with climate forcing for long periods of time, and therefore trends in ice volume are difficult to distinguish from its natural variability. With our reduced model, we demonstrate the connection between memory time scale and sensitivity to climate forcing, and discuss the implications that a changing memory time scale has on the trajectory of ice area and volume in a warming climate. Our findings indicate that it is unlikely that a “tipping point” in September ice area and volume will be

  16. Effects of environmental factors on child survival in Bangladesh: a case control study.

    Science.gov (United States)

    Hoque, B A; Chakraborty, J; Chowdhury, J T; Chowdhury, U K; Ali, M; el Arifeen, S; Sack, R B

    1999-03-01

    The need for further studies on relationships between deaths and environmental variables has been reported in the literature. This case-control study was, therefore, carried out to find out the associations between several social and environmental variables and deaths of children due to infectious diseases such as those leading to diarrhoea, acute respiratory infection, measles and other diseases. Six hundred and twenty-five deaths (cases) and an equal number of matched living children (controls) aged 1-59 months, were studied in rural Matlab. An analysis of crude and adjusted odds ratio showed differential associations. Sources of drinking water, amount of stored water, conditions of latrines, number of persons sleeping with the child and the type of cooking site were statistically significantly associated with deaths due to infectious diseases after controlling for breast feeding, immunization, and the family size. Significant associations were also observed between: (i) the sources of drinking water and deaths due to ARI, and (ii) conditions of latrines and deaths due to diarrhoeal diseases, after controlling for the confounding variables. Several other environmental factors also showed associations with these various death groups, but they were not statistically significant. The size of the samples in death groups (small) and the prevalence of more or less homogeneous environmental health conditions probably diminished the magnitude of the effects. The results of the study reconfirm the importance of environmental health intervention in child survival, irrespective of breast-feeding, immunization, and selected social variables.

  17. Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Truong, Pauline T.; Olivotto, Ivo A.; Kader, Hosam A.; Panades, Miguel; Speers, Caroline H.; Berthelet, Eric

    2005-01-01

    .8%; p 45 years with ≤25% of nodes positive, tumor location and ER status were factors that could be used to further distinguish low-risk from higher risk subsets. Conclusion: Clinical and pathologic factors can identify women with T1-T2 breast cancer and one to three positive nodes at high LRR risk after mastectomy. Age 25% of nodes positive, a medial tumor location, and ER-negative status were statistically significant independent factors associated with greater LRR, meriting consideration and discussion of PMRT. Combinations of these factors further augmented the LRR risk, warranting recommendation of PMRT to optimize locoregional control and potentially improve survival. The absence of high-risk factors identifies women who may reasonably be spared the morbidity of PMRT

  18. Decayed, missing and filled teeth and dental anomalies in long term survived leukemic children: a prospective controlled study

    OpenAIRE

    Lauritano, D; Petruzzi, M; Baldoni, M

    2012-01-01

    Objective: The aim of this prospective controlled study is the comparison between long-term children survived leukaemia and a control group in terms of the decayed, missing or filled permanent teeth (DMFT) and dental anomalies. Study design: Fifty-two long term children survived leukaemia, aged from 8 to 15 years (27 females, 25 males; mean age 11.5 years) were evaluated for the possible effects of the anti-leukaemic therapy on dental development and compared to a control group of 52 healthy ...

  19. The location of locoregional recurrence in pathologic T3N0, non-irradiated lower rectal cancer

    International Nuclear Information System (INIS)

    Kim, Mi Sun; Keum, Ki Chang; Rhee, Woo Joong; Kim, Hyun Ju; Kim, Min Ji; Choi, Seo Hee; Nam, Ki Chang; Koom, Woong Sub

    2013-01-01

    To investigate the patterns of locoregional recurrence of pathologic T3N0 (pT3N0) lower rectal cancer omitting postoperative radiotherapy (RT) and explore the potential of modification of a RT field. From Jan 2003 to Nov 2011, 35 patients omitting preoperative or postoperative RT for pT3N0 lower rectal cancer were included. We defined the lower rectal cancer as the tumor with the inferior margin located below the virtual line-a convergent level between rectal wall and levator ani muscle. All patients had radiologic examinations for recurrence evaluation during the follow-up duration. The median follow-up duration was 66.4 months (range, 1.4 to 126.1 months). Eight (22.9%) of the 35 patients had recurrence. Three (8.6%) was local recurrence (LR) only, 3 (8.6%) was distant metastasis (DM) only, and 2 (5.7%) was LR with DM. All LR were located at primary tumor sites. The overall survival rate, LR-free survival rate, and DM-free survival rate at 5 years was 79.8%, 83%, and 87%, respectively. All LR developed from tumors over 5 cm. However, there was no statistical significance (p = 0.065). There was no other risk factor for LR. Even though the patients included in this study had pathologically favorable pT3N0 rectal cancer, LR developed in 14.3% of patients. Most of the LR was located at primary tumor sites prior to surgery. Based on these findings, it might seem reasonable to consider postoperative RT with a smaller radiation field to the primary tumor site rather than the conventional whole pelvic irradiation.

  20. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    Energy Technology Data Exchange (ETDEWEB)

    Swisher, Stephen G., E-mail: sswisher@mdanderson.org [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Winter, Kathryn A. [Headquarters, Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Komaki, Ritsuko U. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Wu, Tsung T. [Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Konski, Andre A. [Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Willett, Christopher G. [Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2012-04-01

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

  1. Outcomes of patients with loco-regionally recurrent or new primary squamous cell carcinomas of the head and neck treated with curative intent reirradiation at Mayo Clinic

    International Nuclear Information System (INIS)

    Curtis, Kelly K.; Ross, Helen J.; Garrett, Ashley L.; Jizba, Theresa A.; Patel, Ajay B.; Patel, Samir H.; Wong, William W.; Halyard, Michele Y.; Ko, Stephen J.; Kosiorek, Heidi E.; Foote, Robert L.

    2016-01-01

    We reviewed outcomes of patients with loco-regionally recurrent (LRR) or new primary (NP) squamous cell carcinoma of the head and neck (SCCHN) treated at our institution with reirradiation (RRT). Patients received definitive RRT (DRRT) or post-operative RRT following salvage surgery (PRRT) from 2003 to 2011. Measured survival outcomes included loco-regional relapse free survival (LRFS) and overall survival (OS). Among 81 patients (PRRT, 42; DRRT, 39), median PRRT and DRRT doses were 60 Gy (12–70 Gy) and 69.6 Gy (48–76.8 Gy). The majority of patients received IMRT-based RRT (n = 77, 95 %). With median follow-up of 78.1 months (95 % CI, 56–96.8 months), 2-year OS was 53 % with PRRT and 48 % with DRRT (p = 0.12); 23 % of patients were alive at last follow-up. LRFS at 2 years was 60 %, and did not differ significantly between PRRT and DRRT groups. A trend toward inferior LRFS was noted among patients receiving chemotherapy with RRT versus RRT alone (p = 0.06). Late serious toxicities were uncommon, including osteoradionecrosis (2 patients) and carotid artery bleeding (1 patient, non-fatal). OS of PRRT- and DRRT-treated patients in this series appears superior to the published literature. We used IMRT for the majority of patients, in contrast to several series and trials previously reported, which may account in part for this difference. Future studies should seek to improve outcomes among patients with LRR/NP SCCHN via alternative therapeutic modalities such as proton radiotherapy and by incorporating novel systemic agents

  2. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial.

    Science.gov (United States)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied. The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients. Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders. The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283). The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

  3. Survival of pathogenic enterohemorrhagic Escherichia coli (EHEC) and control with calcium oxide in frozen meat products.

    Science.gov (United States)

    Ro, Eun Young; Ko, Young Mi; Yoon, Ki Sun

    2015-08-01

    This study investigated both the level of microbial contamination and the presence of enterohemorrhagic Escherichia coli (EHEC) in frozen meat products, followed by the evaluation of its survival over 180 days under frozen temperature. We also examined the effect of calcium oxide on the populations of EHEC, E. coli O157:H7 and EPEC under both 10 °C and -18 °C storage conditions. Afterward, the morphological changes occurring in EHEC cells in response to freezer storage temperature and calcium oxide (CaO) treatments were examined using transmission electron microscopy. Among the frozen meat products tested, the highest contamination levels of total aerobic counts, coliforms and E. coli were observed in pork cutlets. Examination showed that 20% of the frozen meat products contained virulence genes, including verotoxin (VT) 1 and 2. Over 180 days of frozen storage and after 3 freeze-thaw cycles, the population of EHEC did not change regardless of the type of products or initial inoculated concentration, indicating the strong survival ability of EHEC. Subsequent testing revealed that the growth of three pathogenic E. coli strains was completely inhibited in meat patties prepared with 1% CaO, stored at 10 °C. However, the addition of 2% CaO was necessary to control the survival of EHEC, E. coli O157:H7 and EPEC in meat patties stored at -18 °C. CaO reduced the population of E. coli O157:H7 more effectively than the other EHEC and EPEC strains at both 10 °C and -18 °C. Transmission electron microscopy analysis revealed that exposed EHEC cells were resistant to the freezer storage temperature, although some cells incurred injury and death after several freeze-thaw cycles. Most of the cells exposed to CaO were found to have died or lost their cellular integrity and membranes, indicating that CaO has the potential to be used as a powerful antimicrobial agent for manufacturing frozen meat products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. A multicentre randomized/controlled trial of a conventional versus modestly accelerated radiotherapy in the laryngeal cancer: influence of a 1 week shortening overall time

    International Nuclear Information System (INIS)

    Hliniak, A.; Gwiazdowska, B.; Szutkowski, Z.; Kraszewska, E.; Kukolowicz, P.; Jarzabski, A.; Sochacka, B.; Mazurkiewicz, M.; Paprota, K.; Oliskiewicz, W.; Zadrozna, O.; Milecki, P.; Kubiak, M.; Czopkiewicz, L.; Jagas, M.; Gozdz, S.; Wieczorek, A.; Woytowicz, A.; Cisowska, B.; Magdziarz, H.; Nowakowski, S.; Kosniewski, W.; Laskosz, I.; Serafin, A.; Gradon, E.

    2002-01-01

    Background and purpose: To compare in a phase III study the loco-regional control, disease-free survival and overall survival induced by an accelerated regimen (AF) as compared with conventional regimen (CF) and to analyze the early and late post-radiation morbidity in both arms. Materials and methods: Patients with age≤75, WHO 0-1, suitable for a radical course of radiotherapy T1-T3, N0, M0, stage of glottic and supraglottic laryngeal cancer were randomized to either CF: 66Gy given in 33 fractions over 45 days or AF: 66Gy given in 33 fractions over 38 days (2 fractions every Thursday). A total of 395 patients were included from 05.1995 to 12.1998. Results. Early toxicity: At the end of radiotherapy patients treated with AF complained for more severe reactions than patients treated with CF. In 8 weeks after treatment completion patients treated with AF complained only for more severe pain on swallowing (P=0.027). In 4 months after treatment completion all types of toxicity except for skin teleangiectasia (P=0.001) were similar in the two groups. Loco-regional control: comparison between CF and AF showed no difference in terms of loco-regional control (P=0.37). Conclusions: The improvement in AF in terms of loco-regional control is estimated to be 3-5% in comparison with conventional regimen and is not significant. The intensity of reactions after 4 months was similar in both arms, what suggests the possibility of further shortening of the overall time by few days or enhancing the total dose within the limits of acceptable morbidity

  5. Predicting bat colony survival under controls targeting multiple transmission routes of white-nose syndrome.

    Science.gov (United States)

    Meyer, A D; Stevens, D F; Blackwood, J C

    2016-11-21

    White-nose syndrome (WNS) is a lethal infection of bats caused by the psychrophilic fungus Pseudogymnoascus destructans (Pd). Since the first cases of WNS were documented in 2006, it is estimated that as many as 5.5million bats have succumbed in the United States-one of the fastest mammalian die-offs due to disease ever observed, and the first known sustained epizootic of bats. WNS is contagious between bats, and mounting evidence suggests that a persistent environmental reservoir of Pd plays a significant role in transmission as well. It is unclear, however, the relative contributions of bat-to-bat and environment-to-bat transmission to disease propagation within a colony. We analyze a mathematical model to investigate the consequences of both avenues of transmission on colony survival in addition to the efficacy of disease control strategies. Our model shows that selection of the most effective control strategies is highly dependent on the primary route of WNS transmission. Under all scenarios, however, generalized culling is ineffective and while targeted culling of infected bats may be effective under idealized conditions, it primarily has negative consequences. Thus, understanding the significance of environment-to-bat transmission is paramount to designing effective management plans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Direct lexical control of eye movements in reading: Evidence from a survival analysis of fixation durations

    Science.gov (United States)

    Reingold, Eyal M.; Reichle, Erik D.; Glaholt, Mackenzie G.; Sheridan, Heather

    2013-01-01

    Participants’ eye movements were monitored in an experiment that manipulated the frequency of target words (high vs. low) as well as their availability for parafoveal processing during fixations on the pre-target word (valid vs. invalid preview). The influence of the word-frequency by preview validity manipulation on the distributions of first fixation duration was examined by using ex-Gaussian fitting as well as a novel survival analysis technique which provided precise estimates of the timing of the first discernible influence of word frequency on first fixation duration. Using this technique, we found a significant influence of word frequency on fixation duration in normal reading (valid preview) as early as 145 ms from the start of fixation. We also demonstrated an equally rapid non-lexical influence on first fixation duration as a function of initial landing position (location) on target words. The time-course of frequency effects, but not location effects was strongly influenced by preview validity, demonstrating the crucial role of parafoveal processing in enabling direct lexical control of reading fixation times. Implications for models of eye-movement control are discussed. PMID:22542804

  7. Stereotactic radiosurgery for brainstem metastases: Survival, tumor control, and patient outcomes

    International Nuclear Information System (INIS)

    Hussain, Aamir; Brown, Paul D.; Stafford, Scott L.; Pollock, Bruce E.

    2007-01-01

    Purpose: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. Methods and Materials: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). Results: Median survival time after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. Conclusions: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS

  8. Adoption of SO2 emission control technologies - An application of survival analysis

    International Nuclear Information System (INIS)

    Streeter, Jialu Liu

    2016-01-01

    Using data on coal-fired electric power plants, this article investigates the contributing factors affecting the investment decisions on flue-gas desulfurization (FGD), a capital-intensive emission control technology. The paper makes two contributions to the literature. First, the public regulatory status of electric power plants is found to have a strong influence on whether FGD investment is made. Compared to deregulated power plants, those that are still under rate-of-return regulations by Public Utility Commissions are more likely to install FGD. Second, a higher rate of inspections of polluting facilities (not just electric utility power plants) in a state in the previous year is associated with a higher probability of power plants adopting FGD this year. In addition, sulfur content of coal and plant size are both positively associated with the likelihood of FGD installation. The service length of boilers is negatively associated with the likelihood. - Highlights: • Contributing factors affecting investment decisions on emission control devices. • A survival analysis framework is applied in estimation. • Data cover over 300 coal-fired electric utility power plants, 2002–2012. • Still-regulated power plants are more likely to install FGD than deregulated ones. • State-level inspection frequency leads to more FGD installation.

  9. Survival of Listeria monocytogenes on fresh blueberries (Vaccinium corymbosum) stored under controlled atmosphere and ozone.

    Science.gov (United States)

    Concha-Meyer, Anibal; Eifert, Joseph; Williams, Robert; Marcy, Joseph; Welbaum, Gregory

    2014-05-01

    Listeria monocytogenes is a foodborne pathogen that represents a high risk for consumers because it can grow under refrigeration conditions and can also develop acid tolerance. Fresh blueberries are hand-picked, packed, and transported under refrigeration without receiving a microbial inactivation treatment. The aim of this work was to study the survival of L. monocytogenes in fresh highbush blueberries stored at 4 or 12 °C under different controlled atmosphere conditions, including air (control); 5% O2, 15% CO2, 80% N2 (controlled atmosphere storage [CAS]); or ozone gas (O3), 4 ppm at 4 °C or 2.5 ppm at 12 °C, at high relative humidity (90 to 95%) for a total of 10 days. Fresh blueberries inside a plastic clamshell were spot inoculated with the bacteria and were stored at 4 or 12 °C in isolated cabinets under air, CAS, and O3 atmospheric conditions. Samples were evaluated on days 0, 1, 4, 7, and 10 for microbial growth using modified Oxford agar. CAS did not delay or inhibit L. monocytogenes growth in fresh blueberries after 10 days. O3 achieved 3- and 2-log reductions when compared with air treatment at 4 and 12 °C, respectively. Low concentrations of O3 together with proper refrigeration temperature can ensure product safety throughout transportation. O3 is a strong antimicrobial that safely decomposes to oxygen and water without leaving residues and can be used as an alternative method to prevent bacterial growth during a long transport period.

  10. Preoperative radiotherapy for resectable rectal cancer: improved local control is prognostic for distant metastasis occurrence and survival

    International Nuclear Information System (INIS)

    Zlotecki, Robert A.; Mendenhall, William M.; Copeland, Edward M.; Vauthey, Jean-Nicholas; Marsh, Robert D.; McCarley, Dean L.; Million, Rodney R.

    1996-01-01

    Purpose/Objective: To evaluate the effect of preoperative external beam radiotherapy (RT) on local control (LC), distant metastasis (DM), survival, and perioperative complications in a 15-year single-institution experience. Disease and treatment variables potentially prognostic for local-regional control and survival were evaluated, and the importance of LC as a determinant of DM and survival was also examined. Materials and Methods: Two hundred ten patients with potentially resectable cancers of the rectum were treated with preoperative external beam RT at a single institution between 1975 and 1990. Excluded were patients with 'fixed' unresectable tumors and those treated with palliative intent only. All patients were treated with megavoltage RT to minimum tumor doses of 30 Gy using multiple-field techniques. Preoperative chemotherapy was not used. Surgical resection was performed 3-5 weeks after completion of RT. Abdominoperineal resection was performed in 175 cases, low anterior resection in 25 cases, and other surgical procedures in 10 cases. Pathologic tumor staging was by the Astler-Coller modification of the Dukes system. Minimum follow-up was 5 years. Survival analysis was performed using the Kaplan-Meier method, with univariate and multivariate analysis of disease and treatment variables for prognostic significance. Results: No treatment-specific variables were predictive for LC, DM, absolute survival, or cause-specific survival. Disease-specific variables prognostic for LC were deep tumor infiltration or 'tethering' on digital rectal exam and Dukes pathologic stage. Ten-year LC rates were 91% for freely mobile tumors vs. 82% for tethered lesions (p=.009). LC rates for Dukes A, B, and C stage tumors were 100%, 91%, and 73%, respectively (p=.02). Variables prognostic for DM were tumor length, annular involvement, LC, and Dukes pathologic stage. Absolute survival at 5 and 10 years was 57% and 36%, respectively. Variables prognostic for absolute survival were

  11. Outcomes after curative or palliative surgery for locoregional recurrent breast cancer

    DEFF Research Database (Denmark)

    Juhl, Alexander Andersen; Mele, Marco; Damsgaard, Tine Engberg

    2014-01-01

    Background Locoregional recurrence (LRR) after breast cancer is an independent predictor for later systemic disease and poor long-term outcome. As the surgical treatment is complex and often leaves the patient with extensive defects, reconstructive procedures involving flaps, and thus plastic...... surgical assistance, are often required. The aim of the present study was to evaluate our institution’s approach to surgical treatment for locoregional recurrence of a breast cancer. Methods In the present retrospective, single-centre study, we evaluate our experience with 12 patients who underwent surgery...... for locally recurrent breast cancer at Aarhus University Hospital between 2006 and 2010. Nine patients underwent wide local excision. The remaining three patients underwent full thickness chest wall resection. Results There was no perioperative mortality and no major complications. Minor complications...

  12. Locoregional therapy in HCC; Lokoregionaere Therapie des HCC

    Energy Technology Data Exchange (ETDEWEB)

    Helmberger, T.; Scher, B.; Klaesner, B.; Schneider, P. [Klinikum Bogenhausen, Muenchen (Germany). Inst. fuer Diagnostische and Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin

    2011-09-15

    Hepatocellular carcinomas are the most common hepatic tumors and the most common malignancies worldwide with constantly rising incidence. The potential treatment is ruled mainly by the tumor extent (e.g. tumour size, multifocality, hepatic function, underlying concommittend hepatic disease) whereas local from more systemic-hepatic therapies can be differentiated. Resection and transplantation are considered by definition as curative treatments, however, in clinical reality only about 20% of the patients are eligible for one of this therapies. The majority oft patients will present with an advanced tumor disease with or without an additional hepatic disease. In locally limited tumor burden with respect to tumour size and number percutaneous chemo-ablative, thermo-ablative, and in multifocally or diffuse tumour manifestations transarterial chemo- and radioablative therapies may be administered. Considering indications, radioablation will compete with transarterial, chemoablative treatments (TACE) especially in patients with advanced tumours, whereas in initial studies radioablation presents some advances over TACE regarding progressions-free and overall survival. This promising results have to be confirmed in further studies. (orig.)

  13. ITGA3 and ITGB4 expression biomarkers estimate the risks of locoregional and hematogenous dissemination of oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Nagata, Masaki; Takahashi, Katsu; Kodama, Naoki; Kawase, Tomoyuki; Hoshina, Hideyuki; Ikeda, Nobuyuki; Shingaki, Susumu; Takagi, Ritsuo; Noman, Arhab A; Suzuki, Kenji; Kurita, Hiroshi; Ohnishi, Makoto; Ohyama, Tokio; Kitamura, Nobutaka; Kobayashi, Takanori; Uematsu, Kohya

    2013-01-01

    Molecular biomarkers are essential for monitoring treatment effects, predicting prognosis, and improving survival rate in oral squamous cell carcinoma. This study sought to verify the effectiveness of two integrin gene expression ratios as biomarkers. Gene expression analyses of integrin α3 (ITGA3), integrin β4 (ITGB4), CD9 antigen (CD9), and plakoglobin (JUP) by quantitative real-time PCR were conducted on total RNA from 270 OSCC cases. The logrank test, Cox proportional hazards model, and Kaplan-Meier estimates were performed on the gene expression ratios of ITGA3/CD9 and ITGB4/JUP and on the clinicopathological parameters for major clinical events. A high rate (around 80%) of lymph node metastasis was found in cases with a high ITGA3/CD9 ratio (high-ITGA3/CD9) and invasive histopathology (YK4). Primary site recurrence (PSR) was associated with high-ITGA3/CD9, T3-4 (TNM class), and positive margin, indicating that PSR is synergistically influenced by treatment failure and biological malignancy. A high ITGB4/JUP ratio (high-ITGB4/JUP) was revealed to be a primary contributor to distant metastasis without the involvement of clinicopathological factors, suggesting intervention of a critical step dependent on the function of the integrin β4 subunit. Kaplan-Meier curves revealed positive margin as a lethal treatment consequence in high-ITGA3/CD9 and YK4 double-positive cases. Two types of metastatic trait were found in OSCC: locoregional dissemination, which was reflected by high-ITGA3/CD9, and distant metastasis through hematogenous dissemination, uniquely distinguished by high-ITGB4/JUP. The clinical significance of the integrin biomarkers implies that biological mechanisms such as cancer cell motility and anchorage-independent survival are vital for OSCC recurrence and metastasis

  14. Locoregional Anesthesia for Carotid Endarterectomy: Identification of Patients with Intolerance to Cross-Clamping.

    Science.gov (United States)

    Dellaretti, Marcos; de Vasconcelos, Laura T; Dourado, Jules; de Souza, Renata F; Fontoura, Renato R; de Sousa, Atos A

    2016-03-01

    During carotid endarterectomy (CEA), carotid cross-clamping is performed to allow for artery incision and plaque removal. A small subgroup of patients can tolerate carotid occlusion for only a few seconds, if at all, without presenting neurologic deficit. These patients are described as having ''cross-clamp intolerance.'' The purpose of this study was to demonstrate the safety of locoregional anesthesia in identifying patients with cross-clamp intolerance and factors associated with this condition. From August 2008 to May 2010, 115 consecutive patients were submitted to CEA under locoregional anesthesia at the Santa Casa de Belo Horizonte; the procedure was performed by the main author. Patients who showed intolerance to internal carotid artery (ICA) occlusion for intolerance. Among the 115 participating patients, 9.6% (11 patients) showed intolerance to ICA occlusion and developed deficits in intolerance). The factor that was associated with cross-clamp intolerance was the mean degree of contralateral carotid stenosis, which was 57.5% for those who presented intolerance and 27.8% for those who tolerated ICA occlusion. Locoregional anesthesia is a safe method for identifying patients with cross-clamp intolerance. Patients with cross-clamp intolerance present contralateral stenosis that is greater on average than patients who readily tolerate carotid artery occlusion. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity.

    Science.gov (United States)

    Romano, K D; Pugh, K J; Trifiletti, D M; Libby, B; Showalter, T N

    In 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. From 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. Median followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. This comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  16. Fecundity, survival, and growth of the seahorse Hippocampus ingens (Pisces: Syngnathidae under semi-controlled conditions

    Directory of Open Access Journals (Sweden)

    A.A Ortega-Salas

    2006-12-01

    Full Text Available Estudiamos la fecundidad, supervivencia, y crecimiento del caballito de mar, Hippocampus ingens en condiciones semi-controladas. Tres machos reproductores silvestres de 14.8, 24.5 y 32.0 g produjeron 1 598, 1 703 y 1 658 jóvenes. La densidad utilizada fue de 12 jóvenes por acuario de 60 l. Se agruparon en 1, 12 y 20 días de nacidos por acuario. La supervivencia fue de 78.5, 38.1 y 41.0 % en 35 días. Se les alimentó con una mezcla de rotíferos B. plicatilis y nauplios de Artemia para después transferirlos a estanques de 100 000 l a una densidad de 50/1 000 l, donde se les alimentó con Artemia adulta durante 60 días más. Crecieron de un promedio de 0.7, 1.5, y 2.7 a 4.5, 5.4 6.7 cm, respectivamente, en 95 días. La temperatura del agua marina utilizada varió de 17 a 23 ºC.We studied fecundity, survival, and growth of the seahorse Hippocampus ingens under semi-controlled conditions. Three wild brood stock mature males of 14.8, 24.5, and 32.0 g released 1 598, 1 703, and 1 658 juveniles. Juvenile stocking densities of 12 were settled in 60-l aquariums in groups of 1, 12, and 20 days old organisms. The rate of survival was 21.5, 61.9, and 59.0 %, respectively, in 35 days. Juveniles were fed a mix diet of rotifers B. plicatilis and Artemia nauplii, then they were transferred to a cement tank of 100 000 l at a density of 50/1 000 l and fed with live adult Artemia for 60 days more. They grew from an average of 0.7, 1.5, and 2.7 to 4.5, 5.4, and 6.7 cm, respectively, in 95 days. The seawater temperature varied from 17 to 23 ºC. Rev. Biol. Trop. 54 (4: 1099-1102. Epub 2006 Dec. 15.

  17. Efficacy of argon plasma coagulation for locoregional relapse after chemoradiotherapy for esophageal cancer

    International Nuclear Information System (INIS)

    Kikuchi, Yoshinori; Domon, Kaoru; Otsuka, Takafumi

    2011-01-01

    Salvage therapy for residual or relapsed esophageal cancer after chemoradiotherapy (CRT) has not yet been established. We retrospectively evaluated relapse-free survival (RFS) after local recurrence following CRT and local control rate in patients who underwent argon plasma coagulation (APC). We reviewed the records of 14 patients who underwent APC after CRT for esophageal cancer at our department between 2001 and 2010 and analyzed overall survival (OS), 5-year survival rate, local control rate after APC and RFS-defined as the period between the end of CRT and the time when an iodine-negative area was found. Median OS and median RFS (mRFS) were 33 months and 6 months, respectively. The 5-year survival rate was 16.2%, and the local control rate after APC was 71.4% (10/14). RFS was significantly longer in the T1 group than in the T2/T3 group (p=0.03); the local control rate after APC did not significantly differ between groups. The high-dose (HD) radiation group had a significantly longer RFS and a tendency toward a higher local control rate after APC than did the standard-dose (SD) radiation group. APC was safe and resulted in a high rate of local control, regardless of T factor. HD radiation was associated with longer RFS and greater efficacy of APC treatment for local recurrence. (author)

  18. Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zheng Jijun; Wang Ge; Yang, G.Y.

    2010-01-01

    This Phase II study was conducted to evaluate the activity and feasibility of a regimen of nedaplatin and 5-fluorouracil as induction chemotherapy, followed by intensity-modulated radiotherapy concurrent with chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Patients received neoadjuvant chemotherapy comprised two cycles of 5-fluorouracil at 700 mg/m 2 /day administered on days 1-4 as continuous intravenous infusion and nedaplatin (100 mg/m 2 administered intravenous (i.v.) over 2 h) given after the administration of 5-fluorouracil on day 1, repeated every 3 weeks, followed by intensity-modulated radiotherapy concurrent with nedaplatin. During intensity-modulated radiotherapy, nedaplatin was administered at a dose of 100 mg/m 2 intravenous infusion on days 1, 22 and 43, given -60 min before radiation. Fifty-nine (95.8%) of the 60 patients were assessable for response. Thirty-eight cases of complete response and 14 cases of partial response were confirmed after completion of chemoradiation, with the objective response rate of 86.7% (95% confidence interval (CI), 78.1-95.3%). The median follow-up period was 48 months (range, 30-62 months). The 3-year progression-free survival and overall survival were 75.0% (95% CI, 63.0-87.0%) and 85.5% (95% CI, 75.9-95.1%). No patient showed Grade 3 or higher renal dysfunction. The most commonly observed late effect was xerostomia, but the severity diminished over time, and the detectable xerostomia at 24 months was 10.2%. There were no treatment-related deaths during this study. Neoadjuvant chemotherapy with nedaplatin and 5-fluorouracil followed by concomitant nedaplatin and intensity-modulated radiotherapy is an effective and safe treatment for Southern China patients affected by locoregionally advanced nasopharyngeal carcinoma. (author)

  19. Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?

    International Nuclear Information System (INIS)

    Poulsen, Michael G.; Rischin, Danny; Porter, Ian; Walpole, Euan; Harvey, Jennifer; Hamilton, Chris; Keller, Jacqui; Tripcony, Lee

    2006-01-01

    Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m 2 i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For

  20. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

    2010-01-01

    as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

  1. Aspect controls the survival of ice cliffs on debris-covered glaciers.

    Science.gov (United States)

    Buri, Pascal; Pellicciotti, Francesca

    2018-04-24

    Supraglacial ice cliffs exist on debris-covered glaciers worldwide, but despite their importance as melt hot spots, their life cycle is little understood. Early field observations had advanced a hypothesis of survival of north-facing and disappearance of south-facing cliffs, which is central for predicting the contribution of cliffs to total glacier mass losses. Their role as windows of energy transfer suggests they may explain the anomalously high mass losses of debris-covered glaciers in High Mountain Asia (HMA) despite the insulating debris, currently at the center of a debated controversy. We use a 3D model of cliff evolution coupled to very high-resolution topographic data to demonstrate that ice cliffs facing south (in the Northern Hemisphere) disappear within a few months due to enhanced solar radiation receipts and that aspect is the key control on cliffs evolution. We reproduce continuous flattening of south-facing cliffs, a result of their vertical gradient of incoming solar radiation and sky view factor. Our results establish that only north-facing cliffs are recurrent features and thus stable contributors to the melting of debris-covered glaciers. Satellite observations and mass balance modeling confirms that few south-facing cliffs of small size exist on the glaciers of Langtang, and their contribution to the glacier volume losses is very small ([Formula: see text]1%). This has major implications for the mass balance of HMA debris-covered glaciers as it provides the basis for new parameterizations of cliff evolution and distribution to constrain volume losses in a region where glaciers are highly relevant as water sources for millions of people.

  2. Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: A systematic review

    International Nuclear Information System (INIS)

    Pieters, Bradley R.; Back, Djuna Z. de; Koning, Caro C.E.; Zwinderman, Aeilko H.

    2009-01-01

    Background and Purpose: For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be given by dose-escalated external beam radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or high-dose rate (HDR) brachytherapy (EBTI). Differences in outcome between the modalities were assessed by a systematic review. Materials and methods: A systematic search was performed resulting in 40 articles to be used. Data were extracted on biochemical control and overall survival at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. Comparison of the modalities was done by a Weibull survival analysis and estimation of Hazard Ratio's (HR) was done with 95% confidence intervals (95% CIs). Results: The HR for biochemical recurrence was 1.40 (95% CI 1.31-1.51) for EBRT relative to EBTI, and was 1.37 (95% CI 1.26-1.49) for EBSeeds relative to EBTI. The HR for overall survival was 1.50 (95% CI 1.29-1.73) for EBRT relative to EBTI, and was 2.33 (95% CI 2.04-2.66) for EBSeeds relative to EBTI. Conclusion: The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer.

  3. Strontium-89 for prostate cancer with bone metastases. The potential of cancer control and improvement of overall survival

    International Nuclear Information System (INIS)

    Kuroda, Isao

    2014-01-01

    Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using prostate specific antigen (PSA) as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected. (author)

  4. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. A matched-pair multicenter analysis of outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yi-Yuan [Affiliated Hospital of Guilin Medical University, Department of Radiation Oncology, Guilin (China); Guilin Medical University Affiliated Hospital, Department of Otorhinolaryngology, Guilin (China); Xiang, Chun [Nan Xishan Hospital, Department of Otorhinolaryngology, Guilin (China); Lu, Jian-Xun [Affiliated Hospital of Youjiang Medical University for Nationalities, Department of Oncology, Baise (China); Su, Yi-Xin [Lingshan People' s Hospital, Department of Radiation Oncology, Lingshan (China); Pan, Yu-Fei [Nan Xishan Hospital, Department of Radiation Oncology, Guilin (China); Cai, Rui; Zhang, Rong-Jun; He, Zhuo-Kai; Liu, Mei-Lian; Huang, Hui; Bai, Xue; Tang, Hua-Ying; Shi, Yun-Hua; Wang, Yan; Jiang, Wei [Affiliated Hospital of Guilin Medical University, Department of Radiation Oncology, Guilin (China)

    2016-06-15

    The benefit of adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (NPC) is controversial. This study compared concurrent chemoradiotherapy plus AC (CCRT/AC) with CCRT. Pair-matched analysis based on eight clinicopathological features of 244 patients treated with platinum-based CCRT/AC or CCRT alone was performed. Survival outcomes were assessed using the Kaplan-Meier method and log-rank test. Toxicities and response rates were compared using Fisher's exact test. Four-year overall survival, progression-free survival, distant failure-free survival, and locoregional failure-free survival were 72 %, 61 %, 71 %, and 81 %, respectively, for the CCRT arm, compared to 74 % (hazard ratio, HR 0.89; 95 % confidence interval, CI 0.64-1.23; P = 0.474), 62 % (HR 0.91, 95 % CI 0.68-1.20, P = 0.489), 73 % (HR 0.84, 95 % CI 0.59-1.18, P = 0.316), and 84 % (HR 0.84, 95 % CI 0.52-1.24, P = 0.323), respectively, for the CCRT/AC arm. Cox multivariate regression analysis demonstrated AC was not an independent prognostic factor. Overall, there was a higher incidence of grade 3-4 toxicities in the CCRT/AC arm. The most common grade 3-4 adverse events in the CCRT/AC arm were vomiting (27 %), nausea (43 %), leukopenia/neutropenia (23 %), thrombocytopenia (8.8 %), and anemia (6.2 %). Addition of AC to CCRT increased toxicities but did not improve survival in locoregionally advanced NPC. (orig.) [German] Der Nutzen der adjuvanten Chemotherapie (AC) bei lokoregional fortgeschrittenem nasopharyngealem Karzinom (NPC) ist kontrovers. In dieser Studie wurde die simultane Radiochemotherapie (''concurrent chemoradiotherapy'', CCRT) plus adjuvante Chemotherapie (AC) mit einer alleinigen CCRT verglichen. Die Matched-pair-Analyse basiert auf acht klinisch-pathologischen Merkmalen von 244 Patienten, die mit platinbasierter CCRT/AC oder alleiniger CCRT behandelt wurden. Die Ueberlebensendpunkte wurden mit der Kaplan-Meier-Methode und dem Log

  5. Local Control and Survival Following Concomitant Chemoradiotherapy in Inoperable Stage I Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Campeau, Marie-Pierre; Herschtal, Alan; Wheeler, Greg; Mac Manus, Michael; Wirth, Andrew; Michael, Michael; Hogg, Annette; Drummond, Elizabeth; Ball, David

    2009-01-01

    Purpose: Concomitant chemoradiotherapy (CRT) increases survival rates compared with radical radiotherapy alone (RT) in Stage III non-small-cell lung cancer (NSCLC), as a result of improved local control. The effect of CRT on local control in Stage I NSCLC is less well documented. We retrospectively reviewed local control and survival following CRT or RT for inoperable Stage I NSCLC patients. Methods and materials: Eligible patients had histologically/cytologically proved inoperable Stage I NSCLC and had undergone complete staging investigations including an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Radiotherapy was planned as (1) 60 Gy in 30 fractions over 6 weeks with or without concomitant chemotherapy or (2) 50-55 Gy in 20 fractions without chemotherapy. Results: Between 2000 and 2005, 73 patients met the eligibility criteria and were treated as follows: CRT (60 Gy)-39; RT (60 Gy)-23; RT (50-55 Gy)-11. The median follow-up time for all patients was 18 months (range, 1-81 months). Survival analysis was based on intent to treat. Local progression-free survival (PFS) at 2 years was 66% with CRT and 55% with RT. The 2-year distant PFS was 60% following CRT and 63% after RT. The 2-year PFS rates were 57% and 50%, respectively. The 2-year survival rate for patients treated with CRT was 57% and 33% in patients receiving RT. Conclusions: Despite the use of CRT and routine staging with FDG-PET, both local and distant recurrences remain important causes of treatment failure in patients with inoperable stage I NSCLC.

  6. Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

    Directory of Open Access Journals (Sweden)

    Sema eKurtulus

    2013-01-01

    Full Text Available Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of

  7. Locoregional Recurrence of Breast Cancer in Patients Treated With Breast Conservation Surgery and Radiotherapy Following Neoadjuvant Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Min, Sun Young [Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Surgery, Kyung Hee University, Seoul (Korea, Republic of); Lee, Seung Ju [Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Shin, Kyung Hwan, E-mail: radiat@ncc.re.kr [Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Park, In Hae; Jung, So-Youn; Lee, Keun Seok; Ro, Jungsil; Lee, Seeyoun; Kim, Seok Won [Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Tae Hyun [Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kang, Han-Sung [Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Cho, Kwan Ho [Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2011-12-01

    Purpose: Breast conservation surgery (BCS) and radiotherapy (RT) following neoadjuvant chemotherapy (NCT) have been linked with high locoregional recurrence (LRR) rates and ipsilateral breast tumor recurrence (IBTR) rates. The purpose of this study was to analyze clinical outcomes in patients who exhibited LRR and IBTR after being treated by BCS and RT following NCT. Methods and Materials: In total, 251 breast cancer patients treated with BCS and RT following NCT between 2001 and 2006 were included. All patients had been shown to be clinically node-positive. Clinical stage at diagnosis (2003 AJCC) was II in 68% of patients and III in 32% of patients. Of those, 50%, 35%, and 15% of patients received anthracycline-based, taxane-based, and combined anthracycline-taxane NCT, respectively. All patients received RT. Results: During follow-up (median, 55 months), 26 (10%) patients had LRR, 19 of these patients had IBTR. Five-year actuarial rates of IBTR-free and LRR-free survival were 91% and 89%, respectively. In multivariate analyses, lack of hormone suppression therapy was found to increase both LRR and IBTR rates. Hazard ratios were 7.99 (p < 0.0001) and 4.22 (p = 0.004), respectively. Additionally, pathology stage N2 to N3 increased LRR rate (hazard ratio, 4.22; p = 0.004), and clinical AJCC stage III IBTR rate (hazard ratio, 9.05; p = 0.034). Achievement of pathological complete response and presence of multifocal tumors did not affect LRR or IBTR. Conclusions: In patients with locally advanced disease, who were clinically node-positive at presentation, BCS after NCT resulted in acceptably low rates of IBTR and LRR. Mastectomy should be considered as an option in patients who present with clinical stage III tumors or who are not treated with adjuvant hormone suppression therapy, because they exhibit high IBTR rates after NCT and BCS.

  8. Locoregional Recurrence of Breast Cancer in Patients Treated With Breast Conservation Surgery and Radiotherapy Following Neoadjuvant Chemotherapy

    International Nuclear Information System (INIS)

    Min, Sun Young; Lee, Seung Ju; Shin, Kyung Hwan; Park, In Hae; Jung, So-Youn; Lee, Keun Seok; Ro, Jungsil; Lee, Seeyoun; Kim, Seok Won; Kim, Tae Hyun; Kang, Han-Sung; Cho, Kwan Ho

    2011-01-01

    Purpose: Breast conservation surgery (BCS) and radiotherapy (RT) following neoadjuvant chemotherapy (NCT) have been linked with high locoregional recurrence (LRR) rates and ipsilateral breast tumor recurrence (IBTR) rates. The purpose of this study was to analyze clinical outcomes in patients who exhibited LRR and IBTR after being treated by BCS and RT following NCT. Methods and Materials: In total, 251 breast cancer patients treated with BCS and RT following NCT between 2001 and 2006 were included. All patients had been shown to be clinically node-positive. Clinical stage at diagnosis (2003 AJCC) was II in 68% of patients and III in 32% of patients. Of those, 50%, 35%, and 15% of patients received anthracycline-based, taxane-based, and combined anthracycline-taxane NCT, respectively. All patients received RT. Results: During follow-up (median, 55 months), 26 (10%) patients had LRR, 19 of these patients had IBTR. Five-year actuarial rates of IBTR-free and LRR-free survival were 91% and 89%, respectively. In multivariate analyses, lack of hormone suppression therapy was found to increase both LRR and IBTR rates. Hazard ratios were 7.99 (p < 0.0001) and 4.22 (p = 0.004), respectively. Additionally, pathology stage N2 to N3 increased LRR rate (hazard ratio, 4.22; p = 0.004), and clinical AJCC stage III IBTR rate (hazard ratio, 9.05; p = 0.034). Achievement of pathological complete response and presence of multifocal tumors did not affect LRR or IBTR. Conclusions: In patients with locally advanced disease, who were clinically node-positive at presentation, BCS after NCT resulted in acceptably low rates of IBTR and LRR. Mastectomy should be considered as an option in patients who present with clinical stage III tumors or who are not treated with adjuvant hormone suppression therapy, because they exhibit high IBTR rates after NCT and BCS.

  9. Survival analysis of postoperative nausea and vomiting in patients receiving patient-controlled epidural analgesia

    Directory of Open Access Journals (Sweden)

    Shang-Yi Lee

    2014-11-01

    Conclusion: Survival analysis using Cox regression showed that the average consumption of opioids played an important role in postoperative nausea and vomiting, a result not found by logistic regression. Therefore, the incidence of postoperative nausea and vomiting in patients cannot be reliably determined on the basis of a single visit at one point in time.

  10. Local control and survival after external irradiation for adenocarcinoma of the prostate

    International Nuclear Information System (INIS)

    Rangala, N.; Cox, J.D.; Byhardt, R.W.; Wilson, J.F.; Greenberg, M.; Conceicao, A.L.D.

    1982-01-01

    From 1966 through 1978, 128 patients with biopsy-proven adenocarcinoma of the prostate underwent external irradiation to the entire pelvis followed by additional irradiation with a field that encompassed the entire prostate with generous margins. Local recurrence was diagnosed when palpable regrowth occurred and was confirmed by biopsy. Eighteen patients (14%) had local recurrence. Actuarial (life table) local recurrence rates, however, were 24% for both for Stage B and C patients. Actuarial five year survival was 100% for the 10 Stage A patients, 91% for the 25 Stage B, and 78% for the 93 Stage C patients. Actuarial five year disease-free survival was 59% for Stage B and 69% for Stage C patients. Local recurrence was affected by the total dose to the whole pelvis and the dose at the center of the prostate. Disease-free survival was influenced by differentiation. High dose external irradiation to the prostate and regional lymph nodes offers the greatest probability of long-term disease-free survival for patients with localized disease. Late bowel complications were seen in 14 patients (11%), two of whom required colostomies. Late urinary tract complications were observed in five patients (4%)

  11. Differences in Breast Cancer Survival between Public and Private Care in New Zealand: Which Factors Contribute?

    Science.gov (United States)

    Tin Tin, Sandar; Elwood, J Mark; Lawrenson, Ross; Campbell, Ian; Harvey, Vernon; Seneviratne, Sanjeewa

    2016-01-01

    Patients who received private health care appear to have better survival from breast cancer compared to those who received public care. This study investigated if this applied to New Zealand women and identified factors that could explain such disparities. This study involved all women who were diagnosed with primary breast cancer in two health regions in New Zealand, covering about 40% of the national population, between June 2000 and May 2013. Patients who received public care for primary treatment, mostly surgical treatment, were compared with those who received private care in terms of demographics, mode of presentation, disease factors, comorbidity index and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of breast cancer specific mortality associated with the type of health care received was assessed. Of the 14,468 patients, 8,916 (61.6%) received public care. Compared to patients treated in private care facilities, they were older, more likely to be Māori, Pacifika or Asian and to reside in deprived neighbourhoods and rural areas, and less likely to be diagnosed with early staged cancer and to receive timely cancer treatments. They had a higher risk of mortality from breast cancer (hazard ratio: 1.95; 95% CI: 1.75, 2.17), of which 80% (95% CI: 63%, 100%) was explained by baseline differences, particularly related to ethnicity, stage at diagnosis and type of loco-regional therapy. After controlling for these demographic, disease and treatment factors, the risk of mortality was still 14% higher in the public sector patients. Ethnicity, stage at diagnosis and type of loco-regional therapy were the three key contributors to survival disparities between patients treated in public and private health care facilities in New Zealand. The findings underscore the need for more efforts to improve the quality, timeliness and equitability of public cancer care services.

  12. Locoregional mitomycin C injection for esophageal stricture after endoscopic submucosal dissection.

    Science.gov (United States)

    Machida, H; Tominaga, K; Minamino, H; Sugimori, S; Okazaki, H; Yamagami, H; Tanigawa, T; Watanabe, K; Watanabe, T; Fujiwara, Y; Arakawa, T

    2012-06-01

    This prospective study aimed to evaluate the feasibility and safety of locoregional mitomycin C (MMC) injection to treat refractory esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal carcinoma. Patients with dysphagia and strictures that were refractory to repeated endoscopic balloon dilation (EBD) were eligible. After EBD, MMC was injected into the dilated site. Between June 2009 and August 2010, five patients were recruited. The treatment was performed once in two patients and twice in three patients with recurrent dysphagia or restenosis. In all patients, passing a standard endoscope through the site was easy and the dysphagia grade improved (grade 3→1 in 3 patients, grade 4→2 in 2 patients). No serious complications were noted. During the observation period of 4.8 months, neither recurrent dysphagia nor re-stricture appeared in any of the patients. The combination of locoregional MMC injections and EBD is feasible and safe for the treatment of esophageal strictures after ESD.Recently, endoscopic submucosal dissection (ESD) has been developed and accepted as a new endoscopic treatment for gastrointestinal tumors. ESD is a promising treatment for superficial esophageal carcinoma (SEC), and it has a reliable en bloc resection rate. However, the application of ESD for widespread lesions is challenging because of the high risk of the development of severe strictures, which lead to a low quality of life after ESD. Although endoscopic balloon dilation (EBD) is effective for benign strictures, it needs to be performed frequently until the dysphagia disappears 1. Mitomycin C (MMC), which is a chemotherapeutic agent derived from some Streptomyces species 2, reduces scar formation when topically applied to a surgical lesion. MMC has been applied to treat strictures in a variety of anatomical locations, including a variety of organs 3. The aim of this study was to prospectively evaluate both the feasibility and the safety of

  13. Novel Multisensor Probe for Monitoring Bladder Temperature During Locoregional Chemohyperthermia for Nonmuscle-Invasive Bladder Cancer: Technical Feasibility Study

    Science.gov (United States)

    Geijsen, Debby E.; Zum Vörde Sive Vörding, Paul J.; Schooneveldt, Gerben; Sijbrands, Jan; Hulshof, Maarten C.; de la Rosette, Jean; de Reijke, Theo M.; Crezee, Hans

    2013-01-01

    Abstract Background and Purpose: The effectiveness of locoregional hyperthermia combined with intravesical instillation of mitomycin C to reduce the risk of recurrence and progression of intermediate- and high-risk nonmuscle-invasive bladder cancer is currently investigated in clinical trials. Clinically effective locoregional hyperthermia delivery necessitates adequate thermal dosimetry; thus, optimal thermometry methods are needed to monitor accurately the temperature distribution throughout the bladder wall. The aim of the study was to evaluate the technical feasibility of a novel intravesical device (multi-sensor probe) developed to monitor the local bladder wall temperatures during loco-regional C-HT. Materials and Methods: A multisensor thermocouple probe was designed for deployment in the human bladder, using special sensors to cover the bladder wall in different directions. The deployment of the thermocouples against the bladder wall was evaluated with visual, endoscopic, and CT imaging in bladder phantoms, porcine models, and human bladders obtained from obduction for bladder volumes and different deployment sizes of the probe. Finally, porcine bladders were embedded in a phantom and subjected to locoregional heating to compare probe temperatures with additional thermometry inside and outside the bladder wall. Results: The 7.5 cm thermocouple probe yielded optimal bladder wall contact, adapting to different bladder volumes. Temperature monitoring was shown to be accurate and representative for the actual bladder wall temperature. Conclusions: Use of this novel multisensor probe could yield a more accurate monitoring of the bladder wall temperature during locoregional chemohyperthermia. PMID:24112045

  14. Carotid endarterectomy: review of 10 years of practice of general and locoregional anesthesia in a tertiary care hospital in Portugal

    Directory of Open Access Journals (Sweden)

    Mercês Lobo

    2015-08-01

    Full Text Available BACKGROUND: Retrospective and prospective randomized studies have compared general and locoregional anesthesia for carotid endarterectomy, but without definitive results.OBJECTIVES: Evaluate the incidence of complications (medical, surgical, neurological, and hospital mortality in a tertiary center in Portugal and review the literature.METHODS: Retrospective analysis of patients undergoing endarterectomy between 2000 and 2011, using a software for hospital consultation.RESULTS: A total of 750 patients were identified, and locoregional anesthesia had to be converted to general anesthesia in 13 patients. Thus, a total of 737 patients were included in this analysis: 74% underwent locoregional anesthesia and 26% underwent general anesthesia. There was no statistically significant difference between the two groups regarding per operative variables. The use of shunt was more common in patients undergoing general anesthesia, a statistically significant difference. The difference between groups of strokes and mortality was not statistically significant. The average length of stay was shorter in patients undergoing locoregional anesthesia with a statistically significant difference.CONCLUSIONS: We found that our data are overlaid with the literature data. After reviewing the literature, we found that the number of studies comparing locoregional and general anesthesia and its impact on delirium, cognitive impairment, and decreased quality of life after surgery is still very small and can provide important data to compare the two techniques. Thus, some questions remain open, which indicates the need for randomized studies with larger number of patients and in new centers.

  15. The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins.

    Science.gov (United States)

    Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

    2011-02-01

    To quantify the impact of excision margins on disease-specific survival of patients with primary cutaneous melanoma. Current guidelines recommend narrow margins for the treatment of primary melanoma, although available evidence on this subject is not unequivocal and not always appropriately analyzed. A systematic review of randomized controlled trials (RCT) addressing the issue of wide versus narrow excision margins was performed. Meta-analysis methods for time-to-event data were used to extract hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies, and ultimately to estimate the summary effect of excision margins on patients' survival. The 5 eligible RCT enrolled a total of 3295 patients who were allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor. The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT, respectively. The meta-analysis suggested that narrow margins might be associated with an increased risk of both locoregional disease recurrence (HR: 1.30, CI: 1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06) becomes significant when considering RCT that enrolled patients with thicker melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was analyzed, no risk difference was found. The lack of DSS data from all the available RCT does not allow to draw definitive conclusions. However, current evidence appears sufficient to question the common belief that narrow excision margins are as safe as wide margins in the management of primary melanoma, that calls for further investigation in this field.

  16. Childhood craniopharyngioma: survival, local control, endocrine and neurologic function following radiotherapy

    International Nuclear Information System (INIS)

    Danoff, B.F.; Cowchock, F.S.; Kramer, S.

    1983-01-01

    Between 1961 and 1978, 19 patients with a diagnosis of childhood or teenage craniopharyngioma received supervoltage radiotherapy. All patients had previously undergone either partial surgical resection (10 patients), total gross resection (3 patients), or aspiration and biopsy (6 patients). Fourteen patients were treated primarily and five were treated for recurrence. The five-year survival was 73% with a 10-year survival of 64%. Sixteen percent developed a recurrence following radiotherapy. Long term effects were assesed in terms of neurologic, intellectual, psychological and endocrine function. Seventy-nine percent had none or minimal neurologic disability. The mean full scale IQ for the group was 90. There were no additional endocrine deficiencies that could be directly attributed to radiation. Behavioral disorders occurred in 50%. These results are at least comparable, if not superior, to those of surgery

  17. Impact of point A asymmetry on local control and survival for low dose-rate (LDR) brachytherapy in cervical cancer.

    Science.gov (United States)

    Opfermann, Krisha J; Wahlquist, Amy; Watkins, John; Kohler, Matthew; Jenrette, Joseph

    2012-03-01

    To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS). A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest. The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS. LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.

  18. Treatment outcome and prognostic variables for local control and survival in patients receiving radical radiotherapy for urinary bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fokdal, Lars; Hoeyer, Morten; Maase, Hans von der [Aarhus Univ. Hospital (Denmark). Dept. of Oncology

    2004-12-01

    The aim of this retrospective study was to analyze the outcome of radical radiotherapy in 292 patients with bladder cancer and to identify prognostic factors for local control and survival. Median age was 72.3 years (range 45-83 years). Median follow up was 66 months (range 18-121 months). All patients were treated by use of a standard 3-field technique with 60 Gy in 30 fractions to the tumor and the bladder. The elective lymph nodes were treated with doses in the range from 46 Gy to 60 Gy. Complete response was obtained in 52% of the patients at 3-month control. However, 41% of all patients with an initial CR developed recurrence during follow-up. The 3-year and 5-year overall survival rate was 31% and 21%, respectively. Performance status, T-stage, macroscopic complete TURB, hydronephrosis, and serum creatinine were independent prognostic factors for overall survival and, thus, important for the selection of patients for curative intended radiotherapy. During radiotherapy acute transient side effects were recorded in 78% of the patients; severe bowel complications were recorded in 9 patients (3%). Following radiotherapy, 10 patients (3%) developed intestinal reactions requiring surgery. Three patients (1%) were cystectomized because of severe radiation reactions in the bladder. At 5-year follow-up, the actuarial risk of complications requiring surgery was 15%. Treatment-related mortality was 2%.

  19. MicroRNA-125b-5p suppresses Brucella abortus intracellular survival via control of A20 expression.

    Science.gov (United States)

    Liu, Ning; Wang, Lin; Sun, Changjiang; Yang, Li; Sun, Wanchun; Peng, Qisheng

    2016-07-29

    Brucella may establish chronic infection by regulating the expression of miRNAs. However, the role of miRNAs in modulating the intracellular growth of Brucella remains unclear. In this study, we show that Brucella. abortus infection leads to downregulation of miR-125b-5p in macrophages. We establish that miR-125b-5p targets A20, an inhibitor of the NF-kB activation. Additionally, expression of miR-125b-5p decreases A20 expression in B. abortus-infected macrophages and leads to NF-kB activation and increased production of TNFα. Furthermore, B. abortus survival is attenuated in the presence of miR-125b-5p. These results uncover a role for miR-125b-5p in the regulation of B. abortus intracellular survival via the control of A20 expression.

  20. The Norwegian dietary guidelines and colorectal cancer survival (CRC-NORDIET) study: a food-based multicentre randomized controlled trial.

    Science.gov (United States)

    Henriksen, Hege Berg; Ræder, Hanna; Bøhn, Siv Kjølsrud; Paur, Ingvild; Kværner, Ane Sørlie; Billington, Siv Åshild; Eriksen, Morten Tandberg; Wiedsvang, Gro; Erlund, Iris; Færden, Arne; Veierød, Marit Bragelien; Zucknick, Manuela; Smeland, Sigbjørn; Blomhoff, Rune

    2017-01-30

    Colorectal cancer survivors are not only at risk for recurrent disease but also at increased risk of comorbidities such as other cancers, cardiovascular disease, diabetes, hypertension and functional decline. In this trial, we aim at investigating whether a diet in accordance with the Norwegian food-based dietary guidelines and focusing at dampening inflammation and oxidative stress will improve long-term disease outcomes and survival in colorectal cancer patients. This paper presents the study protocol of the Norwegian Dietary Guidelines and Colorectal Cancer Survival study. Men and women aged 50-80 years diagnosed with primary invasive colorectal cancer (Stage I-III) are invited to this randomized controlled, parallel two-arm trial 2-9 months after curative surgery. The intervention group (n = 250) receives an intensive dietary intervention lasting for 12 months and a subsequent maintenance intervention for 14 years. The control group (n = 250) receives no dietary intervention other than standard clinical care. Both groups are offered equal general advice of physical activity. Patients are followed-up at 6 months and 1, 3, 5, 7, 10 and 15 years after baseline. The study center is located at the Department of Nutrition, University of Oslo, and patients are recruited from two hospitals within the South-Eastern Norway Regional Health Authority. Primary outcomes are disease-free survival and overall survival. Secondary outcomes are time to recurrence, cardiovascular disease-free survival, compliance to the dietary recommendations and the effects of the intervention on new comorbidities, intermediate biomarkers, nutrition status, physical activity, physical function and quality of life. The current study is designed to gain a better understanding of the role of a healthy diet aimed at dampening inflammation and oxidative stress on long-term disease outcomes and survival in colorectal cancer patients. Since previous research on the role of diet for

  1. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  2. Locoregional recurrences following radical external beam irradiation and interstitial implantation for operable breast cancer - a twenty three year experience

    International Nuclear Information System (INIS)

    Leung, S.; Otmezguine, Y.; Calitchi, E.; Mazeron, J.J.; Le Bourgeois, J.P.; Pierquin, B.

    1986-01-01

    Locoregional recurrences are reported in 493 consecutive with T1 T2 N0 N1 breast cancer patients who were treated with radical external beam irradiation and interstitial 192 Ir implant between 1961 and 1979. Follow-up ranges from 5-23 years (mean 10 years) with 195 patients having 10-23 years follow up (mean 12 years). There were 51 (10%) locoregional recurrences with 34 mammary, 14 combined mammary/axillary and 3 isolated axillary recurrences. The 10 year relapse rate was 20/195 (10%). The results have been compared with other series in the literature and changes in the authors' current protocol are described. (Auth.)

  3. Target area acquisition and control system survivability for the National Ignition Facility

    International Nuclear Information System (INIS)

    Hagans, K.; Stathis, P.; Wiedwald, J.; Campbell, D.

    1994-06-01

    The hardening of instruments to survive NIF target emission environments presents a significant challenge. Neutron flux is predicted to be as much as six orders of magnitude greater than the highest achieved neutron flux on NOVA. Not withstanding the high prompt radiation fields, the specifications for the instruments are demanding; requiring high resolution imaging and sub nanosecond transient measurements. We present an analysis of the sensitivity of the proposed NIF instrumentation design to EMP, X-rays, gamma rays, and neutrons. Major components assessed include fiber optic cable transport, high bandwidth cable and charge coupled detector (CCD) imaging systems

  4. Effects of Anticipation in Individually Motivated Behaviour on Survival and Control in a Multi-Agent Scenario with Resource Constraints

    Directory of Open Access Journals (Sweden)

    Christian Guckelsberger

    2014-06-01

    Full Text Available Self-organization and survival are inextricably bound to an agent’s ability to control and anticipate its environment. Here we assess both skills when multiple agents compete for a scarce resource. Drawing on insights from psychology, microsociology and control theory, we examine how different assumptions about the behaviour of an agent’s peers in the anticipation process affect subjective control and survival strategies. To quantify control and drive behaviour, we use the recently developed information-theoretic quantity of empowerment with the principle of empowerment maximization. In two experiments involving extensive simulations, we show that agents develop risk-seeking, risk-averse and mixed strategies, which correspond to greedy, parsimonious and mixed behaviour. Although the principle of empowerment maximization is highly generic, the emerging strategies are consistent with what one would expect from rational individuals with dedicated utility models. Our results support empowerment maximization as a universal drive for guided self-organization in collective agent systems.

  5. Impact of retropharyngeal adenopathy on distant control and survival in HPV-related oropharyngeal cancer treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Samuels, Stuart E.; Vainshtein, Jeffrey; Spector, Matthew E.; Ibrahim, Mohannad; McHugh, Jonathan B.; Tao, Yebin; Schipper, Matthew; Worden, Francis; Eisbruch, Avraham

    2015-01-01

    Purpose: Retropharyngeal adenopathy (RPA) is poor prognostic factor in head and neck (HN) cancer. However, the prognostic significance of RPA in Human Papillomavirus-related (HPV+) oropharyngeal cancer (OPC) is unknown. Patients and methods: 185 patients with HPV + OPC were assessed. Pre-therapy images reviewed by a HN radiologist to determine presence of RPA. Doses to the RPAs were determined from treatment plans. Outcomes analyzed using Kaplan–Meier method, log-rank tests, and correlations determined using Spearman’s rank analyses. Results: 29 (16%) of the HPV + patients had RPA. At median follow-up 49 months, 5-year overall survival (OS), failure-free survival (FFS) and distant failure-free survival (DFFS) were 57% vs. 81% (P = 0.02), 63% vs 80% (P = 0.015) and 70% vs 91% (P = 0.002) for patients with/without RPA, respectively. No differences observed in local/ regional control rates, exceeding 90% in both groups, and No RPA recurrences were observed. In multivariable analysis, stages T4 or N3, and RPA, were independently, statistically significantly associated with both OS and distant failure, while N2c, age, disease site, and smoking status, were not. Conclusion: RPA in HPV + OPC is an independent prognostic factor for distant failure, translating into worse OS. Patients with RPA may not be suitable candidates for trials of systemic treatment de-escalation

  6. Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells

    Science.gov (United States)

    Patzelt, Thomas; Keppler, Selina J.; Gorka, Oliver; Thoene, Silvia; Wartewig, Tim; Reth, Michael; Förster, Irmgard; Lang, Roland; Buchner, Maike; Ruland, Jürgen

    2018-01-01

    The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B cell lineage and report that Foxp1 disruption in developing and mature B cells results in reduced numbers and frequencies of follicular and B-1 B cells and in impaired antibody production upon T cell-independent immunization in vivo. Moreover, Foxp1-deficient B cells are impaired in survival even though they exhibit an increased capacity to proliferate. Transcriptional analysis identified defective expression of the prosurvival Bcl-2 family gene Bcl2l1 encoding Bcl-xl in Foxp1-deficient B cells, and we identified Foxp1 binding in the regulatory region of Bcl2l1. Transgenic overexpression of Bcl2 rescued the survival defect in Foxp1-deficient mature B cells in vivo and restored peripheral B cell numbers. Thus, our results identify Foxp1 as a physiological regulator of mature B cell survival mediated in part via the control of Bcl-xl expression and imply that this pathway might contribute to the pathogenic function of aberrant Foxp1 expression in lymphoma. PMID:29507226

  7. Altered G1 checkpoint control determines adaptive survival responses to ionizing radiation

    International Nuclear Information System (INIS)

    Boothman, David A.; Meyers, Mark; Odegaard, Eric; Wang, Meizhi

    1996-01-01

    Adaptive survival responses (ASRs) are observed when cells become more resistant to a high dose of a cytotoxic agent after repeated low dose exposures to that agent or another genotoxic agent. Confluent (G 0 /G 1 ) human normal (GM2936B, GM2937A, AG2603, IMR-90), cancer-prone (XPV2359), and neoplastic (U1-Mel, HEp-2, HTB-152) cells were primed with repeated low doses of X-rays (ranging from 0.05-10 cGy/day for 4 days), then challenged with a high dose (290-450 cGy) on day 5. U1-Mel and HEp-2 cells showed greater than 2-fold transient survival enhancement when primed with 1-10 cGy. ASRs in U1-Mel or HEp-2 cells were blocked by cycloheximide or actinomycin D. Increases in cyclins A and D1 mRNAs were noted in primed compared to unirradiated U1-Mel and HEp-2 cells; however, only cyclin A protein levels increased. Cyclin D1 and proliferating cell nuclear antigen (PCNA) protein levels were constitutively elevated in HEp-2 and U1-Mel cells, compared to the other human normal and neoplastic cells examined, and were not altered by low or high doses of radiation. Low dose primed U1-Mel cells entered S-phase 4-6 h faster than unprimed U1-Mel cells upon low-density replating. Similar responses in terms of survival recovery, transcript and protein induction, and altered cell cycle regulation were not observed in the other human normal, cancer-prone or neoplastic cells examined. We hypothesize that only certain human cells can adapt to ionizing radiation by progressing to a point later in G 1 (the A point) where DNA repair processes and radioresistance can be induced. ASRs in human cells correlated well with constitutively elevated levels of PCNA and cyclin D1, as well as inducibility of cyclin A. We propose that a protein complex composed of cyclin D1, PCNA, and possibly cyclin A may play a role in cell cycle regulation and DNA repair, which determine ASRs in human cells

  8. Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Minatel, Emilio [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Di Maso, Matteo [Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Drigo, Annalisa; Barresi, Loredana [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Furlan, Carlo [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Pordenone (Italy); Bruschi, Gioia [Department of Pneumology, Pordenone General Hospital, Pordenone (Italy); Fontana, Paolo [Department of Thoracic Surgery, Mestre General Hospital, Mestre (Italy); Pagan, Vittore [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Franchin, Giovanni [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy)

    2015-11-01

    Purpose: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and

  9. Data Acquistion Controllers and Computers that can Endure, Operate and Survive Cryogenic Temperatures, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Current and future NASA exploration flight missions require Avionics systems, Computers, Controllers and Data processing units that are capable of enduring extreme...

  10. Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    Science.gov (United States)

    Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-01-01

    Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days

  11. The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    International Nuclear Information System (INIS)

    Chen Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-01-01

    Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131 Cs, 125 I and 103 Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125 I sources was less affected by edema than PIB using 131 Cs or 103 Pd sources due to the long radioactive decay half-life of 125 I. The effect of edema on PIB using 131 Cs or 103 Pd was similar. The effect of edema on 103 Pd PIB was slightly greater, even though the decay half-life of 103 Pd (17 days) is

  12. Identification of a Novel TGFβ/PKA Signaling Transduceome in Mediating Control of Cell Survival and Metastasis in Colon Cancer

    Science.gov (United States)

    Rajput, Ashwani; Teggart, Carol A.; Brattain, Lisa E.; Weber, Hannah R.; Chowdhury, Aparajita; Brattain, Michael G.

    2011-01-01

    Background Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown. Methodology/Principal Findings Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival. Conclusion/Significance This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors. PMID:21559296

  13. Identification of a novel TGFβ/PKA signaling transduceome in mediating control of cell survival and metastasis in colon cancer.

    Directory of Open Access Journals (Sweden)

    Sanjib Chowdhury

    2011-05-01

    Full Text Available Understanding drivers for metastasis in human cancer is important for potential development of therapies to treat metastases. The role of loss of TGFβ tumor suppressor activities in the metastatic process is essentially unknown.Utilizing in vitro and in vivo techniques, we have shown that loss of TGFβ tumor suppressor signaling is necessary to allow the last step of the metastatic process - colonization of the metastatic site. This work demonstrates for the first time that TGFβ receptor reconstitution leads to decreased metastatic colonization. Moreover, we have identified a novel TGFβ/PKA tumor suppressor pathway that acts directly on a known cell survival mechanism that responds to stress with the survivin/XIAP dependent inhibition of caspases that effect apoptosis. The linkage between the TGFβ/PKA transduceome signaling and control of metastasis through induction of cell death was shown by TGFβ receptor restoration with reactivation of the TGFβ/PKA pathway in receptor deficient metastatic colon cancer cells leading to control of aberrant cell survival.This work impacts our understanding of the possible mechanisms that are critical to the growth and maintenance of metastases as well as understanding of a novel TGFβ function as a metastatic suppressor. These results raise the possibility that regeneration of attenuated TGFβ signaling would be an effective target in the treatment of metastasis. Our work indicates the clinical potential for developing anti-metastasis therapy based on inhibition of this very important aberrant cell survival mechanism by the multifaceted TGFβ/PKA transduceome induced pathway. Development of effective treatments for metastatic disease is a pressing need since metastases are the major cause of death in solid tumors.

  14. Vector control improves survival of three species of prairie dogs (Cynomys) in areas considered enzootic for plague

    Science.gov (United States)

    Biggins, Dean E.; Godbey, Jerry L.; Gage, Kenneth L.; Carter, Leon G.; Montenieri, John A.

    2010-01-01

    Plague causes periodic epizootics that decimate populations of prairie dogs (PDs) (Cynomys), but the means by which the causative bacterium (Yersinia pestis) persists between epizootics are poorly understood. Plague epizootics in PDs might arise as the result of introductions of Y. pestis from sources outside PD colonies. However, it remains possible that plague persists in PDs during interepizootic periods and is transmitted at low rates among highly susceptible individuals within and between their colonies. If this is true, application of vector control to reduce flea numbers might reduce mortality among PDs. To test whether vector control enhances PD survival in the absence of obvious plague epizootics, we reduced the numbers of fleas (vectors for Y. pestis) 96–98% (1 month posttreatment) on 15 areas involving three species of PDs (Cynomys leucurus, Cynomys parvidens in Utah, and Cynomys ludovicianus in Montana) during 2000–2004 using deltamethrin dust delivered into burrows as a pulicide. Even during years without epizootic plague, PD survival rates at dusted sites were 31–45% higher for adults and 2–34% higher for juveniles compared to survival rates at nondusted sites. Y. pestis was cultured from 49 of the 851 flea pools tested (6882 total fleas) and antibodies against Y. pestis were identified in serum samples from 40 of 2631 PDs. Although other explanations are possible, including transmission of other potentially fatal pathogens by fleas, ticks, or other ectoparasites, our results suggest that plague might be maintained indefinitely in PD populations in the absence of free epizootics and widespread mortality among these animals. If PDs and their fleas support enzootic cycles of plague transmission, there would be important implications for the conservation of these animals and other species.

  15. 188Re-Labeled Nimotuzumab in the Locoregional Treatment of Malignant Gliomas

    International Nuclear Information System (INIS)

    Montana, R. Leyva; Barrabi, M. Zamora; Casaco, A.; Torres, L.; Perera, A.; Lopez, G.

    2009-01-01

    A new formulation of 188 Re-Nimotuzumab was developed to evaluate the biodistribution, internal radiation dosimetry and safety in the locoregional treatment of malignant gliomas. A phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary administration of single dose of Nimotuzumab labeled with 188 Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Nine patients with anaplastic astrocytoma or glioblastoma multiforme were intended to be treated with 3 mg of mAb labeled with 10 or 15 mCi of 188 Re. The radioimmunoconjugated showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post- administration. No patient developed human anti-mouse antibody response. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. (author)

  16. Induction chemotherapy for locoregional lung cancer using paclitaxel combination. A preliminary report

    International Nuclear Information System (INIS)

    Takita, H.; Pitoniak, R.F.

    2000-01-01

    Induction chemotherapy has been reported to be effective in treatment of locally advanced, borderline resectable, (Stage III), non small cell lung carcinoma (NSCLC). A logical extension of the indication for the induction chemotherapy may be to treat earlier stage resectable lung cancers (stages I and II) because the cure rate of the resectable lung cancers still remains poor and is below 60% except for stage I A. Thirty eight patients with a diagnosis of loco-regional NSCLC were treated with paclitaxel combination chemotherapy. Following two courses of induction chemotherapy, patients underwent surgical therapy whenever possible. There ten patients with stage I disease, four patients with stage II, 13 with stage IIIA, nine had stage IIIB, and two with stage IV. An overall response rate of 74% was observed. The response rate for 14 resectable patients (stage I and II) was 86%. The chemotherapy regimen was well tolerated and apart from one instance of anaphylaxis, no serious side effects were observed

  17. Postoperative radiotherapy improves local control and survival in patients with uterine leiomyosarcoma

    International Nuclear Information System (INIS)

    Wong, Philip; Han, Kathy; Sykes, Jenna; Catton, Charles; Laframboise, Stephane; Fyles, Anthony; Manchul, Lee; Levin, Wilfred; Milosevic, Michael

    2013-01-01

    To examine the role of radiotherapy (RT) in uterine leiomyosarcomas (LMS) and to determine the patient population who may benefit from RT. From 1998–2008, 69 patients with primary uterine LMS underwent hysterectomy with or without pelvic radiotherapy to a median dose of 45 Gy. Univariate analysis was performed using the Kaplan-Meier method and cumulative-incidence function, and multivariate analyses using Fine and Gray or Cox proportional hazard models. Following surgery, 32 out of 69 patients received RT. There was no evidence of any correlation between patient, disease and treatment characteristics and the use of RT. Median follow-up was 57 months. RT was associated with reduced local recurrence (3y LR 19% vs. 39%; Gray’s p = 0.019) and improved overall survival (3y OS 69% vs. 35%; log-rank p = 0.025) on univariate analysis. Multivariate analysis demonstrated that RT reduced LR (HR: 0.28, CI: 0.11-0.69, p = 0.006) and increased OS (HR: 0.44, CI: 0.23-0.85, p = 0.014) independent of other clinical and pathologic factors. Positive surgical margins increased the odds of LR (HR: 5.6, CI: 2.3-13.4, p = 0.00012). Large tumor size and advanced stage (II-IV) were associated with the development of distant metastases and inferior OS. Postoperative pelvic RT reduces LR and improves OS of patients with uterine LMS

  18. Subjective Symptomology and Postural Control During Simulation of a Survival Environmemt Aboard a Disabled Submarine

    National Research Council Canada - National Science Library

    Cymerman, Allen

    2000-01-01

    Subjective symptoms and postural control were assessed in 7 submariners during 5 days exposure to a simulated disabled submarine environment (DISSUB) (4C, 2.5% carbon dioxide, 16.75% oxygen, 85% humidity...

  19. Loco-regional extensions of central nervous system germ cell tumors. A retrospective radiological analysis of 100 patients

    Energy Technology Data Exchange (ETDEWEB)

    Duron, Loic; Sadones, Flavie; Thiesse, Philippe; Cellier, Cecile; Alapetite, Claire [Institut Curie, Imaging Department, Paris (France); Doz, Francois [Institut Curie, Department of Pediatric, Adolescents and Young Adults Oncology, Paris (France); University Paris Descartes, Paris (France); Frappaz, Didier [Centre Leon Berard, Department of Adult and Pediatric Neuro-Oncology, Lyon (France); Brisse, Herve J. [Institut Curie, Imaging Department, Paris (France); Paris Sciences et Lettres Research University, Paris (France)

    2018-01-15

    The current staging system of central nervous system (CNS) germ cell tumors (GCT) includes a binary classification in ''localized'' or ''metastatic'' disease based on the absence or presence of leptomeningeal dissemination. Loco-regional tumor dissemination has been barely described whereas its accurate definition might be useful in terms of prognosis and treatment, especially for radiation therapy planning. Our purpose was therefore to describe MR patterns and prevalence of loco-regional extensions of these tumors. One hundred consecutive patients (median age 16.3 years, range 7-41 years, sex ratio 7:1) with a histologically or biologically proven CNS GCT were retrospectively included. Brain and spinal MRI at diagnosis were reviewed by two neuroradiologists focusing on MR patterns of primaries and loco-regional extensions. When available, follow-up MR exams were analyzed. Pure germinoma represented 84/100 cases. Primaries were unifocal pineal (n = 49/100), bifocal pineal and supra-sellar (n = 27/100), isolated supra-sellar (n = 21/100), isolated basal ganglia (n = 2/100) or trifocal pineal, supra-sellar, and basal ganglia (n = 1/100). Metastatic disease occurred in 6/100 patients (depicted by MRI in two and CSF cytology in four). Loco-regional extensions were observed in all patients and classified as follows: third ventricle (n = 88/100), thalamus (n = 47/100), midbrain (n = 42/100), distant sub-ependymal areas (n = 19/100), optic pathways (n = 19/100), lateral ventricles (n = 7/100), cavernous sinus (n = 6/100), corpus callosum (n = 4/100), and fourth ventricle (n = 3/100). CNS GCT present with specific loco-regional extensions at diagnosis. Improving their recognition will be helpful to further understand their prognostic value and potentially to optimize the treatment. (orig.)

  20. Control of mitochondrial pH by uncoupling protein 4 in astrocytes promotes neuronal survival

    KAUST Repository

    Lambert, Hélène Perreten

    2014-09-18

    Brain activity is energetically costly and requires a steady and highly regulated flow of energy equivalents between neural cells. It is believed that a substantial share of cerebral glucose, the major source of energy of the brain, will preferentially be metabolized in astrocytes via aerobic glycolysis. The aim of this study was to evaluate whether uncoupling proteins (UCPs), located in the inner membrane of mitochondria, play a role in setting up the metabolic response pattern of astrocytes. UCPs are believed to mediate the transmembrane transfer of protons, resulting in the uncoupling of oxidative phosphorylation from ATP production. UCPs are therefore potentially important regulators of energy fluxes. The main UCP isoforms expressed in the brain are UCP2, UCP4, and UCP5. We examined in particular the role of UCP4 in neuron-astrocyte metabolic coupling and measured a range of functional metabolic parameters including mitochondrial electrical potential and pH, reactive oxygen species production, NAD/NADH ratio, ATP/ADP ratio, CO2 and lactate production, and oxygen consumption rate. In brief, we found that UCP4 regulates the intramitochondrial pH of astrocytes, which acidifies as a consequence of glutamate uptake, with the main consequence of reducing efficiency of mitochondrial ATP production. The diminished ATP production is effectively compensated by enhancement of glycolysis. This nonoxidative production of energy is not associated with deleterious H2O2 production. We show that astrocytes expressing more UCP4 produced more lactate, which is used as an energy source by neurons, and had the ability to enhance neuronal survival.

  1. Early Response of Protein Quality Control in Gills Is Associated with Survival of Hypertonic Shock in Mozambique tilapia

    Science.gov (United States)

    Tang, Cheng-Hao; Lee, Tsung-Han

    2013-01-01

    The protein quality control (PQC) mechanism is essential for cell function and viability. PQC with proper biological function depends on molecular chaperones and proteases. The hypertonicity-induced protein damage and responses of PQC mechanism in aquatic organisms, however, are poorly understood. In this study, we examine the short-term effects of different hypertonic shocks on the levels of heat shock proteins (HSPs, e.g., HSP70 and HSP90), ubiquitin-conjugated proteins and protein aggregation in gills of the Mozambique tilapia (Oreochromis mossambicus). Following transfer from fresh water (FW) to 20‰ hypertonicity, all examined individuals survived to the end of experiment. Moreover, the levels of branchial HSPs and ubiquitin-conjugated proteins significantly increased at 3 and 24 h post-transfer, respectively. Up-regulation of HSPs and ubiquitin-conjugated proteins was sufficient to prevent the accumulation of aggregated proteins. However, the survival rate of tilapia dramatically declined at 5 h and all fish died within 7 h after direct transfer to 30‰ hypertonicity. We presumed that this result was due to the failed activation of gill PQC system, which resulted in elevating the levels of aggregated proteins at 3 and 4 h. Furthermore, in aggregated protein fractions, the amounts of gill Na+/K+-ATPase (NKA) remained relatively low when fish were transferred to 20‰ hypertonicity, whereas abundant NKA was found at 4 h post-transfer to 30‰ hypertonicity. This study demonstrated that the response of PQC in gills is earlier than observable changes in localization of ion-secreting transport proteins upon hypertonic challenge. To our knowledge, this is the first study to investigate the regulation of PQC mechanism in fish and characterize its important role in euryhaline teleost survival in response to hypertonic stress. PMID:23690986

  2. Using copper sulfate on hybrid striped bass eggs to control fungus and increase survival

    Science.gov (United States)

    A major obstacle in fish hatcheries is the inevitable fungal growth on eggs. Copper sulfate (CuSO4) is commonly used for fungus control in channel catfish hatcheries that use troughs, but effectiveness on fish eggs hatched using different systems has only recently been investigated. Fish were spawn...

  3. Wnt modulates MCL1 to control cell survival in triple negative breast cancer

    International Nuclear Information System (INIS)

    Yang, Lixin; Zhang, Hang; Zheng, Shu; Liu, Zheng; Ann, David; Yen, Yun; Perez, Aldwin Apollo; Fujie, Sayuri; Warden, Charles; Li, Jie; Wang, Yafan; Yung, Bryan; Chen, Yun-Ru; Liu, Xiyong

    2014-01-01

    enhanced metastasis and decreased disease-free survival. All our findings suggested that WNT5B/MCL1 cascade is critical for TNBC and understanding its regulatory apparatus provided valuable insight into the pathogenesis of the tumor development and the guidance for targeting therapeutics

  4. Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study

    OpenAIRE

    Gill, Christopher J; Phiri-Mazala, Grace; Guerina, Nicholas G; Kasimba, Joshua; Mulenga, Charity; MacLeod, William B; Waitolo, Nelson; Knapp, Anna B; Mirochnick, Mark; Mazimba, Arthur; Fox, Matthew P; Sabin, Lora; Seidenberg, Philip; Simon, Jonathon L; Hamer, Davidson H

    2011-01-01

    Objective To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare. Design Prospective, cluster randomised and controlled effectiveness study. Setting Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers’ homes, in rural village s...

  5. STAT3 Controls the Long-Term Survival and Phenotype of Repair Schwann Cells during Nerve Regeneration.

    Science.gov (United States)

    Benito, Cristina; Davis, Catherine M; Gomez-Sanchez, Jose A; Turmaine, Mark; Meijer, Dies; Poli, Valeria; Mirsky, Rhona; Jessen, Kristjan R

    2017-04-19

    After nerve injury, Schwann cells convert to a phenotype specialized to promote repair. But during the slow process of axonal regrowth, these repair Schwann cells gradually lose their regeneration-supportive features and eventually die. Although this is a key reason for the frequent regeneration failures in humans, the transcriptional mechanisms that control long-term survival and phenotype of repair cells have not been studied, and the molecular signaling underlying their decline is obscure. We show, in mice, that Schwann cell STAT3 has a dual role. It supports the long-term survival of repair Schwann cells and is required for the maintenance of repair Schwann cell properties. In contrast, STAT3 is less important for the initial generation of repair Schwann cells after injury. In repair Schwann cells, we find that Schwann cell STAT3 activation by Tyr705 phosphorylation is sustained during long-term denervation. STAT3 is required for maintaining autocrine Schwann cell survival signaling, and inactivation of Schwann cell STAT3 results in a striking loss of repair cells from chronically denervated distal stumps. STAT3 inactivation also results in abnormal morphology of repair cells and regeneration tracks, and failure to sustain expression of repair cell markers, including Shh, GDNF, and BDNF. Because Schwann cell development proceeds normally without STAT3, the function of this factor appears restricted to Schwann cells after injury. This identification of transcriptional mechanisms that support long-term survival and differentiation of repair cells will help identify, and eventually correct, the failures that lead to the deterioration of this important cell population. SIGNIFICANCE STATEMENT Although injured peripheral nerves contain repair Schwann cells that provide signals and spatial clues for promoting regeneration, the clinical outcome after nerve damage is frequently poor. A key reason for this is that, during the slow growth of axons through the proximal

  6. Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study.

    Science.gov (United States)

    Gill, Christopher J; Phiri-Mazala, Grace; Guerina, Nicholas G; Kasimba, Joshua; Mulenga, Charity; MacLeod, William B; Waitolo, Nelson; Knapp, Anna B; Mirochnick, Mark; Mazimba, Arthur; Fox, Matthew P; Sabin, Lora; Seidenberg, Philip; Simon, Jonathon L; Hamer, Davidson H

    2011-02-03

    To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare. Prospective, cluster randomised and controlled effectiveness study. Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers' homes, in rural village settings. 127 traditional birth attendants and mothers and their newborns (3559 infants delivered regardless of vital status) from Lufwanyama district. Using an unblinded design, birth attendants were cluster randomised to intervention or control groups. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. Control birth attendants continued their existing standard of care (basic obstetric skills and use of clean delivery kits). The primary outcome was the proportion of liveborn infants who died by day 28 after birth, with rate ratios statistically adjusted for clustering. Secondary outcomes were mortality at different time points; and comparison of causes of death based on verbal autopsy data. Among 3497 deliveries with reliable information, mortality at day 28 after birth was 45% lower among liveborn infants delivered by intervention birth attendants than control birth attendants (rate ratio 0.55, 95% confidence interval 0.33 to 0.90). The greatest reductions in mortality were in the first 24 hours after birth: 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants (0.40, 0.19 to 0.83). Deaths due to birth asphyxia were reduced by 63% among infants delivered by intervention birth attendants (0.37, 0.17 to 0.81) and by 81% within the first two days

  7. Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study

    Science.gov (United States)

    Phiri-Mazala, Grace; Guerina, Nicholas G; Kasimba, Joshua; Mulenga, Charity; MacLeod, William B; Waitolo, Nelson; Knapp, Anna B; Mirochnick, Mark; Mazimba, Arthur; Fox, Matthew P; Sabin, Lora; Seidenberg, Philip; Simon, Jonathon L; Hamer, Davidson H

    2011-01-01

    Objective To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare. Design Prospective, cluster randomised and controlled effectiveness study. Setting Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers’ homes, in rural village settings. Participants 127 traditional birth attendants and mothers and their newborns (3559 infants delivered regardless of vital status) from Lufwanyama district. Interventions Using an unblinded design, birth attendants were cluster randomised to intervention or control groups. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. Control birth attendants continued their existing standard of care (basic obstetric skills and use of clean delivery kits). Main outcome measures The primary outcome was the proportion of liveborn infants who died by day 28 after birth, with rate ratios statistically adjusted for clustering. Secondary outcomes were mortality at different time points; and comparison of causes of death based on verbal autopsy data. Results Among 3497 deliveries with reliable information, mortality at day 28 after birth was 45% lower among liveborn infants delivered by intervention birth attendants than control birth attendants (rate ratio 0.55, 95% confidence interval 0.33 to 0.90). The greatest reductions in mortality were in the first 24 hours after birth: 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants (0.40, 0.19 to 0.83). Deaths due to birth asphyxia were reduced by 63% among infants delivered by

  8. Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

    Science.gov (United States)

    Ross, Cliff; Olsen, Kevin; Henry, Michael; Pierce, Richard

    2015-04-01

    The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales.

  9. Online Adaptive Hyperthermia Treatment Planning During Locoregional Heating to Suppress Treatment-Limiting Hot Spots.

    Science.gov (United States)

    Kok, H Petra; Korshuize-van Straten, Linda; Bakker, Akke; de Kroon-Oldenhof, Rianne; Geijsen, Elisabeth D; Stalpers, Lukas J A; Crezee, Johannes

    2017-11-15

    Adequate tumor temperatures during hyperthermia are essential for good clinical response, but excessive heating of normal tissue should be avoided. This makes locoregional heating using phased array systems technically challenging. Online application of hyperthermia treatment planning could help to improve the heating quality. The aim of this study was to evaluate the clinical benefit of online treatment planning during treatment of pelvic tumors heated with the AMC-8 locoregional hyperthermia system. For online adaptive hyperthermia treatment planning, a graphical user interface was developed. Electric fields were calculated in a preprocessing step using our in-house-developed finite-difference-based treatment planning system. This allows instant calculation of the temperature distribution for user-selected phase-amplitude settings during treatment and projection onto the patient's computed tomographic scan for online visualization. Online treatment planning was used for 14 treatment sessions in 8 patients to reduce the patients' reports of hot spots while maintaining the same level of tumor heating. The predicted decrease in hot spot temperature should be at least 0.5°C, and the tumor temperature should decrease less than 0.2°C. These predictions were compared with clinical data: patient feedback about the hot spot and temperature measurements in the tumor region. In total, 17 hot spot reports occurred during the 14 sessions, and the alternative settings predicted the hot spot temperature to decrease by at least 0.5°C, which was confirmed by the disappearance of all 17 hot spot reports. At the same time, the average tumor temperature was predicted to change on average -0.01°C (range, -0.19°C to 0.34°C). The measured tumor temperature change was on average only -0.02°C (range, -0.26°C to 0.31°C). In only 2 cases the temperature decrease was slightly larger than 0.2°C, but at most it was 0.26°C. Online application of hyperthermia treatment planning is

  10. Common sole larvae survive high levels of pile-driving sound in controlled exposure experiments.

    Directory of Open Access Journals (Sweden)

    Loes J Bolle

    Full Text Available In view of the rapid extension of offshore wind farms, there is an urgent need to improve our knowledge on possible adverse effects of underwater sound generated by pile-driving. Mortality and injuries have been observed in fish exposed to loud impulse sounds, but knowledge on the sound levels at which (sub-lethal effects occur is limited for juvenile and adult fish, and virtually non-existent for fish eggs and larvae. A device was developed in which fish larvae can be exposed to underwater sound. It consists of a rigid-walled cylindrical chamber driven by an electro-dynamical sound projector. Samples of up to 100 larvae can be exposed simultaneously to a homogeneously distributed sound pressure and particle velocity field. Recorded pile-driving sounds could be reproduced accurately in the frequency range between 50 and 1000 Hz, at zero to peak pressure levels up to 210 dB re 1µPa(2 (zero to peak pressures up to 32 kPa and single pulse sound exposure levels up to 186 dB re 1µPa(2s. The device was used to examine lethal effects of sound exposure in common sole (Solea solea larvae. Different developmental stages were exposed to various levels and durations of pile-driving sound. The highest cumulative sound exposure level applied was 206 dB re 1µPa(2s, which corresponds to 100 strikes at a distance of 100 m from a typical North Sea pile-driving site. The results showed no statistically significant differences in mortality between exposure and control groups at sound exposure levels which were well above the US interim criteria for non-auditory tissue damage in fish. Although our findings cannot be extrapolated to fish larvae in general, as interspecific differences in vulnerability to sound exposure may occur, they do indicate that previous assumptions and criteria may need to be revised.

  11. Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Lv X

    2016-08-01

    Full Text Available Xing Lv,1,2,* Wei-Xiong Xia,1,2,* Liang-Ru Ke,1,2 Jing Yang,1,2 Wen-Zhe Qiu,1,2 Ya-Hui Yu,1,2 Hu Liang,1,2 Xin-Jun Huang,1,2 Guo-Yin Liu,1,2 Qi Zeng,1,2 Xiang Guo,1,2 Yan-Qun Xiang1,2 1Key Laboratory of Oncology in South China, 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Objective: Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC. This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC or 5-fluorouracil plus carboplatin (FC followed by concurrent radiation therapy in patients with NPC. Methods: Patients (N=88 were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy with two cycles of carboplatin (area under the curve =5 mg·h/L. Patients were followed up for 8 years. Primary end point was progression-free survival (PFS. Secondary end points included overall survival (OS, toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results: At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5% was higher than in the FC group (10.7%. Neutropenia and leukopenia

  12. Validation of the 16-Gene Recurrence Score in patients with locoregional, high-risk renal cell carcinoma from a phase 3 trial of adjuvant sunitinib.

    Science.gov (United States)

    Rini, Brian I; Escudier, Bernard; Martini, Jean-Francois; Magheli, Ahmed; Svedman, Christer; Lopatin, Margarita; Knezevic, Dejan; Goddard, Audrey D; Febbo, Phillip G; Li, Rachel; Lin, Xun; Valota, Olga; Staehler, Michael; Motzer, Robert J; Ravaud, Alain

    2018-05-17

    Adjuvant sunitinib prolonged disease-free survival (DFS) (hazard ratio [HR] 0.76) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov NCT00375674). The 16-gene Recurrence Score (RS) assay was previously developed and validated to estimate risk for disease recurrence in patients with RCC post-nephrectomy. This analysis further validated the prognostic value of RS assay in patients from S-TRAC and explored association of RS results with prediction of sunitinib benefit. The analysis was prospectively designed with prespecified genes, algorithm, endpoints, and analytical methods. Primary RCC was available from 212 patients with informed consent; primary analysis focused on patients with T3 RCC. Gene expression was quantitated by RT-PCR. Time to recurrence (TTR), DFS, and renal cancer-specific survival (RCSS) were analyzed using Cox proportional hazards regression. Results: Baseline characteristics were similar between patients with and without RS results, and between the sunitinib and placebo arms among patients with RS results. RS results predicted TTR, DFS, and RCSS in both arms, with the strongest results observed in the placebo arm. When high versus low RS groups were compared, HR for recurrence was 9.18 (95% CI, 2.15-39.24; P < 0.001) in the placebo arm; interaction of RS results with treatment was not significant. Conclusions: The strong prognostic performance of the 16-gene RS assay was confirmed in S-TRAC, and the RS assay is now supported by level IB evidence. RS results may help identify patients at high risk for recurrence who may derive higher absolute benefit from adjuvant therapy. Copyright ©2018, American Association for Cancer Research.

  13. Locoregional Recurrent or Second Primary Head and Neck Cancer: Management Strategies and Challenges.

    Science.gov (United States)

    Wong, Stuart J; Heron, Dwight E; Stenson, Kerstin; Ling, Diane C; Vargo, John A

    2016-01-01

    Treatment of patients with locoregional recurrent or second primary head and neck squamous cell cancer (HNSCC) has been guided by well-reasoned principles and informed by carefully tested chemotherapy and radiation regimens. However, clinical decision making for this population is complicated by many factors. Although surgery is generally considered the treatment of choice for patients with HNSCC with recurrent disease or new second primary disease in a previously irradiated field, operability of cases is not always straightforward. Postoperative treatment is frequently warranted but carries significant risk. In addition, the rapid rise in the incidence of HPV-associated HNSCC raises the question of whether established treatment paradigms should be re-examined in this population of patients with a much better prognosis than the non-HPV population. Furthermore, new radiation techniques and new systemic agents show early promising results in recent clinical studies, suggesting potential for practice-changing effects in the future management of this disease. This article examines each of the treatment modalities used in the care of patients with HNSCC with recurrent or new second primary disease and provides a perspective to aid clinicians in the management of this disease.

  14. Role of endoscopic ultrasonography in the loco-regional staging of patients with rectal cancer

    Science.gov (United States)

    Marone, Pietro; de Bellis, Mario; D’Angelo, Valentina; Delrio, Paolo; Passananti, Valentina; Di Girolamo, Elena; Rossi, Giovanni Battista; Rega, Daniela; Tracey, Maura Claire; Tempesta, Alfonso Mario

    2015-01-01

    The prognosis of rectal cancer (RC) is strictly related to both T and N stage of the disease at the time of diagnosis. RC staging is crucial for choosing the best multimodal therapy: patients with high risk locally advanced RC (LARC) undergo surgery after neoadjuvant chemotherapy and radiotherapy (NAT); those with low risk LARC are operated on after a preoperative short-course radiation therapy; finally, surgery alone is recommended only for early RC. Several imaging methods are used for staging patients with RC: computerized tomography, magnetic resonance imaging, positron emission tomography, and endoscopic ultrasound (EUS). EUS is highly accurate for the loco-regional staging of RC, since it is capable to evaluate precisely the mural infiltration of the tumor (T), especially in early RC. On the other hand, EUS is less accurate in restaging RC after NAT and before surgery. Finally, EUS is indicated for follow-up of patients operated on for RC, where there is a need for the surveillance of the anastomosis. The aim of this review is to highlight the impact of EUS on the management of patients with RC, evaluating its role in both preoperative staging and follow-up of patients after surgery. PMID:26140096

  15. Dosimetric comparison of RapidArc with fixed gantry dynamic IMRT for loco-regionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Wu Hao; Han Shukui; Sun Yan; Jiang Fan

    2010-01-01

    Objective: To compare the dosimetric difference of RapidArc and fixed gantry angle dynamic IMRT (dIMRT) for loco-regionally advanced nasopharyngeal carcinoma. Methods: Ten previously treated patients with loco-regionally advanced nasopharyngeal carcinoma were replanned with RapidArc and dIMRT, respectively. The prescription dose was GTV 70 Gy/33 f and PTV 60 Gy/33 f. All plans met the requirement: 95% of PTV was covered by 60 Gy. Dose-volume histogram data, isodose distribution, monitor units, and treatment time were compared. Results: Dose distribution has no significant difference between the two techniques. RapidArc reduced the dose of the brainstem, mandible, and other normal tissues compared with dIMRT. Mean monitor units were 589.5 and 1381.0 for RapidArc and dIMRT (reduced by 57% relatively). Mean treatment time was 2.33 min and 7.82 min for RapidArc and dIMRT (reduced by 70% relatively). Conclusions: Compared with dIMRT, RapidArc achieves equal target coverage and OAR sparing while using fewer monitor units and less time during radiotherapy for patient with loco-regionally advanced nasopharyngeal carcinoma. (authors)

  16. Modelling survival

    DEFF Research Database (Denmark)

    Ashauer, Roman; Albert, Carlo; Augustine, Starrlight

    2016-01-01

    The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test...

  17. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  18. The influence of micrometastases on prognosis and survival in stage I-II colon cancer patients: the Enroute⊕ Study

    Directory of Open Access Journals (Sweden)

    Pruijt Hans FM

    2011-05-01

    Full Text Available Abstract Background The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC. In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0 will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs and/or micrometastases (MMs at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0micro+ patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0micro+ and evaluate the benefits from adjuvant chemotherapy in pN0micro+ CC patients. Methods/design EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an ex vivo sentinel lymph node mapping procedure (SLNM following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0micro+ are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS. Discussion The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0 micro+ CC patients by reducing disease recurrence by adjuvant chemotherapy. Trial Registration ClinicalTrials.gov: NCT01097265

  19. Treatment outcome and prognostic variables for local control and survival in patients receiving radical radiotherapy for urinary bladder cancer

    DEFF Research Database (Denmark)

    Fokdal, Lars; Høyer, Morten; Maase, Hans von der

    2004-01-01

    with an initial CR developed recurrence during follow-up. The 3-year and 5-year overall survival rate was 31% and 21%, respectively. Performance status, T-stage, macroscopic complete TURB, hydronephrosis, and serum creatinine were independent prognostic factors for overall survival and, thus, important...

  20. Effect of Brood Pheromone on Survival and Nutrient Intake of African Honey Bees (Apis mellifera scutellata) under Controlled Conditions.

    Science.gov (United States)

    Démares, Fabien J; Yusuf, Abdullahi A; Nicolson, Susan W; Pirk, Christian W W

    2017-05-01

    The influence of pheromones on insect physiology and behavior has been thoroughly reported for numerous aspects, such as attraction, gland development, aggregation, mate and kin recognition. Brood pheromone (BP) is released by honey bee larvae to indicate their protein requirements to the colony. Although BP is known to modulate pollen and protein consumption, which in turn can affect physiological and morphological parameters, such as hypopharyngeal gland (HPG) development and ovarian activation, few studies have focused on the effect of BP on nutritional balance. In this study, we exposed newly emerged worker bees for 14 d and found that BP exposure increased protein intake during the first few days, with a peak in consumption at day four following exposure. BP exposure decreased survival of caged honey bees, but did not affect either the size of the HPG acini or ovarian activation stage. The uncoupling of the BP releaser effect, facilitated by working under controlled conditions, and the presence of larvae as stimulating cues are discussed.

  1. PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia.

    Science.gov (United States)

    Banh, Robert S; Iorio, Caterina; Marcotte, Richard; Xu, Yang; Cojocari, Dan; Rahman, Anas Abdel; Pawling, Judy; Zhang, Wei; Sinha, Ankit; Rose, Christopher M; Isasa, Marta; Zhang, Shuang; Wu, Ronald; Virtanen, Carl; Hitomi, Toshiaki; Habu, Toshiyuki; Sidhu, Sachdev S; Koizumi, Akio; Wilkins, Sarah E; Kislinger, Thomas; Gygi, Steven P; Schofield, Christopher J; Dennis, James W; Wouters, Bradly G; Neel, Benjamin G

    2016-07-01

    Tumours exist in a hypoxic microenvironment and must limit excessive oxygen consumption. Hypoxia-inducible factor (HIF) controls mitochondrial oxygen consumption, but how/if tumours regulate non-mitochondrial oxygen consumption (NMOC) is unknown. Protein-tyrosine phosphatase-1B (PTP1B) is required for Her2/Neu-driven breast cancer (BC) in mice, although the underlying mechanism and human relevance remain unclear. We found that PTP1B-deficient HER2(+) xenografts have increased hypoxia, necrosis and impaired growth. In vitro, PTP1B deficiency sensitizes HER2(+) BC lines to hypoxia by increasing NMOC by α-KG-dependent dioxygenases (α-KGDDs). The moyamoya disease gene product RNF213, an E3 ligase, is negatively regulated by PTP1B in HER2(+) BC cells. RNF213 knockdown reverses the effects of PTP1B deficiency on α-KGDDs, NMOC and hypoxia-induced death of HER2(+) BC cells, and partially restores tumorigenicity. We conclude that PTP1B acts via RNF213 to suppress α-KGDD activity and NMOC. This PTP1B/RNF213/α-KGDD pathway is critical for survival of HER2(+) BC, and possibly other malignancies, in the hypoxic tumour microenvironment.

  2. Distinct Stromal Cell Factor Combinations Can Separately Control Hematopoietic Stem Cell Survival, Proliferation, and Self-Renewal

    Directory of Open Access Journals (Sweden)

    Stefan Wohrer

    2014-06-01

    Full Text Available Hematopoietic stem cells (HSCs are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation, and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential are variably supported by different Steel factor (SF-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings point to the molecular basis of HSC control and expansion.

  3. A review of the environmental survivability of telerobotic control sensor systems for use in nuclear waste tanks

    International Nuclear Information System (INIS)

    Holcomb, D.E.; Burks, B.L.

    1994-05-01

    This report was prepared by the Oak Ridge National Laboratory (ORNL) and funded by the Department of Energy (DOE) Office of Technology Development (OTD) Robotics Technology Development Program (RTDP). During the next few years field deployment of remotely operated systems in nuclear waste cleanup operations will increase dramatically as DOE strives to efficiently and safely remediate the many waste storage sites. Typically, the most fragile components in remote systems are the sensors that provide feedback to the operators or to computer control algorithms. The purpose of this review is to determine the availability of environmentally hardened sensors to support control of a manipulator or vehicle system in a waste tank environment. The emphasis of the report is on the environmental ruggedness of currently available sensors. For the purpose of this review a set of nominal requirements for survivability were adopted conditions in the single-shell tanks at Hanford. This report is designed to be a practical guide to the state of the art in commercially available environmentally tolerant sensors for use with robotic systems. It is neither intended to be an exhaustive review of the technical literature on potential measurement techniques nor a complete physical review of the functioning of particular sensor systems. This report is intended to be a living document. As additional, corrected, or updated information is received from sensor manufacturers, it will be incorporated into the report database. The physical report will then be periodically revised and released in updated format. The authors wish to apologize to any sources of environmentally hardened sensors that were omitted during this review and encourage submission of new or updated data

  4. EG-VEGF controls placental growth and survival in normal and pathological pregnancies: case of fetal growth restriction (FGR).

    Science.gov (United States)

    Brouillet, S; Murthi, P; Hoffmann, P; Salomon, A; Sergent, F; De Mazancourt, P; Dakouane-Giudicelli, M; Dieudonné, M N; Rozenberg, P; Vaiman, D; Barbaux, S; Benharouga, M; Feige, J-J; Alfaidy, N

    2013-02-01

    Identifiable causes of fetal growth restriction (FGR) account for 30 % of cases, but the remainders are idiopathic and are frequently associated with placental dysfunction. We have shown that the angiogenic factor endocrine gland-derived VEGF (EG-VEGF) and its receptors, prokineticin receptor 1 (PROKR1) and 2, (1) are abundantly expressed in human placenta, (2) are up-regulated by hypoxia, (3) control trophoblast invasion, and that EG-VEGF circulating levels are the highest during the first trimester of pregnancy, the period of important placental growth. These findings suggest that EG-VEGF/PROKR1 and 2 might be involved in normal and FGR placental development. To test this hypothesis, we used placental explants, primary trophoblast cultures, and placental and serum samples collected from FGR and age-matched control women. Our results show that (1) EG-VEGF increases trophoblast proliferation ([(3)H]-thymidine incorporation and Ki67-staining) via the homeobox-gene, HLX (2) the proliferative effect involves PROKR1 but not PROKR2, (3) EG-VEGF does not affect syncytium formation (measurement of syncytin 1 and 2 and β hCG production) (4) EG-VEGF increases the vascularization of the placental villi and insures their survival, (5) EG-VEGF, PROKR1, and PROKR2 mRNA and protein levels are significantly elevated in FGR placentas, and (6) EG-VEGF circulating levels are significantly higher in FGR patients. Altogether, our results identify EG-VEGF as a new placental growth factor acting during the first trimester of pregnancy, established its mechanism of action, and provide evidence for its deregulation in FGR. We propose that EG-VEGF/PROKR1 and 2 increases occur in FGR as a compensatory mechanism to insure proper pregnancy progress.

  5. Gene profiling and circulating tumor cells as biomarker to prognostic of patients with locoregional breast cancer.

    Science.gov (United States)

    Kuniyoshi, Renata K; Gehrke, Flávia de Sousa; Alves, Beatriz C A; Vilas-Bôas, Viviane; Coló, Anna E; Sousa, Naiara; Nunes, João; Fonseca, Fernando L A; Del Giglio, Auro

    2015-09-01

    The gene profile of primary tumors, as well as the identification of circulating tumor cells (CTCs), can provide important prognostic and predictive information. In this study, our objective was to perform tumor gene profiling (TGP) in combination with CTC characterization in women with nonmetastatic breast cancer. Biological samples (from peripheral blood and tumors) from 167 patients diagnosed with stage I, II, and III mammary carcinoma, who were also referred for adjuvant/neoadjuvant chemotherapy, were assessed for the following parameters: (a) the presence of CTCs identified by the expression of CK-19 and c-erbB-2 in the peripheral blood mononuclear cell (PBMC) fraction by quantitative reverse transcription PCR (RT-PCR) and (b) the TGP, which was determined by analyzing the expression of 21 genes in paraffin-embedded tissue samples by quantitative multiplex RT-PCR with the Plexor® system. We observed a statistically significant correlation between the progression-free interval (PFI) and the clinical stage (p = 0.000701), the TGP score (p = 0.006538), and the presence of hormone receptors in the tumor (p = 0.0432). We observed no correlation between the PFI and the presence or absence of CK-19 or HER2 expression in the PBMC fraction prior to the start of treatment or in the two following readouts. Multivariate analysis revealed that only the TGP score significantly correlated with the PFI (p = 0.029247). The TGP is an important prognostic variable for patients with locoregional breast cancer. The presence of CTCs adds no prognostic value to the information already provided by the TGP.

  6. Optimization of dose distributions for adjuvant locoregional radiotherapy of gastric cancer by IMRT

    International Nuclear Information System (INIS)

    Lohr, F.; Dobler, B.; Mai, S.; Hermann, B.; Tiefenbacher, U.; Wieland, P.; Steil, V.; Wenz, F.

    2003-01-01

    Background and Purpose: Locoregional relapse is a problem frequently encountered with advanced gastric cancer. Data from the randomized Intergroup trial 116 suggest effectiveness of adjuvant radiochemotherapy, albeit with significant toxicity. The potential of intensity-modulated radiotherapy (IMRT) to reduce toxicity by significantly reducing maximum and median doses to organs at risk while still applying sufficient dose to the target volume in the upper abdomen was studied. Patient and Methods: For a typical configuration of target volumes and organs, a step-and-shoot IMRT plan (eight beam orientations), developed as a class solution for treatment of tumors in the upper abdomen (Figures 1 to 3), a conventional plan, a combination of the conventional plan with a kidney-sparing boost plan, and a conventional plan with noncoplanar ap and pa fields for improved kidney sparing were compared with respect to coverage of target volume and dose to organs at risk with a dose of 45 Gy delivered as the median dose to the target volume. Results: When using the conventional three-dimensionally planned box techniques, the right kidney could be kept below tolerance, but median dose to the left kidney amounted to between 14.8 and 26.9 Gy, depending on the plan. IMRT reduced the median dose to the left kidney to 10.5 Gy, while still keeping the dose to the right kidney 90% of prescription dose were delivered to > 90% of target volume with IMRT (Table 1). Conclusion: IMRT has the potential to deliver efficient doses to target volumes in the upper abdomen, while delivering dose to organs at risk in a more advantageous fashion than a conventional technique. For clinical implementation, the possibility of extensive organ motion in the upper abdomen has to be taken into account for treatment planning and patient positioning. The multitude of potential risks related to its application has to be the subject of thorough follow-up and further studies. (orig.)

  7. Effects of a psychosocial intervention on survival among patients with stage I breast and prostate cancer: a matched case-control study.

    Science.gov (United States)

    Shrock, D; Palmer, R F; Taylor, B

    1999-05-01

    Psychosocial factors have been linked to the development and progression of cancer and shown to be relevant in cancer care. However, the evidence that psychosocial interventions affect cancer survival is less conclusive. Few methodologically sound studies have addressed this issue. To investigate the effects of a 6-week psychosocial intervention on survival among patients with stage I breast and prostate cancer. Matched case-control. 3 rural hospitals or cancer centers in central Pennsylvania. 21 breast and 29 prostate stage I cancer patients (treatment group) matched with 74 breast and 65 prostate stage I cancer patients from the same hospitals who did not receive the intervention (control group). Six 2-hour health psychology classes conducted by a licensed staff psychologist. Survival time was compared between the 2 groups and with national norms. The intervention group lived significantly longer than did matched controls. At 4- to 7-year follow-up (median = 4.2 years), none of the breast cancer patients in the intervention group died, whereas 12% of those in the control group died. Twice as many matched-control prostate cancer patients died compared with those in the intervention group (28% vs 14%). Control group survival was similar to national norms. These results are consistent with prior clinical trials and suggest that short-term psychosocial interventions that encourage the expression of emotions, provide social support, and teach coping skills can influence survival among cancer patients. However, self-selection bias cannot be ruled out as an alternative explanation for the results. These interventions merit further consideration and research.

  8. Predictors for replanning in loco-regionally advanced nasopharyngeal carcinoma patients undergoing intensity-modulated radiation therapy: a prospective observational study

    International Nuclear Information System (INIS)

    Yan, DanFang; Yan, SenXiang; Wang, QiDong; Liao, XinBiao; Lu, ZhongJie; Wang, YiXiang

    2013-01-01

    Replanning in intensity-modulated radiotherapy (IMRT) has been reported to improve quality of life and loco-regional control in patients with nasopharyngeal cancer (NPC). Determination of the criteria for replanning is, however, urgently needed. We conducted a prospective study to determine when and for what type of patients is replanning preferred through weekly repeat computed tomography (CT) imaging during the course of IMRT. We recruited 20 patients who were diagnosed as having loco-regionally advanced, non-metastatic stage III or IVa NPC and treated with concurrent platinum-based chemoradiotherapy (CRT) using IMRT. Patients received CT simulation (sim-CT) and plain magnetic resonance imaging (MRI) plus diffusion-weighted imaging (DWI) weekly for five consecutive weeks. The gross tumor volume (GTV) and clinical target volume (CTV) were delineated and recorded weekly based on the CT-CT fusion. The relationship between GTV/CTV reduction and clinical characteristics of the patients were assessed using Pearson correlation test. GTV and CTV decreased during the treatment by 36.03 mL (range, 10.91–98.82 mL) and 76.79 mL (range, 33.94–125.14 mL), respectively, after 25 fractions of treatment. The percentage reductions from their initial volume were 38.4% (range, 25.3–50.7%) and 11.8% (range, 6.7–18.3%), respectively. The greatest reductions in GTV and CTV were observed at the fourth week (i.e., upon completion of 20 fractions), compared to pre-treatment sim-CT. Weight loss and CTV reduction were significantly correlated with pre-treatment body mass index (BMI) (r = 0.58, P = 0.012, and r = 0.48, P = 0.046, respectively). However, no significant correlation was observed between CTV reduction and initial tumor volume. In addition, GTV reduction was not significantly correlated with pre-treatment tumor volume (P = 0.65), but negatively correlated with pre-treatment tumor apparent diffusion coefficient (ADC) values (r = −0.46, P = 0.042). Our results indicate

  9. Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas

    International Nuclear Information System (INIS)

    Zhu Weiguo; You Zhenbin; Li Tao; Yu Changhua; Tao Guangzhou; Hu Mingli; Chen Xiaofei

    2011-01-01

    The objective of this study was to investigate the significance of hedgehog signaling pathway in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma. In the present study, we used the method of immunohistochemistry to examine the expression status of two hedgehog components, PTCH1 and glioma-associated oncogene GLI-1, in 100 pre-treated biopsy specimens of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. We find that high levels of PTCH1 and GLI-1 were detected in 76.0 and 72.0% of esophageal squamous cell carcinoma, respectively. Significant associations of high PTCH1 and GLI-1 expression with large tumor size (both P=0.01), locoregional progression (P=0.001 and 0.003, respectively) and the lack of complete response to chemoradiotherapy (P=0.008 and 0.01, respectively) were observed. Univariate analysis revealed that high PTCH1 and GLI-1 expression was associated with poor locoregional progression-free survival, distant progression-free survival and overall survival. Furthermore, esophageal squamous cell carcinoma patients with high PTCH1 and GLI-1 expression have the shorter survival time than the subgroups with negative and low PTCH1 and GLI-1 expression. In multivariate analysis, PTCH1 and GLI-1 expression status were both evaluated as independent prognostic factors for locoregional progression-free survival, distant progression-free survival and overall survival. These findings suggest an important role for the activation of hedgehog signaling in esophageal squamous cell carcinoma progression and that PTCH1 and GLI-1 expression may be significantly associated with esophageal squamous cell carcinoma resistance to chemoradiotherapy. (author)

  10. Survival benefit of TIPS versus serial paracentesis in patients with refractory ascites: a single institution case-control propensity score analysis

    International Nuclear Information System (INIS)

    Gaba, R.C.; Parvinian, A.; Casadaban, L.C.; Couture, P.M.; Zivin, S.P.; Lakhoo, J.; Minocha, J.; Ray, C.E.; Knuttinen, M.G.; Bui, J.T.

    2015-01-01

    Aim: To compare the impact of covered stent-graft transjugular intrahepatic portosystemic shunt (TIPS) versus serial paracentesis on survival of patients with medically refractory ascites. Materials and methods: In this retrospective study, cirrhotic patients who underwent covered stent-graft TIPS for refractory ascites from 2003–2013 were compared with similar patients who underwent serial paracentesis during 2009–2013. Demographic and liver disease data, Model for End-Stage Liver Disease (MELD) scores, and survival outcomes were obtained from hospital electronic medical records and the social security death index. After propensity score weighting to match study group characteristics, survival outcomes were compared using Kaplan–Meier statistics with log-rank analysis. Results: Seventy TIPS (70% men, mean age 55.7 years, mean MELD 15.1) and 80 paracentesis (58% men, mean age 53.5 years, mean MELD 22.5) patients were compared. The TIPS haemodynamic success rate was 100% (mean portosystemic pressure gradient reduction 13 mmHg). Paracentesis patients underwent a mean of 7.9 procedures. After propensity score weighting to balance group features, TIPS patients showed a trend toward enhanced survival compared with paracentesis patients (median survival 1037 versus 262 days, p = 0.074). TIPS conferred a significant increase or trend toward improved survival compared with paracentesis at 1 (66% versus 44%, p = 0.018), 2 (56% versus 38%, p = 0.057), and 3 year (49% versus 32%, p = 0.077) time points. Thirty and 90 day mortality rates were not statistically increased by TIPS. Conclusion: Covered stent-graft TIPS improves intermediate- to long-term survival without significantly increasing short-term mortality of ascites patients, and suggests a greater potential role for TIPS in properly selected ascitic patients when medical management fails. - Highlights: • The survival benefit of TIPS for patients with refractory ascites remains unproven. • A case-control

  11. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial.

    Science.gov (United States)

    Bourke, Stephen C; Tomlinson, Mark; Williams, Tim L; Bullock, Robert E; Shaw, Pamela J; Gibson, G John

    2006-02-01

    Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial. 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured. NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit. In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.

  12. Comparison of MRI and PET-CT in detecting the loco-regional recurrence of soft tissue sarcomas during surveillance

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sun-Young [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of); Hallym University Sacred Heart Hospital, Department of Radiology, Anyang-si, Gyeonggi-do (Korea, Republic of); Chung, Hye Won [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of); Chae, Sun Young [University of Ulsan College of Medicine, Asan Medical Center, Department of Nuclear Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of); Lee, Jong-Seok [University of Ulsan College of Medicine, Asan Medical Center, Department of Orthopedic Surgery, 88, Olympic-ro 43-gil, Songpa-gu, Seoul (Korea, Republic of)

    2016-10-15

    To investigate the diagnostic performance of MRI and PET-CT for the detection of loco-regional recurrences after soft tissue sarcoma (STS) excision. From Dec 2003 to Aug 2014, 394 patients with STSs, who were included in the electronic patient registry for initial or repeated surgery at our hospital, were retrospectively reviewed. We identified 152 patients who underwent regular postoperative follow-ups with both MRI and PET-CT, obtained within a 3 month period of each other. We analyzed differences in the performance of MRI and PET-CT for the diagnosis of loco-regional recurrences using McNemar's test. The receiver-operating characteristic curves and calculations of the area under the curve were used. Twenty patients were found to have a loco-regional recurrence after tumor excision. For MRI and PET-CT, the sensitivities were 90.0 and 95.0 %, and the specificities 97.7 and 95.5 %, respectively, with positive predictive values of 85.7 and 76.0 % and negative predictive values of 98.5 and 99.2 %, respectively. No significant difference was detected between the sensitivities of MRI and PET-CT (p = 0.125). The area under the receiver-operating characteristic curve for PET-CT (0.952) was not significantly greater than that for MRI (0.939; p = 0.6). MRI of the area of interest is recommended for evaluation of tumor recurrence after surgical excision of STS. PET-CT was shown to be effective for detection of STS recurrence, and comparable to MRI. However, if PET-CT or MRI findings are inconclusive, the other modality may be helpful in differentiating tumor recurrence from post-therapeutic tissue change. (orig.)

  13. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

    International Nuclear Information System (INIS)

    Ferreira, Luciana Bueno; Gimba, Etel Rodrigues Pereira; Palumbo, Antonio; Mello, Kivvi Duarte de; Sternberg, Cinthya; Caetano, Mauricio S; Oliveira, Felipe Leite de; Neves, Adriana Freitas; Nasciutti, Luiz Eurico; Goulart, Luiz Ricardo

    2012-01-01

    PCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR) signaling. LNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR) signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide), and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR. LNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions. Our findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in part through modulating AR signaling, which may raise new

  14. Prospective prediction of resistance to neoadjuvant therapy in patients with locoregional esophageal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Rosen DG

    2015-02-01

    Full Text Available Daniel G Rosen,1 Weiwei Shan,2 Natalie Lassen,2 Clare Johnson,2 Kristen Oelschlager,2 Yaeli Bierman-Harrar,1 Kenneth A Kesler,3 Derek Maetzold,2 Sunil Badve,3 Robert W Cook,2 Romil Saxena3 1Baylor College of Medicine, Houston TX, USA; 2Castle Biosciences, Incorporated, Friendswood, TX, USA; 3Indiana University, Indianapolis, IN, USA Background: To clinically validate a multianalyte algorithmic immunohistochemistry (IHC assay that has been previously shown to accurately identify patients with locoregional esophageal adenocarcinoma (EC who will exhibit extreme resistance to neoadjuvant chemoradiotherapy. Methods: Archived biopsy specimens of EC were subject to IHC examination of compartmentalized immunoreactivity of nuclear factor kappa B (NF-κB, Sonic Hedgehog (SHH, and GLI family zinc finger 1 (Gli-1, and a labeling index score was assigned to each biomarker. Test prediction was generated by logistic regression predictive modeling, using the labeling index scores for all three analytes from each sample, referring to a validated training set of 167 EC patients. Accuracy of the test was determined by comparing the predicted outcomes with pathologically determined College of American Pathologists tumor response grade. Analytical validity of the test was measured by comparing validation set prediction results obtained in two independent Clinical Laboratory Improvement Amendment-certified laboratories, and by measuring concordance between two trained labeling index readers. Results: Specimens from 64 patients that met specific criteria were collected. No technical failure was encountered during the IHC labeling procedures. The logistic regression algorithm generated an area under the curve of 0.96 and 0.85 for the 64 sample cohort in two independent clinical laboratories, respectively, comparing predictive results with the established training set. Positive predictive values of 88% and 82% were also achieved in each laboratory, respectively. A

  15. Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

    Energy Technology Data Exchange (ETDEWEB)

    Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2015-01-16

    Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

  16. Influence of nutrient levels in Tamarix on Diorhabda sublineata (Coleoptera: Chrysomelidae) survival and fitness with implications for biological control.

    Science.gov (United States)

    Guenther, D A; Gardner, K T; Thompson, D C

    2011-02-01

    Establishment of the saltcedar leaf beetle (Diorhabda spp.) has been unpredictable when caged or released in the field for saltcedar (Tamarix spp.) biocontrol. It has been observed that one caged tree might be voraciously fed upon by beetles while an adjacent tree in the cage is left untouched. We hypothesized that differences in the nutrient content of individual trees may explain this behavior. We evaluated survival, development rate, and egg production of beetles fed in the laboratory on saltcedar foliage from trees that had been grown under a range of fertilizer treatments. Tissue samples from the experimental trees and from the field were analyzed for percent nitrogen, phosphorus, and potassium. There was essentially no survival of beetle larvae fed foliage from saltcedar trees at nitrogen levels below 2.0%. At levels above 2.0% N, beetle larvae had corresponding increased survival rates and shorter development times. Multiple regression analyses indicated that nitrogen and phosphorus are important for larval survival and faster development rates. Higher levels of potassium were important for increased egg cluster production. The plant tissue analysis showed that the percentage of nitrogen in the experimental trees reflected the range of trees in the field and also that there is high variability within trees in the field. Our research indicates that if beetles are released on trees with poor nutrient quality, the larvae will not survive. © 2011 Entomological Society of America

  17. Effects of Benazepril on Survival of Dogs with Chronic Kidney Disease: A Multicenter, Randomized, Blinded, Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    King, J N; Font, A; Rousselot, J-F; Ash, R A; Bonfanti, U; Brovida, C; Crowe, I D; Lanore, D; Pechereau, D; Seewald, W; Strehlau, G

    2017-07-01

    Chronic kidney disease (CKD) is an important cause of morbidity and mortality in dogs. To evaluate the efficacy in prolonging survival and safety of benazepril administration to dogs with CKD. Forty-nine client-owned dogs with CKD. Dogs were randomized to benazepril (0.25 to benazepril versus placebo was detected for renal survival time in all dogs; median (95% confidence interval (CI)) survival times were 305 (53-575) days in the benazepril group and 287 (152-not available) in the placebo group (P = .53). Renal survival times were not significantly longer with benazepril compared to placebo for subgroups: hazard ratios (95% CI) were 0.50 (0.21-1.22) with P = .12 for initial urine protein-to-creatinine ratio (UPC) >0.5, and 0.38 (0.12-1.19) with P = .080 for initial UPC >0.5 plus plasma creatinine ≤440 μmol/L. Proteinuria, assessed from the UPC, was significantly (P = .0032) lower after treatment with benazepril compared to placebo. There were no significant differences between groups for clinical signs or frequencies of adverse events. Benazepril significantly reduced proteinuria in dogs with CKD. Insufficient numbers of dogs were recruited to allow conclusions on survival time. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. [The survival and development conditions of community-based organizations for HIV/AIDS prevention and control among men who have sex with men in three Chinese cities].

    Science.gov (United States)

    Fu, Xiaojing; Shan, Duo; Qi, Jinlei; Ouyang, Lin; Wang, Hui; Fu, Jie; Sun, Jiangping

    2015-06-01

    To investigate the survival and development conditions of community-based organizations (CBOs) for HIV/AIDS prevention and control among men who have sex with men (MSM) in Chinese cities including Shanghai, Hangzhou, Chongqing. This study employed both qualitative (focus groups) and quantitative (questionnaire survey) methods to obtain information from 15 MSM CBOs in three Chinese cities. The mean work time of the 15 CBOs for HIV/AIDS prevention and control among MSM was 6.7 years (2.1-11.3 years), and the majority of their funds was from international cooperation projects (80 447 000 RMB, 73.0%) from 2006 to 2013. The survival cost of MSM CBOs apart from expenditure of activities was 2 240-435 360 RMB per year. As it was shown in the graph, the survival and development of MSM CBOs was closely related to the development of international cooperation projects. There was a few small size MSM CBOs taking part in the prevention and control of HIV/AIDS and their work content was limited before 2006. From 2006 to 2008, some international cooperation projects were launched in China, such as the China Global Fund AIDS project and the China-Gates Foundation HIV Prevention Cooperation program. As a result, the number of MSM CBOs was increased sharply, and both the scale and 2012, the performance of these programs further promote the establishment of new MSM CBOs and the development of all MSM CBOs with regard to the work places, full-time staffs, work contents, work patterns and the specific targeted population. After 2012, most international cooperation programs were completed and the local department of disease prevention and control continued to cooperate with MSM CBOs. However, the degree of support funds from the local department was different among different regions. Where the funds were below the half of program funds, the development of MSM CBOs ceased and work slowed down. Besides, there were still some constraints for the survival and development of MSM CBOs, such

  19. A comparative study of machine learning methods for time-to-event survival data for radiomics risk modelling.

    Science.gov (United States)

    Leger, Stefan; Zwanenburg, Alex; Pilz, Karoline; Lohaus, Fabian; Linge, Annett; Zöphel, Klaus; Kotzerke, Jörg; Schreiber, Andreas; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Troost, Esther G C; Löck, Steffen; Richter, Christian

    2017-10-16

    Radiomics applies machine learning algorithms to quantitative imaging data to characterise the tumour phenotype and predict clinical outcome. For the development of radiomics risk models, a variety of different algorithms is available and it is not clear which one gives optimal results. Therefore, we assessed the performance of 11 machine learning algorithms combined with 12 feature selection methods by the concordance index (C-Index), to predict loco-regional tumour control (LRC) and overall survival for patients with head and neck squamous cell carcinoma. The considered algorithms are able to deal with continuous time-to-event survival data. Feature selection and model building were performed on a multicentre cohort (213 patients) and validated using an independent cohort (80 patients). We found several combinations of machine learning algorithms and feature selection methods which achieve similar results, e.g. C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with Spearman feature selection. Using the best performing models, patients were stratified into groups of low and high risk of recurrence. Significant differences in LRC were obtained between both groups on the validation cohort. Based on the presented analysis, we identified a subset of algorithms which should be considered in future radiomics studies to develop stable and clinically relevant predictive models for time-to-event endpoints.

  20. Survival of falling robots

    Science.gov (United States)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-01-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  1. Survival of falling robots

    Science.gov (United States)

    Cameron, Jonathan M.; Arkin, Ronald C.

    1992-02-01

    As mobile robots are used in more uncertain and dangerous environments, it will become important to design them so that they can survive falls. In this paper, we examine a number of mechanisms and strategies that animals use to withstand these potentially catastrophic events and extend them to the design of robots. A brief survey of several aspects of how common cats survive falls provides an understanding of the issues involved in preventing traumatic injury during a falling event. After outlining situations in which robots might fall, a number of factors affecting their survival are described. From this background, several robot design guidelines are derived. These include recommendations for the physical structure of the robot as well as requirements for the robot control architecture. A control architecture is proposed based on reactive control techniques and action-oriented perception that is geared to support this form of survival behavior.

  2. Transrectal rigid-hybrid NOTES cholecystectomy can be performed without peritoneal contamination: a controlled porcine survival study.

    Science.gov (United States)

    Müller, Philip C; Senft, Jonas D; Gath, Philip; Steinemann, Daniel C; Nickel, Felix; Billeter, Adrian T; Müller-Stich, Beat P; Linke, Georg R

    2018-01-01

    The risk of infectious complications due to peritoneal contamination is a major concern and inhibits the widespread use of transrectal NOTES. A standardized rectal washout with a reversible colon occlusion device in situ has previously shown potential in reducing peritoneal contamination. The aim of this study was to compare the peritoneal contamination rate and inflammatory reaction for transrectal cholecystectomy after ideal rectal preparation (trCCE) and standard laparoscopic cholecystectomy (lapCCE) in a porcine survival experiment. Twenty pigs were randomized to trCCE (n = 10) or lapCCE (n = 10). Before trCCE, rectal washout was performed with saline solution. A colon occlusion device was then inserted and a second washout with povidone-iodine was performed. The perioperative course and the inflammatory reaction (leukocytes, C-reactive protein) were compared. At necropsy, 14 days after surgery the abdominal cavity was screened for infectious complications and peritoneal swabs were obtained for comparison of peritoneal contamination. Peritoneal contamination was lower after trCCE than after lapCCE (0/10 vs. 6/10; p = 0.003). No infectious complications were found at necropsy in either group and postoperative complications did not differ (p = 1.0). Immediately after the procedure, leukocytes were higher after lapCCE (17.0 ± 2.7 vs. 14.6 ± 2.3; p = 0.047). Leukocytes and C-reactive protein showed no difference in the further postoperative course. Intraoperative complications and total operation time (trCCE 114 ± 32 vs. 111 ± 27 min; p = 0.921) did not differ, but wound closure took longer for trCCE (31.5 ± 19 vs. 13 ± 5 min; p = 0.002). After standardized rectal washout with a colon occlusion device in situ, trCCE was associated without peritoneal contamination and without access-related infectious complications. Based on the findings of this study, a randomized controlled clinical study comparing clinical outcomes of trCCE with

  3. The Preoperative Controlling Nutritional Status Score Predicts Survival After Curative Surgery in Patients with Pathological Stage I Non-small Cell Lung Cancer.

    Science.gov (United States)

    Shoji, Fumihiro; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Maehara, Yoshihiko

    2017-02-01

    The prognostic Controlling Nutritional Status (CONUT) score is used to evaluate immuno-nutritional conditions and is a predictive factor of postoperative survival in patients with digestive tract cancer. We retrospectively analyzed clinicopathological features of patients with pathological stage I non-small cell lung cancer (NSCLC) to identify predictors or prognostic factors of postoperative survival and to investigate the role of preoperative CONUT score in predicting survival. We selected 138 consecutive patients with pathological stage I NSCLC treated from August 2005 to August 2010. We measured their preoperative CONUT score in uni- and multivariate Cox regression analyses of postoperative survival. A high CONUT score was positively associated with preoperative serum carcinoembryonic antigen level (p=0.0100) and postoperative recurrence (p=0.0767). In multivariate analysis, the preoperative CONUT score [relative risk (RR)=6.058; 95% confidence interval (CI)=1.068-113.941; p=0.0407), increasing age (RR=7.858; 95% CI=2.034-36.185; p=0.0029), and pleural invasion (RR=36.615; 95% CI=5.900-362.620; pcancer-specific survival (CS), and overall survival (OS), the group with high CONUT score had a significantly shorter RFS, CS, and OS than did the low-CONUT score group by log-rank test (p=0.0458, p=0.0104 and p=0.0096, respectively). The preoperative CONUT score is both a predictive and prognostic factor in patients with pathological stage I NSCLC. This immuno-nutritional score can indicate patients at high risk of postoperative recurrence and death. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Predicting two-year longitudinal MD Anderson Dysphagia Inventory outcomes after intensity modulated radiotherapy for locoregionally advanced oropharyngeal carcinoma.

    Science.gov (United States)

    Goepfert, Ryan P; Lewin, Jan S; Barrow, Martha P; Fuller, C David; Lai, Stephen Y; Song, Juhee; Hobbs, Brian P; Gunn, G Brandon; Beadle, Beth M; Rosenthal, David I; Garden, Adam S; Kies, Merrill S; Papadimitrakopoulou, Vali A; Schwartz, David L; Hutcheson, Katherine A

    2017-04-01

    To determine the factors associated with longitudinal patient-reported dysphagia as measured by the MD Anderson Dysphagia Inventory (MDADI) in locoregionally advanced oropharyngeal carcinoma (OPC) survivors treated with split-field intensity modulated radiotherapy (IMRT). Retrospective patient analysis. A retrospective analysis combined data from three single-institution clinical trials for stage III/IV head and neck carcinoma. According to trial protocols, patients had prospectively collected MDADI at baseline, 6, 12, and 24 months after treatment. OPC patients with baseline and at least one post-treatment MDADI were included. Longitudinal analysis was completed with multivariate linear mixed effects modeling. There were 116 patients who met inclusion criteria. Mean baseline MDADI composite was 88.3, dropping to 73.8 at 6 months, and rising to 78.6 and 83.3 by 12 and 24 months, respectively (compared to baseline, all P dysphagia early after split-field IMRT for locoregionally advanced OPC that remains apparent 6 months after treatment. MDADI scores recover slowly thereafter, but remain depressed at 24 months compared to baseline. Higher tumor stage and smoking status are important markers of patient-reported function through the course of treatment, suggesting these are important groups for heightened surveillance and more intensive interventions to optimize swallowing outcomes. 4 Laryngoscope, 127:842-848, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  5. Argon plasma coagulation for a patient with locoregional failure after definitive chemoradiotherapy for esophageal carcinoma. A case report

    International Nuclear Information System (INIS)

    Nomura, Tsutomu; Miyashita, Masao; Makino, Hiroshi; Okawa, Keiichi; Katsuta, Miwako; Tajiri, Takashi

    2008-01-01

    Patients who undergo definitive chemoradiotherapy (CRT) face a risk of residual resistant disease or disease recurrence at the primary site; therefore, salvage treatment may be required. An optimum strategy to minimize these risks clearly needs to be established. Argon plasma coagulation (APC) is a safe and convenient procedure now applied widely for therapeutic endoscopy. In this report we describe the successful use of APC over 6 years for the treatment of recurrent esophageal cancer after CRT. A 61-year-old Japanese man underwent CRT for a thoracic esophageal cancer. Pathological examination before CRT revealed a well-differentiated squamous cell carcinoma. Locoregional failure was observed 2 years after CRT, and an initial APC treatment was performed. The patient has now undergone APC ablation 7 times with no postoperative complications. No metastasis to lymph nodes or to other organs has been detected during the last 6 years. The usefulness of APC as a salvage treatment for locoregional failure after definitive CRT has not been established. In our experience, salvage APC is the best treatment option for some patients. (author)

  6. 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)

  7. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors

    DEFF Research Database (Denmark)

    Andrésdóttir, Gudbjörg; Jensen, Majken; Carstensen, Bendix

    2014-01-01

    OBJECTIVE: To evaluate long-term survival, development of renal end points, and decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and diabetic nephropathy (DN) after renin-angiotensin system (RAS) inhibition and multifactorial treatment of cardiovascular risk factors ha...

  8. Survival in Malnourished Older Patients Receiving Post-Discharge Nutritional Support; Long-Term Results of a Randomized Controlled Trial

    NARCIS (Netherlands)

    Neelemaat, F; van Keeken, S; Langius, J A E; de van der Schueren, M A E; Thijs, A; Bosmans, J E

    2017-01-01

    BACKGROUND: Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been

  9. Initial experience with locoregional radioimmunotherapy using {sup 131}I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

    Energy Technology Data Exchange (ETDEWEB)

    Poepperl, G.; Gildehaus, F.J.; Hahn, K.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum Grosshadern, Muenchen (Germany); Goetz, C.; Reulen, H.J. [Klinik und Poliklinik fuer Neurochirurgie, Klinikum Grosshadern, Muenchen (Germany); Yousry, T.A. [Inst. fuer Neuroradiologie der LMU Muenchen, Klinikum Grosshadern, Muenchen (Germany)

    2002-06-01

    Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq {sup 131}labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse anti-bodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remain stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n=89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration

  10. Predictive factors of long-term colorectal cancer survival after ultrasound-controlled ablation of hepatic metastases.

    Science.gov (United States)

    Hernández-Socorro, Carmen Rosa; Saavedra, Pedro; Ramírez Felipe, José; Bohn Sarmiento, Uriel; Ruiz-Santana, Sergio

    2017-04-21

    The risk factors associated to long-term survival were assessed in patients with liver metastases of colorectal carcinoma undergoing ablative therapies. Single-centre cohort study, retrospectively analysed and prospectively collected consecutive patients with unresectable metastatic liver disease of colorectal carcinoma treated with ablative therapies between 1996 and 2013. Factors associated with survival time were identified using Cox's proportional hazard model with time-dependent covariates. A forward variable selection based on Akaike information criterion was performed. Relative risk and 95% confidence intervals for each factor were calculated. Statistical significance was set as P<.05. Seventy-five patients with liver metastases of colorectal cancer, with a mean age of 65.6 (10.3) underwent 106 treatments. Variables selected were good quality of life (RR 0.308, 95% CI 0.150-0.632) and tumour extension (RR 3.070, 95% CI 1.776-5.308). The median overall survival was 18.5 months (95% CI 17.4-24.4). The survival prognosis in median was 13.5 vs. 23.4 months for patients with and without tumour extension, and 23.0 vs. 12.8 months for patients with good and fair or poor quality of life, respectively. Good quality of life and tumour extension were the only statistically significant predictors of long-term survival in patients of colorectal carcinoma with liver metastatic disease undergoing ablative treatment with ultrasound. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  11. Effect of Low Temperature and Wheat Winter-Hardiness on Survival of Puccinia striiformis f. sp. tritici under Controlled Conditions.

    Directory of Open Access Journals (Sweden)

    Lijie Ma

    Full Text Available Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst, is one of the most important diseases of wheat worldwide. Understanding the survival of Pst during the overwintering period is critical for predicting Pst epidemics in the spring. Real-time quantitative PCR (qPCR methods quantifying Pst DNA and RNA (cDNA were developed and compared for the ability to quantify viable Pst in leaf tissues. Both qPCR of DNA and RNA can provide reliable measurement of viable Pst in plant tissues prior to the late sporulation stage for which qPCR of DNA gave a much higher estimate of fungal biomass than qPCR of RNA. The percentage of Pst biomass that was viable in detached and attached leaves under low temperatures decreased over time. Pst survived longer on attached leaves than on detached leaves. The survival of Pst in cultivars with strong winter-hardiness at 0°C and -5°C was greater than those with weak winter-hardiness. However, such differences in Pst survival among cultivars were negligible at -10, -15 and -20°C. Results indicated that Pst mycelia inside green leaves can also be killed by low temperatures rather than through death of green leaves under low temperatures. The relationship of Pst survival in attached leaves with temperature and winter-hardiness was well described by logistic models. Further field evaluation is necessary to assess whether inclusion of other factors such as moisture and snow cover could improve the model performance in predicting Pst overwintering potential, and hence the epidemic in spring.

  12. A Phase II Trial of Brachytherapy Alone After Lumpectomy for Select Breast Cancer: Tumor Control and Survival Outcomes of RTOG 95-17

    International Nuclear Information System (INIS)

    Arthur, Douglas W.; Winter, Kathryn; Kuske, Robert R.; Bolton, John; Rabinovitch, Rachel; White, Julia; Hanson, William F.; Wilenzick, Raymond M.; McCormick, Beryl

    2008-01-01

    Purpose: Radiation Therapy Oncology Group 95-17 is a prospective Phase II cooperative group trial of accelerated partial breast irradiation (APBI) alone using multicatheter brachytherapy after lumpectomy in select early-stage breast cancers. Tumor control and survival outcomes are reported. Methods and Materials: Eligibility criteria included Stage I/II breast carcinoma confirmed to be <3 cm, unifocal, invasive nonlobular histology with zero to three positive axillary nodes without extracapsular extension. APBI treatment was delivered with either low-dose-rate (LDR) (45 Gy in 3.5-5 days) or high-dose-rate (HDR) brachytherapy (34 Gy in 10 twice-daily fractions over 5 days). End points evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival, and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison. Results: Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR brachytherapy and 33 treated with LDR brachytherapy. Eighty-seven patients had T1 lesions and 12 had T2 lesions. Seventy-nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional, and contralateral failure rates of 3%, 5%, and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional, and contralateral failure rates of 6%, 0%, and 6%, respectively. Conclusion: Patients treated with multicatheter partial breast brachytherapy in this trial experienced excellent in-breast control rates and overall outcome that compare with reports from APBI studies with similar extended follow-up

  13. Discussions on attitude determination and control system for micro/nano/pico-satellites considering survivability based on Hodoyoshi-3 and 4 experiences

    Science.gov (United States)

    Nakasuka, Shinichi; Miyata, Kikuko; Tsuruda, Yoshihiro; Aoyanagi, Yoshihide; Matsumoto, Takeshi

    2018-04-01

    The recent advancement of micro/nano/pico-satellites technologies encourages many universities to develop three axis stabilized satellites. As three axis stabilization is high level technology requiring the proper functioning of various sensors, actuators and control software, many early satellites failed in their initial operation phase because of shortage of solar power generation or inability to realize the initial step of missions because of unexpected attitude control system performance. These results come from failure to design the satellite attitude determination and control system (ADCS) appropriately and not considering "satellite survivability." ADCS should be designed such that even if some sensors or actuators cannot work as expected, the satellite can survive and carry out some of its missions, even if not full. This paper discusses how to realize ADCS while taking satellite survivability into account, based on our experiences of design and in-orbit operations of Hodoyoshi-3 and 4 satellites launched in 2014, which suffered from various component anomalies but could complete their missions.

  14. Pretreatment prognostic Factors in Early Stage Carcinoma of the Uterine Cervix

    International Nuclear Information System (INIS)

    Kim, Mi Sook; Ha, Sung Whan

    1992-01-01

    From March 1979 through December 1986, 124 patients with early stage carcinoma of the uterine cervix received curative radiation therapy. According to FIGO classification, 35 patients were stage IB and 89 were stage IIA. In stage IB, five year locoregional control, five year disease A, five year locoregional control, five disease free survival, and five year overall survival were 78.0%, 66.8%, and 72.1%, respectively. To identify prognostic factor, pretreatment including age, ECOG performance status, number of pregnancies, history of diabetes mellitus and hypertension, histology, size and shape of primary tumor, CT findings and blood parameters were retrospectively analyzed in terms of locoregional control, disease free survival and overall survival using univariate analysis and multivariate analysis. In univariate analysis, tumor size on physical examination and rectal invasion on CT significantly affected locoregional control, disease free survival and overal survival. Parametrial involvement on CT was a significant prognostic factor on locoregional control and disease free survival. Hemoglobin level affected disease free survival and overall survival. Histology and age were significant pronostic factor on locoregional control. In multivariate analysis excluding CT finding, tumor size on physical examination was a significant factor in terms of locoregional control and overall survival. Hemoglobin level was significant in terms of disease free survival. In multivarate analysis including CT, histology was a prognostic factor on locoregional control and disease free survival. Hemoglobin level and rectal invasion on CT were significant factors on locoregional control

  15. Toxicity and survival results of a phase II study investigating the role of postoperative chemoradioimmunotherapy for gastric adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bese, N.S.; Yildirim, A.; Oeber, A. [Dept. of Radiation Oncology, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey); Bueyuekuenal, E.; Oezgueroglu, M.; Demir, G.; Mandel, N.M.; Demirelli, F.; Serdengecti, S. [Dept. of Internal Medicine, Medical Oncology Section, Istanbul Univ., Cerrahpasa Medical School, Istanbul (Turkey)

    2005-10-01

    Background and purpose: to investigate the role of postoperative concomitant chemoradioimmunotherapy in gastric adenocarcinoma patients. Patients and methods: 59 pateints, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m{sup 2}/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m{sup 2}/day 5-FU and 25 mg/m{sup 2}/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). Results: median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. Conclusion: although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care. (orig.)

  16. Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: A randomized, controlled trial.

    Science.gov (United States)

    Klek, Stanislaw; Scislo, Lucyna; Walewska, Elzbieta; Choruz, Ryszard; Galas, Aleksander

    2017-04-01

    The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN). In all patients, short- and long-term (5 y) survival was analyzed. Analysis of the overall survival time did not reveal differences between groups (P = 0.663). Until the end of the third month, however, there were nine deaths in the standard enteral nutrition group and no deaths in the EEN group (16.7% versus 0.0%, P = 0.004). The univariate analyses suggested that the EEN group may have lower risk, especially during the first year after intervention. A significant reduction in the risk of death was seen during the early period after surgery (first 6 mo) in the EEN group in stage IV patients (hazard ratio = 0.25, P = 0.049). The use of enriched enteral diet did not influence, however, the risk of dying when patients were analyzed together. The study does not support the beneficial effect of enriched enteral nutrition in long-term survival; however, the positive impact on the stage IV patients suggests the need for further, more detailed studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.

    Science.gov (United States)

    Jacobs, Ian G; Finn, Judith C; Jelinek, George A; Oxer, Harry F; Thompson, Peter L

    2011-09-01

    There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest. We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC). A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR=3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR=2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2. Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Physical activity and survival among Hispanic and non-Hispanic white long-term breast cancer survivors and population-based controls.

    Science.gov (United States)

    Pinkston, Christina M; Baumgartner, Richard N; Connor, Avonne E; Boone, Stephanie D; Baumgartner, Kathy B

    2015-12-01

    We investigated the association of physical activity with survival for 601 Hispanic women and 682 non-Hispanic white women who participated in the population-based breast cancer case-control New Mexico Women's Health Study. We identified 240 deaths among cases diagnosed with a first primary invasive breast cancer between 1992 and 1994, and 88 deaths among controls. Follow-up extended through 2012 for cases and 2008 for controls. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Higher levels of total physical activity were inversely associated with all-cause mortality among Hispanic cases (Quartile (Q)4: HR = 0.55, 95% CI 0.31-0.99). A non-significant trend was observed for recreational activity in Hispanic cases also (Q4: HR = 0.50, 95% CI 0.23-1.09, p for trend = 0.08). No significant associations were noted for non-Hispanic white cases or for controls. The results suggest that increasing physical activity may be protective against mortality in Hispanic women with breast cancer, despite reporting lower levels of recreational activity than non-Hispanic white women or Hispanic controls. Public health programs in Hispanic communities should promote physical activity in women as a means of decreasing breast cancer risk and improving survival.

  19. Survivability enhancement study for C/sup 3/I/BM (communications, command, control and intelligence/battle management) ground segments: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1986-10-30

    This study involves a concept developed by the Fairchild Space Company which is directly applicable to the Strategic Defense Initiative (SDI) Program as well as other national security programs requiring reliable, secure and survivable telecommunications systems. The overall objective of this study program was to determine the feasibility of combining and integrating long-lived, compact, autonomous isotope power sources with fiber optic and other types of ground segments of the SDI communications, command, control and intelligence/battle management (C/sup 3/I/BM) system in order to significantly enhance the survivability of those critical systems, especially against the potential threats of electromagnetic pulse(s) (EMP) resulting from high altitude nuclear weapon explosion(s). 28 figs., 2 tabs.

  20. An osteoblast-derived proteinase controls tumor cell survival via TGF-beta activation in the bone microenvironment.

    Science.gov (United States)

    Thiolloy, Sophie; Edwards, James R; Fingleton, Barbara; Rifkin, Daniel B; Matrisian, Lynn M; Lynch, Conor C

    2012-01-01

    Breast to bone metastases frequently induce a "vicious cycle" in which osteoclast mediated bone resorption and proteolysis results in the release of bone matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis of human breast to bone metastases unexpectedly revealed that bone forming osteoblasts were consistently positive for the proteinase, MMP-2. Given the role of MMP-2 in extracellular matrix degradation and growth factor/cytokine processing, we tested whether osteoblast derived MMP-2 contributed to the vicious cycle of tumor progression in the bone microenvironment. To test our hypothesis, we utilized murine models of the osteolytic tumor-bone microenvironment in immunocompetent wild type and MMP-2 null mice. In longitudinal studies, we found that host MMP-2 significantly contributed to tumor progression in bone by protecting against apoptosis and promoting cancer cell survival (caspase-3; immunohistochemistry). Our data also indicate that host MMP-2 contributes to tumor induced osteolysis (μCT, histomorphometry). Further ex vivo/in vitro experiments with wild type and MMP-2 null osteoclast and osteoblast cultures identified that 1) the absence of MMP-2 did not have a deleterious effect on osteoclast function (cd11B isolation, osteoclast differentiation, transwell migration and dentin resorption assay); and 2) that osteoblast derived MMP-2 promoted tumor survival by regulating the bioavailability of TGFβ, a factor critical for cell-cell communication in the bone (ELISA, immunoblot assay, clonal and soft agar assays). Collectively, these studies identify a novel "mini-vicious cycle" between the osteoblast and metastatic cancer cells that is key for initial tumor survival in the bone microenvironment. In conclusion, the findings of our study suggest that the targeted inhibition of MMP-2 and/or TGFβ would be beneficial for the treatment of bone metastases.

  1. An osteoblast-derived proteinase controls tumor cell survival via TGF-beta activation in the bone microenvironment.

    Directory of Open Access Journals (Sweden)

    Sophie Thiolloy

    Full Text Available Breast to bone metastases frequently induce a "vicious cycle" in which osteoclast mediated bone resorption and proteolysis results in the release of bone matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis of human breast to bone metastases unexpectedly revealed that bone forming osteoblasts were consistently positive for the proteinase, MMP-2. Given the role of MMP-2 in extracellular matrix degradation and growth factor/cytokine processing, we tested whether osteoblast derived MMP-2 contributed to the vicious cycle of tumor progression in the bone microenvironment.To test our hypothesis, we utilized murine models of the osteolytic tumor-bone microenvironment in immunocompetent wild type and MMP-2 null mice. In longitudinal studies, we found that host MMP-2 significantly contributed to tumor progression in bone by protecting against apoptosis and promoting cancer cell survival (caspase-3; immunohistochemistry. Our data also indicate that host MMP-2 contributes to tumor induced osteolysis (μCT, histomorphometry. Further ex vivo/in vitro experiments with wild type and MMP-2 null osteoclast and osteoblast cultures identified that 1 the absence of MMP-2 did not have a deleterious effect on osteoclast function (cd11B isolation, osteoclast differentiation, transwell migration and dentin resorption assay; and 2 that osteoblast derived MMP-2 promoted tumor survival by regulating the bioavailability of TGFβ, a factor critical for cell-cell communication in the bone (ELISA, immunoblot assay, clonal and soft agar assays.Collectively, these studies identify a novel "mini-vicious cycle" between the osteoblast and metastatic cancer cells that is key for initial tumor survival in the bone microenvironment. In conclusion, the findings of our study suggest that the targeted inhibition of MMP-2 and/or TGFβ would be beneficial for the treatment of bone metastases.

  2. Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

    International Nuclear Information System (INIS)

    Matsunuma, Ryoichi; Oguchi, Masahiko; Fujikane, Tomoko; Matsuura, Masaaki; Sakai, Takehiko; Kimura, Kiyomi; Morizono, Hidetomo; Iijima, Kotaro; Izumori, Ayumi; Miyagi, Yumi; Nishimura, Seiichiro; Makita, Masujiro; Gomi, Naoya; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji

    2012-01-01

    Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status. Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.

  3. Dosimetric assessment of an Atlas based automated segmentation for loco-regional radiation therapy of early breast cancer in the Skagen Trial 1: A multi-institutional study

    DEFF Research Database (Denmark)

    Ibrahim, Ahmed Ramadan Mohammed E; Francolini, Giulio; Thomsen, Mette Skovhus

    2017-01-01

    The effect of Atlas-based automated segmentation (ABAS) on dose volume histogram (DVH) parameters compared to manual segmentation (MS) in loco-regional radiotherapy (RT) of early breast cancer was investigated in patients included in the Skagen Trial 1. This analysis supports implementation of ABAS...

  4. Locoregional recurrence after breast-conserving therapy remains an independent prognostic factor even after an event free interval of 10 years in early stage breast cancer

    NARCIS (Netherlands)

    Tanis, E.; van de Velde, C. J. H.; Bartelink, H.; van de Vijver, M. J.; Putter, H.; van der Hage, J. A.

    2012-01-01

    Locoregional recurrence (LRR) after breast-conserving therapy is a well-known independent risk factor associated with unfavourable long-term outcome. Controversy exists concerning the prognostic impact of a LRR after a very long event-free interval. Patients who underwent breast-conserving therapy

  5. Personalisation of breast cancer follow-up: a time-dependent prognostic nomogram for the estimation of annual risk of locoregional recurrence in early breast cancer patients

    NARCIS (Netherlands)

    Witteveen, Annemieke; Vliegen, Ingrid; Sonke, Gabe S.; Klaase, Joost M.; IJzerman, Maarten Joost; Siesling, Sabine

    2015-01-01

    The objective of this study was to develop and validate a time-dependent logistic regression model for prediction of locoregional recurrence (LRR) of breast cancer and a web-based nomogram for clinical decision support. Women first diagnosed with early breast cancer between 2003 and 2006 in all

  6. Towards personalized follow-up : a conditional prediction model and nomogram for risk of locoregional recurrence in early breast cancer patients

    NARCIS (Netherlands)

    Witteveen, Annemieke; Vliegen, Ingrid; Sonke, G.S.; Klaase, J.M.; IJzerman, Maarten Joost; Siesling, Sabine

    2015-01-01

    Background The objective of this study was to develop and validate a conditional logistic regression model for the prediction of locoregional recurrence (LRR) of breast cancer. To make a translation to clinical practice a web based nomogram was made. Methods Women first diagnosed with early breast

  7. Treatment strategies and survival of older breast cancer patients - an international comparison between the Netherlands and Ireland.

    Science.gov (United States)

    Kiderlen, Mandy; Walsh, Paul M; Bastiaannet, Esther; Kelly, Maria B; Audisio, Riccardo A; Boelens, Petra G; Brown, Chris; Dekkers, Olaf M; de Craen, Anton J M; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

    2015-01-01

    Forty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland. From the Dutch and Irish national cancer registries, women aged ≥65 years with non-metastatic breast cancer were included (2001-2009). Proportions of patients receiving guideline-adherent locoregional treatment, endocrine therapy, and chemotherapy were calculated and compared between the countries by stage. Secondly, 5-year relative survival was calculated by stage and compared between countries. Overall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted pNetherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients. Treatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer patients across Europe.

  8. Effecst of Patho- Biological Factors on the Survival of Recurrent Breast Cancer Cases

    Science.gov (United States)

    Akbari, Mohammad Esmaeil; Rohani- Rasaf, Marzieh; Nafissi, Nahid; Akbari, Atieh; Shojaee, Leyla

    2018-04-25

    Background: Recurrence of breast cancer after treatment is generally due to loco-regional invasion or distant metastasis. Although patients with metastasis are considered incurable, existing treatments might prolong a patient’s life while also improving its quality. Choice of approach for individual patients requires identification of relevant survival factors. This study concerns factors influencing survival after recurrence in Iranian breast cancer patients. Methods: This study was performed on 442 recurrent breast cancer patients referred to the Cancer Research Center of Shahid Beheshti University between 1985 and 2015. After confirming recurrence as a distant metastasis or loco-regional invasion, the effects of demographic, clinic-pathologic, biological, type of surgery and type of adjuvant treatment on survival were evaluated using univariate and multivariate stratified Cox models. Results: The mean survival after recurrence was 18 months (5 days to 13 years), 219 patients (70.42%) survived two years, 75 patients (24.12%) survived from 2 to 5 years, and 17 patients (5.47%) survived more than 5 years. In this study, it was found through univariate analysis that the factors of age, lymph node status, DFI, place of recurrence and nodal ratio demonstrated greatest influence on survival after recurrence. On multivariate analysis, the most important factors influencing survival were the place of recurrence and the lymph node status. Conclusion: The results of this study enhance our knowledge of effects of different factors on survival of patients after breast cancer recurrence. Thus, they may be used to inform treatment choice. Creative Commons Attribution License

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  10. Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner.

    Science.gov (United States)

    Xie, Liang; Duncan, Michael B; Pahler, Jessica; Sugimoto, Hikaru; Martino, Margot; Lively, Julie; Mundel, Thomas; Soubasakos, Mary; Rubin, Kristofer; Takeda, Takaaki; Inoue, Masahiro; Lawler, Jack; Hynes, Richard O; Hanahan, Douglas; Kalluri, Raghu

    2011-06-14

    Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis.

  11. Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner

    Science.gov (United States)

    Xie, Liang; Duncan, Michael B.; Pahler, Jessica; Sugimoto, Hikaru; Martino, Margot; Lively, Julie; Mundel, Thomas; Soubasakos, Mary; Rubin, Kristofer; Takeda, Takaaki; Inoue, Masahiro; Lawler, Jack; Hynes, Richard O.; Hanahan, Douglas; Kalluri, Raghu

    2011-01-01

    Whereas the roles of proangiogenic factors in carcinogenesis are well established, those of endogenous angiogenesis inhibitors (EAIs) remain to be fully elaborated. We investigated the roles of three EAIs during de novo tumorigenesis to further test the angiogenic balance hypothesis, which suggests that blood vessel development in the tumor microenvironment can be governed by a net loss of negative regulators of angiogenesis in addition to the well-established principle of up-regulated angiogenesis inducers. In a mouse model of pancreatic neuroendocrine cancer, administration of endostatin, thrombospondin-1, and tumstatin peptides, as well as deletion of their genes, reveal neoplastic stage-specific effects on angiogenesis, tumor progression, and survival, correlating with endothelial expression of their receptors. Deletion of tumstatin and thrombospondin-1 in mice lacking the p53 tumor suppressor gene leads to increased incidence and reduced latency of angiogenic lymphomas associated with diminished overall survival. The results demonstrate that EAIs are part of a balance mechanism regulating tumor angiogenesis, serving as intrinsic microenvironmental barriers to tumorigenesis. PMID:21622854

  12. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  13. A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis

    International Nuclear Information System (INIS)

    Pelz, Joerg OW; Doerfer, Joerg; Hohenberger, Werner; Meyer, Thomas

    2005-01-01

    Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m 2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m 2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality

  14. FDG uptake and glut-1 expression in primary tumors and loco-regional lymph nodes in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Lee, Won Woo; Nguyen, Xuan Canh; Chung, Jin Haeng; Park, So Yeon; Kim, Sang Eun

    2007-01-01

    FDG uptake level by primary tumors in NSCLC may affect the likelihood of malignant involvement in loco-regional lymph nodes (LNs). FDG uptake in tumors has been reported to be mediated by glucose transporter type 1 (Glut-I). Here, we investigated the correlations between primary tumors and loco-regional LNs in NSCLC regarding FDG uptake and Glut-1 expression. 126 NSCLC patients (M: F=103: 23, age=659.7y) who underwent curative resection and loco-regional LN dissection within 4 week period after FDG-PET study were enrolled. Maximum standardized uptake value (maxSUV) by PET and %Glut-1 expression by immunostaining were compared between primary tumors and FDG uptake positive loco-regional LNs. Significant correlations were found between 52 malignant LNs and 37 primary tumors in terms of maxSUV (r=0.6451, p<0.0001) and %Glut-1 expression (r=0.8341, p<0.0001). Linear regression of the relation between maxSUVs of malignant LNs (Y) and maxSUVs of primary tumors (X) yielded the expression Y = 0.5938 + 0.4808 X with an r2 value of 0.4162. On the other hand, no significant correlation was observed between 144 benign LNs and 75 primary tumors in terms of maxSUVs (r= -0.0125, p 0.8831). Moreover, %Glut-1 expressions of pathologically proven benign LNs and primary tumors were found to be correlated (r=0.3863, p=0.0004), but r2 value was low at 0.1492. High correlations were found between primary tumors and loco-regional metastatic LNs in NSCLC regarding FDG uptake and Glut-1 expression. Mediastinal LN staging of NSCLC by FDG-PET may be improved by considering the linear correlation between FDG uptakes of metastatic LNs and primary tumors

  15. The INCA trial (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Casper, Markus; Mengel, Martin; Fuhrmann, Christine; Herrmann, Eva; Appenrodt, Beate; Schiedermaier, Peter; Reichert, Matthias; Bruns, Tony; Engelmann, Cornelius; Grünhage, Frank; Lammert, Frank

    2015-03-08

    Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP. The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms. German Clinical Trials Register DRKS00005616 . Registered 22 January 2014. EU Clinical Trials Register EudraCT 2013-001626-26 . Registered 26 January 2015.

  16. High survival rates of Campylobacter coli under different stress conditions suggest that more rigorous food control measures might be needed in Brazil.

    Science.gov (United States)

    Gomes, Carolina N; Passaglia, Jaqueline; Vilela, Felipe P; Pereira da Silva, Fátima M H S; Duque, Sheila S; Falcão, Juliana P

    2018-08-01

    Campylobacter spp. have been the most commonly reported gastrointestinal bacterial pathogen in many countries. Consumption of improperly prepared poultry meat has been the main transmission route of Campylobacter spp. Although Brazil is the largest exporter of poultry meat in the world, campylobacteriosis has been a neglected disease in the country. The aim of this study was to characterize 50 Campylobacter coli strains isolated from different sources in Brazil regarding the frequency of 16 virulence genes and their survival capability under five different stress conditions. All strains studied presented the cadF, flaA, and sodB genes that are considered essential for colonization. All strains grew at 4 °C and 37 °C after 24 h. High survival rates were observed when the strains were incubated in BHI with 7.5% NaCl and exposed to acid and oxidative stress. In conclusion, the pathogenic potential of the strains studied was reinforced by the presence of several important virulence genes and by the high growth and survival rates of the majority of those strains under different stress conditions. The results enabled a better understanding of strains circulating in Brazil and suggest that more rigorous control measures may be needed, given the importance of contaminated food as vehicles for Campylobacter coli. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Identification of Risk Factors for Locoregional Recurrence in Breast Cancer Patients with Nodal Stage N0 and N1: Who Could Benefit from Post-Mastectomy Radiotherapy?

    Directory of Open Access Journals (Sweden)

    Eunjin Jwa

    Full Text Available The locoregional recurrence (LRR rate was reported as high as approximately 20% in stage I-II breast cancer following mastectomy. To investigate the risk factors for LRR in pT1-2N0-1 breast cancer patients treated with mastectomy but not radiation, and to define a subgroup of patients at high risk of LRR who may benefit from postmastectomy radiotherapy (PMRT.In total, 390 patients with pT1-2N0M0 (n = 307 and pT1-2N1M0 (n = 83 breast cancer who underwent total mastectomy without adjuvant radiotherapy from 2002 to 2011 were enrolled in the study.After a median follow-up period of 5.6 years (range, 0.6-11.3 years, 21 patients had 18 systemic relapses and 12 LRRs including six in the chest wall and eight in the regional nodal area. The 5-year LRR-free survival (LRRFS rates were 97.0% in pN0, 98.8% in pN1, and 97.4% in all patients. Multivariate analysis revealed that age < 50 years (Hazard Ratio, 11.4; p = 0.01 and no adjuvant chemotherapy (Hazard Ratio, 10.2; p = 0.04 were independent risk factors for LRR in pN0 patients. Using these factors, the 5-year LRRFS rates were 100% without any risk factors, 96.4% with one risk factor, and 86.7% with two risk factors. In pN1 patients, multivariate analysis revealed that having a hormone receptor negative tumor (Hazard Ratio, 18.3; p = 0.03 was the only independent risk factor for LRR. The 5-year LRRFS rates were 100.0% for luminal type, and 92.3% for non-luminal type cancer.Patients with pT1-2N0-1 breast cancer who underwent total mastectomy without PMRT could be stratified by nodal stage and risk factors for LRR. PMRT may have of value for node negative patients aged less than 50 years and who are not treated with adjuvant chemotherapy, and for non-luminal type patients with one to three positive nodes.

  18. A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up.

    Science.gov (United States)

    Stagl, Jamie M; Lechner, Suzanne C; Carver, Charles S; Bouchard, Laura C; Gudenkauf, Lisa M; Jutagir, Devika R; Diaz, Alain; Yu, Qilu; Blomberg, Bonnie B; Ironson, Gail; Glück, Stefan; Antoni, Michael H

    2015-11-01

    Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8-15 years post-enrollment. From 1998 to 2005, women (N = 240) 2-10 weeks post-surgery for non-metastatic Stage 0-IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8-15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

  19. Randomized, placebo controlled study of the effect of propentofylline on survival time and quality of life of cats with feline infectious peritonitis.

    Science.gov (United States)

    Fischer, Y; Ritz, S; Weber, K; Sauter-Louis, C; Hartmann, K

    2011-01-01

    Currently there is no drug proven to effectively treat cats with feline infectious peritonitis (FIP). Propentofylline (PPF) can decrease vasculitis, and therefore prolong survival time in cats with FIP, and increase their quality of life. Twenty-three privately owned cats with FIP. Placebo-controlled double-blind trial. FIP was confirmed by histology or immunostaining of feline coronavirus (FCoV) antigen in effusion or tissue macrophages or both. The cats were randomly selected for treatment with either PPF or placebo. All cats received additional treatment with glucocorticoids, antibiotics, and low molecular weight heparin according to methods. There was no statistically significant difference in the survival time of cats treated with PPF (8 days, 95% CI 5.4-10.6) versus placebo (7.5 days, 95% CI 4.4-9.6). The median survival time of all cats was 8 days (4-36 days). There was neither a difference in quality of life (day 7, P = .892), in the amount of effusion (day 7, P = .710), the tumor necrosis factor-alpha (TNF-α) concentration (day 7, P = .355), nor in any other variable investigated in this study, including a complete blood count, and a small animal biochemistry profile. This study did not detect an effect of PPF on the survival time, the quality of life, or any clinical or laboratory parameter in cats with FIP. Therefore, PPF does not appear to be an effective treatment option in cats with a late stage of the disease FIP. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  20. Conservation biological control in strawberry: effect of different pollen on development, survival, and reproduction of Neoseiulus californicus (Acari: Phytoseiidae).

    Science.gov (United States)

    Gugole Ottaviano, María F; Cédola, Claudia V; Sánchez, Norma E; Greco, Nancy M

    2015-12-01

    Wild vegetation surrounding crops may provide temporary habitat and potential food sources for phytoseiids in different seasons. Monthly vegetation samples of wild plants adjacent to strawberry plants and wild plants in a vegetation strip close to the crop were taken. The frequency of Neoseiulus californicus, Tetranychus urticae and other mites and insects was recorded. In addition, in a laboratory assay, the survival, developmental time and fecundity of females fed on pollen of strawberry and pollen of wild plants where N. californicus was recorded during their flowering, were estimated. Pollen from Urtica urens, Lamium amplexicaule, Convolvulus arvensis, Sonchus oleraceous, Galega officinalis, and Fragaria x ananassa (strawberry) allowed development of N. californicus to adult, but not reproduction. Survival was 70-80 % when fed on pollen from S. oleraceus, G. officinalis and C. arvensis, 80-90 % when fed on pollen from U. urens and F. x ananassa, and more than 90 % when fed on T. urticae and on pollen from L. amplexicaule. In autumn and winter, U. urens, L. amplexicaule and S. oleraceous could promote the persistence of N. californicus when prey density in strawberry is low, offering T. urticae, thrips and pollen. In summer, pollen of C. arvensis and G. officinalis would contribute to the persistence of N. californicus when the strawberry crop is ending and offers scarce food resources. Although the pollen of these plants would not enable the predator population to increase, the presence of these plants in the vicinity of strawberry could contribute to the persistence of N. californicus population and help to limit T. urticae growth when this pest begins to colonize the crop.

  1. Survival and local control rates of triple-negative breast cancer patients treated with boost-IOERT during breast-conserving surgery

    Energy Technology Data Exchange (ETDEWEB)

    Fastner, Gerd; Zehentmayr, Franz; Kopp, Peter; Fussl, Christoph; Sedlmayer, Felix [Landeskrankenhaus, Paracelsus Medical University, Department of Radiotherapy and Radio-Oncology, Salzburg (Austria); Hauser-Kronberger, Cornelia [Landeskrankenhaus, Paracelsus Medical University, Department of Pathology, Salzburg (Austria); Moder, Angelika [Landeskrankenhaus, Paracelsus Medical University, Institute of Inborn Errors in Metabolism, Salzburg (Austria); Reitsamer, Roland; Fischer, Thorsten [Landeskrankenhaus, Paracelsus Medical University, Department of Special Gynecology, Salzburg (Austria); Landeskrankenhaus, Paracelsus Medical University, Department of Gynecology, Salzburg (Austria); Deutschmann, Heinrich [Landeskrankenhaus, Paracelsus Medical University, Department of Radiotherapy and Radio-Oncology, Salzburg (Austria); Paracelsus Medical University, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria)

    2016-01-15

    The purpose of this work was to retrospectively evaluate survival and local control rates of triple-negative breast cancer subtypes classified as five marker negative (5NP) and core basal (CB), respectively, after breast-conserving surgery and intraoperative boost radiotherapy with electrons (IOERT) followed by whole breast irradiation. A total of 71 patients with triple-negative breast cancer were enrolled, who were treated with lumpectomy, axillary lymph node dissection, and IOERT with 9.6 Gy (median D{sub max}) followed by normofractionated whole breast irradiation to median total doses of 54 Gy. Chemotherapy was applied in a neoadjuvant (12 %), adjuvant (75 %), or combinational setting (7 %). After a median follow-up of 97 months (range 4-170 months), 5 in-breast recurrences were detected (7.0 %). For all patients, 8-year actuarial rates for local control, metastases-free survival, disease-specific survival, and overall survival amounted to 89, 75, 80, and 69 %, respectively. All local recurrences occurred in grade 3 (G3) tumors irrespective of their specific immunohistochemical phenotype; thus, the local control rate for grades 1/2 (G1/2) was 100 % for both 5NP and CB, while for G3 it was 88 % for 5NP and 90 % for CB (p = 0.65 and 0.82, respectively, n.s.). For disease-specific survival, only the difference of the best-prognosis group 5-NP/G3 vs. the worst-prognosis cohort CB/G1/2 was statistically significant: 90 % vs. 54 % (p = 0.03). Boost-IOERT provides acceptable long-term in-breast control in triple negative breast cancer. The best subgroup in terms of disease-specific survival was represented by 5NP in combination with tumor grading G3. (orig.) [German] Ziel der Studie war es, im Rahmen einer retrospektiven Analyse Ueberlebens- und Lokalkontrollraten bei triple-negativen Mammakarzinomen zu untersuchen. Die Tumoren waren in 5NP(5-Marker-negative)- und CB(core basal)-Subtypen klassifiziert und die Patientinnen hatten nach brusterhaltender Operation und

  2. GCN5 regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress via controlling gene expressions of Syk and Btk.

    Science.gov (United States)

    Kikuchi, Hidehiko; Kuribayashi, Futoshi; Takami, Yasunari; Imajoh-Ohmi, Shinobu; Nakayama, Tatsuo

    2011-02-25

    Histone acetyltransferase(s) (HATs) are involved in the acetylation of core histones, which is an important event for transcription regulation through alterations in the chromatin structure in eukaryotes. General control non-depressible 5 (GCN5) was first identified as a global coactivator and transcription-related HAT. Here we report that GCN5 regulates the activation of phosphatidylinositol 3-kinase (PI3K)/acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) survival pathway in B cells exposed to oxidative stress via controlling gene expressions of spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk). The GCN5-deficiency remarkably caused apoptotic cell death by treatment with exogenous hydrogen peroxide (H(2)O(2)) in chicken DT40 cells. In GCN5-deficient DT40 cells, gene expressions of Syk and Btk, which are involved in activation of PI3K/Akt survival pathway in DT40 cells exposed to exogenous H(2)O(2), were remarkably decreased compared with those in wild type DT40 cells. In addition, phosphorylation of Akt in H(2)O(2)-treated GCN5-deficient cells was remarkably suppressed as compared to that of DT40. Chromatin immunoprecipitation assay revealed that GCN5 binds to proximal 5'-upstream regions of Syk and Btk genes in vivo. These results suggest that GCN5 takes part in transcriptional regulations of the Syk and Btk genes, and plays a key role in epigenetic regulation of PI3K/Akt survival pathway in B cells exposed to reactive oxygen species such as H(2)O(2). Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival.

    Science.gov (United States)

    Eaton, Bree R; Esiashvili, Natia; Kim, Sungjin; Weyman, Elizabeth A; Thornton, Lauren T; Mazewski, Claire; MacDonald, Tobey; Ebb, David; MacDonald, Shannon M; Tarbell, Nancy J; Yock, Torunn I

    2016-01-01

    The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Survival of Antibiotic Resistant Bacteria and Horizontal Gene Transfer Control Antibiotic Resistance Gene Content in Anaerobic Digesters.

    Science.gov (United States)

    Miller, Jennifer H; Novak, John T; Knocke, William R; Pruden, Amy

    2016-01-01

    Understanding fate of antibiotic resistant bacteria (ARB) vs. their antibiotic resistance genes (ARGs) during wastewater sludge treatment is critical in order to reduce the spread of antibiotic resistance through process optimization. Here, we spiked high concentrations of tetracycline-resistant bacteria, isolated from mesophilic (Iso M1-1-a Pseudomonas sp.) and thermophilic (Iso T10-a Bacillus sp.) anaerobic digested sludge, into batch digesters and monitored their fate by plate counts and quantitative polymerase chain reaction (QPCR) of their corresponding tetracycline ARGs. In batch studies, spiked ARB plate counts returned to baseline (thermophilic) or 1-log above baseline (mesophilic) while levels of the ARG present in the spiked isolate [tet(G)] remained high in mesophilic batch reactors. To compare results under semi-continuous flow conditions with natural influent variation, tet(O), tet(W), and sul1 ARGs, along with the intI1 integrase gene, were monitored over a 9-month period in the raw feed sludge and effluent sludge of lab-scale thermophilic and mesophilic anaerobic digesters. sul1 and intI1 in mesophilic and thermophilic digesters correlated positively (Spearman rho = 0.457-0.829, P < 0.05) with the raw feed sludge. There was no correlation in tet(O) or tet(W) ratios in raw sludge and mesophilic digested sludge or thermophilic digested sludge (Spearman rho = 0.130-0.486, P = 0.075-0.612). However, in the thermophilic digester, the tet(O) and tet(W) ratios remained consistently low over the entire monitoring period. We conclude that the influent sludge microbial composition can influence the ARG content of a digester, apparently as a result of differential survival or death of ARBs or horizontal gene transfer of genes between raw sludge ARBs and the digester microbial community. Notably, mesophilic digestion was more susceptible to ARG intrusion than thermophilic digestion, which may be attributed to a higher rate of ARB survival and/or horizontal gene

  5. Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II–III resectable rectal cancer: a meta-analysis of randomized controlled trials

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jin Ho [Gyeongsang National University School of Medicine, Jinju (Korea, Republic of); Jeong, Jae Uk [Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Lee, Jong Hoon; Kim, Sung Hwan [The Catholic University of Korea, Suwon (Korea, Republic of); Cho, Hyeon Min [The Catholic University of Korea, Suwon (Korea, Republic of); Um, Jun Won [University Ansan Hospital, Ansan (Korea, Republic of); Jang, Hong Seok [The Catholic University of Korea, Seoul (Korea, Republic of)

    2017-09-15

    Whether preoperative chemoradiotherapy (CRT) is better than postoperative CRT in oncologic outcome and toxicity is contentious in prospective randomized clinical trials. We systematically analyze and compare the treatment result, toxicity, and sphincter preservation rate between preoperative CRT and postoperative CRT in stage II–III rectal cancer. We searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant trials. Only phase III randomized studies performing CRT and curative surgery were selected and the data were extracted. Meta-analysis was used to pool oncologic outcome and toxicity data across studies. Three randomized phase III trials were finally identified. The meta-analysis results showed significantly lower 5-year locoregional recurrence rate in the preoperative-CRT group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence interval, 0.41–0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55), relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no significant difference between two groups. Acute toxicity was significantly lower in the preoperativeCRT group than in the postoperative-CRT group (p < 0.001). However, there was no significant difference between two groups in perioperative and chronic complications (p = 0.53). The sphincter-saving rate was not significantly different between two groups (p = 0.24). The conversion rate from abdominoperineal resection to low anterior resection in low rectal cancer was significantly higher in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). As compared to postoperative CRT, preoperative CRT improves only locoregional control, not distant control and survival, with similar chronic toxicity and sphincter preservation rate in rectal cancer patients.

  6. Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis.

    Science.gov (United States)

    Fazeli, Bahare; Ravari, Hassan; Assadi, Reza

    2012-08-01

    The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan-Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.

  7. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Etienne Danis

    2016-03-01

    Full Text Available Early T cell precursor acute lymphoblastic leukemia (ETP-ALL is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients.

  8. Sorafenib and locoregional deep electro-hyperthermia in advanced hepatocellular carcinoma: A phase II study

    Science.gov (United States)

    GADALETA-CALDAROLA, GENNARO; INFUSINO, STEFANIA; GALISE, IDA; RANIERI, GIROLAMO; VINCIARELLI, GIANLUCA; FAZIO, VITO; DIVELLA, ROSA; DANIELE, ANTONELLA; FILIPPELLI, GIANFRANCO; GADALETA, COSMO DAMIANO

    2014-01-01

    The standard treatment for advanced hepatocellular carcinoma (HCC) is sorafenib, a multikinase inhibitor of tumor cell proliferation and angiogenesis. Hyperthermia inhibits angiogenesis and promotes apoptosis. Potential synergic antiangiogenic and proapoptotic effects represent the rationale for combining sorafenib with electro-hyperthermia (EHY) in HCC. A total of 21 patients (median age, 64 years; range, 55–73 years) with advanced HCC were enrolled in the current study between February 2009 and September 2010. EHY was achieved by arranging capacitive electrodes with a deep hypothermia radiofrequency field of 13.56 Mhz at 80 W for 60 min, three times per week for six weeks, followed by two weeks without treatment, in combination with sorafenib at a dose of 800 mg every other day. According to the modified Response Evaluation Criteria in Solid Tumors criteria, 50% achieved stable disease, 5% achieved partial response and 45% achieved progressive disease. No complete response was observed. The progression-free survival (PFS) rate at six months was 38%, while the median PFS and overall survival times were 5.2 [95% confidence interval (CI), 4.2–6.2) and 10.4 (95% CI, 10–11) months, respectively. The overall incidence of treatment-related adverse events was 80%, predominantly of grade 1 or 2. Grade 3 toxicity included fatigue, diarrhea, hand-foot skin reaction and hypertension. In the present study, the sorafenib plus EHY combination was feasible and well tolerated, and no major complications were observed. The initial findings indicated that this combination offers a promising option for advanced HCC. PMID:25202410

  9. Activity and Life After Survival of a Cardiac Arrest (ALASCA and the effectiveness of an early intervention service: design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bakx Wilbert GM

    2007-08-01

    Full Text Available Abstract Background Cardiac arrest survivors may experience hypoxic brain injury that results in cognitive impairments which frequently remain unrecognised. This may lead to limitations in daily activities and participation in society, a decreased quality of life for the patient, and a high strain for the caregiver. Publications about interventions directed at improving quality of life after survival of a cardiac arrest are scarce. Therefore, evidence about effective rehabilitation programmes for cardiac arrest survivors is urgently needed. This paper presents the design of the ALASCA (Activity and Life After Survival of a Cardiac Arrest trial, a randomised, controlled clinical trial to evaluate the effects of a new early intervention service for survivors of a cardiac arrest and their caregivers. Methods/design The study population comprises all people who survive two weeks after a cardiac arrest and are admitted to one of the participating hospitals in the Southern part of the Netherlands. In a two-group randomised, controlled clinical trial, half of the participants will receive an early intervention service. The early intervention service consists of several consultations with a specialised nurse for the patient and their caregiver during the first three months after the cardiac arrest. The intervention is directed at screening for cognitive problems, provision of informational, emotional and practical support, and stimulating self-management. If necessary, referral to specialised care can take place. Persons in the control group will receive the care as usual. The primary outcome measures are the extent of participation in society and quality of life of the patient one year after a cardiac arrest. Secondary outcome measures are the level of cognitive, emotional and cardiovascular impairment and daily functioning of the patient, as well as the strain for and quality of life of the caregiver. Participants and their caregivers will be followed

  10. Long term (five-year survival following radical surgical treatment plus adjuvant chemotherapy (FAM in advanced gastric cancer: a controlled study

    Directory of Open Access Journals (Sweden)

    Bresciani Cláudio

    2000-01-01

    Full Text Available Several drugs and their associations are being used for adjuvant or complementary chemotherapy with the aim of improving results of gastric cancer treatment. The objective of this study was to verify the impact of these drugs on nutrition and on survival rate after radical treatment of 53 patients with gastric cancer in stage III of the TNM classification. A control group including 28 patients who had only undergone radical resection was compared to a group of 25 patients who underwent the same operative technique followed by adjuvant polychemotherapy with FAM (5-fluorouracil, Adriamycin, and mitomycin C. In this latter group, chemotherapy toxicity in relation to hepatic, renal, cardiologic, neurological, hematologic, gastrointestinal, and dermatological functions was also studied. There was no significant difference on admission between both groups in relation to gender, race, macroscopic tumoral type of tumor according to the Borrmann classification, location of the tumor in the stomach, length of the gastric resection, or response to cutaneous tests on delayed sensitivity. Chemotherapy was started on average, 2.3 months following surgical treatment. Clinical and laboratory follow-up of all patients continued for 5 years. The following conclusions were reached: 1 The nutritional status and incidence of gastrointestinal manifestation were similar in both groups; 2 There was no occurrence of cardiac, renal, neurological, or hepatic toxicity or death due to the chemotherapeutic method per se; 3 Dermatological alterations and hematological toxicity occurred exclusively in patients who underwent polychemotherapy; 4 There was no significant difference between the rate and site of tumoral recurrence, the disease-free interval, or the survival rate of both study groups; 5 Therefore, we concluded, after a 5-year follow-up, chemotherapy with the FAM regimen did not increase the survival rate.

  11. Hemodialysis versus peritoneal dialysis: a case control study of survival in patients with chronic kidney disease stage 5

    DEFF Research Database (Denmark)

    Maier, Alexandra; Stocks, Franziska; Pommer, Wolfgang

    2009-01-01

    It is still controversial whether the mode of dialysis or preexisting comorbidities may influence the prognosis of patients with chronic kidney disease stage 5. Therefore, we performed a prospective case control study to evaluate whether the mode of dialysis may influence outcome. We found 25 cas...

  12. The regulatory BCL2 promoter polymorphism (-938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Lehnerdt, G F; Franz, P; Bankfalvi, A; Grehl, S; Kelava, A; Nückel, H; Lang, S; Schmid, K W; Siffert, W; Bachmann, H S

    2009-06-01

    Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients' survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (-938C>A) SNP on survival of patients suffering from OSCC. One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. The (-938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan-Meier curves revealed a significant association of the -938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013). The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.

  13. Combined radiotherapy and surgery : Local control and complications in early carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Gerbaulet, A.L.; Haie, C.; Michel, G.; Prade, M.; Lhomme, C.; Masselot, M.; Albano, M.; Dutreix, A.; Chassagne, D.; Kunkler, I.H.; Kerr, G.R.

    1992-01-01

    From January 1975 to December 1984, 41 patients were treated by combined radiotherapy and surgery at Institut Gustave Roussy for Stage IB (288) and II (proximal) (103) carcinoma of uterine cervix. Standard treatment consisted of pre-operative utero-vaginal brachytherapy (60 Gy) using a mould technique followed by colpho-hysterectomy and external iliac lymphadenectomy. Overall 5 year actuarial survival for whole population was 87% and disease-free survival 85%. Locoregional relapse occurred in 23 patients (5%). Of these, 12 where central pelvic failures, 8 regional failures and 3 combined central and regional failures. Of 36 systemic relapses (8%), 12 relapsed concurrently in pelvis. Five year actuarial pelvic disease-free, disease-free and overall survival was 87, 85 and 87%, resp., for the whole population. 340 patients developed one or more complications [Grade 1: 198/441 (44%), Grade 2: 121/441 (27%) and Grade 3 or 4: 21/441 (4.7%)]. Five year actuarial survival for the whole population was poorer for histologically node positive than for node negative (89 vs. 55%, p<0.0001). Pre-operative brachytherapy by surgery can provide good local control with acceptable morbidity in early cervical cancer. (author). 39 refs.; 4 figs.; 4 tabs

  14. Preliminary clinical results of locoregional hyperthermia for primary and secondary bone tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, J.L.; Nagata, Yasushi; Kanamori, Shuichi; Mitsumori, Michihide; Okuno, Yoshishige; Horii, Naotoshi; Nishimura, Yasumasa; Masunaga, Shinitiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-03-01

    Nineteen primary and secondary bone tumors in 16 patients were treated with hyperthermia plus radiotherapy and/or chemotherapy between 1982 and 1997 at Kyoto University Hospital. The thermometric and clinical results were analyzed retrospectively. In 55 of 86 hyperthermia sessions, the intratumor temperature was measured using a thermometer. Of the 19 tumors, 16 (84%) received heat treatment 4-7 times, and 3 (16%) received 1 or 2 treatments of hyperthermia. The mean maximum, mean minimum and average intratumor temperatures were 42.9, 40.4 and 41.6 deg C, respectively, and 12 (67%) reached a tumor maximum temperature above 42.5 deg C. The durations that intratumor points exceeded 42, 41 and 40 deg C were 27, 34 and 38 min, respectively. The local tumor response to treatment was assessed using X-ray computed tomography. The local response rate was 16% and the local pain relief rate was 63%. The 1-year cumulative survival rate was 60%. Our preliminary results indicated that thermoradiotherapy and thermochemotherapy are clinicaly feasible and potentially beneficial in the management of locally advanced bone tumors. (author)

  15. Survival of Betta splendens fish (Regan, 1910) in domestic water containers and its effectiveness in controlling Aedes aegypti larvae (Linnaeus, 1762) in Northeast Brazil.

    Science.gov (United States)

    de Oliveira Lima, José Wellington; de Góes Cavalcanti, Luciano Pamplona; Pontes, Ricardo José Soares; Heukelbach, Jörg

    2010-12-01

    In Northeast Brazil, large domestic containers used to store water are important breeding sites of Aedes aegypti, the main vector of dengue fever. The objective of this study was to estimate the survival of Betta splendens (Perciformes: Osphronemidae) fish in domestic containers in Fortaleza (Ceará State), as well as its effectiveness in the control of premature A. aegypti stages. The use of B. splendens was compared to Bacillus thuringiensis israelensis (Bti) in domestic containers. In a first home visit, B. splendens or Bti were applied to water containers. Two follow-up visits were conducted after 3-4 and 5-6 months to assess the presence of viable fish in the containers and infestation by larvae. Betta splendens fish were still present in 97.6% of containers 45-60 days after application. When the fish was present, the infestation rate was significantly higher (P containers, but that appropriate measures should be taken to assure prolonged survival and the presence of fish in the containers. © 2010 Blackwell Publishing Ltd.

  16. Are dual-phase 18F-FDG PET scans necessary in nasopharyngeal carcinoma to assess the primary tumour and loco-regional nodes?

    International Nuclear Information System (INIS)

    Yen, Tzu-Chen; Chang, Yu-Chen; Chan, Sheng-Chieh; Lin, Kun-Ju; Chang, Joseph Tung-Chieh; Hsu, Ching-Han; Lin, Wuu-Jyh; Fu, Ying-Kai; Ng, Shu-Hang

    2005-01-01

    This prospective study aimed to investigate the efficacy of dual-phase positron emission tomography (PET) in evaluating the loco-regional status of nasopharyngeal carcinoma (NPC). Eighty-four patients with newly diagnosed NPC and a fasting serum glucose level of 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET studies (at 40 min and 3 h after injection of 370 MBq 18 F-FDG) and head and neck magnetic resonance imaging (MRI) were performed within 1 week. Diagnostic criteria for NPC comprised the histopathological findings, the joint judgments of the research team and the post-treatment outcome. Each lesion's maximum standardised uptake value (SUV) and retention index were obtained. SUV data were evaluated using a paired test. Receiver operating characteristic curves and calculation of the area under the curve (AUC) determined the discriminative power. 18 F-FDG PET was significantly superior to MRI in identifying lower neck NPC nodal metastasis (AUC: 1 vs 0. 972, P=0.046) and overall loco-regional metastases (AUC: 0.985 vs 0.958, P=0.036). However, 18 F-FDG PET was similar to MRI in detecting primary tumour, as well as retropharyngeal, upper neck and supraclavicular nodal metastases. There was no significant difference between early phase (40 min) and delayed phase (3 h) 18 F-FDG PET in the detection of primary tumours (accuracy: 100% vs 100%) or loco-regional nodal metastasis (AUC: 0.984 vs 0.985, P=0.834). 18 F-FDG PET is superior to MRI in identifying lower neck nodal metastasis of NPC. Additional 3-h 18 F-FDG PET contributes no further information in the detection of primary tumours or loco-regional metastatic nodes in untreated NPC patients. (orig.)

  17. One life saved by four prevented recurrencies? Update of the early breast cancer trialists confirms. Postoperative radiotherapy improves survival after breast conserving surgery

    International Nuclear Information System (INIS)

    Sautter-Bihl, M.L.; Budach, W.

    2012-01-01

    The debate about the impact of local control on survival in early breast cancer patients is still going on, in spite of the continuously growing evidence that avoidance of locoregional disease reduces the risk of tumor-specific death. Recently, B. Fisher, one of the pioneers of breast conserving therapy claimed that during the last two decades, as a result of the use of systemic therapy in conjunction with breast conserving surgery and radiation, the incidence of locoregional recurrence has been reduced to a level where further reduction is likely to have little impact on survival. The penultimate meta-analysis of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) reported the effect of radiotherapy in early breast cancer on recurrence and survival in 2005 and provided the essential message that four prevented local recurrences at 5 years would avoid one breast cancer death in 15 years. The scientific community has eagerly awaited the quinquennial update of the EBCTCG which has now been published. A total of 17 randomized studies comparing postoperative radiotherapy vs. none were analyzed and comprised 7 new studies in addition to follow-up data of from 9 previously reported trials. A total of 10,801 patients with pT1-2 tumors were included, the majority of whom (n=7,287) were node negative, while 1,050 were node positive (2,464 unknown). In contrast to the previous meta-analysis, all patients received breast conserving surgery, consisting of lumpectomy (n=8,422) or more extensive techniques like quadrantectomy or sectoral resection (n= 2,399). The effect of radiotherapy on 10-year recurrences of any type and their relation to the 15-year breast cancer death rate were studied in correlation to various prognostic parameters and treatment characteristics (e.g., surgery, tamoxifen use). Moreover, a subgroup analysis was performed according to low, intermediate, and high initial risk of recurrence, from which the expected absolute benefit was derived by

  18. Chemotherapy, brachytherapy and surgery of locally evolved uterine cervix carcinomas: prognosis factors of local control and global survival

    International Nuclear Information System (INIS)

    Laude, C.; Montella, A.; Montbarbon, X.; Malet, C.; Racadot, S.; Pommier, P.; Mathevet, P.; Buenerd, A.

    2009-01-01

    The protocol used allows an excellent local control of the uterine cervix carcinoma with an acceptable morbidity. To anticipate the presence of a tumor residue can be an evolution in the therapy management after external radiotherapy, particularly in optimized image-guided brachytherapy (MRI and PET)New utero vaginal applicators with parameters implantation allow to realise the dose complement at the distal parameters. These advances make consider an improvement of results in the management of locally evolved uterine cervix carcinomas. (N.C.)

  19. Can historical controls be used in current clinical trials in osteosarcoma. Metastases and survival in a historical and a concurrent group

    International Nuclear Information System (INIS)

    Brostroem, L.A.; Aparisi, T.; Ingimarsson, S.; Lagergren, C.; Nilsonne, U.; Strander, H.; Soederberg, G.

    1980-01-01

    A historical group consisting of 35 patients with osteosarcoma was compared to a concurrent group of 23 patients. The treatment for the primary tumors differed only slghtly in the two groups. A more active approach was adopted for treatment of pulmonary metastases in the concurrent group. The percentage of patients not developing metastases and the survival rate in the historical group were approximately one half those for the concurrent group. An analysis of prognostic factors disclosed differences between the two groups as regards the size and histological type of the tumor. The results of the study cast doubt on the suitability of historical controls in current clinical trials conducted to ascertain the effectiveness of adjuvant therapy for osteosarcoma

  20. Organochlorine exposures influence on breast cancer risk and survival according to estrogen receptor status: a Danish cohort-nested case-control study

    International Nuclear Information System (INIS)

    Høyer, Annette P; Jørgensen, Torben; Rank, Fritz; Grandjean, Philippe

    2001-01-01

    The relationship between breast cancer and organochlorine exposure is controversial and complex. As estrogen receptor positive and negative breast cancer may represent different entities of the disease, this study was undertaken to evaluate organochlorines influence on breast cancer risk and survival according to receptor status. The background material stems from the Copenhagen City Heart Study (Denmark 1976-78). The breast cancer risk was investigated in a cohort nested case-control design including 161 cases and twice as many breast cancer free controls. The cases served as a cohort in the survival analysis. Serum organochlorine concentrations were determined by gaschromotography. The observed increased breast cancer risk associated with exposure to dieldrin derived from women who developed an estrogen receptor negative (ERN) tumor (Odds ratio [OR] I vs. IV quartile, 7.6, 95% confidence interval [95% CI] 1.4-46.1, p-value for linear trend 0.01). Tumors in women with the highest dieldrin serum level were larger and more often spread at the time of diagnosis than ERP tumors. The risk of dying was for the remaining evaluated compounds higher among patients with ERP breast cancer when compared to those with ERN. In the highest quartile of polychlorinated biphenyls (ΣPCB) it was more than 2-fold increased (Relative risk [RR] I vs. IV quartile, 2.5, 95% CI 1.1-5.7), but no dose-response relation was apparent. The results do not suggest that exposure to potential estrogenic organochlorines leads to development of an ERP breast cancer. A possible adverse effect on prognosis of hormone-responsive breast cancers needs to be clarified

  1. Palliative Radiotherapy in the Presence of Well-Controlled Metastatic Disease after Initial Chemotherapy May Prolong Survival in Patients with Metastatic Esophageal and Gastric Cancer.

    Science.gov (United States)

    Hingorani, Mohan; Dixit, Sanjay; Johnson, Miriam; Plested, Victoria; Alty, Kevin; Colley, Peter; Beavis, Andrew W; Roy, Rajarshi; Maraveyas, Anthony

    2015-10-01

    We report the outcomes of patients treated with palliative radiotherapy (pRT) to the primary tumour in the context of well-controlled metastatic disease after initial chemotherapy. Clinical records of 132 patients with metastatic esophago-gastric (OG) cancer treated with palliative chemotherapy (pCT) between January 2009 and June 2013 were reviewed. Ninetyseven patients had responding or stable disease after 3 months of chemotherapy, of whom 53 patients received pRT to the primary tumour after initial chemotherapy in the presence of well-controlled metastatic disease (group A, pCT-RT). The remaining 44 patients were treated with pCT alone (group B, pCT). Treatment-related outcomes were assessed in above groups including time to local progression (TTLP), progression-free and overall survival. The median overall survival for patients treated with pRT after initial chemotherapy (group A) was 23.3 months (95% confidence interval [CI], 17.70 to 28.89 months) and significantly higher than the 14 months (95% CI, 10.91 to 17.08 months) in patients treated with pCT alone (group B) (p < 0.001). The use of pCT-RT was an independent predictor of OS in multivariate analysis. Local recurrence was observed in 12/53 of patients (23%) in group A compared to 16/44 (36%) in group B. The median TTLP was significantly higher in patients after pCT-RT at 17.3 months (5.23 months to 44.50 months) compared to 8.3 months (range, 4.10 to 25.23 months) in patients treated with pCT alone (p=0.006). The possibility of pRT influencing systemic disease in advanced OG cancer has not been reported, and results from the present study present strong arguments for investigation of this therapeutic strategy in a randomized trial.

  2. Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival

    International Nuclear Information System (INIS)

    Eaton, Bree R.; Esiashvili, Natia; Kim, Sungjin; Weyman, Elizabeth A.; Thornton, Lauren T.; Mazewski, Claire; MacDonald, Tobey; Ebb, David; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.

    2016-01-01

    Purpose: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. Methods and Materials: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Results: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Conclusions: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.

  3. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Science.gov (United States)

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  4. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

    Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

  5. Randomized study of control of the primary tumor and survival using preoperative radiation, radiation alone, or surgery alone in head and beck carcinomas

    International Nuclear Information System (INIS)

    Hintz, B.; Charyulu, K.; Chandler, J.R.; Sudarsanam, A.; Garciga, C.

    1979-01-01

    Fifty-five selected patients with previously untreated squamous cell carcinoma of the head and neck regions were studied in a randomized, prospective manner. The three treatment categories were primary radiation (Gp R), primary surgery (Gp S), and preoperative radiation of 4000 rads in four weeks (Gp R/S). The local control rates for the 44 evaluable patients with a two-year minimum followup were 24%, 39%, and 43%, respectively. Further treatment attempts in patients failing initial therapy yielded local control rates of 35%, 39%, and 43% for Gp R, Gp S, and Gp R/S, respectively. None of the local control rates nor the corresponding survival curves were significantly different at P < 0.10. However, the group sizes were sufficiently small that true differences might not have been detected. Postoperative complications were higher in the primary radiation failures subsequently operated upon compared to the primary surgery group (P = 0.07). A table is included in which the types of postoperative complications are listed and enumerated according to treatment regime

  6. Surviving Sengstaken.

    Science.gov (United States)

    Jayakumar, S; Odulaja, A; Patel, S; Davenport, M; Ade-Ajayi, N

    2015-07-01

    To report the outcomes of children who underwent Sengstaken-Blakemore tube (SBT) insertion for life-threatening haemetemesis. Single institution retrospective review (1997-2012) of children managed with SBT insertion. Patient demographics, diagnosis and outcomes were noted. Data are expressed as median (range). 19 children [10 male, age 1 (0.4-16) yr] were identified; 18 had gastro-oesophageal varices and 1 aorto-oesophageal fistula. Varices were secondary to: biliary atresia (n=8), portal vein thrombosis (n=5), alpha-1-anti-trypsin deficiency (n=1), cystic fibrosis (n=1), intrahepatic cholestasis (n=1), sclerosing cholangitis (n=1) and nodular hyperplasia with arterio-portal shunt (n=1). Three children deteriorated rapidly and did not survive to have post-SBT endoscopy. The child with an aortooesophageal fistula underwent aortic stent insertion and subsequently oesophageal replacement. Complications included gastric mucosal ulceration (n=3, 16%), pressure necrosis at lips and cheeks (n=6, 31%) and SBT dislodgment (n=1, 6%). Six (31%) children died. The remaining 13 have been followed up for 62 (2-165) months; five required liver transplantation, two underwent a mesocaval shunt procedure and 6 have completed endoscopic variceal obliteration and are under surveillance. SBT can be an effective, albeit temporary, life-saving manoeuvre in children with catastrophic haematemesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Diuretic {sup 18}F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: prospective evaluation of a novel technique

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Brusabhanu; Dogra, Prem Nath [All India Institute of Medical Sciences, Department of Urology, New Delhi (India); Naswa, Niraj [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Kumar, Rakesh [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); New Delhi (India)

    2013-03-15

    Positron emission tomography/computed tomography (PET/CT) with {sup 18}F-fluorodeoxyglucose (FDG) has been used with limited success in the past in primary diagnosis and locoregional staging of urinary bladder cancer, mainly because of the pharmacokinetics of renal excretion of {sup 18}F-FDG. In the present prospective study, we have evaluated the potential application of diuretic {sup 18}F-FDG PET/CT in improving detection and locoregional staging of urinary bladder tumours. Twenty-five patients suspected of having primary carcinoma of the urinary bladder were evaluated prospectively for diagnosis and staging. All of these 25 patients underwent conventional contrast-enhanced computed tomography (CECT) of the abdomen/pelvis and whole-body diuretic {sup 18}F-FDG PET/CT. In addition, pelvic PET/CT images were obtained using the special technique of forced diuresis using intravenous furosemide (20-40 mg). Of the 25 patients, 10 underwent radical cystectomy and 15 underwent transurethral resection of the bladder tumour (TURBT). Results of CECT and diuretic {sup 18}F-FDG PET/CT were compared considering histopathology as a reference standard. Of the 25 patients, CECT detected a primary tumour in 23 (sensitivity 92 %), while {sup 18}F-FDG PET/CT was positive in 24 patients (sensitivity 96 %). Mean size and maximum standardized uptake value of the bladder tumours were 3.33 cm (range 1.6-6.2) and 5.3 (range 1.3-11.7), respectively. Of the 25 patients, only 10 patients underwent radical cystectomy based on disease status on TURBT. Among those ten patients, nine had locoregional metastases. Among the nine patients who had positive lymph nodes for metastasis on histopathology, CECT and PET/CT scan had a sensitivity of 44 and 78 %, respectively. {sup 18}F-FDG PET/CT was found to be superior to CECT in the detection of the primary tumour and locoregional staging (p < 0.05). Diuretic {sup 18}F-FDG PET/CT is highly sensitive and specific and plays an important role in improving

  8. Diuretic 18F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: prospective evaluation of a novel technique

    International Nuclear Information System (INIS)

    Nayak, Brusabhanu; Dogra, Prem Nath; Naswa, Niraj; Kumar, Rakesh

    2013-01-01

    Positron emission tomography/computed tomography (PET/CT) with 18 F-fluorodeoxyglucose (FDG) has been used with limited success in the past in primary diagnosis and locoregional staging of urinary bladder cancer, mainly because of the pharmacokinetics of renal excretion of 18 F-FDG. In the present prospective study, we have evaluated the potential application of diuretic 18 F-FDG PET/CT in improving detection and locoregional staging of urinary bladder tumours. Twenty-five patients suspected of having primary carcinoma of the urinary bladder were evaluated prospectively for diagnosis and staging. All of these 25 patients underwent conventional contrast-enhanced computed tomography (CECT) of the abdomen/pelvis and whole-body diuretic 18 F-FDG PET/CT. In addition, pelvic PET/CT images were obtained using the special technique of forced diuresis using intravenous furosemide (20-40 mg). Of the 25 patients, 10 underwent radical cystectomy and 15 underwent transurethral resection of the bladder tumour (TURBT). Results of CECT and diuretic 18 F-FDG PET/CT were compared considering histopathology as a reference standard. Of the 25 patients, CECT detected a primary tumour in 23 (sensitivity 92 %), while 18 F-FDG PET/CT was positive in 24 patients (sensitivity 96 %). Mean size and maximum standardized uptake value of the bladder tumours were 3.33 cm (range 1.6-6.2) and 5.3 (range 1.3-11.7), respectively. Of the 25 patients, only 10 patients underwent radical cystectomy based on disease status on TURBT. Among those ten patients, nine had locoregional metastases. Among the nine patients who had positive lymph nodes for metastasis on histopathology, CECT and PET/CT scan had a sensitivity of 44 and 78 %, respectively. 18 F-FDG PET/CT was found to be superior to CECT in the detection of the primary tumour and locoregional staging (p 18 F-FDG PET/CT is highly sensitive and specific and plays an important role in improving detection of the primary tumour and locoregional staging of

  9. Bonded versus vacuum-formed retainers: a randomized controlled trial. Part 1: stability, retainer survival, and patient satisfaction outcomes after 12 months.

    Science.gov (United States)

    Forde, Katherine; Storey, Madeleine; Littlewood, Simon J; Scott, Paul; Luther, Friedy; Kang, Jing

    2017-10-20

    There is a shortage of evidence on the best type of retainer. Evaluate upper and lower bonded retainers (BRs) versus upper and lower vacuum-formed retainers (VFRs) over 12 months, in terms of stability, retainer survival, and patient satisfaction. Two-arm parallel group multi-centre randomized controlled clinical trial. Sixty consecutive patients completing fixed appliance therapy and requiring retainers were recruited from 3 hospital departments. They were randomly allocated to either upper and lower labial segment BRs (n = 30) or upper and lower full-arch VFRs (n = 30). Primary outcome was stability. Secondary outcomes were retainer survival and patient satisfaction. A random sequence of treatment allocation was computer-generated and implemented by sealing in sequentially numbered opaque sealed envelopes independently prepared in advance. Patients, operators and outcome could not be blinded due to the nature of the intervention. Thirty patients received BRs (median [Mdn] age 16 years, inter-quartile range [IQR] = 2) and 30 received VFRs (Mdn age 17 years, IQR = 4). Baseline characteristics were similar between groups. At 12 months, there were no statistically significant inter-group differences in post-treatment change of maxillary labial segment alignment (BR = 1.1 mm, IQR = 1.56, VFR = 0.76 mm, IQR = 1.55, P = 0.61); however, there was greater post-treatment change in the mandibular VFR group (BR = 0.77 mm, IQR = 1.46, VFR = 1.69mm, IQR = 2.00, P = 0.008). The difference in maxillary retainer survival rates were statistically non-significant, P = 0.34 (BR = 63.6%, 239.3 days, 95% confidence interval [CI] = 191.1-287.5, VFR = 73.3%, 311.1 days, 95% CI = 278.3-344.29). The mandibular BR had a lower survival rate (P = 0.01) at 12 months (BR = 50%, 239.3 days 95% CI = 191.1-287.5, VFR = 80%, 324.9 days 95% CI = 295.4-354.4). More subjects with VFRs reported discomfort (P = 0.002) and speech difficulties (P = 0.004) but found them easier to clean than those with

  10. Survival outcome of malignant minor salivary tumors in Pakistani population

    Directory of Open Access Journals (Sweden)

    Hassan Iqbal

    2014-01-01

    Full Text Available Objective: Malignant tumors of minor salivary glands (MSG are rare. Survival outcome in Pakistani population with malignant MSG tumors remains to be defined. The objective of this study was to report the clinical presentation, treatment modalities, and survival outcome of radically treated malignant tumors of MSG in Pakistani population. Materials and Methods: Between April 2003 and March 2011, 45 patients with malignant tumors of MSG were treated at Shaukat Khanum Cancer Hospital and included in the study. Patient characteristics and treatment modalities were assessed and local, regional, and distant failures determined. Relapse-free (RFS and overall survival (OS was calculated using Kaplan-Meier curves, and log-rank test was used to determine significance. Results: Median age was 40 (17-83 years. Male to female ratio was 1.25:1. Most common site was hard palate in 31 (69% patients. Adenoid cystic carcinoma (51% was the most common histological diagnosis. Nine patients (20% underwent surgery as the only treatment modality, six patients received (13% radiotherapy alone, and 30 patients (67% had surgery followed by adjuvant radiotherapy. Eight patients developed recurrence (four local, two regional, one locoregional, and one distant. The 5-year actuarial overall OS and RFS was 77 and 66%, respectively. Age, T-stage, and treatment modality were significant for RFS, whereas T-stage and treatment modality were significant factors for OS. Conclusion: Surgery as single modality or combined with radiation therapy resulted in acceptable survival in Pakistani population with malignant minor salivary tumors.

  11. Depression and Liver Transplant Survival.

    Science.gov (United States)

    Meller, William; Welle, Nicole; Sutley, Kristen; Thurber, Steven

    Patients who underwent liver transplantation and experienced clinical depression have heretofore evinced lower survival rates when compared to nondepressed counterparts. To investigate the hypothesis that transplant patients who seek and obtain medical treatment for depression would circumvent the prior reduced survival findings. A total of 765 patients with liver transplants were scrutinized for complications following transplantation. Further, 104 patients experienced posttransplant depression as manifested by diagnosis and treatment by medical personnel. Survival analyses were conducted comparing hazard and survival curves for these selected individuals and the remainder of transplant patients. Contrary to prior data and consistent with the aforementioned hypothesis, median survival durations, survival curves, and hazard functions (controlling for age and prolonged posttransplant survival for the depressed patients were better. The improved survival for the depressed patients may simply be related to an amelioration of depressed symptoms via antidepressant medications. However, this interpretation would only be congruent with reduced hazard, not elevated survival, beyond the norm (median) for other transplant participants. Assuming the reliability and generalization of our findings, perhaps a reasonable and compelling interpretation is that combined with the effectiveness of antidepressant medications, the seeking and receiving treatment for depression is a type of proxy measure of a more global pattern of adherence to recommended posttransplant medical regimens. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  12. Microencapsulation increases survival of the probiotic Lactobacillus plantarum IS-10506, but not Enterococcus faecium IS-27526 in a dynamic, computer-controlled in vitro model of the upper gastrointestinal tract.

    Science.gov (United States)

    Surono, I; Verhoeven, J; Verbruggen, S; Venema, K

    2018-02-23

    To test the effect of microencapsulation on the survival of two probiotic strains isolated from Dadih, Indonesian fermented buffalo milk, in a dynamic, computer-controlled in vitro model of the upper gastrointestinal (GI) tract (TIM-1), simulating human adults. Free or microencapsulated probiotics, Lactobacillus plantarum IS-10506 or Enterococcus faecium IS-27526, resuspended in milk were studied for survival in the complete TIM-1 system (stomach + small intestine) or in the gastric compartment of TIM-1 only. Hourly samples collected after the ileal-caecal valve or after the pylorus were plated on MRS agar (for Lactobacillus) or S&B agar (for Enterococcus). Survival of the free cells after transit through the complete TIM-1 system was on average for the E. faecium and L. plantarum 15·0 and 18·5% respectively. Survival of the microencapsulated E. faecium and L. plantarum was 15·7 and 84·5% respectively. The free cells were further assessed in only the gastric compartment of TIM-1. E. faecium and L. plantarum showed an average survival of 39 and 32%, respectively, after gastric passage. There is similar sensitivity to gastric acid as well as survival after complete upper GI tract transit of free cells, but microencapsulation only protected L. plantarum. Survival of microencapsulated L. plantarum IS-10506 is increased compared to free cells in a validated in vitro model of the upper GI tract. It increases its use as an ingredient of functional foods. © 2018 The Society for Applied Microbiology.

  13. KINET: a social marketing programme of treated nets and net treatment for malaria control in Tanzania, with evaluation of child health and long-term survival.

    Science.gov (United States)

    Schellenberg, J R; Abdulla, S; Minja, H; Nathan, R; Mukasa, O; Marchant, T; Mponda, H; Kikumbih, N; Lyimo, E; Manchester, T; Tanner, M; Lengeler, C

    1999-01-01

    We present a large-scale social marketing programme of insecticide-treated nets in 2 rural districts in southwestern Tanzania (population 350,000) and describe how the long-term child health and survival impact will be assessed. Formative and market research were conducted in order to understand community perceptions, knowledge, attitudes and practice with respect to the products to be socially marketed. We identified Zuia Mbu (Kiswahili for 'prevent mosquitoes') as a suitable brand name for both treated nets and single-dose insecticide treatment sachets. A mix of public and private sales outlets is used for distribution. In the first stage of a stepped introduction 31 net agents were appointed and trained in 18 villages: 15 were shop owners, 14 were village leaders, 1 was a parish priest and 1 a health worker. For net treatment 37 young people were appointed in the same villages and trained as agents. Further institutions in both districts such as hospitals, development projects and employers were also involved in distribution. Promotion for both products was intense and used a variety of channels. A total of 22,410 nets and 8072 treatments were sold during the first year: 18 months after launching, 46% of 312 families with children aged under 5 years reported that their children were sleeping under treated nets. A strong evaluation component in over 50,000 people allows assessment of the long-term effects of insecticide-treated nets on child health and survival, anaemia in pregnancy, and the costs of the intervention. This evaluation is based on cross-sectional surveys, and case-control and cohort studies.

  14. Impact of insecticides used to control Spodoptera frugiperda (J.E. Smith in corn on survival, sex ratio, and reproduction of Trichogramma pretiosum Riley offspring

    Directory of Open Access Journals (Sweden)

    Jander R Souza

    2013-06-01

    Full Text Available Corn (Zea mays L. is cultivated in large areas and considered one of the world's major cereal crops. There are several arthropod pests that can reduce its production such as the fall armyworm, Spodoptera frugiperda (J.E. Smith (Lep.: Noctuidae, which is considered to be the main pest for corn. Fall armyworm is primarily controlled by insecticides. The use of biological control agents to manage this pest is growing with an emphasis on the egg parasitoid Trichogramma pretiosum Riley (Hym.: Trichogrammatidae. Thus, the aim of this research was to evaluate the impact of the following insecticides (g ai L-1 beta-cypermethrin (0.03, chlorfenapyr (0.60, chlorpyrifos (0.96, spinosad (0.16, etofenprox (0.10, triflumuron (0.08, alfa-cypermethrin/teflubenzuron (0.0425/0.0425, and lambda-cyhalothrin/thiamethoxam (0.11/0.083 on survival, sex ratio, reproduction, and T. pretiosum offspring. Distilled water was used as a control. Commercial insecticide formulations were diluted in distilled water. Bioassays used Anagasta kuehniella eggs treated with insecticides which were afterwards exposed to parasitism. Bioassays were conducted under controlled conditions at 25 ± 2 °C, 70 ± 10% RH, and 12:12 h photoperiod. Alfa-cypermethrin/teflubenzuron, beta-cypermethrin, chlorpyrifos, chlorfenapyr, spinosad, etofenprox, and lambda-cyhalothrin/thiamethoxam reduced parasitism capacity of maternal generation females as well as the percentage of insect emergence from the F1 generation. Only triflumuron was selective for T. pretiosum and can be recommended along with this parasitoid in fall armyworm management programs in corn.

  15. Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Yolanda D., E-mail: ydt2@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Uno, Hajime [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Hughes, Melissa E. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Niland, Joyce C. [Department of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, California (United States); Wong, Yu-Ning [Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Theriault, Richard [Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blitzblau, Rachel C. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Moy, Beverly [Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Breslin, Tara [Division of Surgical Oncology, Department of Surgery, Northwestern Lake Forest Hospital, Lake Forest, Illinois (United States); Edge, Stephen B. [Baptist Cancer Center, Memphis, Tennessee (United States); Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Hassett, Michael J. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2015-11-01

    Purpose: To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype. Methods and Materials: Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2−, low/intermediate grade), luminal B (ER/PR+, HER2−, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER−, PR−, HER2−). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT. Results: With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively. Conclusions: TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.

  16. Methods for estimating the site of origin of locoregional recurrence in head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Due, A.K.; Vogelius, I.R.; Berthelsen, A.K.; Kristensen, C.A.; Specht, L. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Aznar, M.C. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Copenhagen Univ. (Denmark). Niels Bohr Institute; Bentzen, S.M. [Copenhagen Univ. (Denmark). Dept. of Radiation Oncology Section 3994; Wisconsin Univ., MD (United States). Depts. of Human Oncology and Medical Physics; Korreman, S.S. [Copenhagen Univ. (Denmark). Niels Bohr Institute; Roskilde Univ. (Denmark). Dept. of Science, Systems, and Models

    2012-08-15

    Purpose: Methods to estimate the likely origin of recurrences after radiation therapy for head and neck squamous cell carcinoma are compared. Methods and materials: A total of 25 patients meeting the following inclusion criteria were randomly selected: curatively intended intensity-modulated radiotherapy planned on a positron emission tomography-computed tomography (PET/CT) scan during the period 2005-2009; squamous cell carcinoma in the oral cavity, pharynx or larynx; complete clinical response followed by locoregional recurrence; and a CT scan at recurrence before any salvage therapy. Exclusion criteria were previous cancer in the area, surgery prior to radiotherapy, or a synchronous cancer. Three methods of estimating focal points of recurrence origin and two volume overlap methods assigning the recurrences to the most central target volumes encompassing at least 50% or 95% of the recurrence volumes were tested. Treatment planning and recurrence scans were rigid and deformable co-registered in order to transfer focal points to the treatment planning scan. Double determinations of all volumes, points, and co-registrations were made. Results: The volume overlap methods assigned the recurrences to significantly more peripheral target volumes than focal methods (p < 0.0001 for all comparisons of 95% overlap vs. focal methods, p < 0.028 for all comparisons of 50% overlap vs. focal methods). Repeated registrations of the same point had higher reproducibility with deformable registration than with rigid registration (median distance 0.31 vs. 0.35 cm, p = 0.015). No significant differences were observed among the focal methods. Conclusion: Significant differences between methods were found which may affect strategies to improve radiotherapy based on pattern of failure analyses. (orig.)

  17. Volumetric modulated arc therapy and breath-hold in image-guided locoregional left-sided breast irradiation

    International Nuclear Information System (INIS)

    Osman, Sarah O.S.; Hol, Sandra; Poortmans, Philip M.; Essers, Marion

    2014-01-01

    Purpose: To investigate the effects of using volumetric modulated arc therapy (VMAT) and/or voluntary moderate deep inspiration breath-hold (vmDIBH) in the radiation therapy (RT) of left-sided breast cancer including the regional lymph nodes. Materials and methods: For 13 patients, four treatment combinations were compared; 3D-conformal RT (i.e., forward IMRT) in free-breathing 3D-CRT(FB), 3D-CRT(vmDIBH), 2 partial arcs VMAT(FB), and VMAT(vmDIBH). Prescribed dose was 42.56 Gy in 16 fractions. For 10 additional patients, 3D-CRT and VMAT in vmDIBH only were also compared. Results: Dose conformity, PTV coverage, ipsilateral and total lung doses were significantly better for VMAT plans compared to 3D-CRT. Mean heart dose (D mean,heart ) reduction in 3D-CRT(vmDIBH) was between 0.9 and 8.6 Gy, depending on initial D mean,heart (in 3D-CRT(FB) plans). VMAT(vmDIBH) reduced the D mean,heart further when D mean,heart was still >3.2 Gy in 3D-CRT(vmDIBH). Mean contralateral breast dose was higher for VMAT plans (2.7 Gy) compared to 3DCRT plans (0.7 Gy). Conclusions: VMAT and 3D-CRT(vmDIBH) significantly reduced heart dose for patients treated with locoregional RT of left-sided breast cancer. When D mean,heart exceeded 3.2 Gy in 3D-CRT(vmDIBH) plans, VMAT(vmDIBH) resulted in a cumulative heart dose reduction. VMAT also provided better target coverage and reduced ipsilateral lung dose, at the expense of a small increase in the dose to the contralateral breast

  18. Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database

    International Nuclear Information System (INIS)

    Tseng, Yolanda D.; Uno, Hajime; Hughes, Melissa E.; Niland, Joyce C.; Wong, Yu-Ning; Theriault, Richard; Blitzblau, Rachel C.; Moy, Beverly; Breslin, Tara; Edge, Stephen B.; Hassett, Michael J.; Punglia, Rinaa S.

    2015-01-01

    Purpose: To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype. Methods and Materials: Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2−, low/intermediate grade), luminal B (ER/PR+, HER2−, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER−, PR−, HER2−). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT. Results: With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively. Conclusions: TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.

  19. Nomogram for Predicting the Risk of Locoregional Recurrence in Patients Treated With Accelerated Partial-Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wobb, Jessica L. [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Chen, Peter Y., E-mail: PChen@beaumont.edu [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Shah, Chirag [Department of Radiation Oncology, Summa Health System, Akron, Ohio (United States); Moran, Meena S. [Department of Therapeutic Radiology, Yale School of Medicine, Norwich, Connecticut (United States); Shaitelman, Simona F. [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Vicini, Frank A. [Department of Radiation Oncology, Michigan Healthcare Professionals/21st Century Oncology, Farmington, Michigan (United States); Mbah, Alfred K.; Lyden, Maureen [Biostat International Inc, Tampa, Florida (United States); Beitsch, Peter [Department of Surgery, Dallas Breast Center, Dallas, Texas (United States)

    2015-02-01

    Purpose: To develop a nomogram taking into account clinicopathologic features to predict locoregional recurrence (LRR) in patients treated with accelerated partial-breast irradiation (APBI) for early-stage breast cancer. Methods and Materials: A total of 2000 breasts (1990 women) were treated with APBI at William Beaumont Hospital (n=551) or on the American Society of Breast Surgeons MammoSite Registry Trial (n=1449). Techniques included multiplanar interstitial catheters (n=98), balloon-based brachytherapy (n=1689), and 3-dimensional conformal radiation therapy (n=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox proportional hazards regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a concordance index. Results: Median follow-up was 5.5 years (range, 0.9-18.3 years). Of the 2000 cases, 435 were excluded because of missing data. Univariate analysis found that age <50 years, pre-/perimenopausal status, close/positive margins, estrogen receptor negativity, and high grade were associated with a higher frequency of LRR. These 5 independent covariates were used to create adjusted estimates, weighting each on a scale of 0-100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR, with a concordance index of 0.641. Conclusions: The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.

  20. [Basic Studies on Locoregional Injection of a Newly Designed Chitin Sol].

    Science.gov (United States)

    Chiba, Takehiro; Sugitachi, Akio; Kume, Kouhei; Segawa, Takenori; Nishinari, Yutaka; Ishida, Kaoru; Noda, Hironobu; Nishizuka, Satoshi; Kimura, Yusuke; Koeda, Keisuke; Sasaki, Akira

    2015-11-01

    Systemic chemotherapy in advanced cancer cases often provokes serious adverse events. We aimed to examine the fundamental properties and efficacy of a novel chitin sol, an anti-cancer agent with minor side effects designed to avoid the adverse effects of chemotherapy and enhance the QOL and ADL of patients. DAC-70 was used to create the novel agent termed DAC-70 sol. The anti-proliferative activity was assayed by the WST method using different types of cell lines. The anti-cancer efficacy of the novel agent was examined using cancer-bearing mice. DAC-70 sol was easily injectable through a 21-G needle. The sol suppressed proliferation of the cells in vitro. Intra-tumor injection of DAC-70 sol inhibited the rapid growth of solid tumors in the mice. CDDP-loaded DAC-70 sol, CDDP/DAC-70 sol, successfully controlled malignant ascites in the mice (psol and CDDP/DAC-70 sol is clinically useful as novel cancer chemotherapy for advanced cases. This warrants further clinical studies in cancer chemotherapy.

  1. Quality of Life and Survival Outcome for Patients With Nasopharyngeal Carcinoma Receiving Three-Dimensional Conformal Radiotherapy vs. Intensity-Modulated Radiotherapy-A Longitudinal Study

    International Nuclear Information System (INIS)

    Fang, F.-M.; Chien, C.-Y.; Tsai, W.-L.; Chen, H.-C.; Hsu, H.-C.; Lui, C.-C.; Huang, T.-L.

    2008-01-01

    Purpose: To investigate the changes of quality of life (QoL) and survival outcomes for patients with nasopharyngeal carcinoma (NPC) treated by three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). Methods and Materials: Two hundred and three newly diagnosed NPC patients, who were curatively treated by 3D-CRT (n = 93) or IMRT (n = 110) between March 2002 and July 2004, were analyzed. The distributions of clinical stage according to American Joint Committee on Cancer 1997 were I: 15 (7.4%), II: 78 (38.4%), III: 74 (36.5%), and IV: 36 (17.7%). QoL was longitudinally assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H and N35 questionnaires at the five time points: before RT, during RT (36 Gy), and 3 months, 12 months, and 24 months after RT. Results: The 3-year locoregional control, metastasis-free survival, and overall survival rates were 84.8%, 76.7%, and 81.7% for the 3D-CRT group, respectively, compared with 84.2%, 82.6%, and 85.4% for the IMRT group (p value > 0.05). A general trend of maximal deterioration in most QoL scales was observed during RT, followed by a gradual recovery thereafter. There was no significant difference in most scales between the two groups at each time point. The exception was that patients treated by IMRT had a both statistically and clinically significant improvement in global QoL, fatigue, taste/smell, dry mouth, and feeling ill at the time point of 3 months after RT. Conclusions: The potential advantage of IMRT over 3D-CRT in treating NPC patients might occur in QoL outcome during the recovery phase of acute toxicity

  2. Evaluation of effect of body mass index and weight loss on survival of patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

    International Nuclear Information System (INIS)

    Lin, Yu-Hsuan; Chang, Kuo-Ping; Lin, Yaoh-Shiang; Chang, Ting-Shou

    2015-01-01

    Previous studies report body-mass index (BMI) and percent weight loss (WL) to have prognostic significance when treating patients with nasopharyngeal carcinoma (NPC). However, most of these investigations studied patients treated using different radiotherapeutic techniques. We evaluated the predictive effect of these two nutrition-related measurements on therapeutic outcome in NPC patients who only received intensity-modulated radiation therapy (IMRT) as part of their total treatment program. We retrospectively studied NPC patients treated with IMRT from January 2006 to February 2012. Cox proportional hazards was used to test the association of pretreatment BMI (<23 kg/m 2 vs. ≥23 kg/m 2 ) and percent weight loss (≥5 % vs. <5 %) during therapy and related survival rates while controlling for various potential confounders. Eighty-one (34 %) of the 238 patients had BMIs ≥23 kg/m 2 at pretreatment and 150 (63 %) had significant (≥5 %) weight loss. Median follow-up time was 41.71 months; median radiotherapy was 7.46 ± 0.77 weeks. Those with BMIs ≥23 kg/m 2 did not have a better 3-year overall survival (p = 0.672), 3-year disease specific survival (p = 0.341), 3-year locoregional free survival (p = 0.281), or 3-year distant metastatic free survival (p = 0.134). Those with significant WL (≥5 %) did not have worse 3-year clinical endpoints, even after stratifying magnitude of weight loss by BMI category. In sensitivity test, the adjusted hazard ratio remained statistically insignificant using different cutoffs for BMIs and percent weight loss. This study found no significant relationship between BMI and percent weight loss on survival of NPC patients receiving IMRT based therapy. Further studies might want to consider other nutrition related factors as prognostic indicators when studying the correlate between malnutrition and survival in this population. The online version of this article (doi:10.1186/s13014-015-0443-3) contains supplementary material, which

  3. What controls the survival of ice cliffs on debris-covered glaciers? An investigation into the aspect-dependent evolution of supraglacial cliffs in the Nepalese Himalaya

    Science.gov (United States)

    Pellicciotti, F.; Buri, P.

    2017-12-01

    Supraglacial ice cliffs exist on debris-covered glaciers worldwide, but despite increasing evidence of their important role in the surface melt of debris-covered glaciers, their role and importance at the glacier scale is still little understood. Acting as windows of energy transfer through the debris, they can contribute to very large glacier mass losses. Their abundance and life cycle might thus explain the anomalous behavior of much higher than expected mass losses of the debris-covered glaciers of High Mountain Asia, a controversial finding of recent research in a region where glaciers are highly relevant as water sources for millions of people downstream. Cliffs' evolution in time and distribution in space will determine their total contribution to the mass balance of glaciers, but while spatial distribution has been recently inferred from remote sensing studies, their temporal evolution is largely unknown. Here, we make use of recent advancements in our ability to model these complex features and use a novel 3D numerical model of cliff backwasting and very high resolution topographic data to show that supraglacial ice cliffs existence is controlled by aspect. Because of lack of observed south-facing cliffs, we rotate north-facing cliff systems observed in high detail over the debris-covered Lirung glacier, in the Nepalese Himalaya, towards southerly aspects and use the model coupled to the very high resolution topography to simulate the continuous evolution of selected cliffs over one melt season. Cliffs facing south (in the Northern Hemisphere) do not survive the duration of an ablation season and disappear within few weeks to few months due to very strong solar radiation receipts. Our model shows a progressive, continuous flattening of southerly facing cliffs, which is a result of their vertical gradient of incoming solar radiation. We also show that there is a clear range of aspects (northwest to northeast) that allows cliff survival because of energy and

  4. Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.

    Science.gov (United States)

    Escudero, Andrea; Petzold, Guillermo; Moreno, Jorge; Gonzalez, Marcelo; Junod, Julio; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

    2013-01-01

    Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  5. Survivability Using Controlled Security Services

    Science.gov (United States)

    2005-06-01

    signature scheme secure against adaptive chosen-message attacks. SIAM J. Computing, 17(2):281–308, 1988. [29] ISO TC86 Committee. ISO 8583 : Financial...fsIKXZO ISO bbDU?M&D*P$JSIKD F$LKD[*J>RKX$J\\OINTP$`p]Wf�OP_f�INX$TL’Q�FZOeLNINTJMnTP_[*D*b[^J QhG��J:RObb?OuINX$TL’Q�FZOeLNIf�U?X$D

  6. Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia

    International Nuclear Information System (INIS)

    Cerezo, Laura; Martín, Margarita; López, Mario; Marín, Alicia; Gómez, Alberto

    2009-01-01

    In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy. Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3. At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia. In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control

  7. Stimulated human fibroblast cell survival

    International Nuclear Information System (INIS)

    Smith, B.P.; Gale, K.L.; Einspenner, M.; Greenstock, C.L.; Gentner, N.E.

    1992-01-01

    Techniques for cloning cultured mammalian cells have supported the most universally-accepted method for measuring the induction of lethality by geno-toxicants such as ionizing radiation: the 'survival of colony-forming ability (CFA)' assay. Since most cultured human cell lines exhibit plating efficiency (i.e. the percentage of cells that are capable of reproductively surviving and dividing to form visible colonies) well below 100%, such assays are in essence 'survival of plating efficiency' assays, since they are referred to the plating (or cloning) efficiency of control (i.e. unirradiated) cells. (author). 8 refs., 2 figs

  8. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  9. Controlled copper ion release from phosphate-based glasses improves human umbilical vein endothelial cell survival in a reduced nutrient environment.

    Science.gov (United States)

    Stähli, Christoph; Muja, Naser; Nazhat, Showan N

    2013-02-01

    The success of tissue engineering is dependent on rapid scaffold vascularization after engraftment. Copper ions are well known to be angiogenic but exhibit cytotoxicity at elevated doses. The high sensitivity to copper concentration underlines the need of a controlled release mechanism. This study investigated the effect of copper ions released from phosphate-based glasses (PGs) on human umbilical vein endothelial cells (HUVECs) under standard growth conditions (SGC), as well as in a reduced nutrient environment (RNE) with decreased bovine serum and growth factor concentrations to approximate conditions in the core of large volume scaffolds where nutrient diffusion is limited. Initially, HUVECs were exposed to a range of CuCl(2) concentrations in order to identify an optimal response in terms of their metabolism, viability, and apoptotic activity. Under SGC, HUVEC metabolic activity and viability were reduced in a dose-dependent manner in the presence of 0.44-12 ppm Cu(2+). In contrast, HUVEC death induced by the RNE was delayed by an optimal dose of 4 ppm Cu(2+), which was associated with a down-regulation of apoptosis as evidenced by caspase-3/7 activity. Copper ion release from soluble PGs of the formulation 50P(2)O(5)-30CaO-(20-x)Na(2)O-xCuO [mol%] (x=0, 1, 5 and 10) demonstrated a controllable increase with CuO content. The presence of 4 ppm copper ions released from the 10% CuO PG composition reproduced the delay in HUVEC death in the RNE, suggesting the potential of these materials to extend survival of transplanted endothelial cells in large volume scaffolds.

  10. Quality of Survival and Growth in Children and Young Adults in the PNET4 European Controlled Trial of Hyperfractionated Versus Conventional Radiation Therapy for Standard-Risk Medulloblastoma

    International Nuclear Information System (INIS)

    Kennedy, Colin; Bull, Kim; Chevignard, Mathilde; Culliford, David; Dörr, Helmuth G.; Doz, François; Kortmann, Rolf-Dieter; Lannering, Birgitta; Massimino, Maura; Navajas Gutiérrez, Aurora; Rutkowski, Stefan; Spoudeas, Helen A.; Calaminus, Gabriele

    2014-01-01

    Purpose: To compare quality of survival in “standard-risk” medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Methods and Materials: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Results: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Conclusions: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life

  11. Quality of Survival and Growth in Children and Young Adults in the PNET4 European Controlled Trial of Hyperfractionated Versus Conventional Radiation Therapy for Standard-Risk Medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, Colin, E-mail: crk1@soton.ac.uk [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Bull, Kim [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Chevignard, Mathilde [Hôpitaux de Saint Maurice, Saint Maurice (France); Neurophysiology, University of Pierre et Marie-Curie Paris 6, Paris (France); Culliford, David [University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton (United Kingdom); Dörr, Helmuth G. [Kinder- und Jugendklinik der Universität Erlangen, Erlangen (Germany); Doz, François [Institut Curie and University Paris Descartes, Sorbonne Paris Cité (France); Kortmann, Rolf-Dieter [Department of Radiation Therapy, University of Leipzig, Leipzig (Germany); Lannering, Birgitta [Department of Pediatrics, The Sahlgren Academy, University of Gothenburg, Gothenburg (Sweden); Massimino, Maura [Fondazione Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Istituto Nazionale dei Tumori, Milan (Italy); Navajas Gutiérrez, Aurora [Hospital Universitario Cruces, Baracaldo-Vizcaya (Spain); Rutkowski, Stefan [University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Spoudeas, Helen A. [Center for Pediatric Endocrinology, University College London, London (United Kingdom); Calaminus, Gabriele [Pediatric Oncology, University of Muenster, Muenster (Germany)

    2014-02-01

    Purpose: To compare quality of survival in “standard-risk” medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Methods and Materials: Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Results: Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Conclusions: Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life.

  12. Quality of survival and growth in children and young adults in the PNET4 European controlled trial of hyperfractionated versus conventional radiation therapy for standard-risk medulloblastoma.

    Science.gov (United States)

    Kennedy, Colin; Bull, Kim; Chevignard, Mathilde; Culliford, David; Dörr, Helmuth G; Doz, François; Kortmann, Rolf-Dieter; Lannering, Birgitta; Massimino, Maura; Navajas Gutiérrez, Aurora; Rutkowski, Stefan; Spoudeas, Helen A; Calaminus, Gabriele

    2014-02-01

    To compare quality of survival in "standard-risk" medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial. Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded. Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011). Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The Role of Diffusion-Weighted Imaging (DWI in Locoregional Therapy Outcome Prediction and Response Assessment for Hepatocellular Carcinoma (HCC: The New Era of Functional Imaging Biomarkers

    Directory of Open Access Journals (Sweden)

    Johannes M. Ludwig

    2015-11-01

    Full Text Available Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC. Current response assessment is mainly based on: (1 changes in size, which is at times unreliable and lag behind the result of therapy; and (2 contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI techniques, such as diffusion-weighted imaging (DWI have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement, which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies.

  14. Is it necessary to repeat CT imaging and replanning during the course of intensity-modulated radiation therapy for locoregionally advanced nasopharyngeal carcinoma?

    International Nuclear Information System (INIS)

    Chen Chuanben; Lin Xiang; Pan Jianji; Fei Zhaodong; Chen Lisha; Bai Penggang

    2013-01-01

    Our aim was to evaluate the volumetric and dosimetric changes of target volumes and organs at risk (OARs) during intensity-modulated radiation therapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC) and the necessity of replanning. Twenty locoregionally advanced NPC patients treated by concurrent chemotherapy and IMRT were included. CT and MR images were acquired before treatment and at weeks 2, 3, 4, 5 and 6 during treatment. The target volumes and OARs were contoured based on the fused CT-MRI images and hybrid plans were generated. The changes of volume and dosimetry were measured by comparing original plan and hybrid plans. Significant volumetric changes of target volumes and parotid gland were observed. The primary nasopharyngeal tumor (GTVnx), clinical target volume 1 (CTV1), involved lymph nodes (GTVnd) and left and right parotid glands, shrank at a mean rate of 14.7, 11.56, 11.40, 6.54 and 6.78% per treatment week, respectively. There were no significant dosimetric changes in GTVnx, GTVnd, CTV1, spinal cord and brain stem while the differences of dose to left and right parotid glands were significant (F=6.73, P=0.007; F=7.43, P=0.007). Remarkable volumetric changes were observed. However, the dosimetric changes were inconspicuous except for the parotid. Replanning might contribute to protect the parotid gland. (author)

  15. Can loco-regional irradiation be a routine supplement to high dose chemotherapy with autologous bone marrow transplant in women with poor prognosis breast cancer

    International Nuclear Information System (INIS)

    Wobeck, Linda K.; Holland, H. Kent; Landry, Jerome C.; Lynn, Michael J.; Hughes, Lorie L.

    1997-01-01

    internal mammary fields were treated in 89 %, 34 % and 19 % respectively. Median elapsed days of irradiation was 42 (range 24 - 144 days). When patients were compared by treatment facility, Emory University System patients (n=10) versus outside facility patients (n=69), averaged total elapsed days of 39 Vs 48 days, respectively (p=0.008). No patient had an acute skin reaction worse than RTOG score of 2 and only 3 patients developed radiation pneumonitis. Average decrease in pre-irradiation values of platelets, hemoglobin, and white blood count was 24.5%, 2% and 32% respectively. Nineteen patients with pretreatment platelets of 100,000. The average duration of irradiation was not statistically different nor was the change in hematological values during their irradiation. Only 7 patients required transfusions or growth factors during treatment. Ninety four percent of patients completed treatment, though 20% had a treatment interruption. Three patients did not complete treatment due to myelosupression and 2 patients refused the boost portion. Patterns of care analysis revealed two treatment groups: those treated with loco-regional XRT, and those treated to the breast/chestwall only. Local control is 95% ((75(79))) at an average follow up of 865 days. Two patients who had a local failure received local chestwall treatment only, to a dose of 45 Gy. Conclusions: Despite the intent to include irradiation as a major modality in the post BMT treatment regimen for women with localized, poor prognosis breast cancer, only 84 % ((79(103))-excludes refusal) were able to receive XRT. However for those patients that did receive XRT, it was generally well tolerated, even for patients with beginning platelet values of less than 100,000. Based on our findings, we feel it is preferable to begin XRT when the platelet level is 75,000 versus postponing or forgoing XRT, if there is slow hematological recovery

  16. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice

    DEFF Research Database (Denmark)

    Kamoun, Walid S; Ley, Carsten D; Farrar, Christian T

    2009-01-01

    anti-VEGF agents may decrease tumor contrast-enhancement, vascularity, and edema, the mechanisms leading to improved survival in patients remain incompletely understood. Our goal was to determine whether alleviation of edema by anti-VEGF agents alone could increase survival in mice. METHODS: We treated...... mice bearing three different orthotopic models of glioblastoma with a VEGF-targeted kinase inhibitor, cediranib. Using intravital microscopy, molecular techniques, and magnetic resonance imaging (MRI), we measured survival, tumor growth, edema, vascular morphology and function, cancer cell apoptosis...... by an increase in plasma collagen IV. These rapid changes in tumor vascular morphology and function led to edema alleviation -- as measured by MRI and by dry/wet weight measurement of water content -- but did not affect tumor growth. By immunohistochemistry, we found a transient decrease in macrophage...

  17. Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

    International Nuclear Information System (INIS)

    Sher, David J.; Posner, Marshall R.; Tishler, Roy B.; Sarlis, Nicholas J.; Haddad, Robert I.; Holupka, Edward J.; Devlin, Phillip M.

    2011-01-01

    Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥ 70 Gy. Radiotherapy treatment time was analyzed as binary (≤ 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

  18. Relationship Between Radiation Treatment Time and Overall Survival After Induction Chemotherapy for Locally Advanced Head-and-Neck Carcinoma: A Subset Analysis of TAX 324

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: dsher@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Posner, Marshall R. [Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Sarlis, Nicholas J. [Sanofi-Aventis US, Bridgewater, NJ (United States); Haddad, Robert I. [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Holupka, Edward J. [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA (Israel); Devlin, Phillip M. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States)

    2011-12-01

    Purpose: To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). Methods and Materials: TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of {>=} 70 Gy. Radiotherapy treatment time was analyzed as binary ({<=} 8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). Results: A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p = 0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p = 0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. Conclusions: In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential

  19. Relationship between radiation treatment time and overall survival after induction chemotherapy for locally advanced head-and-neck carcinoma: a subset analysis of TAX 324.

    Science.gov (United States)

    Sher, David J; Posner, Marshall R; Tishler, Roy B; Sarlis, Nicholas J; Haddad, Robert I; Holupka, Edward J; Devlin, Phillip M

    2011-12-01

    To analyze the relationship between overall survival (OS) and radiation treatment time (RTT) and overall treatment time (OTT) in a well-described sequential therapy paradigm for locally advanced head-and-neck carcinoma (LAHNC). TAX 324 is a Phase III study comparing TPF (docetaxel, cisplatin, and fluorouracil) with PF (cisplatin and fluorouracil) induction chemotherapy (IC) in LAHNC patients; both arms were followed by carboplatin-based chemoradiotherapy (CRT). Prospective radiotherapy quality assurance was performed. This analysis includes all patients who received three cycles of IC and a radiation dose of ≥70 Gy. Radiotherapy treatment time was analyzed as binary (≤8 weeks vs. longer) and continuous (number of days beyond 8 weeks) functions. The primary analysis assessed the relationship between RTT, OTT, and OS, and the secondary analysis explored the association between treatment times and locoregional recurrence (LRR). A total of 333 (of 501) TAX 324 patients met the criteria for inclusion in this analysis. There were no significant differences between the treatment arms in baseline or treatment characteristics. On multivariable analysis, PF IC, World Health Organization performance status of 1, non-oropharynx site, T3/4 stage, N3 status, and prolonged RTT (hazard ratio 1.63, p=0.006) were associated with significantly inferior survival. Performance status, T3/4 disease, and prolonged RTT (odds ratio 1.68, p=0.047) were independently and negatively related to LRR on multivariable analysis, whereas PF was not. Overall treatment time was not independently associated with either OS or LRR. In this secondary analysis of the TAX 324 trial, TPF IC remains superior to PF IC after controlling for radiotherapy delivery time. Even with optimal IC and concurrent chemotherapy, a non-prolonged RTT is a crucial determinant of treatment success. Appropriate delivery of radiotherapy after IC remains essential for optimizing OS in LAHNC. Copyright © 2011 Elsevier Inc

  20. Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.

    Science.gov (United States)

    Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng

    2017-12-01

    There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. The correlation between the levels of tissue inhibitor of metalloproteinases 1 in plasma and tumour response and survival after preoperative radiochemotherapy in patients with rectal cancer

    International Nuclear Information System (INIS)

    Oblak, Irena; Velenik, Vaneja; Anderluh, Franc; Mozina, Barbara; Ocvirk, Janja

    2013-01-01

    The aim of this study was to analyse whether the level of tissue inhibitor of metalloproteinases (TIMP) 1 is associated with the tumour response and survival to preoperative radiochemotherapy in rectal cancer patients. Ninety-two patients with histologically confirmed non-metastatic rectal cancer of clinical stage I– III were treated with preoperative radiochemotherapy, surgery and postoperative chemotherapy. Plasma TIMP-1 concentrations were measured prior to the start of the treatment with an enzyme-linked immunosorbent assay (ELISA). Median follow-up time was 68 months (range: 3–93 months) while in survivors it was 80 months (range: 68–93 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) rates for all patients were 80.2%, 56.4%, 63.7% and 52.2%, respectively. The median TIMP-1 level was 185 ng/mL (range: 22–523 ng/mL) and the mean level (±standard deviation) was 192 (±87) ng/mL. Serum TIMP-1 levels were found to be significantly increased in patients with preoperative CRP>12 mg/L and in those who died from rectal cancer or had cT4 tumours. No correlation was established for age, gender, carcinoembriogenic antigene (CEA) level, platelets count, histopathological grade, response to preoperative therapy, resectability and disease reappearance. On univariate analysis, various parameters favourably influenced one or more survival endpoints: TIMP-1 <170 ng/mL, CRP <12 mg/L, platelets count <290 10E9/L, CEA <3.4mg/L, age <69 years, male gender, early stage disease (cN0 and/or cT2–3), radical surgery (R0) and response to preoperative radiochemotherapy. In multivariate model, LRC was favourably influenced by N-downstage, DFS by lower CRP and N-downstage, DSS by lower CRP and N-downstage and OS by lower TIMP-1 level, lower CRP and N-downstage. Although we did not find any association between pretreatment serum TIMP-1 levels and primary tumour response to preoperative

  2. Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.

    LENUS (Irish Health Repository)

    Bass, G A

    2014-04-01

    Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials.

  3. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer.

    Science.gov (United States)

    Tremblay, Gabriel; Livings, Christopher; Crowe, Lydia; Kapetanakis, Venediktos; Briggs, Andrew

    2016-01-01

    Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. A piecewise model, in which the Kaplan-Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses.

  4. Survival of bonded lingual retainers with chemical or photo polymerization over a 2-year period: a single-center, randomized controlled clinical trial

    NARCIS (Netherlands)

    Pandis, N.; Fleming, P.S.; Kloukos, D.; Polychronopoulou, A.; Katsaros, C.; Eliades, T.

    2013-01-01

    INTRODUCTION: The objective of this trial was to compare the survival rates of mandibular lingual retainers bonded with either chemically cured or light-cured adhesive after orthodontic treatment. METHODS: Patients having undergone orthodontic treatment at a private orthodontic office were randomly

  5. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Tremblay G

    2016-06-01

    Full Text Available Gabriel Tremblay,1 Christopher Livings,2 Lydia Crowe,2 Venediktos Kapetanakis,2 Andrew Briggs3 1Global Health Economics and Health Technology Assessment, Eisai Inc., Woodcliff Lake, NJ, USA; 2Health Economics, Decision Resources Group, Bicester, Oxfordshire, 3Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131 from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and

  6. Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy

    International Nuclear Information System (INIS)

    Huang, Pei-Yu; Zeng, Ting-Ting; Ban, Xiaojiao; Li, Meng-Qing; Zhang, Bao-Zhu; Zhu, Ying-Hui; Hua, Wen-Feng; Mai, Hai-Qiang; Zhang, Li; Guan, Xin-Yuan; Li, Yan

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. Increasing evidence supports that the accumulation of additional genetic and epigenetic abnormalities is important in driving the NPC tumorigenic process. In this study, we aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes. The expression status of EIF5A2 was investigated in the NPC tissue microarray. Tissues were from 166 NPC patients staging II-IV, collected between 1999 and 2005. All patients were administered 2–3 cycles of DDP (cisplatin) + 5-Fu (5-fluorouracil) induction therapy and then treated with a uniform conventional two-dimensional radiotherapy. Cell motility assay, tumor growth assay and cytotoxicity assay were performed on the EIF5A2 overexpressed cells and control cells. siRNA was also used in the in vitro studies. Positive staining of EIF5A2 was observed in 85.4 % (105/123) informative tumor cases. Multivariate analyses demonstrated that EIF5A2 was an independent prognostic marker of poor overall survival (OS) (P = 0.041), failure-free survival (FFS) (P = 0.029), and distant failure-free survival (D-FFS) (P = 0.043) in patients with locoregionally advanced NPC patients treated with cisplatin + 5-Fu chemoradiotherapy. The forced expression of EIF5A2 in NPC cells enhanced the cells’ motility and growth ability. Knock-down of EIF5A2 in NPC cells decreased the cell’s motility and growth ability. Our results also demonstrated that EIF5A2 overexpression induced chemoresistance of NPC cells to 5-Fu. Our findings suggested that EIF5A2 expression, as examined by immunohistochemistry, could function as an independent prognostic factor of outcomes in NPC patients with cisplatin + 5-Fu chemoradiotherapy. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress. The online version of this article (doi:10.1186/s12885

  7. Early prediction of response to cetuximab and radiotherapy by FDG-PET/CT for the treatment of a locoregionally advanced squamous cell carcinoma of the hypopharynx

    Directory of Open Access Journals (Sweden)

    Mindaugas Grybauskas

    2014-01-01

    Full Text Available Cetuximab (CTX is used for the concurrent treatment with radiotherapy (RT in squamous cell carcinoma of head and neck (HNSCC. There are no reliable clinical predictive markers of effectiveness of CTX at yet. We describe the clinical case of patient who received a CTX/RT to cure locoregionally advanced hypopharyngeal SCC. 2-Deoxy-2-[18F]fluoro-d-glucose positron emission tomography and computed tomography (18FDG-PET/CT was performed before the treatment and repeated 10 days after CTX induction dose. A repeated 18FDG-PET/CT scan showed dramatic decrease of metabolic parameters. Patient had a complete response after treatment and is still alive and cured after 5 years.

  8. Impact of target area selection in 125 Iodine seed brachytherapy on locoregional recurrence in patients with non-small cell lung cancer.

    Science.gov (United States)

    Yan, Wei-Liang; Lv, Jin-Shuang; Guan, Zhi-Yu; Wang, Li-Yang; Yang, Jing-Kui; Liang, Ji-Xiang

    2017-05-01

    Computed tomography (CT)-guided percutaneous implantation of 125 Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P  area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-15

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

  10. Incremental Cancer Detection of Locoregional Restaging with Diagnostic Mammography Combined with Whole-Breast and Regional Nodal Ultrasound in Women with Newly Diagnosed Breast Cancer.

    Science.gov (United States)

    Candelaria, Rosalind P; Huang, Monica L; Adrada, Beatriz E; Bassett, Roland; Hunt, Kelly K; Kuerer, Henry M; Smith, Benjamin D; Chavez-MacGregor, Mariana; Yang, Wei Tse

    2017-02-01

    This study aims to determine if locoregional restaging with diagnostic mammography and ultrasound (US) of the whole breast and regional nodes performed for quality assurance in women with newly diagnosed breast cancer who were referred to a tertiary care center yields incremental cancer detection. An institutional review board-approved retrospective, single-institution database review was performed on the first 1000 women referred to our center in 2010 with a provisional breast cancer diagnosis. Locoregional restaging consisted of diagnostic full-field digital mammography combined with US of the whole breast and regional nodal basins. Bilateral whole-breast US was performed in women with contralateral mammographic abnormality or had heterogeneously or extremely dense parenchyma. Demographic, clinical, and pathologic factors were analyzed. Final analyses included 401 women. Of the 401 women, 138 (34%) did not have their outside images available for review upon referral. The median age was 54 years (range 21-92); the median tumor size was 2.9 cm (range 0.6-18.0) for women whose disease was upstaged and 2.2 cm (range 0.4-15.0) for women whose disease was not upstaged. Incremental cancer detection rates were 15.5% (62 of 401) in the ipsilateral breast and 3.9% (6 of 154) in the contralateral breast (P breast and regional nodal US that is performed for standardization of the imaging workup for newly diagnosed breast cancer patients can reduce underestimation of disease burden and impact therapeutic planning. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  11. Mycobacterium tuberculosis Modulates miR-106b-5p to Control Cathepsin S Expression Resulting in Higher Pathogen Survival and Poor T-Cell Activation

    Directory of Open Access Journals (Sweden)

    David Pires

    2017-12-01

    Full Text Available The success of tuberculosis (TB bacillus, Mycobacterium tuberculosis (Mtb, relies on the ability to survive in host cells and escape to immune surveillance and activation. We recently demonstrated that Mtb manipulation of host lysosomal cathepsins in macrophages leads to decreased enzymatic activity and pathogen survival. In addition, while searching for microRNAs (miRNAs involved in posttranscriptional gene regulation during mycobacteria infection of human macrophages, we found that selected miRNAs such as miR-106b-5p were specifically upregulated by pathogenic mycobacteria. Here, we show that miR-106b-5p is actively manipulated by Mtb to ensure its survival in macrophages. Using an in silico prediction approach, we identified miR-106b-5p with a potential binding to the 3′-untranslated region of cathepsin S (CtsS mRNA. We demonstrated by luminescence-based methods that miR-106b-5p indeed targets CTSS mRNA resulting in protein translation silencing. Moreover, miR-106b-5p gain-of-function experiments lead to a decreased CtsS expression favoring Mtb intracellular survival. By contrast, miR-106b-5p loss-of-function in infected cells was concomitant with increased CtsS expression, with significant intracellular killing of Mtb and T-cell activation. Modulation of miR-106b-5p did not impact necrosis, apoptosis or autophagy arguing that miR-106b-5p directly targeted CtsS expression as a way for Mtb to avoid exposure to degradative enzymes in the endocytic pathway. Altogether, our data suggest that manipulation of miR-106b-5p as a potential target for host-directed therapy for Mtb infection.

  12. Fledgling survival increases with development time and adult survival across north and south temperate zones

    Science.gov (United States)

    Lloyd, Penn; Martin, Thomas E.

    2016-01-01

    Slow life histories are characterized by high adult survival and few offspring, which are thought to allow increased investment per offspring to increase juvenile survival. Consistent with this pattern, south temperate zone birds are commonly longer-lived and have fewer young than north temperate zone species. However, comparative analyses of juvenile survival, including during the first few weeks of the post-fledging period when most juvenile mortality occurs, are largely lacking. We combined our measurements of fledgling survival for eight passerines in South Africa with estimates from published studies of 57 north and south temperate zone songbird species to test three predictions: (1) fledgling survival increases with length of development time in the nest; (2) fledgling survival increases with adult survival and reduced brood size controlled for development time; and (3) south temperate zone species, with their higher adult survival and smaller brood sizes, exhibit higher fledgling survival than north temperate zone species controlled for development time. We found that fledgling survival was higher among south temperate zone species and generally increased with development time and adult survival within and between latitudinal regions. Clutch size did not explain additional variation, but was confounded with adult survival. Given the importance of age-specific mortality to life history evolution, understanding the causes of these geographical patterns of mortality is important.

  13. Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Wenjin Yin

    Full Text Available BACKGROUND: Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors. METHODS: Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data. FINDINGS: With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001 from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018. Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001 but bore a higher incidence of CNS recurrence (P = 0.010, while statistical significance failed to be discerned for either overall survival (P = 0.069 or CNS metastasis (P = 0.374 between the sequential and observation arms. CONCLUSION: This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

  14. Risk factors for locoregional recurrence in patients with resected N1 non-small cell lung cancer: a retrospective study to identify patterns of failure and implications for adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Fan, Chengcheng; Gao, Shugeng; Hui, Zhouguang; Liang, Jun; Lv, Jima; Wang, Xiaozhen; He, Jie; Wang, Luhua

    2013-01-01

    Meta-analysis of randomized trials has shown that postoperative radiotherapy (PORT) had a detrimental effect on overall survival (OS) in patients with resected N1 non–small cell lung cancer (NSCLC). Conversely, the locoregional recurrence (LR) rate is reported to be high without adjuvant PORT in these patients. We have evaluated the pattern of failure, actuarial risk and risk factors for LR in order to identify the subset of N1 NSCLC patients with the highest risk of LR. These patients could potentially benefit from PORT. We conducted a retrospective study on 199 patients with pathologically confirmed T1–3N1M0 NSCLC who underwent surgery. None of the patients had positive surgical margins or received preoperative therapy or PORT. The median follow-up was 53.8 months. Complete mediastinal lymph node (MLN) dissection and examination was defined as ≥3 dissected and examined MLN stations; incomplete MLN dissection or examination (IMD) was defined as <3 dissected or examined MLN stations. The primary end point of this study was freedom from LR (FFLR). Differences between patient groups were compared and risk factors for LR were identified by univariate and multivariate analyses. LR was identified in 41 (20.6%) patients, distant metastasis (DM) was identified in 79 (39.7%) patients and concurrent LR and DM was identified in 25 (12.6%) patients. The 3- and 5-year OS rates in patients with resected N1 NSCLC were 78.4% and 65.6%, respectively. The corresponding FFLR rates were 80.8% and 77.3%, respectively. Univariate analyses identified that nonsmokers, ≤23 dissected lymph nodes, visceral pleural invasion and lymph node ratio >10% were significantly associated with lower FFLR rates (P < 0.05). Multivariate analyses further confirmed positive lymph nodes at station 10 and IMD as risk factors for LR (P < 0.05). The 5-year LR rate was highest in patients with both these risk factors (48%). The incidence of LR in patients with surgically resected T1–3N1M0 NSCLC is

  15. Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition

    LENUS (Irish Health Repository)

    Cathcart, Mary Clare

    2011-06-01

    Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng\\/ml) and cell survival\\/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation\\/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis\\/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor\\/potential target in

  16. Network survivability performance

    Science.gov (United States)

    1993-11-01

    This technical report has been developed to address the survivability of telecommunications networks including services. It responds to the need for a common understanding of, and assessment techniques for network survivability, availability, integrity, and reliability. It provides a basis for designing and operating telecommunications networks to user expectations for network survivability and a foundation for continuing industry activities in the subject area. This report focuses on the survivability of both public and private networks and covers a wide range of users. Two frameworks are established for quantifying and categorizing service outages, and for classifying network survivability techniques and measures. The performance of the network survivability techniques is considered; however, recommended objectives are not established for network survivability performance.

  17. Survival of Sami cancer patients

    Directory of Open Access Journals (Sweden)

    Leena Soininen

    2012-07-01

    Full Text Available Objectives. The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design. The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods. The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results. There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30 and for non-Sami 1.02 (0.86–1.20, indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion. Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

  18. A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Sayan, Mutlay; Nelson, Carl; Gagne, Havaleh; Rubin, Deborah; Heimann, Ruth [Dept. of Radiation Oncology, University of Vermont Medical Center, Burlington (United States); Wilson, Karen [University of Vermont Cancer Center, Burlington (United States)

    2017-03-15

    Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

  19. Laryngeal sarcoidosis: a case-control study.

    Science.gov (United States)

    Duchemann, Boris; Lavolé, Armelle; Naccache, Jean-Marc; Nunes, Hilario; Benzakin, Sylvain; Lefevre, Marine; Kambouchner, Marianne; Périé, Sophie; Valeyre, Dominique; Cadranel, Jacques

    2014-10-20

    We undertook a study on a series of laryngeal sarcoidosis (LS), a very rare and often threatening localization to better specify laryngeal manifestations, sarcoidosis clinical expression and long-term follow-up. This was a retrospective case-control study. All LS patients from two French centers were included and compared to sarcoidosis patients without laryngeal localization with two controls for one patient. Twelve consecutive LS patients were recruited between 1993 and 2011. LS revealed sarcoidosis in eight cases (67%). The most common symptoms were hoarseness (77%), inspiratory dyspnea (38%) and