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Sample records for adjuvant concurrent chemoradiation

  1. Concurrent chemoradiation for vaginal cancer.

    David T Miyamoto

    Full Text Available BACKGROUND: It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT or concurrent chemoradiation therapy (CRT. METHODS: Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS and disease-free survival (DFS rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. RESULTS: The median age at diagnosis was 61 years (range, 18-92 years and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011. Twenty-three patients (45% in the RT group had a relapse at any site compared to 3 (15% in the CRT group (p = 0.027. With regard to the sites of first relapse, 10 patients (14% had local only, 4 (6% had local and regional, 9 (13% had regional only, 1 (1% had regional and distant, and 2 (3% had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10-0.97; p = 0.04. CONCLUSIONS: Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients.

  2. Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

    Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.

  3. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

    Hyung-Sik Lee; Min-Chan Kim; Youngmin Choi; Won-Joo Hur; Hyo-Jin Kim; Hyuk-Chan Kwon; Sung-Hyun Kim; Jae-Seok Kim; Jong-Hoon Lee; Ghap-Joong Jung

    2006-01-01

    AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection.METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage Ⅲ and Ⅳ (MO) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo.RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy.Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed.CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival.

  4. Survival After Chemoradiation in Resected Pancreatic Cancer: The Impact of Adjuvant Gemcitabine

    Purpose: To evaluate survival in patients with resected pancreatic cancer treated with concurrent chemoradiation with or without adjuvant gemcitabine (Gem). Methods and Materials: From 1998 to 2010, 86 patients with pancreatic adenocarcinoma who underwent resection were treated with adjuvant concurrent chemoradiation. Thirty-four patients received concurrent 5-fluorouracil–based chemoradiation (5-FU/RT) with traditional field radiation (range, 45–61.2 Gy; median, 50.4 Gy) without further adjuvant therapy. Thirty patients received traditional field 5-FU/RT (range, 45–60.4 Gy; median, 50.4 Gy) with Gem (1,000 mg/m2 weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m2 weekly)–based chemoradiation (Gem/RT), consisting of involved-field radiation (range, 27–38 Gy; median, 36 Gy) followed by further adjuvant Gem. Results: The median age of the cohort was 65 years (range, 40–80 years). Of the patients, 58 had T3 tumors (67%), 22 had T2 tumors (26%), and 6 had T1 tumors (7%). N1 disease was present in 61 patients (71%), whereas 18 patients (21%) had R1 resections. Performance status, lymph node status, and margin status were all similar among the treatment groups. Median follow-up was 19.0 months. Median overall survival (OS) (19.2 months, 19.0 months, and 21.0 months) and 3-year OS rates (26.5%, 27.2%, and 32.1%) were similar among patients with 5-FU/RT with no adjuvant Gem, those with 5-FU/RT with adjuvant Gem, and those with Gem/RT with adjuvant Gem, respectively (p = 0.88). Patients who received adjuvant Gem had a similar median OS (22.1 months) and 3-year OS rate (29%) compared to patients who did not (19.2 months and 26.5%, respectively) (p = 0.62). There was a trend for improved 3-year OS rates in patients with R0 vs. R1 resections (28.1% vs. 14.2%, p = 0.06) and in patients with T1 and T2 vs. T3 tumors (38% vs. 20%, p = 0.09). Node-negative patients had an improved 3

  5. Analysis of adjuvant treatment with chemoradiation in gastric cancer

    The Hospital San Juan de Dios has analyzed the benefit of patients with gastric cancer who undergo surgery after receiving adjuvant chemoradiation. A retrospective study was performed reviewing records of patients during the period 1 January 2001 to December 31, 2005. These patients have been discharged with a diagnosis of gastric cancer and have received a complete resection with curative gastric malignancy and adjuvant chemoradiation according to the protocol established by Dr. MacDonald. In the study 0116. 743 patients were discharged to Hospital San Juan de Dios, 1 in 20 has been possible to diagnose gastric cancer at early stages for a total of 28 patients. The results obtained were compared at the Hospital San Juan de Dios with those published by Dr. MacDonald. The over-life of 3 years in the chemoradiation group in Hospital San Juan de Dios has been of 42.9% and 50% in the study MacDonald. The group that has not received adjuvant the over-life in the same period has been of 20 % in HSJD and 41% in the study MacDonald, being lower percentage of patients with this over-life, but greater range of difference.

  6. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to

  7. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Ghosn Marwan G

    2010-06-01

    Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

  8. Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

    Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy

  9. A pulmonary artery pseudoaneurysm caused by concurrent chemoradiation therapy for lung cancer

    Kim, Jung Ho; Han, Sang Hoon

    2015-01-01

    Pulmonary artery pseudoaneurysms are rarely associated with lung cancer, and to our knowledge, have never been reported as a complication of concurrent chemoradiation therapy for lung cancer. We here report on a 64-year-old man with stage IIIA lung cancer who achieved partial response with concurrent chemoradiation therapy. However, 11 weeks later, he presented with massive hemoptysis, and computed tomography revealed a pulmonary artery pseudoaneurysm. From the findings of this case, we concl...

  10. Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital - Mayo Clinic collaborative study

    The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation. Patients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007) and at the Mayo Clinic (n = 130; 1977-2005) were reviewed. Patients with <60 days of follow-up, metastatic disease at surgery, or insufficient pathologic data were excluded. The final combined study consisted of 186 patients (n = 104 Johns Hopkins, n = 82 Mayo). Most patients received 5-FU based chemoradiation with conformal radiation. Cox proportional hazards models were used for survival analysis. Median overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002), node positive status (RR = 3.18, p < 0.001), and poor histological grade (RR = 1.69, p = 0.011). Patients who received adjuvant chemoradiation (n = 66) vs. surgery alone (n = 120) showed a higher rate of T3/T4 stage disease (57.6% vs. 30.8%, P < 0.001), lymph node involvement (72.7% vs. 30.0%, P < 0.001), and close or positive margins (4.6% vs. 0.0%, P = 0.019). Five year survival rates among node negative and node positive patients were 58.7% and 18.4% respectively. When compared with surgery alone, use of adjuvant chemoradiation improved survival among node positive patients (mOS 32.1 vs. 15.7 mos, 5 yr OS: 27.5% vs. 5.9%; RR = 0.47, P = 0.004). After adjusting for adverse prognostic factors on multivariate analysis, patients treated with adjuvant chemoradiation demonstrated a significant survival benefit (RR = 0.40, P < 0.001). Disease relapse occurred in 37.1% of all patients, most commonly metastatic

  11. Eluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital - Mayo Clinic collaborative study

    Zhou Jessica

    2011-09-01

    Full Text Available Abstract Background The role of adjuvant chemoradiation therapy for ampullary carcinoma is unknown. Previous literature suggests that certain populations with high risk factors for recurrence may benefit from adjuvant chemoradiation. We combined the experience of two institutions to better delineate which patients may benefit from adjuvant chemoradiation. Methods Patients who underwent curative surgery for ampullary carcinoma at the Johns Hopkins Hospital (n = 290; 1992-2007 and at the Mayo Clinic (n = 130; 1977-2005 were reviewed. Patients with Results Median overall-survival was 39.9 months with 2- and 5-year survival rates of 62.4% and 39.1%. On univariate analysis, adverse prognostic factors for overall survival included T3/T4 stage disease (RR = 1.86, p = 0.002, node positive status (RR = 3.18, p Conclusions Node-positive patients with resected ampullary adenocarcinoma may benefit from 5-FU based adjuvant chemoradiation. Since a significant proportion of patients develop metastatic disease, there is a need for more effective systemic treatment.

  12. Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

    Morganti, Alessio G. [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso (Italy); Falconi, Massimo [Department of Surgery, University of Verona, Verona (Italy); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology (MAASTRO), GROW, University Medical Centre Maastricht (Netherlands); Mattiucci, Gian-Carlo, E-mail: gcmattiucci@rm.unicatt.it [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Alfieri, Sergio [Department of Surgery, Università Cattolica S. Cuore, Rome (Italy); Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University, Madrid (Spain); Dubois, Jean-Bernard [Département de Radiothérapie, CRLC, Montpellier Cedex (France); Fastner, Gerd [Department of Radiotherapy, PMU, Salzburg (Austria); Herman, Joseph M. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Maidment, Bert W. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Reni, Michele [Department of Oncology, S. Raffaele Scientific Institute, Milan (Italy); Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Ippolito, Edy [Department of Radiation Oncology, University Campus Biomedico, Roma (Italy); and others

    2014-11-15

    Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

  13. Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

    Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT

  14. Neoadjuvant Concurrent Chemoradiation for Curative Treatment of Penile Squamous Cell Carcinoma

    Arpit Chhabra

    2014-01-01

    Full Text Available Introduction. Penile cancer is a rare malignancy often treated with neoadjuvant chemotherapy followed by surgery. However, the utility of neoadjuvant chemoradiation, particularly when the tumor is resistant to chemotherapy alone, has not been established. In this study, we report a case of pT3cN3M0 penile squamous cell carcinoma with progression of nodal disease on chemotherapy, which was cured with use of neoadjuvant concurrent chemoradiation. Case Report. A 65-year-old male presented with a fixed left inguinal lymph node with associated firmness of the penile glans. Biopsies of both sites revealed evidence of squamous cell carcinoma. The patient underwent partial penectomy for the primary lesion and began neoadjuvant chemotherapy to reduce the size of the unresectable left inguinal node. However, he displayed disease progression in the left inguinal node. As such, we attempted concurrent chemoradiation therapy with regression of his nodal disease. The patient was able to undergo left inguinal node dissection and has no evidence of disease 18 months since his initial surgery. Conclusion. The use of neoadjuvant chemoradiation for bulky cN2-3 disease seems appropriate in the setting of progressive disease. Further studies are necessary to assess the utility of concurrent chemoradiation both in the neoadjuvant and salvage setting.

  15. Molecular Markers Predict Distant Metastases After Adjuvant Chemoradiation for Rectal Cancer

    Kim, Jun Won; Kim, Yong Bae [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Jun Jeong [Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Koom, Woong Sub [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hoguen [Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Nam-Kyu [Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Ahn, Joong Bae [Department of Medical Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Ikjae; Cho, Jae Ho [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Keum, Ki Chang, E-mail: kckeum@yuhs.ac [Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-12-01

    Purpose: The outcomes of adjuvant chemoradiation for locally advanced rectal cancer are nonuniform among patients with matching prognostic factors. We explored the role of molecular markers for predicting the outcome of adjuvant chemoradiation for rectal cancer patients. Methods and Materials: The study included 68 patients with stages II to III rectal adenocarcinoma who were treated with total mesorectal excision and adjuvant chemoradiation. Chemotherapy based on 5-fluorouracil and leucovorin was intravenously administered each month for 6-12 cycles. Radiation therapy consisted of 54 Gy delivered in 30 fractions. Immunostaining of surgical specimens for COX-2, EGFR, VEGF, thymidine synthase (TS), and Raf kinase inhibitor protein (RKIP) was performed. Results: The median follow-up was 65 months. Eight locoregional (11.8%) and 13 distant (19.1%) recurrences occurred. Five-year locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates for all patients were 83.9%, 78.7%, 66.7%, and 73.8%, respectively. LRFFS was not correlated with TNM stage, surgical margin, or any of the molecular markers. VEGF overexpression was significantly correlated with decreased DMFS (P=.045), while RKIP-positive results were correlated with increased DMFS (P=.025). In multivariate analyses, positive findings for COX-2 (COX-2+) and VEGF (VEGF+) and negative findings for RKIP (RKIP-) were independent prognostic factors for DMFS, DFS, and OS (P=.035, .014, and .007 for DMFS; .021, .010, and <.0001 for DFS; and .004, .012, and .001 for OS). The combination of both COX-2+ and VEGF+ (COX-2+/VEGF+) showed a strong correlation with decreased DFS (P=.007), and the combinations of RKIP+/COX-2- and RKIP+/VEGF- showed strong correlations with improved DFS compared with the rest of the patients (P=.001 and <.0001, respectively). Conclusions: Molecular markers can be valuable in predicting treatment outcome of adjuvant

  16. Predicting the response of localised oesophageal cancer to neo-adjuvant chemoradiation

    Reynolds John

    2007-08-01

    Full Text Available Abstract Background A complete pathological response to neo-adjuvant chemo-radiation for oesophageal cancer is associated with favourable survival. However, such a benefit is seen in the minority. If one could identify, at diagnosis, those patients who were unlikely to respond unnecessary toxicity could be avoided and alternative treatment can be considered. The aim of this review was to highlight predictive markers currently assessed and evaluate their clinical utility. Methods A systematic search of Pubmed and Google Scholar was performed using the following keywords; "neo-adjuvant", "oesophageal", "trimodality", "chemotherapy", "radiotherapy", "chemoradiation" and "predict". The original manuscripts were sourced for further articles of relevance. Results Conventional indices including tumour stage and grade seem unable to predict histological response. Immuno-histochemical markers have been extensively studied, but none has made its way into routine clinical practice. Global gene expression from fresh pre-treatment tissue using cDNA microarray has only recently been assessed, but shows considerable promise. Molecular imaging using FDG-PET seems to be able to predict response after neo-adjuvant chemoradiation has finished, but there is a paucity of data when such imaging is performed earlier. Conclusion Currently there are no clinically useful predictors of response based on standard pathological assessment and immunohistochemistry. Genomics, proteomics and molecular imaging may hold promise.

  17. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Wood, Laura D. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Blackford, Amanda L. [Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Ellsworth, Susannah [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hidalgo, Manuel [Centro Nacional de Investigaciones Oncologicas, Madrid (Spain); Donehower, Ross C. [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Schulick, Richard D.; Edil, Barish H. [Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado (United States); Choti, Michael A. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hruban, Ralph H. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); and others

    2013-07-15

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

  18. Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

    Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer

  19. Postoperative adjuvant chemoradiation in completely resected locally advanced gastric cancer

    Background: The 5-year survival of patients with completely resected node-positive gastric cancer ranges from 15% to 25%. We explored the feasibility of a chemoradiation regime consisting of concomitant hyperfractionated radiotherapy and 5-fluorouracil protracted venous infusion (5-FU PVI). Materials and Methods: Forty patients received a total or partial gastrectomy operation and D2 nodal resection for Stage III gastric cancer; they were then irradiated by linac with 6-15-MV photons. The target included the gastric bed, the anastomosis, stumps, and regional nodes. A total dose of 55 Gy was given in 50 fractions using 1.1 Gy b.i.d. All patients received a concomitant 200 mg/m2/day 5-FU PVI. Patients were examined during the follow-up period as programmed. Toxicity was recorded according to RTOG criteria. Results: After a median follow-up of 75.6 months (range: 22-136 months), 24 (60%) patients had died, and 16 (40%) were alive and free of disease. The 5-year actuarial incidence of relapse was 39%, 22%, and 2% for distant metastases, out-field peritoneal seeding, and in-field local regional recurrences, respectively. The 5-year actuarial cause-specific survival was 43%. Three patients survived more than 11 years. Acute ≥ Grade 3 toxicity consisted of hematologic (22.5%) and gastrointestinal toxicity (nausea and vomiting 22.5%, diarrhea 2.8%, and abdominal pain 2.6%). No late toxicity was observed. Conclusion: This regime of concomitant 5-FU PVI and hyperfractionated radiotherapy was well tolerated and resulted in successful locoregional control and satisfactory survival

  20. Variable uterine uptake of FDG in adenomyosis during concurrent chemoradiation therapy for cervical cancer

    Yu, Jeong Il; Huh, Seung Jae; Kim, Young Il; Kim, Tae-Joong; Park, Byung Kwan

    2011-01-01

    To avoid improper tumor volume contouring in radiation therapy (RT) and other invasive procedures, we report a case of uterine adenomyosis showing increased 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) mimicking malignant tumor in a 44-year-old woman during concurrent chemoradiation therapy (CCRT) for uterine cervical cancer. The adenomyosis was not associated with her menstrual cycle or with normal endometrium uptake, and it resolved one ...

  1. Concurrent chemoradiation for unresectable advanced head and neck cancer

    Concurrent chemoradiotherapy were performed for 18 patients with unresectable head and neck squamous cell cancer. Chemotherapy, consisting of CDDP (40 mg/m2, Day 1 and 8) and 5-FU (200 mg/m2, 24-h continuous infusion through Day 1-5 and 8-12), with concurrent radiotherapy (2 Gy/day, 5 days/w) were administered and repeated 2-3 courses in every 5 weeks. Mucositis and myelo-suppression were the main side effects observed, but all of them were tolerable. Total response rate and complete response rate was 94.4% and 55.6%, respectively. Out of six patients requiring tracheotomy for airway obstruction due to bulky tumor, four achieved sufficient tumor shrinkage by the treatment and could obtain closure of the stoma. Two patients whose neck lymph nodes were still remaining after chemoradiotherapy, could obtain local control by supplemental neck dissection surgery. These regimen is feasible and effective for locally advanced head and neck cancer. (author)

  2. Concurrent chemoradiation for unresectable advanced head and neck cancer

    Shimizu, Wakako; Ogino, Takashi; Ishikura, Satoshi [National Cancer Center, Kashiwa, Chiba (Japan). Hospital East] [and others

    1998-03-01

    Concurrent chemoradiotherapy were performed for 18 patients with unresectable head and neck squamous cell cancer. Chemotherapy, consisting of CDDP (40 mg/m{sup 2}, Day 1 and 8) and 5-FU (200 mg/m{sup 2}, 24-h continuous infusion through Day 1-5 and 8-12), with concurrent radiotherapy (2 Gy/day, 5 days/w) were administered and repeated 2-3 courses in every 5 weeks. Mucositis and myelo-suppression were the main side effects observed, but all of them were tolerable. Total response rate and complete response rate was 94.4% and 55.6%, respectively. Out of six patients requiring tracheotomy for airway obstruction due to bulky tumor, four achieved sufficient tumor shrinkage by the treatment and could obtain closure of the stoma. Two patients whose neck lymph nodes were still remaining after chemoradiotherapy, could obtain local control by supplemental neck dissection surgery. These regimen is feasible and effective for locally advanced head and neck cancer. (author)

  3. Outcomes of pediatric glioblastoma treated with adjuvant chemoradiation with temozolomide and correlation with prognostic factors

    Supriya Mallick

    2015-01-01

    Full Text Available Background: Pediatric glioblastoma (pGBM patients are underrepresented in major trials for this disease. We aimed to explore the outcome of pGBM patients treated with concurrent and adjuvant temozolomide (TMZ. Materials and Methods: 23 patients of pGBM treated from 2004 to 2010 were included in this retrospective analysis. Adjuvant therapy included conformal radiation 60 gray at 2 gray/fraction daily over 6 weeks with concurrent TMZ 75 mg/m 2 followed by six cycles of adjuvant TMZ 150-200 mg/m 2 (day 1-5 every 4 weeks. Kaplan-Meier estimates of overall survival (OS were determined. Univariate analysis with log-rank test was used to determine the impact of prognostic variables on survival. Results: Median age at presentation was 11.5 years (range: 7-19 years and M:F ratio was 15:8. All patients underwent maximal safe surgical resection; 13 gross total resection and 10 sub-total resection. At a median follow-up of 18 months (range: 2.1-126 months, the estimated median OS was 41.9 months. The estimated median OS for patients receiving only concurrent TMZ was 8 months while that for patients receiving concurrent and adjuvant TMZ was 41.9 months (P = 0.081. Estimated median OS for patients who did not complete six cycles of adjuvant TMZ was 9.5 months versus not reached for those who completed at least six cycles (P = 0.0005. Other prognostic factors did not correlate with survival. Conclusions: Our study shows the benefit of TMZ for pGBM patients. Both concurrent and adjuvant TMZ seem to be important for superior OS in this group of patients.

  4. A prospective randomised controlled trial of concurrent chemoradiation versus concurrent chemoradiation along with gefitinib in locally advanced squamous cell carcinoma of head and neck

    Biswamit Bhattacharya

    2014-01-01

    Full Text Available Background: The primary aim of the study was to find out whether addition of Gefitinib to standard cisplatin-based chemo-radiation can offer better treatment outcome at the cost of acceptable toxicities. Materials and Methods: Between January 2011 and June 2012, 64 patients were enrolled in the study following obtaining institutional ethical committee clearance and proper informed consent from the patients. Patients recruited were randomly allocated into a control arm (who received External Beam Radiotherapy with conventional 2 Gy/fraction, 5 days a week for 7 weeks up to total dose of 66 Gy along with concomitant injection cisplatin at the dose of 30 mg/m 2 of body surface area on every week during radiation and study arm (who received radiotherapy with 2 Gy/fraction, 5 days a week for 7 weeks up to total dose of 66 Gy, along with concomitant injection cisplatin at the dose of 30 mg/m 2 of body surface area on every week during radiation, plus Tablet Gefitinib (250 mg/day orally during the total duration of radiation treatment. However, only 61 patients (31 in the control arm and 30 in the study arm were available for analysis. The two groups were comparable in terms of age distribution, sex distribution, performance status, stage, primary site and histological grade. Results: 29.03% patients achieved complete response (CR in the control arm while 36.67% patients achieved CR in the study arm (CR, but the difference was not significant statistically (P = 0.5255. Total number of patients achieving overall response (CR + partial response in control arm was 19 (61.29% while it was 23 in the study arm (76.67%. However, the difference of overall response between the study arm and the control arm was not statistically significant (P = 0.1947. Disease free survival (DFS rate at 1 year was 22.58% for the control arm and 33.33% for the study arm but it was not statistically significant (P = 0.515. Addition of Gefitinib to standard concurrent cisplatin

  5. Pseudomembranous colitis within radiotherapy field following concurrent chemoradiation therapy: a case report

    Shen BJ

    2013-01-01

    Full Text Available Bing-Jie Shen,1 Shih-Chiang Lin,2 Pei-Wei Shueng,1,3 Yueh-Hung Chou,4 Li-Ming Tseng,5 Chen-Hsi Hsieh1,6,71Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan; 2Division of Oncology and Hematology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 3Department of Radiation Oncology, National Defense Medical Center, Taipei, Taiwan; 4Department of Anatomical Pathology, Far Eastern Memorial Hospital, Taipei, Taiwan; 5Division of Colorectal Surgery, Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, TaiwanAbstract: Development of nonantibiotic-associated pseudomembranous colitis has been reported in patients receiving chemotherapy. Herein, we report a case of a 70-year-old man with diabetes mellitus and hypertension who received concurrent chemoradiation therapy after surgery for stage III pT3N1M0 rectal cancer. After completion of the therapy, the patient presented with a 2-week history of intermittent watery diarrhea (seven to nine times per day. However, the patient was afebrile and laboratory examination revealed no evidence of leukocytosis. Computed tomography disclosed inflammation of the sigmoid colon, infiltrative changes around the anastomotic site, and edematous changes straddling the serosal surface. Colonoscopic examination revealed multiple whitish patches within the radiation field, a finding suggestive of pseudomembranous colitis. No concomitant antibiotics were used during the period of concurrent chemoradiation therapy. Empirical oral metronidazole (500 mg every 8 hours was administrated for 2 weeks. At the end of this treatment, stool culture was negative for Clostridium difficile. Physicians should be aware of the potential for the development of

  6. Variable uterine uptake of FDG in adenomyosis during concurrent chemoradiation therapy for cervical cancer

    Yu, Jeong Il; Huh, Seung Jae; Kim, Young Il; Kim, Tae Joong; Park, Byung Kwan [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-09-15

    To avoid improper tumor volume contouring in radiation therapy (RT) and other invasive procedures, we report a case of uterine adenomyosis showing increased 18F-fl uorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) mimicking malignant tumor in a 44-year-old woman during concurrent chemoradiation therapy (CCRT) for uterine cervical cancer. The adenomyosis was not associated with her menstrual cycle or with normal endometrium uptake, and it resolved one month after completion of RT. This case indicates that uterine adenomyosis in a premenopausal woman may show false positive uptake of 18FDG-PET/CT associated with CCRT.

  7. Variable uterine uptake of FDG in adenomyosis during concurrent chemoradiation therapy for cervical cancer

    To avoid improper tumor volume contouring in radiation therapy (RT) and other invasive procedures, we report a case of uterine adenomyosis showing increased 18F-fl uorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) mimicking malignant tumor in a 44-year-old woman during concurrent chemoradiation therapy (CCRT) for uterine cervical cancer. The adenomyosis was not associated with her menstrual cycle or with normal endometrium uptake, and it resolved one month after completion of RT. This case indicates that uterine adenomyosis in a premenopausal woman may show false positive uptake of 18FDG-PET/CT associated with CCRT.

  8. Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

    Purpose: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Methods and Materials: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34–86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34–56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up duration was 29 months. Results: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size ≥2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). Conclusion: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.

  9. Phase II Study of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer: Preliminary Results

    Purpose: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. Methods and Materials: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m2 (Day 1) and 5-fluorouracil 1000 mg/m2 (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. Results: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). Conclusions: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile

  10. A dose escalation study of concurrent chemoradiation therapy with nedaplatin for cervical cancer

    Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m2 as Level 1 or at 90 mg/m2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting toxicity (DLT) was observed in 1 of 6 patients receiving 80 mg/m2 of CDGP and in all 2 patients receiving 90 mg/m2 of CDGP; therefore, Level 2 was regarded as the maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs consisted of delayed improvement in the leukocyte count in 2 patients and anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count is the main DLT of this combination therapy. The main side effects were digestive disorders such as nausea and anorexia and bone marrow suppression, such as leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were more mild than in the Level 2 group. The efficacy was partial response (PR) or better in all patients. The complete response (CR) rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the Level 2 group; there was no marked difference between the two groups. These results suggest that CCRT involving administration CDGP at 80 mg/m2 on Days 1 and 29 is safe and effective. (author)

  11. Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

    Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

  12. Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

    Chon, Young Eun [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Beom Kyung [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cha, Jihye [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seung Up; Park, Jun Yong; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of); Shin, Sung Kwan, E-mail: kaarma@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Do Young, E-mail: dyk1025@yuhs.ac [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Gastroenterology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Liver Cirrhosis Clinical Research Center, Seoul (Korea, Republic of)

    2011-12-01

    Purpose: Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Methods and Materials: Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. Results: A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p = 0.043). There were no radiation-related deaths. Conclusions: Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

  13. Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of the vulva

    Purpose: To determine the impact of primary or adjuvant chemotherapy and radiation (CRT) on the survival rates of patients with locally advanced vulvar carcinoma. Methods and Materials: Between 1973 and 1998, 54 patients with vulvar cancer were treated with radiation therapy, among which 20 received CRT, while 34 patients received radiation therapy (RT) alone. Of the 20 patients, 14 were treated for primary or recurrent disease (pCRT), and 6 after radical vulvectomy for high-risk disease (aCRT). Of the 34 patients, 12 were treated primarily (pRT) and 22 received adjuvant treatment (aRT). Chemotherapy consisted of 2 courses of 5-fluorouracil (5-FU) and mitomycin C administered during RT. Six patients received cisplatin in place of mitomycin C. In CRT groups, radiation was administered to the vulva, pelvic, and inguinal lymph nodes to a median dose of 45 Gy with additional 6-17 Gy to gross disease. In RT groups, the median dose to the microscopic diseases was 45 Gy. Nine patients received external beam boost and 16 patients received supplementary brachytherapy in the forms of 226Ra or 241Am plaques to sites of macroscopic disease. Results: Overall survival was superior in the patients treated with pCRT versus pRT with statistical significance (p 0.04). There was also a statistically significant improvement in disease-specific (p = 0.03) and relapse-free survival (p = 0.01) favoring pCRT. No statistically significant trends of improved survival rates favoring aCRT over aRT were observed. Conclusion: Concurrent radiation therapy and chemotherapy decreases local relapse rate, improves disease-specific and overall survival over RT alone as primary treatment for locally advanced vulvar cancer

  14. Concurrent chemoradiotherapy in adjuvant treatment of breast cancer

    The optimal sequencing of chemotherapy and radiotherapy after breast surgery was largely studied but remains controversial. Concurrent chemo-radiotherapy is a valuable method for adjuvant treatment of breast cancer which is under ongoing research program in our hospital. We are evaluating the feasibility of the concomitant use of chemotherapy retrospectively. Two hundred forty four women having breast cancer were investigated in a retrospective study. All patients were either treated by radical surgery or breast conservative surgery. The study compares two adjuvant treatments associating concomitant chemotherapy and radiotherapy. In the first group (group A) the patients were treated by chemotherapy and radiotherapy in concomitant way using anthracycline (n = 110). In the second group (group B) the patients were treated by chemotherapy and radiotherapy in concomitant way using CMF treatment (n = 134). Chemotherapy was administered in six cycles, one each 3 weeks. Radiotherapy delivered a radiation dose of 50 Gy on the whole breast (or on the external wall) and/or on the lymphatic region. The Kaplan-Meier method was used to estimate the rates of disease free survival, loco-regional recurrence-free survival and overall survival. The Pearson Khi2 test was used to analyse the homogeneity between the two groups. The log-rank test was used to evaluate the differences between the two groups A and B. After 76.4 months median follow-up (65.3 months mean follow up), only one patient relapsed to loco-regional breast cancer when the treatment was based on anthracycline. However, 8 patients relapsed to loco-regional breast cancer when the treatment was based on CMF. In the anthracycline group, the disease free survival after 5 years, was 80.4% compared to 76.4% in the CMF group (Log-rank test: p = 0.136). The overall survival after 5 years was 82.5% and 81.1% in the anthracycline and CMF groups respectively (Log-rank test: p = 0.428). The loco-regional free survival at 5 years

  15. Comparison of concomitant boost radiotherapy against concurrent chemoradiation in locally advanced oropharyngeal cancers: A phase III randomised trial

    Purpose: To test the toxicity and efficacy of concomitant boost radiotherapy alone against concurrent chemoradiation (conventional fractionation) in locally advanced oropharyngeal cancer in our patient population. Methods and materials: In this open-label, randomised trial, 216 patients with histologically proven Stage III–IVA oropharyngeal cancer were randomly assigned between June 2006 and December 2010 to receive either chemoradiation (CRT) to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (100 mg/m2 on days 1, 22 and 43) or accelerated radiotherapy with concomitant boost (CBRT) to a dose of 67.5 Gy in 40 fractions over 5 weeks. The compliance, toxicity and quality of life were investigated. Disease-free survival (DFS) and overall survival (OS) curves were estimated with the Kaplan–Meier method and compared using log rank test. Results: The compliance to radiotherapy was superior in concomitant boost with lesser treatment interruptions (p = 0.004). Expected acute toxicities were significantly higher in CRT, except for grade 3/4 mucositis which was seen more in CBRT arm (39% and 55% in CRT and CBRT, respectively; p = 0.02). Late toxicities like Grade 3 xerostomia were significantly high in CRT arm than CBRT arm (33% versus 18%; p 2 cm had significantly better DFS with CRT (p = 0.05; HR-1.59, 95%CI-0.93–2.7). Conclusion: In selected patients of locally advanced oropharyngeal cancer, concomitant boost offers a better compliance, toxicity profile and quality of life with similar disease control, than chemoradiation

  16. Is extended-field concurrent chemoradiation an option for radiologic negative paraaortic lymph node, locally advanced cervical cancer?

    The aim was to evaluate whether extended-field concurrent chemoradiation (EF-CCRT) leads to results better than those obtained by standard whole-pelvis concurrent chemoradiation (WP-CCRT) in locally advanced cervical cancer with radiologic negative paraaortic lymph nodes (PALNs). A total of 102 patients with histopathologically proven squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma, and radiologic negative PALN locally advanced cervical cancer, stage IIB-IVA, were accrued between July 2007 and April 2008 and were randomly assigned to WP-CCRT (50 patients) or EF-CCRT (52 patients), followed by high-dose rate brachytherapy. Data regarding the safety profile, response rates, and occurrence of local, PALN, or distant failure were recorded. During a median follow-up time of 60 months (18–66), 74/102 patients completed the treatment protocol and were analyzed. Overall PALN, distant-metastasis control, disease-free survival, and overall survival rates were 97.1%, 86.9%, 80.3%, and 72.4% in EF-CCRT respectively in comparison with WP-CCRT (82.1%,74.7%, 69.1%, and 60.4%), with P-values of 0.02, 0.03, 0.03 and 0.04 respectively. No difference in acute toxicity profile was seen between the groups, and late toxicities were mild and minimal. Prophylactic EF-CCRT can be a reasonable option in patients with locally advanced cervical cancer with radiologic positive pelvic lymph nodes and radiologic negative PALN

  17. Risk of endocrine pancreatic insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer

    Background: Adjuvant radiotherapy combined with 5-fluorouracil based chemotherapy has become the new standard after curative resection in high risk gastric cancer. Beside many complications due to surgery, the addition of chemotherapy and radiotherapy as adjuvant treatment may lead to both acute and late toxicities. Pancreatic tissue irradiation during this adjuvant treatment because of incidental and unavoidable inclusion of the organ within the radiation field may affect exocrine and endocrine functions of the organ. Materials and methods: Fifty-three patients with gastric adenocarcinoma were evaluated for adjuvant chemoradiotherapy after surgery. While 37 out of 53 patients were treated postoperatively due to either serosal or adjacent organ or lymph node involvement, 16 patients without these risk factors were followed up regularly without any additional treatment and they served as the control group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1c), insulin and C-peptide levels were measured in the control and study groups after the surgery and 6 months and 1 year later. Results: At the baseline there was no difference in FBG, HbA1c, C-peptide and insulin levels between the control and the study groups. At the end of the study there was a statistically significant decline in insulin and C-peptide levels in the study group, (7.5 ± 6.0 vs 4.5 ± 4.4 IU/L, p: 0.002 and 2.3 ± 0.9 vs 1.56 ± 0.9 ng/ml, p: 0.001) respectively. Conclusions: Adjuvant radiotherapy in gastric cancer leads to a decrease in beta cell function and insulin secretion capacity of the pancreas with possible diabetes risk. Radiation-induced pancreatic injury and late effects of radiation on normal pancreatic tissue are unknown, but pancreas is more sensitive to radiation than known. This organ should be studied extensively in order to determine the tolerance doses and it should be contoured during abdominal radiotherapy planning as an organ at risk

  18. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Kyubo, E-mail: kyubokim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chie, Eui Kyu [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Jin Ho [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jang, Jin-Young; Kim, Sun Whe [Department of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Ha, Sung W. [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of)

    2013-11-01

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy.

  19. Nomogram Prediction of Survival and Recurrence in Patients With Extrahepatic Bile Duct Cancer Undergoing Curative Resection Followed by Adjuvant Chemoradiation Therapy

    Purpose: To develop nomograms for predicting the overall survival (OS) and relapse-free survival (RFS) in patients with extrahepatic bile duct cancer undergoing adjuvant chemoradiation therapy after curative resection. Methods and Materials: From January 1995 through August 2006, a total of 166 consecutive patients underwent curative resection followed by adjuvant chemoradiation therapy. Multivariate analysis using Cox proportional hazards regression was performed, and this Cox model was used as the basis for the nomograms of OS and RFS. We calculated concordance indices of the constructed nomograms and American Joint Committee on Cancer (AJCC) staging system. Results: The OS rate at 2 years and 5 years was 60.8% and 42.5%, respectively, and the RFS rate at 2 years and 5 years was 52.5% and 38.2%, respectively. The model containing age, sex, tumor location, histologic differentiation, perineural invasion, and lymph node involvement was selected for nomograms. The bootstrap-corrected concordance index of the nomogram for OS and RFS was 0.63 and 0.62, respectively, and that of AJCC staging for OS and RFS was 0.50 and 0.52, respectively. Conclusions: We developed nomograms that predicted survival and recurrence better than AJCC staging. With caution, clinicians may use these nomograms as an adjunct to or substitute for AJCC staging for predicting an individual's prognosis and offering tailored adjuvant therapy

  20. Epidermal Growth Factor Receptor Expression As Prognostic Marker in Patients With Anal Carcinoma Treated With Concurrent Chemoradiation Therapy

    Purpose: To investigate the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment tumor biopsy specimens of patients with anal cancer treated with concurrent 5-fluorouracil and mitomycin C-based chemoradiation therapy (CRT). Methods and Materials: Immunohistochemical staining for EGFR was performed in pretreatment biopsy specimens of 103 patients with anal carcinoma. EGFR expression was correlated with clinical and histopathologic characteristics and with clinical endpoints, including local failure-free survival (LFFS), colostomy-free survival (CFS), distant metastases-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Results: EGFR staining intensity was absent in 3%, weak in 23%, intermediate in 36% and intense in 38% of the patients. In univariate analysis, the level of EGFR staining was significantly correlated with CSS (absent/weak vs intermediate/intense expression: 5-year CSS, 70% vs 86%, P=.03). As a trend, this was also observed for DMFS (70% vs 86%, P=.06) and LFFS (70% vs 87%, P=.16). In multivariate analysis, N stage, tumor differentiation, and patients’ sex were independent prognostic factors for CSS, whereas EGFR expression only reached borderline significance (hazard ratio 2.75; P=.08). Conclusion: Our results suggest that elevated levels of pretreatment EGFR expression could be correlated with favorable clinical outcome in anal cancer patients treated with CRT. Further studies are warranted to elucidate how EGFR is involved in the response to CRT

  1. Preoperative chemoradiation therapy for lower rectal cancer

    Murotani, Masahiro; Tsujinaka, Toshimasa; Takami, Motohisa [Toyonaka Municipal Hospital, Osaka (Japan)] [and others

    1996-09-01

    To identify appropriate candidates with rectal cancer for preoperative chemoradiation therapy, the local recurrence rate and clinicopathological characteristics of 232 patients with rectal cancer undergoing curative resection in our department were investigated. The local recurrence rates were 3.8%, 10.8% and 16.5% in the Rs, Ra and Rb lesions, respectively. Regarding lower (Rb) rectal cancer, depth of lesion (>a{sub 1}) and nodal metastasis consisted of high factors for local recurrence. Basing on these results, entery criteria for preoperative chemoradiation therapy were established, and concurrent chemoradiation therapy with fluorouracil and cisplatin was delivered preoperatively in 9 primary cases of locally advanced rectal cancer and 3 cases with local recurrence. A partial response was obtained in 7 of 12 cases with a response rate of 58%, size-reduction of the distant metastatic lesions was found in 2 cases, and clinical symptoms were improved in all cases. The histological responses of the 6 resected cases were Grade 2 in 2 cases and Grade 1b in 4 cases. The toxicities of this chemoradiation regimen were well tolerable. As a postoperative complication, infection of the perineal wound was most frequent. Preoperative chemoradiation therapy with the present regimen would be a useful adjuvant treatment for advanced lower rectal cancer. (author)

  2. Concurrent Boost with Adjuvant Breast Hypofractionated Radiotherapy and Toxicity Assessment

    Mona M. Sayed

    2015-01-01

    Full Text Available Background: The use of shorter radiotherapy schedules has an economic and logistic advantage for radiotherapy departments, as well as a high degree of patient convenience. The aim of this study is to assess the acute and short-term late toxicities of a hypofractionated radiotherapy schedule with a concomitant boost. Methods: We enrolled 57 eligible patients as group A. These patients received 42.5 Gy in 16 fractions of 2.66 Gy each to the whole breast over 3.2 weeks. A concomitant electron boost of 12 Gy in 16 fractions was also administered which gave an additional 0.75 Gy daily to the lumpectomy area for a total radiation dose of 54.5 Gy. Toxicity was recorded at three weeks and at three months for this group as well as for a control group (group B. The control group comprised 76 eligible patients treated conventionally with 50 Gy to the whole breast over five weeks followed by a sequential electron boost of 12 Gy in 2 Gy per fraction. Results: There were no statistically significant differences observed in the incidence of acute skin toxicity, breast pain, and edema recorded at three weeks or pigmentation and fibrosis recorded at three months between the two groups (P0.05. Conclusion: The results of this study suggest there are no increased acute and shortterm late toxicities affiliated with the hypofractionated schedule plus a concomitant boost as prescribed compared to the conventional fractionation of adjuvant breast radiotherapy. Large randomized trials and long-term follow-up are needed to confirm these favorable findings.

  3. Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

    Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m2/day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

  4. Concurrent chemoradiation with weekly Cisplatin, Docetaxel and Gefitinib: A study to assess feasibility, toxicity and immediate response

    Prasad Eswaran

    2013-01-01

    Full Text Available Objectives: Addition of docetaxel in the treatment regimen has shown improvement in survival of head and neck squamous cell carcinoma (HNSCC patients. This study was conducted to evaluate the maximum tolerated dose of weekly docetaxel when combined with concurrent administration of weekly cisplatin, daily gefitinib, and radiation therapy. Materials and Methods: 21 patients with newly diagnosed HNSCC were included. Radiation therapy was planned to a dose of 66 Gy/33 fractions. Doses of cisplatin and gefitinib were kept constant at 30 mg/m 2 and 250 mg respectively. Dose of weekly docetaxel started with 5 mg/m 2 and escalated 5 mg/m 2 up to a maximum of 20 mg/m 2 . Serious adverse event was defined as grade 3/4 hematological and non-hematological toxicities. Results: All patients (three in dose level 1 [5 mg/m 2 ], level 2 [10 mg/m 2 ] and level 3 [15 mg/m 2 ] did not experience any hematological serious adverse events. Weekly docetaxel of 20 mg/m 2 could not be tolerated with the combination, and we encountered two hematological (neutropenia serious grade 4 adverse event and one grade 3 mucositis at level 4. Six patients were treated by omitting week 3 chemotherapy reducing the number of weekly cycles to a minimum of four. Gefitinib was continued throughout the treatment period. All patients tolerated the treatment well although with grade 2 hematological/non hematological toxicities. Conclusion: The maximal tolerated dose of weekly docetaxel added to weekly cisplatin and daily gefitinib during concurrent chemoradiation is 15 mg/m 2 . Toxicity profile is tolerable with a break in the chemotherapy regimen during radiation therapy. Aggressive nutritional support is essential prior to this regimen.

  5. Clinical study of concurrent chemoradiation with superselective intra-arterial docetaxel-nedaplatin for oral cancers

    Recently, superselective intra-arterial chemotherapy concurrent with radiotherapy has become popular in advanced head and neck carcinoma treatment. Twenty patients with advanced oral cancers were treated by radiation (66 Gy) and chemotherapy with superselective intra-arterial docetaxel (40 mg/mm2)-nedaplatin (80 mg/mm2) infusion between 2003 and 2009. Complete response in the primary and regional cervical region was obtained in 17 (85%) out of the 20 patients. Five-year survival rate was 74.1% and major adverse effects were leukopenia and mucositis. Five patients (25%) developed distant metastasis post-treatment. Intra-arterial docetaxel-nedaplatin infusion concurrent with radiotherapy is an effective treatment for advanced oral cancers but severe complications and distant metastasis are problems that need to be solved. (author)

  6. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    Park, In Ja [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Kim, Hee Cheol [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Nam Kyu [Section of Colon and Rectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Hyeong-Rok [Department of Surgery, Chonnam National University Hwansun Hospital, Gwangju (Korea, Republic of); Kang, Sung-Bum [Department of Surgery, Seoul National University Bungdang Hospital, Bundang (Korea, Republic of); Choi, Gyu-Seog [Division of Colorectal Cancer Center, Kyungpook National University Medical Center, Daegu (Korea, Republic of); Lee, Kang Young [Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Seon-Hahn [Department of Surgery, Korea University Anam Hospital, Seoul (Korea, Republic of); Oh, Seung Taek [Department of Surgery, Seoul St. Mary Hospital, Catholic University, Seoul (Korea, Republic of); Lim, Seok-Byung; Kim, Jin Cheon [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Oh, Jae Hwan; Kim, Sun Young [Center for Colorectal Cancer, National Cancer Center, Goyang-si (Korea, Republic of); Lee, Woo Yong [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jung Bok [Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of); Yu, Chang Sik, E-mail: csyu@amc.seoul.kr [Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul (Korea, Republic of)

    2015-07-01

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.

  7. Role of Adjuvant Chemotherapy in ypT0-2N0 Patients Treated with Preoperative Chemoradiation Therapy and Radical Resection for Rectal Cancer

    Objective: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. Patients and Methods: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (−). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. Results: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (−), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). Conclusions: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits

  8. Preoperative concurrent chemo-radiation in rectal cancer; Radiochimiotherapie concomitante preoperatoire pour cancer du rectum

    Berger, C.; Kirscher, S.; Felix-Faure, C.; Chauvet, B.; Vincent, P.; Brewer, Y.; Reboul, F. [Clinique Sainte-Catherine, 84 - Avignon (France)

    1998-05-01

    To evaluate retrospectively treatment-related morbidity of concurrent radiotherapy and chemotherapy for rectal cancer. Between 1992 and 1995, 38 patients (median age: 60) were treated for locally advanced resectable rectal cancer. Median dose of radiotherapy was 45 Gy/25 fractions/5 weeks. Chemotherapy consisted of two courses of 5-fluorouracil and leucovorin administered during the first and the fifth weeks of radiotherapy. Median dose of 5-fluorouracil was 350 mg/m{sup 2}/day, and median dose of leucovorin was 350 mg/m{sup 2}/day, day 1 to day 5. Surgery was performed 5 weeks after completion of radiotherapy. Before surgery, one patient died of febrile neutropenia and sepsis after two cycles of chemotherapy and 45 Gy. Main pre-operative grade 3-4 toxicities were respectively: neutropenia: 3% ; nausea/vomiting: 3%; diarrhea: 3%; proctitis: 5%; radiation dermatitis: 8%. Twenty-six patients underwent a low anterior resection and 11 an abdomino-perineal resection. A temporary colostomy was performed in 12 patients. Pathologic complete response rate was 27 %. There was one post-operative death due to thrombo-embolic disease. Major post-operative grade 3-4 complications were: pelvic infection: 14 %; abdominal infection : 5%; perineal sepsis: 8%; anastomotic dehiscence: 8%; cardiac failure: 5%. Delayed perineal wound healing was observed in six patients. No significant prognostic factor of post-operative complications has been observed. Median duration of hospitalization was 22 days. With a median follow-up of 24 months, 2-year overall and disease-free survival rates were 82 and 64%. Tolerance of preoperative concurrent chemoradiotherapy was acceptable. Ongoing controlled studies will assess the impact of this combined treatment on survival. (authors)

  9. A Matched-Case Comparison to Explore the Role of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer

    Purpose: The aim of this study was to compare the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) and CCRT alone in patients with locally advanced cervical carcinoma. Methods and Materials: Using medical records from January 2001 to December 2007, 39 patients treated with consolidation chemotherapy after CCRT (Group 1) were matched to 39 patients treated with CCRT alone (Group 2). Consolidation chemotherapy consisted of three additional cycles of chemotherapy with cisplatin 60 mg/m2 (Day 1) and 5-fluorouracil 1,000 mg/m2 per day (Days 1−5) given every 3 weeks. The primary endpoint was overall survival. Results: During a median follow-up period of 35 months (range, 8−96 months), 10 (25.6%) and 16 (41.0%) patients showed disease progression in Groups 1 and 2, respectively. Distant recurrence with or without locoregional/lymphogenous recurrence occurred more frequently in Group 2 than in Group 1 (23.1% vs. 7.7%, p = 0.06). By contreast, there was no difference in locoregional or lymphogenous recurrence between the two groups. The rate of overall survival was higher in Group 1 than in Group 2 (92.7% vs. 69.9%, p = 0.042), whereas the difference in progression-free survival between the groups was not statistically significant (70.1% vs. 55.1%, p = 0.079). Although the difference was not statistically significant, neutropenia was more common in Group 1 than in Group 2 (10.9% vs. 4.7%, p = 0.07). Conclusions: Consolidation chemotherapy after CCRT may improve survival and reduce distant recurrence without additional toxicity compared to CCRT alone in patients with locally advanced cervical carcinoma.

  10. A Matched-Case Comparison to Explore the Role of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer

    Choi, Chel Hun; Lee, Yoo-Young; Kim, Min Kyu; Kim, Tae-Joong; Lee, Jeong-Won [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Nam, Hee Rim; Huh, Seung Jae [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Je-Ho; Bae, Duk-Soo [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Byoung-Gie, E-mail: bksong.kim@samsung.com [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2011-12-01

    Purpose: The aim of this study was to compare the efficacy and toxicity of consolidation chemotherapy after concurrent chemoradiation (CCRT) and CCRT alone in patients with locally advanced cervical carcinoma. Methods and Materials: Using medical records from January 2001 to December 2007, 39 patients treated with consolidation chemotherapy after CCRT (Group 1) were matched to 39 patients treated with CCRT alone (Group 2). Consolidation chemotherapy consisted of three additional cycles of chemotherapy with cisplatin 60 mg/m{sup 2} (Day 1) and 5-fluorouracil 1,000 mg/m{sup 2} per day (Days 1-5) given every 3 weeks. The primary endpoint was overall survival. Results: During a median follow-up period of 35 months (range, 8-96 months), 10 (25.6%) and 16 (41.0%) patients showed disease progression in Groups 1 and 2, respectively. Distant recurrence with or without locoregional/lymphogenous recurrence occurred more frequently in Group 2 than in Group 1 (23.1% vs. 7.7%, p = 0.06). By contreast, there was no difference in locoregional or lymphogenous recurrence between the two groups. The rate of overall survival was higher in Group 1 than in Group 2 (92.7% vs. 69.9%, p = 0.042), whereas the difference in progression-free survival between the groups was not statistically significant (70.1% vs. 55.1%, p = 0.079). Although the difference was not statistically significant, neutropenia was more common in Group 1 than in Group 2 (10.9% vs. 4.7%, p = 0.07). Conclusions: Consolidation chemotherapy after CCRT may improve survival and reduce distant recurrence without additional toxicity compared to CCRT alone in patients with locally advanced cervical carcinoma.

  11. Intravenous 5-fluorouracil versus oral doxifluridine as preoperative concurrent chemoradiation for locally advanced rectal cancer. Prospective randomized trails

    Preoperative radiation treatment with concomitant intravenous infusion of 5-fluorouracil (5-FU) is known to be effective in shrinking and downstaging of tumors. However, chemotherapy has often been limited by its toxicity and poor patient compliance. Oral 5-FU is known to have several advantages over conventional intravenous 5-FU infusion such as lower toxicity and higher quality of life without compromising the efficacy of the treatment. The aim of this study was to compare intravenous 5-FU with oral doxifluridine with respect to tumor response, toxicity and quality of life. Twenty-eight patients with rectal cancer, staged as over T3N1 or T4 by transrectal ultrasonography between July 1997 and December 1998, were included in this study. Intravenous 5-FU (450 mg/m2) and leucovorin (20 mg/m2) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n=14). Oral doxifluridine (700 mg/m2/day) and leucovorin (20 mg/m2) were given daily during radiation treatment (n=14). Quality of life was scored according to 22 activity items (good, >77; fair, >58; poor, <57). Surgical resection was performed 4 weeks after completion of concurrent chemoradiation treatment. Tumor response was classified into CR (complete remission), PR (partial response; 50% diminution of tumor volume or downstaging) and NR (no response). Tumor response was CR 3/14 (21.4%), PR 7/14 (50%) and NR 4/14 (28.6%) in the IV arm versus CR 2/14 (14.2%), PR 6/14 (42.9%) and NR 6/14 (42.9%) in the Oral arm (p=0.16, 0.23, 0.24), respectively. The quality of life was poor (36.4% versus 33.3%), fair and good (63.6% versus 66.7%) between the IV arm and Oral arm, respectively. Gastrointestinal toxicity was 2/14 (14.3%) in the IV arm versus 5/14 (35.7%) in the Oral arm, respectively. Stomatitis was only observed in the IV arm (1/14, 7.1%). Hematological toxicity was 3/14 (21.4%) in the IV arm versus 4/14 (28.5%) in the Oral arm, respectively. Systemic recurrence during the

  12. Adjuvant chemoradiation after laparoscopically assisted radical vaginal hysterectomy (LARVH) in patients with cervical cancer. Oncologic outcome and morbidity

    Gruen, Arne; Musik, Thabea; Stromberger, Carmen; Budach, Volker; Marnitz, Simone [Charite Univ. Medicine Berlin, Campus Virchow-Klinikum, Berlin (Germany). Dept. of Radiooncology; Koehler, Christhardt; Schneider, Achim [Charite Univ. Medicine Berlin, Campus Mitte- und Benjamim Franklin, Berlin (Germany). Dept. of Gynaecology; Fueller, Juergen; Wendt, Thomas [Jena Univ. Hospital (Germany). Dept. of Radiooncology

    2011-06-15

    Compared to laparotomic surgery, laparoscopically assisted radical vaginal hysterectomy (LARVH) offers decreased blood loss during surgery and faster convalescence of the patient postoperatively, while at the same time delivering similar oncologic results. However, there is no data on outcome and toxicity of LARVH followed by (chemo)radiation. A total of 55 patients (range 28-78 years) with cervical cancer on FIGO stages IB1-IIIA (Tables 1 and 2) with risk factors were submitted to either external beam radiotherapy alone [EBRT, n = 8 (14%), including paraaortic irradiation, n = 4 (2.2%); EBRT and brachytherapy (BT), n = 33 (60%); BT alone, n = 14 (25.5%)] or chemoradiation after LARVH. At a median follow-up of 4.4 years, the 5-year disease-free survival (DFS) was 81.8% with 84.5% overall survival (OS). Acute grade 3 side effects were seen in 4 patients. These were mainly gastrointestinal (GI) and genitourinary (GU) symptoms. Grade 4 side effects were not observed. With similar oncologic outcome data and mostly mild side effects, LARVH followed by (chemo)radiation is a valid alternative in the treatment of cervical cancer patients. (orig.)

  13. Adjuvant chemoradiation after laparoscopically assisted radical vaginal hysterectomy (LARVH) in patients with cervical cancer. Oncologic outcome and morbidity

    Compared to laparotomic surgery, laparoscopically assisted radical vaginal hysterectomy (LARVH) offers decreased blood loss during surgery and faster convalescence of the patient postoperatively, while at the same time delivering similar oncologic results. However, there is no data on outcome and toxicity of LARVH followed by (chemo)radiation. A total of 55 patients (range 28-78 years) with cervical cancer on FIGO stages IB1-IIIA (Tables 1 and 2) with risk factors were submitted to either external beam radiotherapy alone [EBRT, n = 8 (14%), including paraaortic irradiation, n = 4 (2.2%); EBRT and brachytherapy (BT), n = 33 (60%); BT alone, n = 14 (25.5%)] or chemoradiation after LARVH. At a median follow-up of 4.4 years, the 5-year disease-free survival (DFS) was 81.8% with 84.5% overall survival (OS). Acute grade 3 side effects were seen in 4 patients. These were mainly gastrointestinal (GI) and genitourinary (GU) symptoms. Grade 4 side effects were not observed. With similar oncologic outcome data and mostly mild side effects, LARVH followed by (chemo)radiation is a valid alternative in the treatment of cervical cancer patients. (orig.)

  14. Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer – a retrospective single center analysis

    We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT). The medical records of 49 patients with histologically proven primary nasopharygeal carcinoma treated with IMRT and concurrent platin-based CHT (predominantly cisplatin weekly) were retrospectively reviewed. The majority of patients showed advanced clinical stages (stage III/IV:72%) with undifferentiated histology (82%). IMRT was performed in step-and-shoot technique using an integrated boost concept in 84%. In this concept, the boost volume covered the primary tumor and involved nodes with doses of 66–70.4 Gy (single dose 2.2 Gy). Uninvolved regional nodal areas were covered with doses of 54–59.4 Gy (median single dose 1.8 Gy). At least one parotid gland was spared. None of the patients received adjuvant CHT. The median follow-up for the entire cohort was 48 months. Radiation therapy was completed without interruption in all patients and 76% of the patients received at least 80% of the scheduled CHT. Four local recurrences have been observed, transferring into 1-, 3-, and 5-year Local Control (LC) rates of 98%, 90% and 90%. One patient developed an isolated regional nodal recurrence, resulting in 1-, 3-, and 5-year Regional Control (RC) rates of 98%. All locoregional failures were located inside the radiation fields. Distant metastases were found in six patients, transferring into 1-, 3, and 5-year Distant Control (DC) rates of 92%, 86% and 86%. Progression free survival (PFS) rates after 1, 3 and 5 years were 86%, 70% and 69% and 1-, 3- and 5-year Overall Survival (OS) rates were 96%, 82% and 79%. Acute toxicity ≥ grade III mainly consisted of dysphagia (32%), leukopenia (24%), stomatitis (16%), infection (8%) and nausea (8%). Severe late toxicity (grade III) was documented in 18% of the patients, mainly as xerostomia (10%). Concurrent chemoradiation

  15. Adjuvant chemotherapy prior to postoperative concurrent chemoradiotherapy for locoregionally advanced head and neck cancer

    Background and purpose: Induction chemotherapy prior to definitive concurrent chemoradiotherapy (CCRT) is a promising treatment option for unresectable head and neck cancer (HNC). In the postoperative setting, the efficacy of such an approach with adjuvant chemotherapy (AdjCT) followed by postoperative CCRT is unclear. Materials and methods: Forty-one postoperative patients with stage III-IV (M0) HNC enrolled on 3 consecutive phase II clinical trials were retrospectively analyzed. Twenty-five of the patients were treated on a protocol which included AdjCT with carboplatin and paclitaxel prior to postoperative CCRT (AdjCT group). Sixteen were treated on protocols with similar postoperative CCRT but without AdjCT (control group). CCRT consisted of paclitaxel, 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy. Results: After a median follow-up of 72 months, there were no locoregional failures (LRF) or distant metastases (DM) in the AdjCT group. In the control group, there were 2 LRF and 2 DM. The 5-year risk of disease recurrence was 0% in the AdjCT group, compared to 28.9% in the control group (p = 0.0074). No patients had disease progression during AdjCT, and all proceeded to postoperative CCRT without delay. Conclusions: Adjuvant chemotherapy after surgery followed by CCRT may be a treatment strategy associated with favorable disease outcomes in locoregionally advanced HNC. These results pose a hypothesis which warrants further investigation.

  16. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

    2015-04-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

  17. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m2 and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [18F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [61Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging demonstrates measureable

  18. Outcomes of Adjuvant Chemoradiation After Pancreaticoduodenectomy With Mesenterico-Portal Vein Resection for Adenocarcinoma of the Pancreas

    Purpose: Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma. Methods and Materials: Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes, including median survival, overall survival, and complication rates were assessed for both groups. Results: Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-occlusive disease or graft failure/leakage. Conclusion: In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.

  19. Incidence and patterns of isolated brain failure in stage III non-small-cell lung cancer treated with concurrent chemoradiation therapy

    The incidence and patterns of isolated brain failure was examined in patients with stage III non-small-cell lung cancer (NSCLC) treated with concurrent chemoradiation (CCRT). Between 1996 and 2003, a total of 68 patients with stage III NSCLC were treated with radical CCRT. Among them, 63 patients were evaluable. Radiation therapy with a mean total dose of 61.4 Gy and chemotherapy (typically platinum-based) were administered concurrently. Other than locoregional failure, isolated brain failure was the most common failure pattern as the initial failure, occurring 2-37 months (median 6.5 months) after radical CCRT. The isolated brain failure rates as the initial failure at 1, 3, and 4 years were 9%, 13%, and 25%, respectively. Isolated brain failure as the initial failure occurred more frequently in T4 cases (39% at 4 years) compared to T1-3 cases (14% at 4 years) in our series (P=0.0099). Except for locoregional failure, isolated brain failure was the most common initial failure pattern of stage III NSCLCs treated with radical CCRT. Isolated brain failure as the initial failure occurred even after 3 years. Isolated brain failure as the initial failure occurred more frequently in T4 cases than in T1-3 cases. (author)

  20. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m2, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m2 given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m2), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC

  1. A prospective randomized controlled trial to study the role of sulfasalazine in prevention of acute gastrointestinal toxicity associated with concurrent chemoradiation in carcinoma cervix

    Santanu Pal

    2013-01-01

    Full Text Available Background: The primary aim of the study was to evaluate the effectiveness of sulfasalazine in reducing the incidence of acute radiation-induced enteritis in carcinoma cervix patients receiving pelvic external beam radiotherapy along with concurrent cisplatin-based chemotherapy. Materials and Methods: Between November 2011 and July 2012 a total of 98 patients of locoregionally advanced carcinoma of cervix (49 each in study and control arms were enrolled in this study. Patients in both the arms were treated with whole pelvis external beam radiotherapy with total dose of 50 Gy in conventional fractionation. Along with this inj. cisplatin was given concurrently at the dose of 40 mg/m 2 of body surface area every week during radiation for 5 weeks. Concurrent chemoradiation was followed by brachytherapy after a gap of 2 weeks. Patients in the study arm also received tablet sulfasalazine 1,000 mg orally twice daily from the day of starting of radiotherapy to 1 week after completion of treatment. Weekly follow-up of all patients to assess acute toxicities was done using common toxicity criteria version 4.0 (CTC v4.0 toxicity scores. Data analysis was carried out by SPSS version 20.0 software. Results: Incidence of grade II or higher grade, lower gastrointestinal toxicity was 19.14% (09/47 in study arm and 41.66% (20/48 in control arm which was statistically significant (P = 0.017. Conclusion: The study shows that sulfasalazine can significantly reduce the acute radiation-induced diarrhea (ARID in patients undergoing whole pelvis external beam radiotherapy for carcinoma cervix. The drug is safe, cheap, and readily available.

  2. Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

    Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease

  3. Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

    Nakamura, Takatoshi; Yamashita, Keishi; Sato, Takeo; Ema, Akira; Naito, Masanori; Watanabe, Masahiko, E-mail: midoris@med.kitasato-u.ac.jp

    2014-07-01

    Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

  4. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    Tan, Terence, E-mail: trdtwk@nccs.com.sg [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Lim, Wan-Teck [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Ong, Whee-Sze; Tan, Sze-Huey [Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore (Singapore); Yip, Connie; Quah, Daniel [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Soo, Khee-Chee [Division of Surgical Oncology, National Cancer Centre Singapore (Singapore); Wee, Joseph [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore)

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  5. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

    Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Oh, Jae Hwan [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Lee, Jong Hoon; Jang, Hong Seok [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Jun-Gi [Department of Surgery, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Myung Ah [Department of Internal Medicine, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Nam, Taek-Keun [Department of Radiation Oncology, Chonnam National University Hospital, Gwang-Ju (Korea, Republic of)

    2013-05-01

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

  6. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m2/day) and leucovorin (20 mg/m2/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique

  7. Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

    Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2–2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of

  8. Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

    Schoenfeld, Jonathan D., E-mail: jdschoenfeld@partners.org [Department of Radiation Oncology, Harvard Radiation Oncology Program, Boston, MA (United States); Sher, David J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States); Norris, Charles M. [Department of Surgery, Division of Otolaryngology, Brigham and Women' s Hospital, Boston, MA (United States); Haddad, Robert I.; Posner, Marshall R. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (United States); Department of Medicine, Brigham and Women' s Hospital, Boston, MA (United States); Balboni, Tracy A.; Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, MA (United States)

    2012-01-01

    Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of

  9. Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

    Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6–60.8 Gy), usually administered in conventional fractionations (1.8–2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m2 intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4–37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

  10. Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

    Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.jp [Department of Radiology, University of the Ryukyus, Okinawa (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center, Tokyo (Japan); Hirokawa, Naoki [Department of Radiology, Sapporo Medical University, Sapporo (Japan); Shibuya, Keiko [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto (Japan); Kokubo, Masaki [Department of Radiation Oncology, Institute of Biomedical Research and Innovation Hospital, Kobe (Japan); Ogo, Etsuyo [Department of Radiation Oncology, Kurume University, Kurume (Japan); Shibuya, Hitoshi [Department of Radiology, Tokyo Medical and Dental University, Tokyo (Japan); Saito, Tsutomu [Department of Radiation Oncology, Nihon University Itabashi Hospital, Tokyo (Japan); Onishi, Hiroshi [Department of Radiology, Yamanashi University, Yamanashi (Japan); Karasawa, Katsuyuki [Department of Radiation Oncology, Tokyo Metropolitan Komagome Hospital, Tokyo (Japan); Nemoto, Kenji [Department of Radiation Oncology, Yamagata University, Yamagata (Japan); Nishimura, Yasumasa [Department of Radiation Oncology, Kinki University School of Medicine, Osaka (Japan)

    2012-06-01

    Purpose: To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. Methods and Materials: Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m{sup 2} intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). Results: Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. Conclusions: CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.

  11. Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer

    Background and purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort. Materials and methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients. Patients received low-dose cisplatin (6 mg/m2, daily infusions, 20-25 days) with concomitant accelerated radiotherapy (70 Gy). Results: Audiometry up to 16 kHz was performed before therapy and 31 days (median) post-treatment. The total incidence of ototoxicity in CTCAEv3.0 was 31% in audiograms up to 8 kHz, and 5% of ears tested qualified for HAs due to treatment. The mean hearing loss at speech frequencies was 2.6 dB (SD 5.7) and 2.3 dB (SD 9.2) at PTA 1-2-4 kHz air-conduction and bone-conduction, respectively. The mean hearing loss at ultra-high frequencies (PTA AC 8-10-12.5 kHz) was 9.0 dB (SD 8.1). Low-dose cisplatin CRT caused less acute hearing loss (CTCAE 31%), compared to high-dose cisplatin CRT (CTCAE 78%). Conclusions: Low-dose cisplatin chemo-irradiation for HNSCC is a relatively safe treatment protocol with respect to ototoxicity

  12. Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

    Purpose: We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. Methods and Materials: A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1 = weight loss (WL); group 2 = weight preservation/gain (WP) for comparative analyses. Results: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Conclusions: Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT

  13. Concurrent chemoradiation with weekly Cisplatin, Docetaxel and Gefitinib: A study to assess feasibility, toxicity and immediate response

    Prasad Eswaran; Kumaravelu S Azmi

    2013-01-01

    Objectives: Addition of docetaxel in the treatment regimen has shown improvement in survival of head and neck squamous cell carcinoma (HNSCC) patients. This study was conducted to evaluate the maximum tolerated dose of weekly docetaxel when combined with concurrent administration of weekly cisplatin, daily gefitinib, and radiation therapy. Materials and Methods: 21 patients with newly diagnosed HNSCC were included. Radiation therapy was planned to a dose of 66 Gy/33 fractions. Doses of ci...

  14. Time-window of early detection of response to concurrent chemoradiation in cervical cancer by using diffusion-weighted MR imaging: a pilot study

    To investigate the feasibility of DWI in evaluating early therapeutic response of uterine cervical cancer to concurrent chemoradiation (CCR) and establish optimal time window for early detection of treatment response. This was a prospective study and informed consent was obtained from all patients. Thirty-three patients with uterine cervical cancer who received CCR underwent conventional MRI and DWI examinations prior to therapy (base-line) and at 3 days (postT1), 7 days (postT2), 14 days (postT3), 1 month (postT4) and 2 months (postT5) after the therapy initiated. Tumor response was determined by comparing the base-line and postT5 MRI by using RECIST criterion. Percentage ADC change (γADC) of complete response (CR) group at each follow up time was greater than that of partial response (PR) group, and the differences were significant at postT3 (p = 0.007), postT4 (p = 0.001), and postT5 (p = 0.019). There was positive correlation between γADC at each follow-up time and percentage size reduction at postT5. The day of 14 after the therapy initiated can be considered as the optimal time for monitoring early treatment response of uterine cervical cancer to CCR, and the representative and sensitive index was γADC. With the cut-off value of 35.4 %, the sensitivity and specificity for prediction of CR group were 100 % and 73.1 %, respectively. It is feasible to use DWI to predict and monitor early treatment response in patients with uterine cervical cancer that undergoing CCR, and optimal time window for early detection of tumor response is the day of 14 after therapy initiated

  15. Phase I study of hypofractionated intensity modulated radiation therapy with concurrent and adjuvant temozolomide in patients with glioblastoma multiforme

    To determine the safety and efficacy of hypofractionated intensity modulated radiation therapy (Hypo-IMRT) using helical tomotherapy (HT) with concurrent low dose temozolomide (TMZ) followed by adjuvant TMZ in patients with glioblastoma multiforme (GBM). Adult patients with GBM and KPS > 70 were prospectively enrolled between 2005 and 2007 in this phase I study. The Fibonacci dose escalation protocol was implemented to establish a safe radiation fractionation regimen. The protocol defined radiation therapy (RT) dose level I as 54.4 Gy in 20 fractions over 4 weeks and dose level II as 60 Gy in 22 fractions over 4.5 weeks. Concurrent TMZ followed by adjuvant TMZ was given according to the Stupp regimen. The primary endpoints were feasibility and safety of Hypo-IMRT with concurrent TMZ. Secondary endpoints included progression free survival (PFS), pattern of failure, overall survival (OS) and incidence of pseudoprogression. The latter was defined as clinical or radiological suggestion of tumour progression within three months of radiation completion followed by spontaneous recovery of the patient. A total of 25 patients were prospectively enrolled with a median follow-up of 12.4 months. The median age at diagnosis was 53 years. Based on recursive partitioning analysis (RPA) criteria, 16%, 52% and 32% of the patients were RPA class III, class IV and class V, respectively. All patients completed concurrent RT and TMZ, and 19 patients (76.0%) received adjuvant TMZ. The median OS was 15.67 months (95% CI 11.56 - 20.04) and the median PFS was 6.7 months (95% CI 4.0 – 14.0). The median time between surgery and start of RT was 44 days (range of 28 to 77 days). Delaying radiation therapy by more than 6 weeks after surgery was an independent prognostic factor associated with a worse OS (4.0 vs. 16.1 months, P = 0.027). All recurrences occurred within 2 cm of the original gross tumour volume (GTV). No cases of pseudoprogression were identified in our cohort of patients. Three

  16. Chemoradiation for adenocarcinoma of the anus

    Purpose: To assess the efficacy and limitations of definitive chemoradiation for adenocarcinoma of the anal canal and to propose a treatment strategy that addresses the limitations of treatment. Methods and Materials: Between 1976 and 1998, 16 patients with localized adenocarcinoma of the anal canal were treated with radiotherapy with or without chemotherapy with curative intent. Available histologic slides were reviewed for evidence of primary adenocarcinoma of anal duct origin. The treatment results for these patients were compared with those of a group of patients with epidermoid histologic features who were all treated with definitive chemoradiation (55 Gy with concurrent 5-fluorouracil and cisplatin, n=92) between 1989 and 1998. The hospital records were reviewed for all patients. Patients with epidermoid carcinoma presented with more advanced primary tumors (42% vs. 19% Stage T3 or greater). All adenocarcinoma patients were treated with radiotherapy (median dose 55 Gy): 11 received concurrent 5-fluorouracil-based chemotherapy and 5 received radiotherapy alone. The initial surgical procedures included abdominoperineal resection, excisional biopsies (n=5), and local excision (n=1). Abdominoperineal resection was performed as salvage therapy after local recurrence in 5 patients. The Kaplan-Meier method was used to calculate 5-year actuarial pelvic control, distant disease control, disease-free survival, and overall survival. The median follow-up was 45 months (range 5-196) for patients with adenocarcinoma and 44 months (range 9-115) for patients with epidermoid histologic features. Results: Both local and distant recurrence rates were significantly greater in the adenocarcinoma patients. Of 16 patients with adenocarcinoma, 7 (5-year actuarial rate 54%) had recurrence at the primary site compared with 16 (5-year actuarial rate 18%) of 92 patients with epidermoid histologic features (p=0.004). Distant disease developed in more patients with adenocarcinoma (5-year

  17. The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

    Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors—number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)—on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0–18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.

  18. The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

    Showalter, Timothy N. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Winter, Kathryn A. [Radiation Therapy Oncology Group, RTOG Statistical Center, Philadelphia, PA (United States); Berger, Adam C., E-mail: adam.berger@jefferson.edu [Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Safran, Howard [Department of Medicine, Miriam Hospital, Brown University Oncology Group, Providence, RI (United States); Hoffman, John P. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Benson, Al B. [Division of Hematology-Oncology, Northwestern University, Chicago, IL (United States); MacDonald, John S. [St. Vincent' s Cancer Care Center, New York, NY (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2011-12-01

    Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.

  19. Prognostic Significance of Tumor Response as Assessed by Sequential 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography During Concurrent Chemoradiation Therapy for Cervical Cancer

    Purpose: To investigate the prognostic role of metabolic response by the use of serial sets of positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer who were treated with concurrent chemoradiation therapy (CCRT). Methods and Materials: A total of 60 patients who were treated with CCRT between February 2009 and December 2010 were analyzed. Three sequential PET/CT images were acquired for each patient: pre-CCRT, during-CCRT at 4 weeks of CCRT, and 1 month post-CCRT PET/CT. Metabolic responses were assessed qualitatively. The percentage changes in the maximum values of standardized uptake value (ΔSUVmax%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUVmax% could predict complete response (CR) on the post-CCRT PET/CT and to identify the best cutoff value. Prognostic factors of progression-free survival (PFS) were analyzed. Results: During-CCRT PET/CT showed that 8 patients (13%) had CR, and the other 52 patients (87%) had partial response (PR). On the post-CCRT PET/CT, 43 patients (73%) had CR, 12 patients (20%) had PR, and 4 patients (7%) had progressive disease. The average SUVmax in primary tumors was 16.3 (range, 6.4-53.0) on the pre-CCRT PET/CT images and 5.3 (range, 0-19.4) on the during-CCRT PET/CT images. According to ROC curve analysis, ΔSUVmax% could predict CR response on post-CCRT PET/CT (Pmax% ≥60% (P=.045) and CR response on the post-CCRT PET/CT (P=.012) were statistically significant predictors of PFS. Conclusion: Metabolic responses on the during-CCRT images at 4 weeks of treatment and 1-month post-CCRT PET/CT images may predict treatment outcomes in patients with cervical cancer. ΔSUVmax% ≥60% at 4 weeks of CCRT may predict CR response on 1-month post-CCRT PET/CT and also PFS

  20. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial

    Francis, P.; Crown, J.; Di, Leo A.;

    2008-01-01

    of doxorubicin and docetaxel. METHODS: Patients with lymph node-positive breast cancer (n = 2887) were randomly assigned to one of four treatments: 1) sequential control (four cycles of doxorubicin at 75 mg/m2, followed by three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]); 2......BACKGROUND: Docetaxel is more effective than doxorubicin for patients with advanced breast cancer. The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration...... (four cycles of doxorubicin at 50 mg/m2 plus docetaxel at 75 mg/m2, followed by three cycles of CMF). The primary comparison evaluated the efficacy of including docetaxel regardless of schedule and was planned after 1215 disease-free survival (DFS) events (ie, relapse, second primary cancer, or death...

  1. Preliminary Results of a Prospective Randomized Trial Comparing Concurrent Chemoradiotherapy Plus Adjuvant Chemotherapy With Radiotherapy Alone in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma in Endemic Regions of China

    Purpose: A prospective randomized trial was performed to evaluate the efficacy of concurrent chemotherapy and adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) in endemic regions of China. Methods and Materials: Between July 2002 and September 2005, 316 eligible patients were randomly assigned to receive either radiotherapy alone (RT) or chemoradiotherapy concurrent with adjuvant chemotherapy (CRT). All patients received 70 Gy in 7 weeks using standard RT portals and techniques. The CRT patients were given concurrent cisplatin (40 mg/m2 on Day 1) weekly during RT, followed by cisplatin (80 mg/m2 on Day 1) and fluorouracil (800 mg/m2 on Days 1-5) every 4 weeks (Weeks 5, 9, and 13) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. Results: The two groups were well-balanced in all prognostic factors and RT parameters. The CRT group experienced significantly more acute toxicity (62.6% vs. 32%, p = 0.000). A total of 107 patients (68%) and 97 patients (61%) completed all cycles of concurrent chemotherapy and adjuvant chemotherapy, with a median follow-up time of 29 months. The 2-year overall survival rate, failure-free survival rate, distant failure-free survival rate, and locoregional failure-free survival rate for the CRT and RT groups were 89.8% vs. 79.7% (p = 0.003), 84.6% vs. 72.5% (p = 0.001), 86.5% vs. 78.7% (p = 0.024), and 98.0% vs. 91.9% (p = 0.007), respectively. Conclusions: This trial demonstrated the significant survival benefits of concurrent chemotherapy plus adjuvant chemotherapy in patients with locoregionally advanced NPC in endemic regions of China

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

    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

  3. Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

    Purpose: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Methods and Materials: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m2) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. Results: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. Conclusions: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival

  4. Long-term Follow-up Results of a Multi-institutional Phase 2 Study of Concurrent Chemoradiation Therapy for Locally Advanced Cervical Cancer in East and Southeast Asia

    Kato, Shingo, E-mail: s_kato@saitama-med.ac.jp [Department of Radiation Oncology, International Medical Center, Saitama Medical University, Saitama (Japan); National Institute of Radiological Sciences of Japan, Chiba (Japan); Ohno, Tatsuya [Gunma University Heavy Ion Medical Center, Gunma University, Gunma (Japan); Thephamongkhol, Kullathorn; Chansilpa, Yaowalak [Division of Radiation Oncology, Department of Radiology, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok (Thailand); Cao, Jianping [School of Radiation Medicine and Public Health, Soochow University, Soochow (China); Xu, Xiaoting [Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Devi, C. R. Beena; Swee, Tang Tieng [Department of Radiotherapy and Oncology, Hospital Umum Sarawak, Kuching (Malaysia); Calaguas, Miriam J.C. [Department of Radiation Oncology, St. Luke' s Medical Center, Quezon City, the Philippines (Philippines); Reyes, Rey H. de los [Department of Obstetrics and Gynecology, Dr Jose R. Reyes Memorial Medical Center, Manila, the Philippines (Philippines); Cho, Chul-Koo [Department of Radiation Oncology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Dung, To Anh [Department of Breast and Gynecology Radiotherapy, National Cancer Institute, Hanoi (Viet Nam); Supriana, Nana [Department of Radiation Therapy, Faculty of Medicine, University of Indonesia, Dr Cipto Mangunkusumo General Hospital, Jakarta (Indonesia); Erawati, Dyah [Division of Radiotherapy, Dr Soetomo General Hospital, Surabaya (Indonesia); Mizuno, Hideyuki [National Institute of Radiological Sciences of Japan, Chiba (Japan); Nakano, Takashi [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma (Japan); Tsujii, Hirohiko [National Institute of Radiological Sciences of Japan, Chiba (Japan)

    2013-09-01

    Purpose: To report the long-term survival and toxicity of a multi-institutional phase 2 study of concurrent chemoradiation therapy (CCRT) for locally advanced cervical cancer in east and southeast Asia. Methods and Materials: Ten institutions from 8 Asian countries participated in the study. Between April 2003 and March 2006, 120 patients (60 with bulky stage IIB and 60 with stage IIIB) were treated with CCRT. Radiation therapy consisted of pelvic external beam radiation therapy and either high-dose-rate or low-dose-rate intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m{sup 2}) were administered during the course of radiation therapy. Treatment results were evaluated by the rates of local control, overall survival, and late toxicities. Results: Median follow-up was 63.7 months, and the follow-up rate at 5 years was 98%. The 5-year local control and overall survival rates for all patients were 76.8% and 55.1%, respectively. The 5-year rates of major late toxicities of the rectum and bladder were 7.9% and 0%, respectively. Conclusions: The long-term results have suggested that CCRT is safe and effective for patients with locally advanced cervical cancer in east and southeast Asia. However, further efforts are needed to improve overall survival.

  5. Clinical Usefulness of {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography in Patients With Locally Advanced Pancreatic Cancer Planned to Undergo Concurrent Chemoradiation Therapy

    Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin; Kim, Kyung Hwan [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Jeong Youp; Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Arthur; Yun, Mijin; Lee, Jong Doo [Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: jsseong@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-01

    Purpose: To assess the role of coregistered {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials: From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results: FDG-PET detected unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) <3.5 and/or SUV decline ≥60% had significantly better OS and PFS than those having none, even after adjustment for all potential confounding variables (all P<.001). Conclusions: FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.

  6. A retrospective study of the safety of BCNU wafers with concurrent temozolomide and radiotherapy and adjuvant temozolomide for newly diagnosed glioblastoma patients.

    Pan, Edward; Mitchell, Susan B; Tsai, Jerry S

    2008-07-01

    Despite aggressive therapy, most patients with glioblastoma multiforme (GBM) die within 2 years of diagnosis. The efficacy and safety of carmustine (BCNU) wafers followed by radiotherapy have been demonstrated in patients with malignant glioma. However, there is a reluctance to recommend them for newly diagnosed GBM patients due to the potential toxicity of BCNU wafers combined with temozolomide (TMZ) chemotherapy and radiotherapy. The purpose of this study was to assess the safety of BCNU wafers implanted at initial surgery, followed by concurrent TMZ and radiotherapy, and then adjuvant TMZ for the treatment of newly diagnosed GBM. We conducted a retrospective analysis of clinic and hospital records of 21 newly diagnosed GBM patients who received multimodal therapy at Florida Hospital Cancer Institute from January 2003 to December 2005. Three of 21 patients had grade 3 toxicities (two with cerebritis, one with psychosis). Grade 4 toxicities were not observed. Median overall survival was 17 months, median progression-free survival was 8.5 months, and 2-year survival was 39%. Multimodal treatment with surgery, BCNU wafers, radiotherapy, and TMZ did not result in a notable increase in significant toxicities. Survival outcomes were comparable to those in other studies in which patients were treated with concurrent TMZ and radiotherapy followed by adjuvant TMZ. Thus, the implantation of BCNU wafers prior to TMZ and radiotherapy appears safe in newly diagnosed GBM patients. PMID:18389176

  7. The population benefit of radiotherapy for cervical cancer: Local control and survival estimates for optimally utilized radiotherapy and chemoradiation

    Purpose: Population benefits of radiotherapy if evidence-based guidelines were routinely followed across the entire population are largely unknown. The aim of this study was to investigate population-based benefits for cervical cancer. Methods: Overall survival (OS) and local control (LC) benefits were investigated. XRT benefit was defined as the absolute benefit of radiotherapy, over no treatment, for radical indications and defined as the benefit of adjuvant radiation over surgery alone for adjuvant indications. The concurrent chemoradiation (CRT) benefit was the incremental benefit of CRT over XRT. Australian population benefits were modeled using decision trees. Citation databases were systematically queried. Meta-analysis was performed if multiple sources of the same evidence level existed. Robustness of the model assumptions was tested through sensitivity analysis. Results: 53% of all cervix patients had adjuvant or curative radiotherapy indications. 96% were for CRT. The estimated 5-year absolute benefits of optimally utilized radiotherapy alone were: LC: 31% (95% Confidence Interval 29%, 34%), OS: 17% (15%, 18%). These were over and above the contribution of other modalities to outcomes. The incremental 5-year absolute benefits of CRT were: LC 4% (2%, 5%), OS 3% (1%, 5%). In sensitivity analysis, the model was robust. Conclusions: Optimally utilized radiotherapy provides substantial population OS and LC benefits for cervical cancer. Chemoradiation provides a modest population benefit over XRT. The population-based model was robust

  8. Does Concurrent Radiochemotherapy Affect Cosmetic Results in the Adjuvant Setting After Breast-Conserving Surgery? Results of the ARCOSEIN Multicenter, Phase III Study: Patients' and Doctors' Views

    Purpose: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. Methods and Materials: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107 in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. Results: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair (κ = 0.62). Conclusion: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis

  9. Treatment adherence in concurrent chemoradiation in patients with locally advanced non-small cell lung carcinoma: Results of daily intravenous prehydration

    Purpose: To test the hypothesis that daily intravenous pre-hydration decreases renal toxicity and improves chemotherapy adherence in patients receiving daily cisplatin to concurrent radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: Patients with locally advanced NSCLC were treated between 2008 and August 2012 with daily 6 mg/m2 cisplatin as a bolus injection in 10 ml; of saline and 66 Gy/24 fr radiotherapy in 32 days. Since January 2011, the administration of cisplatin was routinely preceded by intravenous pre-hydration with 1 L of natriumchloride 0.9%. Patients were divided in a pre-hydrated (PH) and non-pre-hydrated (NPH) cohort. Serum-creatinine and glomerular filtration rate (GFR) were assessed twice weekly during treatment. Retrospectively, baseline data, toxicity, treatment adherence and efficacy data were compared. Results: Of the 356 patients 232 NPH patients and 100 PH patients were eligible. Patient-and treatment characteristics compared equally. The median of the maximum decrease in GFR was 24% and 8% for NPH and PH (p < 0.01), respectively. Sixty-nine percent of the patients in the NPH group completed the 24 administrations of cisplatin, as compared to 83% of the PH group (p < 0.01). Nineteen percent vs. 2% of the patients in the NPH and PH group discontinued cisplatin treatment because of renal toxicity. Surprisingly, the incidence of acute esophageal toxicity grade ⩾2 decreased following prehydration: 62% vs. 34% (p < 0.001) for the NPH and PH groups, respectively. The one-year survival was comparable between groups (75% for NPH and 71% for PH). Conclusion: Daily pre-hydration was associated with a reduced rate of both renal and acute esophageal toxicity and an increased chemotherapy adherence in patients receiving daily dose of cisplatin and concurrent radiotherapy for locally advanced NSCLC

  10. Phase 2 Trial of Hypofractionated High-Dose Intensity Modulated Radiation Therapy With Concurrent and Adjuvant Temozolomide for Newly Diagnosed Glioblastoma

    Iuchi, Toshihiko, E-mail: tiuchi@chiba-c.jp [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hatano, Kazuo; Kodama, Takashi [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan); Sakaida, Tsukasa [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Yokoi, Sana [Division of Gene Diagnosis, Chiba Cancer Center, Chiba (Japan); Kawasaki, Koichiro; Hasegawa, Yuzo [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hara, Ryusuke [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan)

    2014-03-15

    Purpose/Objectives: To assess the effect and toxicity of hypofractionated high-dose intensity modulated radiation therapy (IMRT) with concurrent and adjuvant temozolomide (TMZ) in 46 patients with newly diagnosed glioblastoma multiforme (GBM). Methods and Materials: All patients underwent postsurgical hypofractionated high-dose IMRT. Three layered planning target volumes (PTVs) were contoured. PTV1 was the surgical cavity and residual tumor on T1-weighted magnetic resonance images with 5-mm margins, PTV2 was the area with 15-mm margins surrounding the PTV1, and PTV3 was the high-intensity area on fluid-attenuated inversion recovery images. Irradiation was performed in 8 fractions at total doses of 68, 40, and 32 Gy for PTV1, PTV2, and PTV3, respectively. Concurrent TMZ was given at 75 mg/m{sup 2}/day for 42 consecutive days. Adjuvant TMZ was given at 150 to 200 mg/m{sup 2}/day for 5 days every 28 days. Overall and progression-free survivals were evaluated. Results: No acute IMRT-related toxicity was observed. The dominant posttreatment failure pattern was dissemination. During a median follow-up time of 16.3 months (range, 4.3-80.8 months) for all patients and 23.7 months (range, 12.4-80.8 months) for living patients, the median overall survival was 20.0 months after treatment. Radiation necrosis was diagnosed in 20 patients and was observed not only in the high-dose field but also in the subventricular zone (SVZ). Necrosis in the SVZ was significantly correlated with prolonged survival (hazard ratio, 4.08; P=.007) but caused deterioration in the performance status of long-term survivors. Conclusions: Hypofractionated high-dose IMRT with concurrent and adjuvant TMZ altered the dominant failure pattern from localized to disseminated and prolonged the survival of patients with GBM. Necrosis in the SVZ was associated with better patient survival, but the benefit of radiation to this area remains controversial.

  11. Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation

    Background: Oral mucositis (OM) is a complication of chemoradiotherapy treatment of head and neck squamous cell carcinoma (HNSCC) patients with no effective therapy. This study was designed to assess the efficacy of preventive low-level laser therapy (LLLT) in reducing the incidence of grade 3–4 OM. Material and methods: From June 2007 to December 2010, 94 HNSCC patients entered a prospective, randomized, double-blind, placebo-controlled phase III trial. Chemoradiotherapy consisted of conventional radiotherapy plus concurrent cisplatin every 3 weeks. A diode InGaAlP (660 nm–100 mW–1 J–4 J/cm2) was used. OM evaluation was performed by WHO and OMAS scales and quality of life by EORTC questionnaires (QLQ). Results: A six-fold decrease in the incidence of grades 3–4 OM was detected in the LLLT group compared to the placebo; (6.4% versus 40.5%). LLLT impacted the incidence of grades 3–4 OM to a relative risk ratio of 0.158 (CI 95% 0.050–0.498). After treatment QLQ-C30 showed, differences favoring LLLT in physical, emotional functioning, fatigue, and pain; while the QLQ-H and N35 showed improvements in LLLT arm for pain, swallowing, and trouble with social eating. Conclusion: Preventive LLLT in HNSCC patients receiving chemoradiotherapy is an effective tool for reducing the incidence of grade 3–4 OM. Efficacy data were corroborated by improvements seen in quality of life

  12. Concurrent and adjuvant temozolomide-based chemoradiotherapy schedules for glioblastoma. Hypotheses based on two prospective phase II trials

    Balducci, M. [Catholic Univ. of the Sacred Heart, Rome (Italy). Dept. of Radiation Oncology; Fiorentino, A. [IRCCS/CROB, Rionero in Vulture (Italy). Dept. of Radiation Oncology; De Bonis, P. [Catholic Univ. of the Sacred Heart, Rome (Italy). Dept. of Neurosurgery; and others

    2013-11-15

    Aim: To investigate the impact of nonstandard concomitant temozolomide (TMZ) administration in two prospective phase II studies for glioblastoma (GBM). Patients and methods: From October 2000 to June 2008, 104 patients were enrolled in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received concomitant TMZ (75 mg/m{sup 2}/day) from Monday to Friday during the first and last weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m{sup 2}) was administered for 5 days every 28 days. Results: Median progression-free (PFS) and overall survival (OS) were 9 and 16 months, respectively, with no significant difference between the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were 32 and 3 %, respectively, and similar to those observed with standard treatment regimens. Conclusion: Our data support the hypothesis that adjuvant TMZ is more important than concomitant chemotherapy (CH) and that RT is the more important element of the concomitant treatment schedule. (orig.)

  13. Concurrent and adjuvant temozolomide-based chemoradiotherapy schedules for glioblastoma. Hypotheses based on two prospective phase II trials

    Aim: To investigate the impact of nonstandard concomitant temozolomide (TMZ) administration in two prospective phase II studies for glioblastoma (GBM). Patients and methods: From October 2000 to June 2008, 104 patients were enrolled in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received concomitant TMZ (75 mg/m2/day) from Monday to Friday during the first and last weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m2) was administered for 5 days every 28 days. Results: Median progression-free (PFS) and overall survival (OS) were 9 and 16 months, respectively, with no significant difference between the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were 32 and 3 %, respectively, and similar to those observed with standard treatment regimens. Conclusion: Our data support the hypothesis that adjuvant TMZ is more important than concomitant chemotherapy (CH) and that RT is the more important element of the concomitant treatment schedule. (orig.)

  14. Concurrent chemoradiation of metastases with capecitabine and oxaliplatin and 3D-CRT in patients with oligometastatic colorectal cancer: results of a phase I study

    Local control appears to be an important treatment aim in patients with limited metastases (oligometastases) of colorectal cancer (CRC). Those patients show a favourable prognosis, if - in addition to the local effective treatment - an occurrence of new metastases may also be postponed by effective systemic therapy. The purpose of this dose escalation phase I study was to establish the efficacy of local radiotherapy (RT) of oligometastatic CRC with a concurrent standard chemotherapy regimen. Patients with first-, second- or third-line therapy of oligometastatic CRC (1–3 metastases or local recurrence plus max. 2 metastases) received capecitabine (825 mg/m2/d BID d 1–14; 22–35) and oxaliplatin (50 mg/m2 d 1, 8, 22, 29). 3D-conformal RT of all metastatic lesions was delivered in 2.0 Gy up to 36 Gy to 50 Gy (3 dose levels). Primary endpoint was the maximal tolerable dose (MTD) of RT defined as the level at which two or more of six patients experienced dose-limiting toxicity (DLT). Between 09/2004 and 08/2007, 9 patients (7 male, 2 female, 50–74 years) were enrolled, 6 patients treated at dose level 1 (36 Gy), 3 patients at dose level 2 (44 Gy). 1 patient from the first cohort experienced DLT (oxaliplatin-related hypersensitivity reaction). No radiation-induced DLT occurred. 6/9 patients achieved objective response (partial remission). One year after initiation, all patients were alive, 6 patients survived (16 to 54 months) patients died of tumor progression (14 to 23 months). The phase II part of the trial had to be closed due to recruitment failure. Local 3D-CRT to metastatic lesions in addition to standard chemotherapy was feasible, DLT was not documented. 3/9 patients survived for a period of 3.5 to 4.4 years (time at the last evaluation). Radiotherapy of metastatic lesions should be incorporated into subsequent trials

  15. The Role of 18F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

    To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Preand post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/posttreatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5±0.8 and 7.2±4.2/1.9±0.7 for complete responders and 5.7±2.6 and 12.8±6.9/3.7±0.7 for patients with residual tumor (p 18F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria for cervical cancer in post-CCRT PET/CT might help to detect residual tumor

  16. Adjuvant low single dose cisplatin-based concurrent radiochemotherapy of oral cavity and oropharynx carcinoma. Impact of extracapsular nodal spread on distant metastases

    Background: The aim of this study was to analyze the prognostic importance of extracapsular nodal spread (ECS) in patients with locally advanced squamous cell carcinoma (SCC) of the oral cavity or oropharynx, and the impact of adjuvant low single dose cisplatin-based radiochemotherapy on distant metastases-free survival (DMFS). Patients and Methods: The study population was selected from 195 patients with high-risk oral cavity or oropharyngeal cancer, who had either adjuvant radiotherapy (RT) or radiochemotherapy (RCT) between January 1, 1997 and December 31, 2006, at the University Clinic of Radiation Oncology of the Martin-Luther-University Halle-Wittenberg. A total of 42 matched pairs of patients with UICC stage III-IVa,b disease were analyzed. The patients were matched (one to one) according to tumor site, sex, T stage, N stage, ECS, resection margin status, and Karnofsky performance status. To analyze the correlation between the treatment modality (RT vs. RCT) and the impact of ECS on DMFS, the Cox proportional hazard model was used. Survival rates were calculated using the Kaplan-Meier method. Results: There was a strong correlation between the degree of nodal involvement and ECS (pN1: 33%; pN2b: 45%; pN2c: 71%). Moreover, the 5-year locoregional control rates (LC) in patients with ECS were 76% vs. 63% (n.s.) for RT and RCT, respectively. However, for patients without ECS, the LC was more favorable after RCT (RT vs. RCT: 62% vs. 88%, p < 0.05). DMFS again was better after RT, and this observation was independent of the presence or absence of ECS. Finally, in multivariate analyses, the presence of ECS significantly decreased the DMFS (p = 0.04, hazard ratio (HR) 2.64). Conclusions: Patients with ECS have an increased risk of distant metastases. Adjuvant low single dose cisplatin-based concurrent chemotherapy seems to have no influence on occult microscopic systemic disease. (orig.)

  17. Concurrent chemoradiation of metastases with capecitabine and oxaliplatin and 3D-CRT in patients with oligometastatic colorectal cancer: results of a phase I study

    Dellas Kathrin

    2012-06-01

    Full Text Available Abstract Background Local control appears to be an important treatment aim in patients with limited metastases (oligometastases of colorectal cancer (CRC. Those patients show a favourable prognosis, if - in addition to the local effective treatment - an occurrence of new metastases may also be postponed by effective systemic therapy. The purpose of this dose escalation phase I study was to establish the efficacy of local radiotherapy (RT of oligometastatic CRC with a concurrent standard chemotherapy regimen. Methods Patients with first-, second- or third-line therapy of oligometastatic CRC (1–3 metastases or local recurrence plus max. 2 metastases received capecitabine (825 mg/m2/d BID d 1–14; 22–35 and oxaliplatin (50 mg/m2 d 1, 8, 22, 29. 3D-conformal RT of all metastatic lesions was delivered in 2.0 Gy up to 36 Gy to 50 Gy (3 dose levels. Primary endpoint was the maximal tolerable dose (MTD of RT defined as the level at which two or more of six patients experienced dose-limiting toxicity (DLT. Results Between 09/2004 and 08/2007, 9 patients (7 male, 2 female, 50–74 years were enrolled, 6 patients treated at dose level 1 (36 Gy, 3 patients at dose level 2 (44 Gy. 1 patient from the first cohort experienced DLT (oxaliplatin-related hypersensitivity reaction. No radiation-induced DLT occurred. 6/9 patients achieved objective response (partial remission. One year after initiation, all patients were alive, 6 patients survived (16 to 54 months patients died of tumor progression (14 to 23 months. The phase II part of the trial had to be closed due to recruitment failure. Conclusions Local 3D-CRT to metastatic lesions in addition to standard chemotherapy was feasible, DLT was not documented. 3/9 patients survived for a period of 3.5 to 4.4 years (time at the last evaluation. Radiotherapy of metastatic lesions should be incorporated into subsequent trials.

  18. The Role of {sup 18}F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy

    Choi, Jiyoun; Kim, Hyun Jeong; Jeong, Yong Hyu; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Yong Bae; Kim, Young Tae; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Preand post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/posttreatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5±0.8 and 7.2±4.2/1.9±0.7 for complete responders and 5.7±2.6 and 12.8±6.9/3.7±0.7 for patients with residual tumor (p < 0.05). The pre-treatment SUVmax and pre-/post-treatment serum SCC levels of the complete responders tended to be lower than those of patients with residual tumor, but this did not have statistical significance. Using ROC analysis, an optimal cutoff SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and 99 %, respectively (p <0.001). Persistent cervical FDG uptake in {sup 18}F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post

  19. Challenges in optimizing chemoradiation in locally advanced non small-cell lung cancers in India

    Sushma Agrawal

    2013-01-01

    Data supporting use of concurrent chemoradiation in locally advanced lung cancers comes from clinical trials from developed countries. Applicability and outcomes of such schedules in developing countries is not widely reported. There are various challenges in delivering chemoradiation in locally advanced non small cell lung cancer in developing countries which is highlighted by an audit of patients treated with chemoradiation in our center. This article deals with the challenges in the contex...

  20. Standardized pathologic evaluation of the esophagus after neoadjuvant chemoradiation

    Muijs, Christina T.; Smit, Justin K.; Karrenbeld, Arend; Beukema, Jannet C.; Langendijk, Johannes A.; Plukker, John Theodorus

    2012-01-01

    Background: The main objective of this study was to develop and validate a method to reconstruct the gross and clinical tumor volume (GTV and CTV) on the esophageal specimen in order to facilitate a good pathologic examination of the original tumor area after neo-adjuvant chemoradiation (CRT). Metho

  1. Adjuvant Therapy of Pancreatic Cancer

    Chakra P Chaulagain

    2011-07-01

    Full Text Available There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145 represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients’ survival. Another study by Fan et al. (Abstract #269 examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.

  2. Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer

    Purpose: To assess the toxicity and efficacy of preoperative chemoradiation in pancreatic cancer. Methods and Materials: Between November 1996 and December 2001, 32 patients with biopsy-proven pancreatic adenocarcinoma (28 head; 4 body) were treated by chemoradiation consisting of either split-course therapy (two courses of 15 Gy separated by a 2-week break, n = 10) or standard-fractionation therapy (45 Gy during 5 weeks, n 22). Concurrent chemotherapy included continuous infusion of 5-fluorouracil and a cisplatin bolus. Pancreatic resection was scheduled for 4-6 weeks after completion of chemoradiation treatment. Results: All 32 patients completed the chemoradiation protocol. Only 2 cases of Grade 3 toxicity (weight loss, vomiting) and one fatal Grade 4 infection occurred. Of the 32 patients, 19 underwent curative resection. Two patients had a complete pathologic response. One patient died 36 months after diagnosis of late treatment-related toxicity (acute superior mesenteric artery thrombosis) with no evidence of disease. The 2-year overall survival rate for the entire group and the resected patients was 37.3% (95% confidence interval 18.2-56.4%) and 59.3% (95% confidence interval 34.1-84.9%), respectively. Conclusion: Preoperative chemoradiation with 5-fluorouracil and cisplatin is feasible and promising

  3. Adjuvant Therapy of Pancreatic Cancer

    Chakra P Chaulagain; Muhammad Wasif Saif; Goodman, Martin D.; John Ng

    2011-01-01

    There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposiu...

  4. Overcoming toxicity-challenges in chemoradiation for non-small cell lung cancer

    2016-01-01

    Concurrent chemoradiation (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (NSCLC) with a modest survival benefit over sequential chemoradiation or radiotherapy (SCRT) alone. However, this benefit is at the cost of increasing acute toxicity such as esophagitis. Previous analysis revealed several predictive parameters in dose-volume and patient characteristics which helped us to identify those patients at risk for severe esophagus toxicity. As a result, supportive care interventions including individualized patient information, dietary guidance, adequate medication, hydration and tubefeeding could be initiated. This paper discusses the challenges in overcoming chemoradiation induced acute esophageal toxicity (AET).

  5. An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach

    Purpose: The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric-cancer patients has not been defined yet. We investigated the effect of postoperative chemoradiotherapy on the relapse rate and survival rate of patients with D2-resected gastric cancer. Methods and Materials: From August 1995 to April 2001, 544 patients received postoperative CRT after curative D2 resection. During the same period of time, 446 patients received surgery without further adjuvant treatment. The adjuvant CRT consisted of 400 mg/m2 of fluorouracil plus 20 mg/m2 of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy. Results: The median duration of overall survival was significantly longer in the CRT group than in the comparison group (95.3 months vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p = 0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year survival rates were consistently longer in the CRT group at Stages II, IIIA, IIIB, and IV than those in the comparison group. The CRT was associated with increases in the median duration of relapse-free survival (75.6 months vs. 52.7 months; hazard ratio for relapse, 0.80, p = 0.0160). Conclusion: Our results highly suggest that the postoperative chemoradiotherapy in D2-resected gastric-cancer patients can prolong survival and decrease recurrence

  6. Concurrent adjuvant radiochemotherapy versus standard chemotherapy followed by radiotherapy in operable breast cancer after breast conserving therapy: A meta-analysis

    Ou Huang

    2016-01-01

    Conclusion: Our study demonstrated that the concurrent administration of chemotherapy (anthracycline-based and radiotherapy was superior to the sequential administration in locoregional recurrence-free survival for the operable node positive breast cancer patients. However, choose of treatment for operable breast cancer patients must be cautious due to high risk of lymphedema.

  7. Topotecan and cisplatin in combination with concurrent twice-daily chemoradiation in limited disease small cell lung cancer-a Danish Oncological Lung Cancer Group (DOLG) phase II trial

    Sorensen, Morten; Lassen, Ulrik; Palshof, Torben;

    2007-01-01

    topotecan with concurrent twice-daily radiochemotherapy in LD SCLC. PATIENT AND METHODS: Multicentre phase II study of three cycles of regimen A (topotecan i.v., 1.5mg/m(2), day 1-5; cisplatin 50mg/m(2), day 1) and three cycles of regimen B (etoposide i.v., 120mg/m(2), day 1-3; carboplatin, AUC=5, day 1......; vincristine, 1.3mg/m(2), day 1) given in the following sequence: A-B-B-A-B-A every 21 days. Twice-daily radiotherapy (1.5Gyx30, 10fr/wk, 45Gy) was delivered concurrently with the first cycle B. Prophylactic cranial irradiation was offered to patients (pts) in complete remission. Eligible were pts with LD SCLC...... with no prior treatment for SCLC, adequate organ functions, and WHO performance status (PS) two times the upper limit were excluded. RESULT: Fourty-five pts were included in four centres. Five patients did not meet the inclusion criteria. The median age of the eligible pts was 60 years, range 43-75. PS...

  8. Expression profiling in head and neck cancer: Predicting response to chemoradiation

    Pramana, J.

    2014-01-01

    The goal of this thesis was to find biomarkers through gene expression profiling, using microarray techniques, which can predict outcome after concurrent chemoradiation in head and neck cancer. The main endpoints for outcome were local control, locoregional control and disease free survival.

  9. Chemoradiation With Paclitaxel and Carboplatin in High-Risk Cervical Cancer Patients After Radical Hysterectomy: A Korean Gynecologic Oncology Group Study

    Lee, Taek Sang [Department of Obstetrics and Gynecology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Soon Beom, E-mail: tslee70@gmail.com [Department of Obstetrics and Gynecology, Konkuk University Medical Center, Seoul (Korea, Republic of); Kim, Young Tak [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Park, Byung Joo [Department of Preventive Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Man [Department of Obstetrics and Gynecology, Asan Medical Center, Seoul (Korea, Republic of); Lee, Jong Min [Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Young Tae [Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Jae Hoon [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung Tai [Department of Obstetrics and Gynecology, Hanyang University Medical Center, Seoul (Korea, Republic of)

    2013-06-01

    Purpose: To evaluate the efficacy and toxicity of concurrent chemoradiation with paclitaxel and carboplatin in patients with high-risk cervical cancer. Methods and Materials: Patients after radical hysterectomy for cervical cancer, with at least 1 high-risk characteristic, were administered paclitaxel 135 mg/m{sup 2}, carboplatin area under the curve = 5 every 3 weeks for 3 cycles concomitant with radiation therapy as adjuvant treatment. Results: This prospective study enrolled 71 consecutive patients. Sixty-six patients (93%) completed the planned treatment. The majority of grade 3/4 neutropenia or nonhematologic toxicities were usually self-limited. Diarrhea grades 3/4 were observed in 4 patients (5.6%). One patient developed anaphylactic shock after infusion of paclitaxel. With a median follow-up of 57 months, recurrences occurred in 16 patients. Multivariable analysis indicated that common iliac lymph node involvement is an independent risk factor for disease recurrence (odds ratio 13.48; 95% confidence interval 2.93-62.03). In the intent-to-treat population (n=71), the estimated 5-year disease-free survival and overall survival rates were 77.3% and 80.3% respectively. In the per-protocol population (n=62), disease-free survival was 78.9% and overall survival was 83.9%. Conclusions: Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and seems to be effective for patients who undergo radical hysterectomy. Therefore, a prospective, randomized controlled study should be designed to evaluate efficacy of this approach for patients with high-risk cervical cancer.

  10. Concurrent administration of adjuvant chemotherapy and radiotherapy after breast-conservative surgery enhances late toxicities; La chimiotherapie concomitante de la radiotherapie augmente la toxicite tardive apres chirurgie conservatrice du cancer du sein

    Toledano, A. [Hopital Tenon, Service d' oncologie-radiotherapie 75 - Paris (France); Garaud, P.; Body, G.; Le Floch, O.; Calais, G. [Centre Hospitalier Universitaire Bretonneau, 37 - Tours (France); Serin, D. [Institut Sainte-Catherine, 84 - Avignon (France); Fourquet, A. [Institut Curie, 75 - Paris (France); Bosset, J.F.; Miny-Buffet, J. [Centre Hospitalier Universitaire Minjoz, 25 - Besancon (France); Favre, A. [Centre Hospitalier Universitaire La Source, 45 - Orleans (France); Azria, D. [Centre de Lutte Contre le Cancer Val d' Aurelle, 34 Montpellier (France)

    2006-06-15

    In 1996, a multicenter randomized study comparing after breast-conservative surgery. sequential vs concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen patients were included in this trial. After a median follow-up of 6.7 (4.3 -9) years, we decided to prospectively evaluate the late effects of these two strategies. Patients and methods - A total of 297 patients were asked to follow-up from the five larger including institutions. Seventy-two percent (214 patients) were eligible for late toxicity. After breast-conserving surgery with axillary dissection, patients were treated either with sequential treatment with CT first followed by RT (arm A) or CT administered concurrently with RT (arm B). In all patients, CT regimen combined mitoxantrone (12 mg/m{sup 2}). 5-FU (500 mg/m{sup 2}), and cyclophosphamide (500 mg/m{sup 2}), 6 cycles (day 1-day 21). In arm B, patients received concurrently the first 3 cycles of CT with RT. In arm A, RT started 3 to 5 weeks after the 6. cycle of CT. Conventional RT was delivered to the whole breast using a 2 Gy-fraction protocol to a total dose of 50 Gy ({+-} boost to the primary tumour bed). The assessment of toxicity was blinded to treatment and was graded by the radiation oncologist according to the LENT-SOMA scale. Skin pigmentation was also evaluated using a personal 5-points scoring system (excellent, good, moderate, poor, very poor). Results - Among the 214 evaluated patients, 107 were treated in each arm. The two populations were homogeneous for patients', tumors' and treatment characteristics. Subcutaneous fibrosis (SF), telangiectasia (T), skin pigmentation (SP), and breast atrophy (BA) were significantly increased in arm B. Twenty patients experienced grade superior or equal to 2 (SF) in arm B vs five in arm A (P 0.003). Twenty-five and seven patients showed grade superior or equal to 2 (T) in ann B and A, respectively (P = 0.001). Forty-four and

  11. Phase II trial of temozolomide plus concurrent whole-brain radiation followed by TNV regimen as adjuvant therapy for patients with newly diagnosed primary CNS lymphoma

    Yong Wang

    2013-01-01

    Full Text Available Background: Primary central nervous system lymphoma (PCNSL is an aggressive extranodal non-Hodgkin′s lymphoma limited to the CNS. Treatment of PCNSL with high-dose methotrexate (HD-MTX-based chemotherapy and whole-brain radiotherapy (WBRT is associated with high rates of relapse and severe treatment-related neurotoxicity. Aim: To report our experience of treating newly diagnosed PCNSL with temozolomide, nedaplatin, and vincristine (TNV, as the replacement of HD-MTX, in combination with concurrent chemoradiotherapy. Materials and Methods: Newly diagnosed PCNSL patients were given concurrent temozolomide (75 mg/m 2 , orally daily during WBRT. Then, the TNV regimen was given after four weeks. The TNV regimen consisted of temozolomide (200 mg/m 2 orally: Days 1-5, nedaplatin (80 mg/m 2 intravenous: Day 1, and vincristine (1.4 mg/m 2 intravenous: Day 1. Each cycle was of a duration of four weeks and a maximum of six cycles were applied. The primary end point was response to treatment obtained by magnetic resonance imaging (MRI. Secondary end points were progression-free survival (PFS and fewer toxic effects. Results: The study subjects included 14 patients (median age: 53.5, median Karnofsky Performance Scale (KPS: 75. The median number of TNV cycles given was five. Response to treatment: Complete response in 12 (85.7% patients, partial response in 2 (14.3% patients, and none with progressive disease. The objective response rate was 100%, and median PFS was 21.4 months. Toxicity was relatively mild, which mainly included nausea in six and fatigue in five, grade 3-4 hematotoxicity in one, and abnormal liver functions in five patients. No neurotoxicity has been observed till date. Conclusion: The efficacy outcomes in this study are comparable to other reported HD-MTX-based regimens plus WBRT, with an added favorable toxicity profile. Prospective, randomized controlled trials are warranted to confirm such results.

  12. Efficacy of intensity-modulated radiotherapy with concurrent carboplatin in nasopharyngeal carcinoma

    The aim of the prospective phase II study was to evaluate the efficacy and toxicities of concurrent carboplatin with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). Between October 2005 and November 2011, 73 stage II–IVB NPC patients received IMRT 70 Gy concurrently with three cycles of carboplatin (AUC 5) every three weeks, followed by three cycles of adjuvant carboplatin (AUC 5) and 5-FU (1,000 mg/m2/day for four days) every four weeks. All patients were evaluated for tumour response using response evaluation criteria in solid tumour (RECIST) criteria, survival analysis using Kaplan-Meier methods, and toxicities according to common terminology criteria for adverse events (CTCAE) version 4.0. At three months after chemoradiation, 82.2% and 17.8% of patients achieved complete and partial response, respectively. With a median follow-up of 48.1 months (1.3–97.8 months), 9.6% and 17.8% had local recurrence and distant metastasis, respectively. The median survival was not reached. A three-year overall survival was 83.6% and a progression-free survival was 65.3%. Regarding treatment compliance, 97.2%, 68.5% and 69.8% completed radiation treatment, concurrent carboplatin and adjuvant chemotherapy, respectively. Grade 3–4 acute toxicities were oral mucositis (16.4%), dysphagia (16.4%), xerostomia (15.1%) and haematotoxicity (6.8%). Carboplatin concurrently with IMRT provided excellent tumour response, manageable toxicities and good compliance. This should be considered as an alternative treatment for NPC patients

  13. Primary Chemoradiation as Definitive Treatment for Unresectable Cancer of the Trachea

    Gregory MM Videtic

    2003-01-01

    Full Text Available A 64-year-old man was diagnosed with unresectable cancer of the trachea. He was treated definitively with a novel chemoradiation regimen. Cisplatin-based chemotherapy (ChT was given for two cycles as induction, followed by concurrent administration of this ChT with external beam radiotherapy (RT (total dose 60 Gy. An unexpected partial tumour response was noted after the induction of ChT alone. Six weeks after finishing ChT/RT, complete response of the lesion was noted on computed tomography imaging. Two years later, the patient was free of disease. Primary chemoradiation appears to be effective in managing locally advanced tracheal cancer.

  14. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer

    Purpose: Capecitabine (Xeloda) is a new orally administered fluoropyrimidine carbamate that was rationally designed to exert its effect by tumor-selective activation. We attempted to evaluate the efficacy and toxicity of preoperative chemoradiation using capecitabine in locally advanced rectal cancer. Methods and Materials: Between July 1999 and March 2001, 45 patients with locally advanced rectal cancer (cT3/T4 or N+) were treated with preoperative chemoradiation. Radiation of 45 Gy/25 fractions was delivered to the pelvis, followed by a 5.4 Gy/3 fractions boost to the primary tumor. Chemotherapy was administered concurrent with radiotherapy and consisted of 2 cycles of 14-day oral capecitabine (1650 mg/m2/day) and leucovorin (20 mg/m2/day), each of which was followed by a 7-day rest period. Surgery was performed 6 weeks after the completion of chemoradiation. Results: Thirty-eight patients received definitive surgery. Primary tumor and node downstaging occurred in 63% and 90% of patients, respectively. The overall downstaging rate, including both primary tumor and nodes, was 84%. A pathologic complete response was achieved in 31% of patients. Twenty-one patients had tumors located initially 5 cm or less from the anal verge; among the 18 treated with surgery, 72% received sphincter-preserving surgery. No Grade 3 or 4 hematologic toxicities developed. Other Grade 3 toxicities were as follows: hand-foot syndrome (7%), fatigue (4%), diarrhea (4%), and radiation dermatitis (2%). Conclusion: These preliminary results suggest that preoperative chemoradiation with capecitabine is a safe, well-tolerated, and effective neoadjuvant treatment modality for locally advanced rectal cancer. In addition, this preoperative treatment has a considerable downstaging effect on the tumor and can increase the possibility of sphincter preservation in distal rectal cancer

  15. Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?

    Purpose: To retrospectively compare the toxicity and efficacy of concurrent gemcitabine-based chemoradiation with that of concurrent 5-fluorouracil (5-FU)-based chemoradiation in patients with unresectable pancreatic cancer. Patients and Methods: Between September 1996 and May 2000, 114 patients with localized unresectable adenocarcinoma of the pancreas were treated with concurrent chemoradiation. Locally advanced unresectable disease was defined as low-density tumor in contact with the superior mesenteric artery (SMA) or celiac artery, or occlusion of the superior mesenteric-portal venous confluence. Fifty-three patients were selected to receive gemcitabine in 7 weekly cycles (250-500 mg/m2) with concurrent radiotherapy (median dose 30 Gy, range 30-33 Gy in 10-11 fractions). The remaining 61 patients received continuous-infusion 5-FU (200-300 mg/m2) with concurrent radiotherapy (30 Gy in 10 fractions). Radiotherapy was delivered to the primary tumor and regional lymphatics. Patients receiving gemcitabine and those receiving 5-FU had a similar mean Karnofsky performance status (KPS, 89% vs. 86%), distribution of tumor grade (43% vs. 33% poorly differentiated), and percent weight loss (all p=NS). However, patients treated with gemcitabine had a significantly larger median maximum cross-sectional tumor area (TA, 8.8 cm2 vs. 5.7 cm2, p=0.046) and were significantly younger (median age 60 vs. 68 years, p10 cm2 (p=0.03) and poor differentiation (p=0.07) were associated with a worse survival duration; however, other factors, such as KPS and weight loss >10% and age did not influence OS. Conclusion: Despite the selection of healthier patients to receive gemcitabine, there was a significantly higher severe toxicity rate than with 5-FU. The median and 1-year survivals were not significantly different with the use of concurrent gemcitabine; however, the tumors treated were significantly larger. Additionally, a small number of patients with minimal arterial involvement whose

  16. Outcomes and Tolerability of Chemoradiation Therapy for Pancreatic Cancer Patients Aged 75 Years or Older

    Purpose: To review the outcomes and tolerability of full-dose chemoradiation in elderly patients aged 75 years or older with localized pancreatic cancer. Methods and Materials: We retrospectively reviewed patients aged 75 years or older with nonmetastatic pancreatic cancer treated with chemoradiation therapy at two institutions from 2002 to 2007. Patients were analyzed for treatment toxicity, local recurrences, distant metastases, and survival. Results: A total of 42 patients with a median age of 78 years (range, 75-90 years) who received chemoradiation therapy for pancreatic cancer were identified. Of the patients, 24 had locally advanced disease treated with definitive chemoradiation, and 18 had disease treated with surgery and chemoradiation. Before chemoradiotherapy, the mean Eastern Cooperative Oncology Group performance status was 1.0 ± 0.8, and the mean 6-month weight loss was 5.3 ± 3.8 kg. The mean radiation dose delivered was 48.1 ± 9.2 Gy. All patients received fluoropyrimidine-based chemotherapy concurrently with radiotherapy. In all, 8 patients (19%) were hospitalized, 7 (17%) had an emergency room visit, 15 (36%) required a radiation treatment break, 3 (7%) required a chemotherapy break, 9 (21%) did not complete therapy, and 22 (49%) had at least one of these adverse events. The most common toxicities were nausea, pain, and failure to thrive. Median overall survival was 8.6 months (95% confidence interval, 7.2-13.1) in patients who received definitive chemoradiation therapy and 20.6 months (95% confidence interval, 9.5-∞) in patients who underwent resection and chemoradiation therapy. Conclusions: In this dataset of very elderly patients with pancreatic cancer and good Eastern Cooperative Oncology Group performance status, outcomes after chemoradiotherapy were similar to those among historic controls for patients with locally advanced and resected pancreatic cancer, although many patients experienced substantial treatment-related toxicity.

  17. Adjuvant Strategies for Resectable Pancreatic Cancer: Have We Made Progress?

    Suzanne Russo

    2012-03-01

    Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.

  18. Adjuvant therapy in pancreatic cancer

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  19. Gemcitabine-induced radiation recall phenomenon in a post-operative and post-radiotherapy case of peri-ampullary carcinoma during adjuvant chemotherapy

    Jayanta Biswas

    2012-01-01

    Full Text Available Radiation recall phenomenon is an inflammatory process occurring at sites of previous radiation subsequent to administration of pharmacologic agents. The most common chemotherapeutic agents implicated with radiation recall phenomenon are anthracyclines and taxanes. Skin is the most common site for radiation recall. About 63% of the radiation recall events are reported to manifest as dermatitis. This finding differs from radiation recall due to Gemcitabine, in which approximately 70% cases manifested as inflammation of internal organs or tissues and 30% manifested as dermatitis. Here, we report a case of post-operative peri-ampullary carcinoma who developed radiation recall dermatitis during adjuvant chemotherapy with inj. Gemcitabine and inj. Carboplatin after concurrent chemoradiation with capecitabine.

  20. Preclinical studies of concomitant chemoradiation

    Animal models are widely used in preclinical studies in order to explain the mechanisms of action of chemotherapy, radiotherapy and concomitant chemoradiation, to analyze pathophysiology of tumors and to evaluate the treatment of choice for malignant tumors. The choice of murine tumor or human tumor xenograft system is still debated. Xenografted human tumors have two main advantages: their human origin and wanted pathological type, which is necessary for future clinical studies. There are a lot of disadvantages of xenografted tumors: the stroma and vascular network of transplanted tumors have murine origin, the graft is mostly ectopic, the volume of transplanted tumors at the time of chemoradiotherapy is much smaller than that of the tumor in man; due to residual immunity it is difficult to determine response to cytotoxic treatment. It is still impossible to extrapolate the results obtained in a tumor model in animal to man. These investigations are useful for interpretation of clinical results and for proposing the less empirical method of chemoradiation for phase II clinical trials. (author)

  1. Maintenance chemotherapy after chemoradiation improves survival of patients with locally advanced pancreatic carcinoma. A retrospective analysis of prospectively recruited patients

    Background and purpose: currently, there is no treatment standard for patients with locally advanced pancreatic cancer (PaCa) after chemoradiation. The aim of the present study was to retrospectively assess overall survival and toxicity of chemotherapy in addition to chemoradiation in this patient group. Patients and methods: three-dimensional conformal irradiation to the primary tumor (55.8 Gy) and the lymphatics (50.4 Gy) was combined with 5-fluorouracil- or gemcitabine-based chemotherapy followed by additional chemotherapy with gemcitabine until progression or no further treatment. Decision for chemotherapy was taken at the discretion of the attending physician considering the patient's desire. Results: a total of 172 patients were addressed to the local tumor board. Patients with (neo)adjuvant treatment or metastatic disease were excluded (n = 90). 82 patients were treated with chemoradiation and had additional chemotherapy (n = 40) or no further treatment (n = 42). Characteristics of the two groups were equally distributed. Patients with chemotherapy had significantly longer overall survival as compared to patients without (13 months vs. 8 months; p < 0.0001; median survival = 10.7 months for all patients). Acute toxicity of maintenance chemotherapy was relatively mild. Conclusion: maintenance chemotherapy after chemoradiation for patients with locally advanced PaCa may significantly increase survival rates without severe side effects and is therefore recommended as standard treatment following chemoradiation. (orig.)

  2. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

    Kelly, Patrick; Das, Prajnan; Pinnix, Chelsea C.; Beddar, Sam; Briere, Tina; Pham, Mary; Krishnan, Sunil; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H., E-mail: ccrane@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-01

    Purpose: Improving local control is critical to improving survival and quality of life for patients with locally advanced unresectable pancreatic cancer (LAPC). However, previous attempts at radiation dose escalation have been limited by duodenal toxicity. In order to guide future studies, we analyzed the clinical and dosimetric factors associated with duodenal toxicity in patients undergoing fractionated chemoradiation for LAPC. Methods and Materials: Medical records and treatment plans of 106 patients with LAPC who were treated with chemoradiation between July 2005 and June 2010 at our institution were reviewed. All patients received neoadjuvant and concurrent chemotherapy. Seventy-eight patients were treated with conventional radiation to 50.4 Gy in 28 fractions; 28 patients received dose-escalated radiation therapy (range, 57.5-75.4 Gy in 28-39 fractions). Treatment-related toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to assess prognostic influence of clinical, pathologic, and treatment-related factors by using Kaplan-Meier and Cox regression methods. Results: Twenty patients had treatment-related duodenal toxicity events, such as duodenal inflammation, ulceration, and bleeding. Four patients had grade 1 events, 8 had grade 2, 6 had grade 3, 1 had grade 4, and 1 had grade 5. On univariate analysis, a toxicity grade ≥2 was associated with tumor location, low platelet count, an absolute volume (cm{sup 3}) receiving a dose of at least 55 Gy (V{sub 55} {sub Gy} > 1 cm{sup 3}), and a maximum point dose >60 Gy. Of these factors, only V{sub 55} {sub Gy} ≥1 cm{sup 3} was associated with duodenal toxicity on multivariate analysis (hazard ratio, 6.7; range, 2.0-18.8; P=.002). Conclusions: This study demonstrates that a duodenal V{sub 55} {sub Gy} >1 cm{sup 3} is an important dosimetric predictor of grade 2 or greater duodenal toxicity and establishes it as a

  3. Retiform hemangioendothelioma over forehead: A rare tumor treated with chemoradiation and a review of literature

    Anup Sunil Tamhankar

    2015-01-01

    Full Text Available Retiform hemangioendothelioma (RH is low grade tumor of skin and subcutaneous tissue. It needs to be differentiated from angiosarcoma as RH has excellent prognosis. It is usually seen in young adults on extremities. Sometimes it may mimic benign conditions and can delay treatment. Surgery has been mainstay of its treatment with or without adjuvant radiation. We present first case of RH on face. This is only second case being treated with definitive chemoradiation. So it′s important to distinguish RH from angiosarcoma due to treatment implications as well.

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

    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

    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. Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer

    To evaluate efficacy and secondary resectability in patients with locally advanced pancreatic cancer (LAPC) treated with neoadjuvant chemoradiotherapy (CRT). A total of 215 patients with locally advanced pancreatic cancer were treated with chemoradiation at a single institution. Radiotherapy was delivered with a median dose of 52.2 Gy in single fractions of 1.8 Gy. Chemotherapy was applied concomitantly as gemcitabine (GEM) at a dose of 300 mg/m2 weekly, followed by adjuvant cycles of full-dose GEM (1000 mg/m2). After neoadjuvant CRT restaging was done to evaluate secondary resectability. Overall and disease-free survival were calculated and prognostic factors were estimated. After CRT a total of 26% of all patients with primary unresectable LAPC were chosen to undergo secondary resection. Tumour free resection margins could be achieved in 39.2% (R0-resection), R1-resections were seen in 41.2%, residual macroscopic tumour in 11.8% (R2) and in 7.8% resection were classified as Rx. Patients with complete resection after CRT showed a significantly increased median overall survival (OS) with 22.1 compared to 11.9 months in non-resected patients. Median OS and disease-free survival (DFS) of all patients were 12.3 and 8.1 months respectively. In most cases the first site of disease progression was systemic with hepatic (52%) and peritoneal (36%) metastases. A high percentage of patients with locally advanced pancreatic cancer can undergo secondary resection after gemcitabine-based chemoradiation and has a relative long-term prognosis after complete resection

  7. Promising long-term results with attenuated adverse effects by methotrexate-containing sequential chemoradiation therapy in locally advanced head and neck squamous cell carcinoma

    To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation. Two induction courses of methotrexate (40 mg/m2/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m2/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m2/day) and 5-fluorouracil (400 mg/m2/day) on day 1. Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and concurrent chemoradiotherapy (CCRT), respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis. Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicity-acceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach. (author)

  8. Management of adenocarcinoma of the esophagus with chemoradiation alone or chemoradiation followed by esophagectomy: results of sequential nonrandomized phase II studies

    Purpose: The incidence of adenocarcinoma of the esophagus is increasing, but the optimal treatment for this disease is unknown. We evaluated the efficacy of chemoradiation and chemoradiation followed by esophagectomy as treatment for adenocarcinoma of the esophagus in sequential prospective nonrandomized phase II studies. Methods and Materials: Between May 1981 and June 1992, all previously untreated patients (N = 35) with potentially resectable adenocarcinoma of the esophagus (clinical Stage I or II) were treated with curative intent in sequential prospective Phase II studies. From May 1981 to August 1987, 11 patients (median age 66) were treated with concurrent chemotherapy [mitomycin C, and 5-fluorouracil (5-FU)] and radiotherapy to a median dose of 60 Gy (CRT group). From September 1987 to June 1992, 24 patients (median age 65) were treated with the same regimen of chemoradiation followed by planned esophagectomy (CRT + PE group). Of these, 12 patients (median age 62) actually underwent esophagectomy (CRT + E subgroup). Results: The median overall survival was 19 months for the CRT group and 15 months for the CRT + PE group. For the CRT + E subgroup, the median overall survival was 33 months. The 3-year actuarial overall survival for the CRT and the CRT + PE groups were 36 and 28% (p = 0.949). The subset of patients treated with chemoradiation followed by esophagectomy had a 3-year actuarial overall survival of 33% (p = 0.274). The 3-year actuarial freedom from local failure rates were similar: 62% in the CRT group vs. 58% in the CRT + PE group. Of the 12 patients who underwent esophagectomy (CRT + E group), 9 (75%) were free of local failure. Four of 12 (33%) patients had no pathologic evidence of malignancy in their surgical specimen. Six of 11 patients (55%) in the CRT group were free of local failure at the time of analysis. Two of five patients in this group who had local recurrence at 2 and 10 months underwent surgical salvage with subsequent survivals of

  9. The single institutional outcome of postoperative radiotherapy and concurrent chemoradiotherapy in resected non-small cell lung cancer

    Lee, Hyo Chun; Kim, Yeon Si; Oh, Se Jin; Lee, Yun Hee; Lee, Dong Soo; Song, Jin Ho; Kang, Jin Hyung; Park, Jae Ki [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-09-15

    This study was conducted to observe the outcomes of postoperative radiotherapy (PORT) with or without concurrent chemotherapy in resected non-small cell lung cancer (NSCLC) in single institution. From 2002 to 2013, 78 patients diagnosed with NSCLC after curative resection were treated with radiotherapy alone (RT, n = 48) or concurrent chemoradiation (CCRT, n = 30). The indications of adjuvant radiation therapy were N2 node positive (n = 31), close or involved resection margin (n = 28), or gross residual disease due to incomplete resection (n = 19). The median radiation dose was 57.6 Gy (range, 29.9 to 66 Gy). Median survival time was 33.7 months (range, 4.4 to 140.3 months). The 5-year overall survival (OS) rate was 49.5% (RT 46% vs. CCRT 55.2%; p = 0.731). The 3-year disease-free survival rate was 45.5% (RT 39.4% vs. CCRT 55.3%; p = 0.130). The 3-year local control rate was 68.1% (RT 64.4% vs. CCRT 77.7%; p = 0.165). The 3-year DMFS rate was 56.1% (RT 52.6% vs. CCRT 61.7%; p = 0.314). In multivariate analysis, age > or =66 years and pathologic stage III were significant poor prognostic factors for OS. Treatment failure occurred in 40 patients. Four patients had radiologically confirmed grade 3 radiation pneumonitis. In NSCLC, adjuvant RT or CCRT after curative surgery is a safe and feasible modality of treatment. OS gain was seen in patients less than 66 years. Postoperative CCRT showed a propensity of achieving better local control and improved disease-free survival compared to RT alone according to our data.

  10. Chemoradiation therapy for anal cancer

    Chemoradiation therapy for anal cancer was carried out in 58 patients using low-dose, continuous infusion of 5-fluorouracil (5-FU) with or without continuous infusion of cisplatin (cDDP) and external beam irradiation (chemoXRT). Thirty-nine patients received 5-FU chemoXRT resulting in a local control rate of 50% in those receiving a total dose of 60 Gy. The actuarial local control rate at 2 years was 77% after chemoXRT alone; overall local control was 67% at 5 years. In 18 patients receiving 5-FU plus cisplatin with radiation doses of 54-55 Gy, actuarial local control was 85% at 2 years. Fifteen patients failed chemoXRT, 13 of whom had abdominoperineal resection for salvage; the overall local control rate was 93% (54/58). The actuarial survival at 5 years was 81% for the 5-FU chemoXRT group and 94% at 2 years for the 5-FU plus cisplatin chemoXRT group; median follow-up was 54 and 20 months, respectively. Diarrhea and nausea were the most frequent early reactions and were ameliorated by limiting the duration of chemotherapy to 5 days/week and by using XRT techniques to exclude the small bowel from the radiation portal. Serious late radiation complications have not been observed and may be related to XRT fraction and the use of protracted chemotherapy infusion. The absence of late morbidity coupled with the high local control rate by the use of this chemoXRT program is an area to investigate for improving the therapeutic ratio for the treatment of anal cancers. (author)

  11. Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

    We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

  12. Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study

    Purpose: To determine if patients with carcinoma of the vulva, with N2/N3 lymph nodes, could undergo resection of the lymph nodes and primary tumor following preoperative chemo-radiation. Methods and Materials: Fifty-two patients were entered in the study, but six patients did not meet the criteria of the protocol and were excluded. The remaining 46 patients are the subject of this report. Patients underwent a split course of radiation, 4760 cGy to the primary and lymph nodes, with concurrent chemotherapy, cisplatin/5-FU, followed by surgery. Results: Four patients did not complete the chemo-radiation, because three expired and one refused to complete the treatment. Four patients who completed chemo-radiation did not undergo surgery, because two of them died of non-cancer-related causes, and in the other two patients, the nodes remained unresectable. Following chemo-radiation, the disease in the lymph nodes became resectable in 38/40 patients. Two patients who completed the course of chemo-radiation did not undergo surgery as per protocol because of pulmonary metastasis. One underwent radical vulvectomy and unilateral node dissection and the other radical vulvectomy only. The specimen of the lymph nodes was histologically negative in 15/37 patients. Nineteen patients developed recurrent and/or metastatic disease. The sites of failure were as follows: primary area only, 9; lymph node area only, 1; primary area and distant metastasis, 1; distant metastasis only, 8. Local control of the disease in the lymph nodes was achieved in 36/37 and in the primary area in 29/38 of the patients. Twenty patients are alive and disease-free, and five have expired without evidence of recurrence or metastasis. Two patients died of treatment-related complications. Conclusion: High resectability and local control rates of the lymph nodes were obtained in patients with carcinoma of the vulva with N2/N3 nodes treated preoperatively with chemo-radiation

  13. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

  14. Buschke-Löwenstein tumor with squamous cell carcinoma treated with chemo-radiation therapy and local surgical excision: report of three cases

    Indinnimeo, Marileda; Impagnatiello, Alessio; D’Ettorre, Gabriella; Bernardi, Gloria; Moschella, Cosima Maria; Gozzo, Paolo; Ciardi, Antonio; Bangrazi, Caterina; De Felice, Francesca; Musio, Daniela; TOMBOLINI, VINCENZO

    2013-01-01

    Treatment of anorectal Buschke-Löwenstein tumor (BLT) with squamous cell carcinoma (SCC) transformation is not univocal given the rarity of the disease. BLT is characterized by its large size and tendency to infiltrate into underlying tissues. Malignant transformation can occur and it is important to identify the presence of neoplastic foci to decide the proper treatment. Our aim was to assess the effectiveness of neo-adjuvant chemo-radiation therapy (CRT) and local excision in order to avoid...

  15. Outcome after neoadjuvant chemoradiation and correlation with nutritional status in patients with locally advanced pancreatic cancer

    Naumann, P.; Habermehl, D.; Welzel, T.; Combs, S.E. [University Clinic Heidelberg (Germany). Dept. of Radiation Oncology; Debus, J. [University Clinic Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum, Heidelberg (Germany)

    2013-09-15

    Background: Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival. Methods: Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation. Results: After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer. Conclusions: In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients' BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future. (orig.)

  16. Neoadjuvant chemoradiation with capcitabine and celecoxib in stage II and III rectal adenocarcinoma

    Aghili M

    2010-10-01

    Full Text Available "nBackground: Colorectal cancer is the third common cancer world wide and the forth in Iran. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluate the efficacy a cox-2 inhibitor on pathologic response, sphincter preservation and acute toxicity during neoadjuvant chemoradiation."n "nMethods: Thirty-six patients that have adenocarcinoma of rectum was enrolled (up to 15 cm of anal verge. The patients were undergone Endometrial Ultrasound (EUS, abdomino-pelvic and chest CT for staging. Then received neoadjuvant concurrent chemo radiation (xeloda 825 mg/m2 bid in combination with celecoxib 100 mg qid and 50-50.4Gy/25-28f. Surgery was done 4-8 weeks after chemoradiation. During the chemoradiation the patients was observed for the probable complication one year. Tumor regression grade was reported."n "nResults: From 36 surgery patients, Total Mesorectal Excision (TME was done in 30 patients. Pathologic complete response was seen in eight of 30 patients (26.7%. Tumor regression grade was calculated in three and five grade system: in three grade system 17 patients had grade 1 (60.7%, eight patients had grade 2 (28.6% and three patients had grade 3 (10.7%. In five grade system of tumor regression eight patients had grade 1 (28.6%, nine patients had grade 2 (32.1%, eight patients grade 3 (28.6%, three patients had grade 4 (10.7%. T down staging was 43.3%. N downstaging was 30.8%. No patient had skin reaction or cardio-vascular complication."n "nConclusion: Based on our study results, Celecoxib in combination with neoadjuvant chemoradiation is safe and is associated with low complications. This combination can promote pathologic complete response, TRG and T and N downstaging in Rectal adenocarcinoma.

  17. Outcome after neoadjuvant chemoradiation and correlation with nutritional status in patients with locally advanced pancreatic cancer

    Background: Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival. Methods: Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation. Results: After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer. Conclusions: In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients' BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future. (orig.)

  18. Buschke-Löwenstein tumor with squamous cell carcinoma treated with chemo-radiation therapy and local surgical excision: report of three cases.

    Indinnimeo, Marileda; Impagnatiello, Alessio; D'Ettorre, Gabriella; Bernardi, Gloria; Moschella, Cosima Maria; Gozzo, Paolo; Ciardi, Antonio; Bangrazi, Caterina; De Felice, Francesca; Musio, Daniela; Tombolini, Vincenzo

    2013-01-01

    Treatment of anorectal Buschke-Löwenstein tumor (BLT) with squamous cell carcinoma (SCC) transformation is not univocal given the rarity of the disease. BLT is characterized by its large size and tendency to infiltrate into underlying tissues. Malignant transformation can occur and it is important to identify the presence of neoplastic foci to decide the proper treatment. Our aim was to assess the effectiveness of neo-adjuvant chemo-radiation therapy (CRT) and local excision in order to avoid abdomino-perineal resection (APR). Three cases of anorectal BLT with SCC transformation are presented. All patients were HIV positive and treated with antiretroviral drugs. They underwent preoperative endoanal ultrasound, biopsies, total body tomography and anal brushing. Treatment consisted of neo-adjuvant chemo-radiation therapy (45 Gy to the pelvis plus a boost with 14.40 Gy to the primary tumor for a total of 59.40 Gy, and mitomycin-C in bolus on the first day, plus 5-fluorouracil by continuous infusion in the first and in the sixth week) and subsequent local surgical excision. During the follow-up, patients were subjected to the same preoperative diagnostic investigations and high resolution anoscopy. All patients showed a complete regression of the lesion after CRT and were treated by local surgical excision, thus avoiding permanent colostomy. In conclusion neo-adjuvant chemo-radiation therapy with local surgical excision could be considered an effective therapy in the treatment of anorectal BLT with SCC transformation to avoid APR. PMID:24040860

  19. Sensory neural hearing loss after concurrent cisplatin and radiation therapy for nasopharyngeal carcinoma

    Sensory neural hearing loss (SNHL) was evaluated in the patients who were treated with concurrent chemoradiation therapy for nasopharyngeal carcinoma. Ten from 48 ears showed persistent SNHL. Radiotherapy techniques, radiation dose to inner ear and post-treatment otitis media were significant predicting factors for SNHL

  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

    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% (α = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg2/day), cisplatin (15 mg/mg2/day), and paclitaxel (200 mg/mg2/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg2/day) with cisplatin (15 mg/mg2/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. 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

    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%).

  2. Cancer stem cells and chemoradiation resistance

    Cancer is a disease of genetic and epigenetic alterations, which are emphasized as the central mechanisms of tumor progression in the multistepwise model. Discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. The heterogeneity of tumors can be explained with the help of CSCs supported by antiapoptotic signaling. CSCs mimic normal adult stem cells by demonstrating resistance to toxic injuries and chemoradiation therapy. Moreover, they might be responsible for tumor relapse following apparent beneficial treatments. Compared with hematopoietic malignancies, conventional therapy regimes in solid tumors have improved the overall survival marginally, illustrating the profound impact of treatment resistance. This implies that the present therapies, which follow total elimination of rapidly dividing and differentiated tumor cells, need to be modified to target CSCs that repopulate the tumor. In this review article, we report on recent findings regarding the involvement of CSCs in chemoradiation resistance and provide new insights into their therapeutic implications in cancer. (author)

  3. Radiation dose ≥54 Gy and CA 19–9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation

    Unresectable pancreatic cancer (UPC) has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT) as definitive treatment for UPC and the CA 19–9 response to therapy have an impact on overall survival (OS). From 1997–2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy). All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other) and 24 received adjuvant chemotherapy. 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy). Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19–9 post-CRT <90 U/mL was favorably associated with OS (12.3 versus 8.8 months, p = 0.012). Radiotherapy dose ≥54 Gy trended towards improved OS (11.3 versus 6.8 months, p = 0.089). By multivariable analysis, a delivered RT dose of ≥54 Gy (HR 0.47, p = 0.028) and minimum CA 19–9 post-CRT of <90 U/mL (HR 0.35, p = 0.008) were associated with OS. CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19–9 <90 U/mL had improved likelihood of long-term survival

  4. Randomized Trial of Postoperative Adjuvant Therapy in Stage II and III Rectal Cancer to Define the Optimal Sequence of Chemotherapy and Radiotherapy: 10-Year Follow-Up

    Purpose: To determine the optimal sequence of postoperative adjuvant chemotherapy and radiotherapy in patients with Stage II or III rectal cancer. Methods and Materials: A total of 308 patients were randomized to early (n = 155) or late (n = 153) radiotherapy (RT). Treatment included eight cycles of chemotherapy, consisting of fluorouracil 375 mg/m2/day and leucovorin 20 mg/m2/day, at 4-week intervals, and pelvic radiotherapy of 45 Gy in 25 fractions. Radiotherapy started on Day 1 of the first chemotherapy cycle in the early RT arm and on Day 1 of the third chemotherapy cycle in the late RT arm. Results: At a median follow-up of 121 months for surviving patients, disease-free survival (DFS) at 10 years was not statistically significantly different between the early and late RT arms (71% vs. 63%; p = 0.162). A total of 36 patients (26.7%) in the early RT arm and 49 (35.3%) in the late RT arm experienced recurrence (p = 0.151). Overall survival did not differ significantly between the two treatment groups. However, in patients who underwent abdominoperineal resection, the DFS rate at 10 years was significantly greater in the early RT arm than in the late RT arm (63% vs. 40%; p = 0.043). Conclusions: After the long-term follow-up duration, this study failed to show a statistically significant DFS advantage for early radiotherapy with concurrent chemotherapy after resection of Stage II and III rectal cancer. Our results, however, suggest that if neoadjuvant chemoradiation is not given before surgery, then early postoperative chemoradiation should be considered for patients requiring an abdominoperineal resection.

  5. Prognostic value of pretherapy platelet elevation in oropharyngeal cancer patients treated with chemoradiation.

    Shoultz-Henley, Sara; Garden, Adam S; Mohamed, Abdallah S R; Sheu, Tommy; Kroll, Michael H; Rosenthal, David I; Gunn, G Brandon; Hayes, Amos J; French, Chloe; Eichelberger, Hillary; Kalpathy-Cramer, Jayashree; Smith, Blaine D; Phan, Jack; Ayoub, Zeina; Lai, Stephen Y; Pham, Brian; Kies, Merrill; Gold, Kathryn A; Sturgis, Erich; Fuller, Clifton D

    2016-03-01

    The purpose of this study is to evaluate potential associations between increased platelets and oncologic outcomes in oropharyngeal cancer patients receiving concurrent chemoradiation. A total of 433 oropharyngeal cancer patients (OPC) treated with intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy between 2002 and 2012 were included under an approved IRB protocol. Complete blood count (CBC) data were extracted. Platelet and hemoglobin from the last phlebotomy (PLTpre-chemoRT, Hgbpre-chemoRT ) before start of treatment were identified. Patients were risk-stratified using Dahlstrom-Sturgis criteria and were tested for association with survival and disease-control outcomes. Locoregional control (LRC), freedom from distant metastasis (FDM) and overall survival (OS) were decreased (p nomograms predicting 3-, 5- and 10-year OS. In conclusion, pretreatment platelet elevation is a promising predictor of prognosis, and further work should be done to elucidate the utility of antiplatelets in modifying risk in OPC patients. PMID:26414107

  6. Is neo-adjuvant chemotherapy a better option for management of cervical cancer patients of rural India?

    G A Dastidar

    2016-01-01

    Full Text Available Objectives: To explore alternate modality of treatment in patients of advanced cancer cervix by neo-adjuvant chemotherapy (NACT followed by External Beam Radiotherapy (ERT and Brachytherapy (BT. Short- (6 months and long- (12 months term follow-up data from these patients were compared with the retrospective data from an urban cancer centre, where standard protocol of concurrent chemo-radiotherapy is practiced. Materials and Methods: Two hundred patients of advanced cervical cancer, treated at our rural cancer centre between January 2007 and December 2007, were included in the study arm (Group A. These patients received three cycles of neo-adjuvant chemotherapy with Cisplatin, Bleomycin, and Vincristine before External-Beam Radiotherapy (EBT followed by brachytherapy. Patients in the control arm (Group B of an urban cancer centre, received EBT with weekly concomitant Cisplatin, followed by brachytherapy. Short- (6 months and long- (12 months term follow-up data from our patients were compared with the retrospective data from the urban cancer centre. Results and Analysis: Complete response rate was comparatively higher among patients of Group A, also correspondingly proportion of patients showing progressive disease and stable disease was lower among them. Local treatment failure was 87.5% among patients from Group A and 94.4% in Group B patients. Concomitant chemoradiation (CRT was associated with more GI toxicities. Conclusion: Our result suggests NACT arm is as effective as CRT arm in respect of complete response with less pelvic failure and G.I toxicities. Further follow-up data are needed before arriving at a definite conclusion.

  7. Trends in Chemoradiation Use in Elderly Patients with Head and Neck Cancer: Changing treatment patterns with cetuximab

    Baxi, Shrujal S.; O’Neill, Caitriona; Sherman, Eric J.; Atoria, Coral L.; Lee, Nancy Y.; Pfister, David G.; Elkin, Elena B.

    2016-01-01

    Background Cetuximab was approved for use in chemoradiation (CTRT) for locally-advanced head and neck squamous cell carcinoma (HNSCC) in 2006. Methods Among 3,705 patients with locally-advanced HNSCC identified in the linked Surveillance Epidemiology and End Results (SEER)-Medicare database, we assessed treatment trends including surgery, RT, CTRT and specific agents used in CTRT. We examined the influence of demographic and clinical characteristics on the likelihood of receiving CTRT before and after 2006. Results Chemoradiation use increased from 29% of patients diagnosed in 2001 to 61% in 2009 (p<0.0001). Compared to prior to 2006, neither age nor comorbidity score was associated with receipt of CTRT after 2006. Platinum combinations were the most commonly used concurrent chemotherapies before 2006, but since then cetuximab has become the most commonly used agent. Conclusions The use of CTRT has increased substantially and cetuximab may have increased CTRT use, especially in older and sicker patients. PMID:25535104

  8. Is S-1 a Potential Game Changer in Adjuvant Therapy of Pancreatic Cancer?

    Chakra P Chaulagain; Muhammad Wasif Saif; Janice Rothschild

    2013-01-01

    There remains a lack of consensus on the optimal adjuvant therapy for pancreatic cancer. In general, chemoradiation is favored in the United States and gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free survivals and in some studies overall survival. We present the summary of three abstracts from the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting and discuss their poten...

  9. MRI Risk Stratification for Tumor Relapse in Rectal Cancer Achieving Pathological Complete Remission after Neoadjuvant Chemoradiation Therapy and Curative Resection.

    Honsoul Kim

    Full Text Available Rectal cancer patients achieving pCR are known to have an excellent prognosis, yet no widely accepted consensus on risk stratification and post-operative management (e.g., adjuvant therapy has been established. This study aimed to identify magnetic resonance imaging (MRI high-risk factors for tumor relapse in pathological complete remission (pCR achieved by rectal cancer patients who have undergone neoadjuvant concurrent chemoradiation therapy (CRT and curative resection.We analyzed 88 (male/female = 55/33, median age, 59.5 years [range 34-78] pCR-proven rectal cancer patients who had undergone pre-CRT MRI, CRT, post-CRT MRI and curative surgery between July 2005 and December 2012. Patients were observed for post-operative tumor relapse. We analyzed the pre/post-CRT MRIs for parameters including mrT stage, mesorectal fascia (mrMRF status, tumor volume, tumor regression grade (mrTRG, nodal status (mrN, and extramural vessel invasion (mrEMVI. We performed univariate analysis and Kaplan-Meier survival analysis.Post-operative tumor relapse occurred in seven patients (8.0%, n = 7/88 between 5.7 and 50.7 (median 16.8 months. No significant relevance was observed between tumor volume, volume reduction rate, mrTRG, mrT, or mrN status. Meanwhile, positive mrMRF (Ppre-CRT = 0.018, Ppre/post-CRT = 0.006 and mrEMVI (Ppre-CRT = 0.026, Ppre-/post-CRT = 0.008 were associated with higher incidence of post-operative tumor relapse. Kaplan-Meier survival analysis revealed a higher risk of tumor relapse in patients with positive mrMRF (Ppre-CRT = 0.029, Ppre-/post-CRT = 0.009 or mrEMVI (Ppre-CRT = 0.024, Ppre-/post-CRT = 0.003.Positive mrMRF and mrEMVI status was associated with a higher risk of post-operative tumor relapse of pCR achieved by rectal cancer patients, and therefore, can be applied for risk stratification and to individualize treatment plans.

  10. Aspiration rate following chemoradiation for head and neck cancer: An underreported occurrence

    Background and purpose: We would like to assess the prevalence of aspiration before and following chemoradiation for head and neck cancer. Patients and methods: We reviewed retrospectively the Modified Barium Swallow (MBS) in 63 patients who underwent concurrent chemotherapy and radiation for head and neck cancer. MBS was performed prior to treatment to determine the need for immediate gastrostomy tube placement. MBS was repeated following treatment to assess the safety of oral feeding prior to removal of tube feeding. All patients were cancer free at the time of the swallowing study. No patient had surgery. Dysphagia severity was graded on a scale of 1-7. Tube feedings were continued if patients were diagnosed to have severe aspiration (grade 6-7) or continued weight loss. Patients with abnormal swallow (grade 3-7) received swallowing therapy following MBS. Results: Before treatment, there were 18 grade 1, 18 grade 2, 9 grade 3, 8 grade 4, 3 grade 5, 3 grade 6, and 4 grade 7. Following chemoradiation, at a median follow-up of 2 months (1-10 months), one patient had grade 1, eight patients had grade 2, nine patients had grade 3, eight patients had grade 4, 13 patients had grade 5, seven patients had grade 6, and 11 patients had grade 7. Six patients died from aspiration pneumonia (one before, three during, and two post-treatment), and did not have the second MBS. Overall, 37/63 (59%) patients developed aspiration, six of them (9%) fatal. If we excluded the 10 patients who had severe aspiration at diagnosis and the six patients who died from pneumonia, the prevalence of severe aspiration was 33% (21/63). Conclusions: Aspiration remained a significant morbidity following chemoradiation for head and neck cancer. Its prevalence is underreported in the literature because of its often silent nature. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, and for rehabilitation

  11. The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery

    Bökkerink Guus MJ

    2011-12-01

    Full Text Available Abstract Background The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer. Methods/Design Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine. Transanal Endoscopic Microsurgery (TEM will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response. Primary objective is to determine the number of patients with a (near complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol. Discussion The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051

  12. Adjuvant chemo radiation in gastric cancer Hospital Dr. R. A. Calderon Guardia

    This work establishes the associated factors to the early recurrence of gastric cancer in the patients who have received adjuvant chemoradiation in the Hospital Dr. R. A. Calderon Guardia. It was determined if the personal factors such as age and gender influence in the evolution of theses cases. The importance of characteristics of the tumour as T, N, location, Borrmann type and histological type in the evolution of the disease was estimated, too. It mentions the epidemiological characteristics of patients who have received the therapy and describes the toxicity of the treatment. A retrospective-descriptive method was utilized and the clinical records of the patients of the hospital with gastric cancer diagnosis were reviewed. These patients were surgery candidates and then they received adjuvant ia with chemoradiation from 2003 and with at lest 12 months of monitoring. The main conclusions are: Hospital Calderon Guardia practices the surgery with D2 ganglionar dissection as treatment of potentially curable gastric cancer. The population with gastric cancer has a predominance of men and people between seventh and fifth decade of life. The studied series had a recurrent tendency for female sex. To major pT (pathologic size) of the tumour there is more risks of recurrence. The pattern of regional recurrence in peritoneal carcinomathosis shape is which has a tendency to predominate after the adjuvant treatment in gastric cancer. The toxicity of the adjuvant treatment for gastric cancer is not severe and it is manageable without necessity of suspend the treatment in the majority of the cases

  13. P17.57COMBINED CHEMORADIATION IN ELDERLY PATIENTS WITH GLIOBLASTOMA: COMPARISON OF TWO RADIATION SCHEDULES

    Minniti, G.; Scaringi, C.; Falco, T.; Lanzetta, G.; De Sanctis, V.; Enrici, R. Maurizi

    2014-01-01

    BACKGROUND: Current treatment of glioblastoma (GBM) in the elderly population includes surgery, radiotherapy (RT) and chemotherapy, however the optimal management of disease remains a matter of debate. Both standard and hypofractionated RT in combination with temozolomide (TMZ) have been employed with reported survival benefit; however, aggressive treatments in this population may be associated with high risks of neurological toxicity. We have compared the efficacy of concomitant and adjuvant TMZ in combination with standard RT (60 Gy in 30 fractions) or short-term RT (40 Gy in 15 fractions) in patients aged 70 years and older with a newly diagnosed GBM. PATIENTS AND METHODS: Ninety-five consecutive patients ≥ 70 years old with a newly diagnosed GBM were treated with standard RT plus TMZ at the dose of 75 mg/m2 per day followed by adjuvant TMZ (150-200 mg/m2 for 5 days during each 28-day cycle) up to 12 cycles. Overall survival (OS), progression-free survival (PFS) and toxicity were evaluated and compared with the results observed in a prospective trial of elderly patients with GBM treated with an abbreviated course of RT. RESULTS: Median OS was 12 months in patients treated with standard chemoradiation and 12.4 months in those treated with short-term RT plus TMZ (p= 0.2), and respective 1-year survival rates were 50% and 58%. The median and 1-year PFS rates were 6 months and 23% in standard RT plus TMZ group and 6 months and 20% in short-term RT plus TMZ group, respectively. Grade 3 or 4 hemathological toxicity was similar in both groups. Neurological grade 2/3 toxicity occurred in 35% of patients treated with standard RT/TMZ and 10% of those treated with short-term RT/TMZ. MGMT promoter methylation was associated with longer survival in both groups. CONCLUSIONS: A combination of an abbreviated course of RT plus concomitant and adjuvant TMZ is associated with similar survival benefit as for standard chemoradiation, although with potential lower risks of

  14. 胰腺癌:辅助治疗%Pancreatic cancer-Adjuvant therapy

    Asma Sultana; John Neoptolemos; Paula Ghaneh

    2007-01-01

    Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%-15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation (with or without maintenance chemotherapy) has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level Ⅰ evidence (from the ESPAC-1 trial) is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.

  15. Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer

    Purpose: The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer. Methods: Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m2/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups. Results: The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p=0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p<0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p<0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months. Conclusions: EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer

  16. CELECOXIB - Chemoradiation therapy for reducing mucositis and other acute side effects in advance head and neck carcinoma

    Izadi Sh

    2009-02-01

    Full Text Available "nBackground: Chemo-radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay or interruption of treatment plan, cyclo-oxygenase 2 (COX2 is an inducible enzyme primarily expressed in inflamed and tumoral tissues. COX-2 inhibitors have shown promise to reduce chemoradiation induce toxicities. We conducted a phase III, randomized double blind clinical trial to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with chemoradiation for locally advanced head and neck cancer. Here in we report the first report about the role of COX-2 inhibitor in acute toxicicities. "nMethods: Patients with stage III/IV (locally advance head and neck carcinoma who referred to department of radiation-oncology were eligible. Patients were treated with chemotherapy with cisplatin concurrently with radiation (60-70Gy. Celecoxib (100mg qid was started at the first day of radiotherapy and was given for a total of 8 weeks. Acute toxicities were evaluated every week by WHO scale. "nResults: One hundred twenty two patients were enrolled into the study, (61 patients for each group. In repeated mesurment analysis of variance there is a significant difference in the time of onset of grade II acute toxicities between the two groups; The mucositis, dysphagia, epidermitis and oral pain score changed significantly over the typical five weeks in two groups but these changes were more sever in placebo group (p=0.0001. In the analysis of the overall changes in the following laboratory parame-ters: WBC, hemoglobin and platelet showed that these parameters decreased over time in both groups without a significant difference between groups. "nConclusion: The results of these study showed that the use of a COX-2 inhibitor (celecoxib that is a safe and inexpensive drug may reduce acute toxicities of chemoradiation specially

  17. [Influenza vaccine and adjuvant].

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  18. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract

    Matuschek C

    2011-06-01

    Full Text Available Abstract Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection.

  19. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract.

    Matuschek, C; Bölke, Edwin; Peiper, M; Knoefel, W T; Budach, W; Erhardt, A; Scherer, A; Gerber, P A; Buhren, B A; Gattermann, N; Baldus, S E; Rusnak, E; Shukla, V; Orth, K

    2011-06-21

    Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemo?radiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection. PMID:21810561

  20. Preoperative chemoradiation therapy for oesophageal cancer - results of the Australasian study IG 9401

    The role of preoperative adjuvant chemoradiation therapy remains controversial. We performed a randomised phase III trial to determine whether one cycle of chemotherapy combined with radiation therapy resulted in improved relapse-free and overall survival in resectable oesophageal carcinoma. Two hundred and fifty seven patients from 25 institutions were randomised over 70 months from Australia, New Zealand and Singapore. Patients were stratified for histology, gender and institution. The neoadjuvant regimen consisted of cisplatin 80mg/m2 day 1 and fluorouracil 800mg/m2 days 2 - 5 combined with radiation therapy 35 Gy in 15 fractions. Surgery was performed 4 - 6 weeks after the radiation was completed. Two hundred and fifty six patients were eligible. The median age was 62yrs (range 28 - 81). There were 206 males and 50 females. Most (61%) had adenocarcinomas. More than 80% completed the intended protocol including the surgery. The toxicity of the chemoradiation therapy was mild with no effect on the morbidity of surgery or the hospital stay. The overall treatment related mortality was low. The median survival of those receiving neoadjuvant therapy was 21 months and for those receiving surgery alone 19 months (p = 0.38). Three year survival was 33% and 28% respectively. There was a suggestion of improvement in relapse-free survival for patients with squamous cell carcinoma. Preoperative therapy resulted in a significantly lower rate of positive resection margins and lymph node involvement. The pathological complete response rate in those receiving preooperative therapy was 15%. The combination of one cycle of chemotherapy and moderate dose radiation therapy followed by surgery does not improve survival

  1. Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

    Tham, Chee Kian; Choo, Su Pin; Poon, Donald Yew Hee; Toh, Han Chong; Ong, Simon Yew Kuang; Tan, Sze Huey; Wang, Michael Lian Chek; Foo, Kian Fong

    2010-01-01

    AIM: To analyze the outcome of patients who received concurrent capecitabine (Xeloda) and radiation (XRT) compared to the established concurrent 5-fluorouracil (5-FU) with radiation (5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.

  2. Radiotherapy with concurrent or sequential temozolomide in elderly patients with glioblastoma multiforme

    The objective of this article was to evaluate therapeutic outcomes of elderly patients with glioblastoma multiforme (GBM) treated by surgery followed by combined modality therapy and compare achievable outcomes to those of a younger age population. Seventy-eight adult patients with histologically confirmed grade IV astrocytoma were treated at King Hussein Cancer Center (Amman, Jordan) between September 2004 and December 2008. Records were retrospectively reviewed and included 55 males and 23 females between 19 and 78 years of age (median age 50 years). This case series included 20 patients aged 60 years or older. All patients underwent craniotomy followed radiotherapy and concurrent or sequential temozolomide. The follow-up ranged from 1 to 56 months (median 9.4 months). The median survival for the whole cohort was 13.8 months. The median survival for patients less than 60 years was 14.3 months and for patients 60 years or older was 12.3 months (P = 0.19). Among elderly patients, radical surgical resection (P = 0.002), concurrent delivery of chemoradiation (0.041) and radiotherapy dose ≥5400 cGy (P = 0.0001) conferred statistically significant improvements in overall survival. Management of GBM in elderly patients should include maximal surgical resection followed by radiotherapy and temozolomide whenever medically feasible. Outcomes comparable to those obtained in younger age groups can be expected. Our results indicate that concurrent chemoradiation is superior to sequential chemoradiation in these patients.

  3. Is interferon-α and retinoic acid combination along with radiation superior to chemo-radiation in the treatment of advanced carcinoma of cervix?

    Basu Partha

    2006-01-01

    Full Text Available Locally advanced cervical cancers comprise a large majority of the gynecologic cancers in India and other developing countries. Concurrent chemo-radiation has improved the survival of high risk stage I and stage II cervical cancers. There is no evidence that the same survival benefit has been achieved with chemo-radiation in stage III and stage IV disease. Interferon-a and Retinoic acid have synergistic anti-proliferative activity. In combination with radiation, they substantially enhance the sensitivity of the squamous carcinoma cells to radiation. Based on these observations from the in vitro studies, a few clinical trials have evaluated the combination of interferon-a and Retinoic acid, concomitant with radiation, to treat cervical cancers. The results from these early trials were encouraging and the combination had minimal toxicities. However, till date, no phase III randomized controlled trial has been done to evaluate this therapeutic modality.

  4. A randomized phase II trial of concurrent chemo-RT of oral vinorelbine and 60 Gy or 66 Gy, in locally advanced NSCLC

    Hansen, O.; Knap, M.; Khalil, A.;

    2015-01-01

    Purpose/Objective: Concurrent chemo-radiation (CRT) is the treatment of choice for local advanced NSCLC patients. Despite the curative intent of the treatment, survival is poor with a median survival of about 16-18 months (m) and a 5 year (y) survival of 15%. The loco-regional control rate at 2 y...

  5. ADJUVANTS IN MODERN VACCINOLOGY

    Belozersky V. I.

    2013-12-01

    Full Text Available A concept of adjuvants and their story of creation ischaracterized in the article. They’re presented thevarious types of non-specific stimulators of immunesysteme, thier excipients and classification. They’redescribed basic properties of adjuvant systems, their significant advantages and disadvantages. Particular attention is paid to the numerous antigen delivery systems, including alive vectors, nanoparticles, bacterial toxins, etc. They’re considered non-specific stimulators mechanisms of action on immune system and theirinteraction with antigens. They’re given examples of different adjuvants in licensed vaccines use.

  6. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer

    Purpose: To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. Methods and Materials: Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m2/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. Results: Posttreatment tumor stages were T1-2, N0 in 35%, T3 N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. Conclusions: Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further

  7. ADJUVANTS IN MODERN VACCINOLOGY

    Belozersky V. I; Zhdamarova L.A.; Yelyseyeva I. V; Babych Ye. M.; Isaenko Ye. Yu.; Kolpak S. A

    2013-01-01

    A concept of adjuvants and their story of creation ischaracterized in the article. They’re presented thevarious types of non-specific stimulators of immunesysteme, thier excipients and classification. They’redescribed basic properties of adjuvant systems, their significant advantages and disadvantages. Particular attention is paid to the numerous antigen delivery systems, including alive vectors, nanoparticles, bacterial toxins, etc. They’re considered non-specific stimulators mechanisms of a...

  8. Architecting software concurrency

    Dumitru Ciorba; Victor Besliu

    2011-01-01

    Nowadays, the majority of software systems are inherently concurrent. Anyway, internal and external concurrent activities increase the complexity of systems' behavior. Adequate architecting can significantly decrease implementation errors. This work is motivated by the desire to understand how concurrency can constrain or influence software architecting. As a result, in the paper a methodological architecting framework applied for systems with "concurrency-intensive architecture" is described...

  9. Basic Concurrency Theory

    Løvengreen, Hans Henrik

    2002-01-01

    In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming.......In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming....

  10. Concurrent weighted logic

    Xue, Bingtian; Larsen, Kim Guldstrand; Mardare, Radu Iulian

    2015-01-01

    We introduce Concurrent Weighted Logic (CWL), a multimodal logic for concurrent labeled weighted transition systems (LWSs). The synchronization of LWSs is described using dedicated functions that, in various concurrency paradigms, allow us to encode the compositionality of LWSs. To reflect these,...

  11. Concurrent weighted logic

    Xue, Bingtian; Larsen, Kim Guldstrand; Mardare, Radu Iulian

    2015-01-01

    We introduce Concurrent Weighted Logic (CWL), a multimodal logic for concurrent labeled weighted transition systems (LWSs). The synchronization of LWSs is described using dedicated functions that, in various concurrency paradigms, allow us to encode the compositionality of LWSs. To reflect these...

  12. [Retrospective Study of Induction Chemotherapy and Concurrent Chemoradiation Therapy for Oropharyngeal Cancer].

    Asakage, Takahiro; Ando, Mizuo; Yoshida, Masafumi; Saito, Yuki; Omura, Go; Yamasoba, Tatsuya

    2015-10-01

    We carried out this study to clarify the treatment outcomes and problems associated with induction chemotherapy (using taxotere, cisplatin and 5-FU [TPF therapy]) and chemoradiotherapy in patients with oropharyngeal cancer. The data of 44 patients receiving their initial treatment for oropharyngeal cancer (including 2, 9 and 33 patients with stage II, stage III and stage IV disease, respectively, and 31, 8 and 3 patients with side wall, front wall and upper wall (soft palate and uvula) involvement) were examined. Of the 44 patients, 33 received induction chemotherapy and 11 received chemoradiotherapy. The feasibility, incidence of neutropenia, response rate, and 3 year disease-specific survival rate in the induction chemotherapy group vs. chemoradiotherapy group were 70%, 88%, 82% and 73%, respectively, vs. 63%, 91%, 82% and 55%, respectively. A statistically significant difference in the 3-year disease-specific survival rate was seen between the p16-positive and p16-negative patients in the induction chemotherapy group: while the rate was 100% in the p16-positive patients, it was only 51% in the p16-negative patients (p=0.004). Of the patients undergoing chemoradiotherapy, 3 developed mandibular osteomyelitis, which was considered as one of the important problems associated with this therapy. PMID:26727822

  13. Concurrent chemoradiation for stage III non small cell lung cancer: present results and future prospects

    The prognosis of stage III non small cell lung cancer is reportedly poor, particularly in patients with mediastinal lymph node involvement. These patients may be either good surgical candidates, marginally resectable, or inoperable for technical or medical reasons, but, in any case, surgery and/or radiotherapy are curative in only a minority of them. The high incidence of early distant failures underscores the need for early and effective systemic therapy in association with local treatment, since occult metastatic disease is present in most patients at the time of diagnosis. Recent phase III trials have demonstrated significant benefit to induction chemotherapy prior to irradiation or surgery in reducing the distant metastasis rate. However, poor local control remains a major issue in these locally advanced tumors. In patients with inoperable disease, the concomitant use of chemotherapy along with radiotherapy substantially improves local control. For operable patients, induction chemotherapy with concomitant moderate-dose radiotherapy improves local control as well, and may facilitate surgical resection in marginally operable cases. Currently, a number of phase II clinical trials report encouraging results with concomitant chemoradiotherapy used either prior to surgery or with curative intent in locally advanced non small cell lung cancer. (authors). 27 refs

  14. Recombine Endostatin With Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation in Advanced Nasopharynx Cancer

    2013-03-11

    1、Enough Cases; 2、Elekta Precise 1343 Digital Control Electron Linear Accelerator; Can Undertake Nasopharyngeal Carcinoma Specimens in the Materia,; Image Department of Nose Pharynx Ministry MRI Dynamic Testing,

  15. Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection.. Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation

    Habermehl, D.; Lindel, K.; Rieken, S.; Haase, K.; Welzel, T.; Debus, J.; Combs, S.E. [University Hospital of Heidelberg (Germany). Dept. of Radiation Oncology; Goeppert, B.; Schirmacher, P. [Heidelberg Univ. (Germany). Inst. of Pathology; Buechler, M.W. [University Hospital of Heidelberg (Germany). Dept. of Visceral Surgery

    2012-09-15

    Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease. Patients and methods: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups. Results: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups. Conclusion: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials. (orig.)

  16. Fractures of the Sacrum After Chemoradiation for Rectal Carcinoma: Incidence, Risk Factors, and Radiographic Evaluation

    Purpose: Sacral insufficiency fractures after adjuvant radiation for rectal carcinoma can present similarly to recurrent disease. As a complication associated with pelvic radiation, it is important to be aware of the incidence and risk factors associated with sacral fractures in the clinical assessment of these patients. Methods and Materials: Between 1998 and 2007, a total of 582 patients with locally advanced rectal carcinoma received adjuvant chemoradiation and surgical excision. Of these, 492 patients had imaging studies available for review. Hospital records and imaging studies from all 492 patients were retrospectively evaluated to identify risk factors associated with developing a sacral insufficiency fracture. Results: With a median follow-up time of 3.5 years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral fracture free rate was 0.91. Univariate analysis showed that increasing age (≥60 vs. <60 years), female sex, and history of osteoporosis were significantly associated with shorter time to sacral fracture (P=.01, P=.004, P=.001, respectively). There was no significant difference in the time to sacral fracture for patients based on stage, radiotherapy dose, or chemotherapy regimen. Multivariate analysis showed increasing age (≥60 vs. <60 years, hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR = 2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23-8.50, P=.02) were independent risk factors associated with sacral fracture. Conclusions: Sacral insufficiency fractures after pelvic radiation for rectal carcinoma occur more commonly than previously described. Independent risk factors associated with fracture were osteoporosis, female sex, and age greater than 60 years.

  17. Fractures of the Sacrum After Chemoradiation for Rectal Carcinoma: Incidence, Risk Factors, and Radiographic Evaluation

    Kim, Han Jo [Department of Orthopedic Surgery, Washington University, St. Louis, Missouri (United States); Boland, Patrick J. [Department of Surgery, Orthopaedic Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Meredith, Dennis S. [Hospital for Special Surgery, Department of Orthopaedic Surgery, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang Zhigang; Shi Weiji [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yamada, Yoshiya J. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A., E-mail: goodmank@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2012-11-01

    Purpose: Sacral insufficiency fractures after adjuvant radiation for rectal carcinoma can present similarly to recurrent disease. As a complication associated with pelvic radiation, it is important to be aware of the incidence and risk factors associated with sacral fractures in the clinical assessment of these patients. Methods and Materials: Between 1998 and 2007, a total of 582 patients with locally advanced rectal carcinoma received adjuvant chemoradiation and surgical excision. Of these, 492 patients had imaging studies available for review. Hospital records and imaging studies from all 492 patients were retrospectively evaluated to identify risk factors associated with developing a sacral insufficiency fracture. Results: With a median follow-up time of 3.5 years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral fracture free rate was 0.91. Univariate analysis showed that increasing age ({>=}60 vs. <60 years), female sex, and history of osteoporosis were significantly associated with shorter time to sacral fracture (P=.01, P=.004, P=.001, respectively). There was no significant difference in the time to sacral fracture for patients based on stage, radiotherapy dose, or chemotherapy regimen. Multivariate analysis showed increasing age ({>=}60 vs. <60 years, hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR = 2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23-8.50, P=.02) were independent risk factors associated with sacral fracture. Conclusions: Sacral insufficiency fractures after pelvic radiation for rectal carcinoma occur more commonly than previously described. Independent risk factors associated with fracture were osteoporosis, female sex, and age greater than 60 years.

  18. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed

  19. Adjuvant radiotherapy in patients with endometrial cancers; Place de la radiotherapie dans la prise en charge postoperatoire des patientes atteintes de cancer de l'endometre

    Mazeron, R.; Monnier, L.; Belaid, A.; Berges, O.; Haie-Meder, C. [Service de curietherapie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif cedex (France); Morice, P. [Service de chirurgie gynecologique, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif cedex (France); Pautier, P. [Service d' oncologie medicale, Institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif cedex (France)

    2011-07-15

    The treatment of patients with endometrial cancer has been extensively modified in recent years. Several randomized studies have redefined the indications for adjuvant therapy in tumours staged 1. In the absence of poor prognostic factors, the management tends to be less aggressive than before, often limited to vaginal brachytherapy. Conversely, for more advanced lesions, for which prognosis is poor, combinations of chemo-radiation are currently being evaluated. This literature review aims to provide an update on recent developments in the management of adjuvant radiotherapy for endometrial carcinoma. (authors)

  20. Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

    You, Kai-Yun; Huang, Rong; Yu, Xin; Liu, Yi-Min; Gao, Yuan-Hong

    2016-01-01

    Abstract The long duration of 4 months of postoperative adjuvant chemotherapy is currently recommended for locally advanced rectal cancer after preoperative chemoradiation and surgery. Whether a short duration could be applied in these patients is unknown. So, the purpose of this study is to evaluate the effects on prognosis based on different durations of adjuvant chemotherapy for rectal cancer. We performed a retrospective study of 200 rectal cancer patients who were treated with preoperative chemoradiation and were pathologically graded as ypII and ypIII stages between March 2003 and May 2012. All patients were divided into 2 groups according to the median duration of adjuvant chemotherapy of 2 months. Overall survival (OS) and disease-free survival (DFS) were compared between patients with duration shorter and longer than 2 months in the whole group and subgroups of ypII and ypIII. Recurrence patterns were also analyzed in all subgroups. Multivariate analysis was performed to explore clinical factors that were significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival. In subgroup of ypII stage, the 5-year OS and DFS were similar between patients in long and short durations of adjuvant chemotherapy. For patients of ypIII stage, although no significant difference was found in OS between patients in short and long durations, DFS was showed to be higher in the group of long duration. Further analysis showed that longer duration of adjuvant chemotherapy could lead to improved control of distant metastasis and no impact on local control. Multivariable analysis indicated that long duration of adjuvant chemotherapy is significantly associated with longer distant metastasis-free survival in patients with ypIII stage, but not in those with ypII stage. A long duration of at least 2 months of postoperative adjuvant chemotherapy is necessary for patients with ypIII stage, whereas it may not be absolutely appropriate for those

  1. Adjuvant therapy for pancreas cancer in an era of value based cancer care

    Ahn, Daniel H.; Williams, Terence M.; Goldstein, Daniel A.; El-Rayes, Bassel; Bekaii-Saab, Tanios

    2016-01-01

    In resected pancreas cancer, adjuvant therapy improves outcomes and is considered the standard of care for patients who recover sufficiently post operatively. Chemotherapy or combined chemotherapy and radiation therapy (chemoradiation; CRT) are strategies used in the adjuvant setting. However, there is a lack of evidence to suggest whether the addition of RT to chemotherapy translates to an improvement in clinical outcomes. This is true even when accounting for the subset of patients with a higher risk for recurrence, such as those with R1 and lymph node positive disease. When considering the direct and indirect costs, impact on quality of life and questionable added clinical benefit, the true “net health benefit” from added RT to chemotherapy becomes more uncertain. Future directions, including the utilization of modern RT, integration of novel therapies, and intensifying chemotherapy regimens may improve outcomes in resected pancreas cancer. PMID:26620819

  2. ERM immersion vaccination and adjuvants

    Skov, J.; Chettri, J. K.; Jaafar, R. M.;

    2015-01-01

    Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were the...

  3. Concurrent Software Engineering Project

    Stankovic, Nenad; Tillo, Tammam

    2009-01-01

    Concurrent engineering or overlapping activities is a business strategy for schedule compression on large development projects. Design parameters and tasks from every aspect of a product's development process and their interdependencies are overlapped and worked on in parallel. Concurrent engineering suffers from negative effects such as excessive…

  4. Temporal Concurrent Constraint Programming

    Nielsen, Mogens; Palamidessi, Catuscia; Valencia, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied...

  5. Capecitabine with radiation is an effective adjuvant therapy in gastric cancers

    Chee; Kian; Tham; Su; Pin; Choo; Donald; Yew; Hee; Poon; Han; Chong; Toh; Simon; Yew; Kuang; Ong; Sze; Huey; Tan; Michael; Lian; Chek; Wang; Kian; Fong; Foo

    2010-01-01

    AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT o...

  6. Chemoradiation therapy in treatment of patients with IIB cervical cancer

    The authors present the experience of chemoradiation therapy application in patients with IIB cervical cancer. A combination of radiation with cisplatin and 5-fluoruracil in radiomodifying doses , 5-year relapse-free survival was 42%, 5-year total survival was 48%. Only in 6% of patients who died before 5 years the death was caused by distant metastases. The most frequent cause of death was relapses in the small pelvis, which made 67.5% of all relapses

  7. Drug Combinations in Preoperative Chemoradiation for Rectal Cancer.

    Glynne-Jones, Rob; Carvalho, Carlos

    2016-07-01

    Preoperative radiotherapy has an accepted role in reducing the risk of local recurrence in locally advanced resectable rectal cancer, particularly when the circumferential resection margin is breached or threatened, according to magnetic resonance imaging. Fluoropyrimidine-based chemoradiation can obtain a significant down-sizing response and a curative resection can then be achieved. Approximately, 20% of the patients can also obtain a pathological complete response, which is associated with less local recurrences and increased survival. Patients who achieve a sustained complete clinical response may also avoid radical surgery. In unresectable or borderline resectable tumors, around 20% of the patients still fail to achieve a sufficient down-staging response with the current chemoradiation schedules. Hence, investigators have aspired to increase pathological complete response rates, aiming to improve curative resection rates, enhance survival, and potentially avoid mutilating surgery. However, adding additional cytotoxic or biological agents have not produced dramatic improvements in outcome and often led to excess surgical morbidity and higher levels of acute toxicity, which effects on compliance and in the global efficacy of chemoradiation. PMID:27238473

  8. Is S-1 a Potential Game Changer in Adjuvant Therapy of Pancreatic Cancer?

    Chakra P Chaulagain

    2013-07-01

    Full Text Available There remains a lack of consensus on the optimal adjuvant therapy for pancreatic cancer. In general, chemoradiation is favored in the United States and gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free survivals and in some studies overall survival. We present the summary of three abstracts from the 2013 American Society of Clinical Oncology (ASCO Annual Meeting and discuss their potential impact on our clinical practice. Adjuvant oral chemotherapy with S-1 (Fukutomi et al., Abstract#4008 has now emerged as a promising alternative to the traditional gold standard of intravenous gemcitabine in a relatively large randomized phase III clinical trial. Another study by Yoshitomi et al. (Abstract #4056 examined the value of adjuvant chemotherapy with S-1 alone versus combination of S-1 and gemcitabine versus gemcitabine alone in a three arm phase II clinical trial (CAP-002 Study. In terms of biomarkers in pancreatic cancer, Neoptolemos et al. presented the impact of hENT1 tumor levels on the outcome of the patients with pancreatic cancer (Abstract #4006 who had received adjuvant chemotherapy with either 5-flurouracil or gemcitabine in the ESPAC trial.

  9. Computed tomography to assess pulmonary injury associated with concurrent chemo-radiotherapy for inoperable non-small cell lung cancer

    To characterize serial computed tomography (CT) findings of pulmonary injury after a uniform regimen of concurrent chemo-radiotherapy in inoperable non-small cell lung cancer, and to compare the radiation-induced lung toxicity with other concurrent chemo-radiation regimens. Twenty-four patients with advanced non-small cell lung cancer received 2 induction cycles of cisplatin and vinblastine, followed by 2 further cycles of cisplatin and vinblastine, concurrent with 60 Gy radiation at 2 Gy per fraction. Radiation-induced lung injury in the acute and chronic phases was assessed by serial CT scans and compared with preradiation baseline scans. Acute radiation pneumonitis was evaluated using the Common Toxicity Criteria, and chronic radiation fibrosis was graded according to the European Organisation for Research and Treatment of Cancer - Radiation Therapy Oncology Group Scale. Seventeen (81%) patients had characteristic CT findings of radiation induced pulmonary damage, which were confined to the radiation ports. Although patchy nonhomogeneous and air-space opacities characterized acute radiation pneumonitis, and homogeneous opacities with loss of volume were typical for chronic fibrosis, ground-glass opacities were found frequently in both phases. Acute radiation pneumonitis grade 1 was seen in 29% and grade 2 in 9.5%. Chronic radiation fibrosis grades 1, 2 and 3 were found in 14%, 33% and 19% of the patients respectively. Median survival time was 13 months. CT enables detailed evaluation of radiation-induced pulmonary injury after concurrent chemo-radiation for inoperable non-small cell lung cancer. Although survival time with the present regimen is comparable to other concurrent chemo-radiation regimens, a high incidence of radiation injury was found, though the severity was not life threatening. (author)

  10. Temporal Concurrent Constraint Programming

    Nielsen, Mogens; Valencia Posso, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied....... Furthermore, the expressive power of this fragment is illustrated by examples. Basic Research in Computer Science, Centre of the Danish National Research Foundation....

  11. Composing concurrent objects

    Bergmans, Louis Marie Johannes

    1994-01-01

    Adopting the object-oriented paradigm for the development of large and complex software systems offers several advantages, of which increased extensibility and reusability are the most prominent ones. The object-oriented model is also quite suitable for modelling concurrent systems. However, it appears that extensibility and reusability of concurrent applications is far from trivial. In addition, very little attention has been paid by the conventional object-oriented development methodologies...

  12. Adjuvant Treatment for Ampullary Cancer

    Richard Kim; John Chabot; Muhammad Wasif Saif

    2011-01-01

    Ampullary cancer is an uncommon tumor and tends to have a better prognosis than pancreatic cancer. However, one half of patients will die from recurrent disease suggesting the need for effective adjuvant therapy. Currently, there is lack of randomized trials to guide the use of adjuvant therapy in ampullary cancer. At the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, the largest trial (Abstract #4006) evaluating adjuvant treatment of ampullary cancer was presented.

  13. Adjuvant Treatment for Ampullary Cancer

    Richard Kim

    2011-07-01

    Full Text Available Ampullary cancer is an uncommon tumor and tends to have a better prognosis than pancreatic cancer. However, one half of patients will die from recurrent disease suggesting the need for effective adjuvant therapy. Currently, there is lack of randomized trials to guide the use of adjuvant therapy in ampullary cancer. At the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, the largest trial (Abstract #4006 evaluating adjuvant treatment of ampullary cancer was presented.

  14. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    Dikken, Johan L. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Coit, Daniel G. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Baser, Raymond E.; Gönen, Mithat [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brennan, Murray F. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jansen, Edwin P.M. [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Boot, Henk [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Velde, Cornelis J.H. van de [Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Cats, Annemieke [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Verheij, Marcel, E-mail: m.verheij@nki.nl [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2014-03-01

    Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

  15. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies

  16. Changes in hemoglobin concentration during chemoradiation of locally advanced head and neck tumors

    Background: Despite multimodality treatment strategies of locally advanced head and neck cancers long-term results leave much to be desired. There is evidence that oxygenation status of head and neck tumors is directly influenced by the hemoglobin concentration. The aim of this study was to verify changes in the hemoglobin level during combined radio-chemotherapy of locally advanced head and neck tumors. Patients and methods: Sixty-eight patients with locally advanced head and neck cancer had primary or adjuvant radiotherapy with doses of 60 to 74 Gy in combination with cisplatin (±5-FU) or carboplatin chemotherapy in the first and fifth week of treatment. Hemoglobin levels were analyzed before and at the end of radiotherapy. Results: In 41% of all patients the initial hemoglobin concentration was below normal levels. The mean hemoglobin values in all patients dropped significantly from 12.9±1.7 g/dl before to 11.6±1.6 g/dl at the end of treatment. In 12 cases (18%) allogeneic erythrocytes had to be transfused during treatment. At the end of treatment 76% of all patients had anemic hemoglobin levels. In the groups of patients with cisplatin and carboplatin chemotherapy a significant decrease in hemoglobin levels was seen without meaningful statistical difference between these 2 groups. Conclusions: In patients with locally advanced head and neck cancer a high initial rate of anemia was registered (41%): This rate was nearly doubled during chemoradiation (76%). Since several studies have shown a correlation between hemoglobin levels and local tumor control, there is evidence, that this group might benefit from correcting anemia before combined radio-chemotherapy. (orig.)

  17. Adjuvant Therapy Trials.

    Ursem, Carling; Van Loon, Katherine; Venook, Alan

    2016-01-01

    In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598

  18. Aplastic anemia with concurrent temozolomide treatment in a patient with glioblastoma multiforme

    J. Oh; Kutas, G.J.; Davey, P.; Morrison, M; Perry, J R

    2010-01-01

    Temozolomide (tmz) is an oral alkylating agent used during concurrent and adjuvant chemotherapy for newly diagnosed glioblastoma multiforme. Temozolomide is generally well tolerated and improves survival; however, severe adverse events have occasionally been reported. Here, we report the case of a patient who developed aplastic anemia with related complications in the setting of concurrent tmz treatment with radiotherapy. This case illustrates that aplastic anemia is a rare side effect of tmz...

  19. Preoperative chemoradiation for extraperitoneal T3 rectal cancer: Acute toxicity, tumor response, and sphincter preservation

    Purpose: To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control. Methods and Materials: Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m2, Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m2, Days 1-4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4-6 weeks after the end of chemoradiation. Results: Total Grade 3-4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a

  20. Channel's Concurrence and Quantum Teleportation

    LING Yin-Sheng

    2005-01-01

    Concurrence can measure the entanglement property of a system. If the channel is a pure state, positive concurrence state can afford the good performance in the teleportation process. If the channel ia a mixed state, positive concurrence state cannot assure the good performance in the teleportation. The conditions of the positive concurrence and the quantum teleportation in the Heisenberg spin ring is derived.

  1. Channel's Concurrence and Quantum Teleportation

    Concurrence can measure the entanglement property of a system. If the channel is a pure state, positive concurrence state can afford the good performance in the teleportation process. If the channel ia a mixed state, positive concurrence state cannot assure the good performance in the teleportation. The conditions of the positive concurrence and the quantum teleportation in the Heisenberg spin ring is derived.

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

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.)

  3. Adjuvant therapies for colorectal cancer

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  4. Droit de la concurrence

    2009-01-01

    Le critère de l’efficience est au cœur d’un changement de paradigme qui s’observe dans les réflexions sur la politique et le droit de la concurrence au sein de l’UE et qui se reflète dans cette « more economic approach » que préconise la Commission. Ce constat avait incité en 2004 le groupe de travail Concurrence du vénérable Verein für Socialpolitik à rassembler autour de cette thématique praticiens (gardiens de la concurrence, entreprises) et scientifiques de renom. Au fond, le concept d’ef...

  5. Concurrency and network disassortativity.

    Khor, Susan

    2010-01-01

    The relationship between a network's degree-degree correlation and a loose version of graph coloring is studied on networks with broad degree distributions. We find that, given similar conditions on the number of nodes, number of links, and clustering levels, fewer colors are needed to color disassortative than assortative networks. Since fewer colors create fewer independent sets, our finding implies that disassortative networks may have higher concurrency potential than assortative networks. This in turn suggests another reason for the disassortative mixing pattern observed in biological networks such as those of protein-protein interaction and gene regulation. In addition to the functional specificity and stability suggested by Maslov and Sneppen, a disassortative network topology may also enhance the ability of cells to perform crucial tasks concurrently. Hence, increased concurrency may also be a driving force in the evolution of biological networks. PMID:20586579

  6. Dose escalation without split-course chemoradiation for anal cancer: results of a phase II RTOG study

    PURPOSE: An attempt at radiotherapy (RT) dose escalation (from 45 Gy to 59.6 Gy) in a Radiation Therapy Oncology Group (RTOG) chemoradiation protocol for advanced anal cancers had resulted in an unexpectedly high 1-year colostomy rate (23%) and local failure (The Cancer Journal from Scientific American 2 (4):205-211, 1996). This was felt to be probably secondary to the split course chemoradiation (CR) that was mandated in the protocol. A second phase of this dose escalation study was therefore undertaken without a mandatory split and with an identical RT dose (59.6 Gy) and chemotherapy. MATERIALS AND METHODS: Twenty patients with anal cancers ≥2 cms were treated with a concurrent combination of 59.6 Gy to the pelvis and perineum (1.8 Gy daily, 5 times per week in 33 fractions over 6 (1(2)) weeks) and two cycles of 5 fluorouracil infusion (1000 mg/m2 over 24 hours for 4 days) and mitomycin C (10 mg/m2 bolus). A 10 day rest period was allowed only for severe skin reactions. A comparative analysis was made with the 47 patients in the earlier phase of this study who were treated with the identical chemoradiation course but with a mandatory 2-week break at the 36.00 Gy level. RESULTS: Predominant Grade 3 and 4 toxicities in 18 evaluable patients with dermatitis ((14(18)) or 78%), hematologic ((14(18)) or 78%), infection ((3(18)) or 17%) and gastrointestinal ((5(18)) or 28%). There were no fatalities. Nine patients (50%) completed the planned course without a break; 9 others (50%) had their treatments interrupted for a median of 11 days (range 7-19 days) at a median dose of 41.4 Gy (range 32.4 to 48.6 Gy). This compared to (40(47)) patients (85%) who had a 12 day treatment interruption at 36 Gy total dose in a planned break group. One patient had an abdomino-perineal resection (APR) for persistent disease and another for an anal fissure for (2(18)) or 11% 1-year colostomy rate. This was again favorably comparable to 23% 1-year colostomy rate for the earlier group of

  7. A VLSI Architecture for Concurrent Data Structures

    Dally, William J.

    1986-01-01

    Concurrent data structures simplify the development of concurrent programs by encapsulating commonly used mechanisms for synchronization and communication into data structures. This thesis develops a notation for describing concurrent data structures, presents examples of concurrent data structures, and describes an architecture to support concurrent data structures. Concurrent Smalltalk (CST), a derivative of Smalltalk-80 with extensions for concurrency, is developed to describe concurre...

  8. A Concurrent Logical Relation

    Birkedal, Lars; Sieczkowski, Filip; Thamsborg, Jacob Junker

    2012-01-01

    We present a logical relation for showing the correctness of program transformations based on a new type-and-effect system for a concurrent extension of an ML-like language with higher-order functions, higher-order store and dynamic memory allocation. We show how to use our model to verify a number...... expressions. To the best of our knowledge, this is the first such result for a concurrent higher-order language with higher-order store and dynamic memory allocation....

  9. Temporal Concurrent Constraint Programming

    Valencia, Frank Dan

    Concurrent constraint programming (ccp) is a formalism for concurrency in which agents interact with one another by telling (adding) and asking (reading) information in a shared medium. Temporal ccp extends ccp by allowing agents to be constrained by time conditions. This dissertation studies...... structures, robotic devises, multi-agent systems and music applications. The calculus is provided with a denotational semantics that captures the reactive computations of processes in the presence of arbitrary environments. The denotation is proven to be fully-abstract for a substantial fragment...

  10. Failure of odontogenesis after chemo-radiation therapy for rhabdomyosarcoma

    Choi, Sun Young; Hong, Sung Woo; Koh, Kwang Joon [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Chonbuk National University, Chonju (Korea, Republic of)

    1998-02-15

    This report details a case of 8-year-old girl showing failure of odontogenesis after chemo-radiation therapy for rhabdomysarcoma at the age of 4. The observed results were as follows: 1. Past history revealed that she had received for a total radiation dose od 4430 cGy, 29 fractions in 6 weeks and chemotherapy with vincristine, actinomycin D and cytoxan, followed as maintenance phase for 2 years. 2. The patient was symptom-free and appointed for the treatment of multiple dental caries. 3. Oral examination showed hypoplastic enamel on whole erupted permanent teeth and showed retarded eruption. 4. Conventional radiograms showed failure of root development including abrupt cessation of root formation and root agenesis, and microdobtia, missing teeth, irregular enamel, dislocation of the impacted teeth. Additional finding showed good healing bone pattern on the left mandibular ramus and angle area. 5. Cehalometric analysis revealed failure of bite raising due to incomplete eruption of all the first molars and made it possible to suspect entrapped mandibular growth and then Class II tendency growth. 6. There was correlation between the time of chemo-radiation therapy and the damage of the teeth.

  11. Failure of odontogenesis after chemo-radiation therapy for rhabdomyosarcoma

    This report details a case of 8-year-old girl showing failure of odontogenesis after chemo-radiation therapy for rhabdomysarcoma at the age of 4. The observed results were as follows ; 1. Past history revealed that she had received for a total radiation dose od 4430 cGy, 29 fractions in 6 weeks and chemotherapy with vincristine, actinomycin D and cytoxan, followed as maintenance phase for 2 years. 2. The patient was symptom-free and appointed for the treatment of multiple dental caries. 3. Oral examination showed hypoplastic enamel on whole erupted permanent teeth and showed retarded eruption. 4. Conventional radiograms showed failure of root development including abrupt cessation of root formation and root agenesis, and microdobtia, missing teeth, irregular enamel, dislocation of the impacted teeth. Additional finding showed good healing bone pattern on the left mandibular ramus and angle area. 5. Cehalometric analysis revealed failure of bite raising due to incomplete eruption of all the first molars and made it possible to suspect entrapped mandibular growth and then Class II tendency growth. 6. There was correlation between the time of chemo-radiation therapy and the damage of the teeth.

  12. Building Safe Concurrency Abstractions

    Madsen, Ole Lehrmann

    2014-01-01

    as well as programming, and we describe how this has had an impact on the design of the language. Although Beta supports the definition of high-level concurrency abstractions, the use of these rely on the discipline of the programmer as is the case for Java and other mainstream OO languages. We...

  13. The Concurrent Language Aldwych

    Huntbach, Matthew

    2000-01-01

    Aldwych is proposed as the foundation of a general purpose language for parallel applications. It works on a rule-based principle, and has aspects variously of concurrent functional, logic and object-oriented languages, yet it forms an integrated whole. It is intended to be applicable both for small-scale parallel programming, and for large-scale open systems.

  14. Algebraic topology and concurrency

    Fajstrup, Lisbeth; Raussen, Martin; Goubault, Eric

    2006-01-01

    We show in this article that some concepts from homotopy theory, in algebraic topology,are relevant for studying concurrent programs. We exhibit a natural semantics of semaphore programs, based on partially ordered topological spaces, which are studied up to “elastic deformation” or homotopy...

  15. Morse Theory and Concurrency

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...

  16. Composing concurrent objects

    Bergmans, Louis Marie Johannes

    1994-01-01

    Adopting the object-oriented paradigm for the development of large and complex software systems offers several advantages, of which increased extensibility and reusability are the most prominent ones. The object-oriented model is also quite suitable for modelling concurrent systems. However, it appe

  17. Efficacy and toxicity of chemoradiation in patients with anal cancer - a retrospective analysis

    Concurrent chemotherapy and radiation therapy is the preferred standard of care for patients with anal cancer. Several studies have suggested a benefit of intensity-modulated radiation therapy (IMRT) compared with 3D-conformal radiation (3D-CRT) regarding acute toxicity. This study evaluates outcome and toxicity of patients undergoing IMRT/Tomotherapy or 3D-CRT at our institution. A cohort of 105 anal cancer patients was treated with chemoradiation or radiation alone (16.2%) between January 2000 and December 2011. 37 patients received 3D-CRT while 68 patients were treated with IMRT. Follow-up exams were performed every 3 to 6 months for a minimum of 3 years and then annually. Median follow-up was 41.4 months (2.8 – 158.4). Overall survival (OS), Progression-free survival (PFS) and local control (LC) at 3 years was 70.3%, 66.5%, 78.3% in the 3D-CRT group and 82.9%, 66.5%, 75.3% in the IMRT group without statistically significant difference. 3-year Colostomy-free survival (CFS) was 85.7% in the IMRT/Tomotherapy group and 91.8% in the 3D-CRT group (p = 0.48). No grade 4 toxicity was found in both groups. Severe (G2/3) acute skin toxicity (94.6% vs. 63.2%; p < 0.001) and acute gastrointestinal toxicity rate (67.6% vs. 47.1%; p = 0.03) was significantly higher with 3D-CRT compared to IMRT/Tomotherapy. The use of IMRT can reduce acute severe side effects of the skin and gastrointestinal tract but did not demonstrate improved results regarding OS, PFS, LC and CFS

  18. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    Kordes, Sil, E-mail: s.kordes@amc.uva.nl [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Hulshof, Maarten C. [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands); Bergman, Jacques J.G.H.M. [Department of Gastroenterology, Academic Medical Center, Amsterdam (Netherlands); Vliet, Hans J. van der [Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam (Netherlands); Kapiteijn, Ellen [Department of Medical Oncology, Leiden University Medical Center, Leiden (Netherlands); Laarhoven, Hanneke W.M. van; Richel, Dick J. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Klinkenbijl, Jean H.G. [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Meijer, Sybren L. [Department of Pathology, Academic Medical Center, Amsterdam (Netherlands); Wilmink, Johanna W. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands)

    2014-09-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m{sup 2}) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.

  19. Pathologic downstaging of T3-4Nx rectal cancer after chemoradiation: 5-fluorouracil vs. Tegafur

    Purpose: To describe downstaging effects in locally advanced rectal cancer induced by 2 fluopirimidine radiosensitizing agents given through different routes in conjunction with preoperative radiotherapy. Methods and Materials: From March 1995 to December 1999, two consecutive groups of patients with cT3-4Nx rectal cancer (94% CT scan, 71% endorectal ultrasound) were treated with either (1) 45-50 Gy (1.8 Gy/day, 25 fractions) and 5-fluorouracil (5-FU) (500-1,000 mg/m2 by 24-h continuous i.v. infusion on Days 1-4 and 21-25) or (2) oral Tegafur (1,200 mg/day on Days 1-35, including weekends). Surgery was performed 4 to 6 weeks after the completion of chemoradiation. Results: The total T downstaging rate was 46% in the 5-FU group and 53% in the Tegafur group. Subcategories were downstaged by the sensitizing agents (5-FU vs. Tegafur) as follows: pT0-1, 14% vs. 23%; pT2, 32% vs. 32%; pT3, 49% vs. 37%; pT4, 5% vs. 7%; and N0, 74% vs. 86%. Analysis of residual malignant disease in the specimen discriminated mic/mac subgroups (mic: <20% of microscopic cancer residue), with evident superior downstaging effects in the Tegafur-treated group: pTmic 23% vs. 58% (p 0.002). Conclusions: When administered concurrent with pelvic irradiation, oral Tegafur induced downstaging rates in both T and N categories superior to those induced by intermediate doses of 5-FU by continuous i.v. infusion. In this pilot experience, oral Tegafur reproduced the characteristics of downstaging described previously when full doses of 5-FU have been combined with radiotherapy

  20. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m2) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%

  1. Concurrent Chemotherapy for Cervical Cancer Patients Primarily Treated with Radiotherapy: Is It Necessary for All?

    Ji-Hong Hong

    2006-12-01

    Full Text Available Concurrent cisplatin-based chemotherapy has been strongly recommended in womenwith cervical cancer requiring radiotherapy (RT. However, our studies have shown a subsetof patients can achieve good treatment outcome by RT alone and the benefit of treating themwith concurrent chemoradiation (CCRT is questionable. On the other hand, patients withpositive lymph node, squamous cell carcinoma antigen (SCC-ag level > 10 or stage III/IVAdisease have a higher risk of distant metastasis and weekly single-agent cis-platinum mightbe ineffective in reducing systemic relapse. This review will present our rationales and suggestionsfor the selection of cervical cancer patients who should receive different forms ofCCRT or RT alone. We believe the intensity of CCRT for cervical cancer should varybetween patients based on their individual risk for local and distant relapse.

  2. Concurrent capecitabine and upper abdominal radiation therapy is well tolerated

    Delclos Marc E

    2006-10-01

    Full Text Available Abstract We retrospectively evaluated acute toxicity in 88 patients that were treated with capecitabine and concurrent radiotherapy to the upper abdomen. These patients included 28 (32% with pancreatic adenocarcinoma, 18 (20% with cholangiocarcinoma, 11 (13% with ampullary carcinoma, 11 (13% with other primary tumors, 14 (16% with liver metastases, and 6 (7% with metastases at other sites. The median dose of radiotherapy was 45 Gy (range 30–72 Gy. The median dose of capecitabine was 850 mg/m2 twice daily, with 77% receiving 800–900 mg/m2 twice daily. The highest grade of acute toxicity was Common Terminology Criteria (CTC grade 0 in 5 (6%, grade 1 in 60 (68%, grade 2 in 18 (20%, and grade 3 in 5 (6% patients. No patient had CTC grade 4 toxicity. The most common grade 2 toxicities were nausea, hand-foot syndrome, fatigue, anorexia and diarrhea. The grade 3 toxicities included nausea, vomiting and fatigue. Three patients (3% required hospitalization due to grade 3 acute toxicity. Capecitabine was interrupted, discontinued or given at an adjusted dose in 13 (15% patients because of acute toxicity. Therefore, capecitabine and concurrent radiotherapy to the upper abdomen appears to be well tolerated. Capecitabine may serve as an alternative to bolus or infusional 5-FU during chemoradiation for upper gastrointestinal malignancies.

  3. Concurrent capecitabine and upper abdominal radiation therapy is well tolerated

    We retrospectively evaluated acute toxicity in 88 patients that were treated with capecitabine and concurrent radiotherapy to the upper abdomen. These patients included 28 (32%) with pancreatic adenocarcinoma, 18 (20%) with cholangiocarcinoma, 11 (13%) with ampullary carcinoma, 11 (13%) with other primary tumors, 14 (16%) with liver metastases, and 6 (7%) with metastases at other sites. The median dose of radiotherapy was 45 Gy (range 30–72 Gy). The median dose of capecitabine was 850 mg/m2 twice daily, with 77% receiving 800–900 mg/m2 twice daily. The highest grade of acute toxicity was Common Terminology Criteria (CTC) grade 0 in 5 (6%), grade 1 in 60 (68%), grade 2 in 18 (20%), and grade 3 in 5 (6%) patients. No patient had CTC grade 4 toxicity. The most common grade 2 toxicities were nausea, hand-foot syndrome, fatigue, anorexia and diarrhea. The grade 3 toxicities included nausea, vomiting and fatigue. Three patients (3%) required hospitalization due to grade 3 acute toxicity. Capecitabine was interrupted, discontinued or given at an adjusted dose in 13 (15%) patients because of acute toxicity. Therefore, capecitabine and concurrent radiotherapy to the upper abdomen appears to be well tolerated. Capecitabine may serve as an alternative to bolus or infusional 5-FU during chemoradiation for upper gastrointestinal malignancies

  4. Feature conversion for concurrent engineering

    De Kraker, J.K.

    1998-01-01

    Feature conversion for concurrent engineering integrates two modern product development paradigms. Concurrent engineering is a product development paradigm in which multiple engineering disciplines participate. It optimizes a product with respect to available resources and product quality, for which

  5. Domain Theory for Concurrency

    Nygaard, Mikkel

    Concurrent computation can be given an abstract mathematical treatment very similar to that provided for sequential computation by domain theory and denotational semantics of Scott and Strachey. A simple domain theory for concurrency is presented. Based on a categorical model of linear logic and...... nondeterministic dataflow. The domain theory can be generalised to presheaf models, providing a more refined treatment of nondeterministic branching and supporting notions of bisimulation. The operational semantics for HOPLA is guided by the idea that derivations of transitions in the operational semantics should...... correspond to elements of the presheaf denotations. Similar guidelines lead to an operational semantics for the first-order fragment of Affine HOPLA. An extension of the operational semantics to the full language is based on a stable denotational semantics which associates to each computation the minimal...

  6. Semantics of Concurrent Revisions

    Burckhardt, Sebastian; Leijen, Daan

    Enabling applications to execute various tasks in parallel is difficult if those tasks exhibit read and write conflicts. We recently developed a programming model based on concurrent revisions that addresses this challenge in a novel way: each forked task gets a conceptual copy of all the shared state, and state changes are integrated only when tasks are joined, at which time write-write conflicts are deterministically resolved.

  7. Innate immunity and adjuvants.

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  8. CONCURRENT ENGINEERING WITH CONSTRAINT NETWORKS

    Steve Minnaar; Robert Reinecke

    2012-01-01

    Concurrent engineering is a systematic approach to the integrated, concurrent design of products and their related processes, including manufacture and support. It allows the consideration of all elements of the product's life cycle, from conception through disposal, including quality, cost, manufacturing, and customer requirements. Constraint networks as an approach to concurrent engineering provides considerable advantages over the conventional approaches to improve engineering. Constraint ...

  9. A review of concurrent engineering

    Juárez Varón, David; Peydro, M. A.; MENGUAL RECUERDA, ANA; Ferrándiz Bou, Santiago

    2015-01-01

    This paper attempts to explain and disaggregate different focuses of concurrent engineering, analyzing their application to product development and highlighting the improvements involved in their enforcement. Improvements can be observed in projects (quality), in scheduling (reducing the duration) and the cost of implementation (savings), basic achievements of concurrent engineering. Companies that already apply concurrent engineering are often multinationals, being the majority group in use....

  10. Dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer

    Nguyen, Nam P. [Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, VA North Texas Health Care System, Radiation Oncology Service (140), 4500 S, Lancaster Road, Dallas, TX 72516 (United States)]. E-mail: NamPhong.Nguyen@med.va.gov; Moltz, Candace C. [Audiology and Speech Pathology Service (126), VA North Texas Health Care System, Dallas, TX 75216 (United States); Frank, Cheryl [Audiology and Speech Pathology Service (126), VA North Texas Health Care System, Dallas, TX 75216 (United States); Karlsson, Ulf [Department of Radiation Oncology, East Carolina University, Greenville, NC 27858 (United States); Nguyen, Phuc D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center at Dallas, VA North Texas Health Care System, Radiation Oncology Service (140), 4500 S, Lancaster Road, Dallas, TX 72516 (United States); Vos, Paul [Department of Biostatistics, East Carolina University, Greenville, NC 27858 (United States); Smith, Herbert J. [Radiology Service, VA North Texas Health Care System, Dallas, TX 75216 (United States); Dutta, Suresh [Department of Radiation Oncology, University of Southern California, Los Angeles, CA 90033 (United States); Nguyen, Ly M. [Public Health School, University of Michigan, Ann Arbor, MI 48109 (United States); Lemanski, Claire [Department of Radiation Oncology, Val D' Aurelle, Montpellier (France); Chan, Wayne [Radiation Oncology Service, VAMC, Jackson, MS 39216 (United States); Sallah, Sabah [Division of Hematology/Oncology Research, Novo Nordisk, Athens (Greece)

    2006-09-15

    Objective: The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. Materials and methods: We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1-7. Patients were grouped according to the dysphagia severity: mild (grades 2-3), moderate (grades 4-5), and severe (grades 6-7). Results: Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant (p = 0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant (p = 0.29). There was a higher proportion of patients with large tumor (T3-T4) in the chemoradiation group who developed severe dysphagia. Conclusion: Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent.

  11. Dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer

    Objective: The purpose of the study is to evaluate dysphagia severity following chemoradiation and postoperative radiation for head and neck cancer, and particularly the aspiration risk because of its potential life-threatening consequence. Materials and methods: We reviewed retrospectively the modified barium swallow (MBS) results in 110 patients who complained of dysphagia following chemoradiation (57) and postoperative radiation (53) of their head and neck cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1-7. Patients were grouped according to the dysphagia severity: mild (grades 2-3), moderate (grades 4-5), and severe (grades 6-7). Results: Mean and median dysphagia grades were 4.84/5 and 4.12/4 for chemoradiation and postoperative radiation respectively. The mean difference between the two groups is statistically significant (p = 0.02). Mild dysphagia occurred in 13 patients (22%) of the chemoradiation group and 17 (32%) of the postoperative group. Corresponding number for the moderate group was 25 (43%) and 25 (48%), respectively. Severe dysphagia was significant in the chemoradiation group (34%) compared to the postoperative group (19%). However, the difference was not statistically significant (p = 0.29). There was a higher proportion of patients with large tumor (T3-T4) in the chemoradiation group who developed severe dysphagia. Conclusion: Dysphagia remained a significant morbidity of chemoradiation and postoperative radiation for head and neck cancer. Dysphagia may be more severe in the chemoradiation group because of the higher proportion of patients with large tumor, the high radiation dose, and a high number of oropharyngeal tumors. Aspiration occurred in both groups. Diagnostic studies such as MBS should be part of future head and neck cancer prospective studies to assess the prevalence of aspiration, as it may be silent

  12. TROG 97.01 and 99.06 : Two sequential phase II studies of chemoradiation in the management of localised muscle invasive bladder TCC

    Full text: Between January 1997 and Dec 2000, 113 patients with localised muscle invasive bladder TCC were accrued to the two sequential multi institutional studies { carried out under the auspices of the Trans- Tasman Radiation Oncology Group } investigating the use of concurrent weekly Cisplatin and Radical External Beam Radiation in the definitive management of there disease. The second study TROG 99.06 ) had some modifications made to the Chemotherapy and Radiation Schedules based on the experience with first trial (TROG 97.01). Results from these studies compare favourably with those reported from other Phase II studies of Chemo-radiation reported from other centres around the world. Detailed analysis will be presented at the meeting

  13. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    Jeong, J; Deasy, J O [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  14. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation

  15. [Symptomatic and concurrent depressions].

    Terra, J L

    1999-04-01

    The symptomatic and concurrent depressions description need to resort to comorbidity and symptomatic co-occurrence concepts. Patients with depressive symptoms or in a major depressive episode may also be suffering from another nonmood psychiatric disorders as alcoholism, anxiety or eating disorders. Many general medical conditions which are link with depression are illustrated with the examples of cancer, coronary artery disease, endocrinologic diseases, dementia, stroke and chronic fatigue syndrome. When depression and another psychiatric or medical conditions occur together, it is important to provide to the practitioner guidelines for the decision to treat one of the two disorders. This paper contains an example of decisional algorithm. PMID:10337217

  16. Mastering concurrency in Go

    Kozyra, Nathan

    2014-01-01

    A practical approach covering everything you need to know to get up and running with Go, starting with the basics and imparting increasingly more detail as the examples and topics become more complicated. The book utilizes a casual, conversational style, rife with actual code and historical anecdotes for perspective, as well as usable and extensible example applications. This book is intended for systems developers and programmers with some experience in either Go and/or concurrent programming who wish to become fluent in building high-performance applications that scale by leveraging single-c

  17. Role of Adjuvant Radiotherapy in Granulosa Cell Tumors of the Ovary

    Purpose: To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. Methods and Materials: The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. Results: A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p = .02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p = .004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Conclusion: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.

  18. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

    2015-10-01

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

  19. Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

    Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered

  20. Adjuvant chemotherapy and cancer cure

    The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

  1. Chemo-radiation with or without mandatory split in anal carcinoma: experiences of two institutions and review of the literature

    The split-course schedule of chemo-radiation for anal cancer is controversial. Eighty-four patients with invasive anal cancer treated with definitive external beam radiotherapy (RT) with a mandatory split of 12 days (52 patients, Montreal, Canada) or without an intended split (32 patients, Zurich, Switzerland) were reviewed. Total RT doses were 52 Gy (Montreal) or 59.4 Gy (Zurich) given concurrently with 5-FU/MMC. After a mean follow-up of 40 ± 27 months, overall survival and local tumor control at 5 years were 57% and 78% (Zurich) compared to 67% and 82% (Montreal), respectively. Split duration of patients with or without local relapse was 15 ± 7 d vs. 14 ± 7 d (Montreal, NS) and 11 ± 11 d vs. 5 ± 7 d (Zurich; P < 0.001). Patients from Zurich with prolonged treatment interruption (≥ 7 d) had impaired cancer-specific survival compared with patients with only minor interruption (<7 d) (P = 0.06). Bowel toxicity was associated with prolonged RT (P = 0.03) duration as well as increased relapse probability (P = 0.05). Skin toxicity correlated with institution and was found in 79% (Montreal) and 28% (Zurich) (P < 0.0001). The study design did not allow demonstrating a clear difference in efficacy between the treatment regimens with or without short mandatory split. Cause-specific outcome appears to be impaired by unplanned prolonged interruption

  2. Usefulness of concurrent chemotherapy and radiotherapy of head and neck cancer

    The usefulness of concurrent chemotherapy and radiotherapy in head and neck cancer was reviewed based on the results of randomized comparative trials. First, the schedules of chemotherapy and radiotherapy were assessed. Chemotherapy was classified into 4 categories according to the schedules: neo-adjuvant chemotherapy, concurrent chemotherapy, alternating chemotherapy, and adjuvant chemotherapy. Each schedules has its own purpose, e.g., tumor reduction, prevention of remote metastasis, and radiosensitizing effect. The most important purpose is the improvement of long-term outcome. Meta-analysis by Munro showed that the survival rate after neo-adjuvant chemotherapy was a mere 3.7%, as opposed to 12.1% for concurrent chemotherapy. Second, the results of 10 randomized comparative trials in the literature were reviewed. The radiation doses were 40-70 Gy. BLM, MTX, 5-FU, and MMC were administered in 7 trials, and 2 drugs, 5-FU and CDDP, and 5-FU and MMC, were combined in 3 trials. A statistically significant improvement in long-term outcome was only found in one study. In 7 studies it was reported that improvement of results is prospective, but further examination is necessary. Augmentation of the acute radiation effects by concurrent chemotherapy has been reported in many studies. A more adequate randomized comparative study should be carried out based on these findings. (K.H.)

  3. Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

    Palma, David A., E-mail: david.palma@uwo.ca [Department of Radiation Oncology, London Regional Cancer Program, London (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Tsujino, Kayoko [Department of Radiation Oncology, Hyogo Cancer Center, Hyogo (Japan); Barriger, Robert B. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Moreno, Marta [Department of Oncology, Radiation Oncology Division, Clinica Universidad de Navarra, University of Navarra, Pamplona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Kim, Tae Hyun [Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi (Korea, Republic of); Ramella, Sara [Radiotherapy Unit, Campus Bio-Medico University, Rome (Italy); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); De Petris, Luigi [Department of Oncology, Radiumhemmet, Karolinska University Hospital Solna, Stockholm (Sweden); Stitt, Larry [Department of Epidemiology and Biostatistics, University of Western Ontario, London (Canada); Rodrigues, George [Department of Radiation Oncology, London Regional Cancer Program, London (Canada); Department of Epidemiology and Biostatistics, University of Western Ontario, London (Canada)

    2013-02-01

    Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade {>=}2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving {>=}20 Gy (V{sub 20}) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V{sub 20}, and lower-lobe tumor location. Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

  4. Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

    Background: Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods and Materials: After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results: The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V20) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V20, and lower-lobe tumor location. Conclusions: Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

  5. Muramyl dipeptide-induced adjuvant arthritis.

    Nagao, S.; Tanaka, A.

    1980-01-01

    Muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine, induced adjuvant arthritis in WKA rats when injected in a water-in-oil emulsion prepared with Freund incomplete adjuvant (Difco), but not when emulsified with Drackeol and Arlacel A.

  6. Concurrent Chemoradiotherapy in Locally Advanced Esophageal Cancer

    This study was designed to evaluate the results of local control, survival rate, prognostic factors, and failure pattern in locally advanced esophageal cancer. We retrospectively studied 50 patients with locally advanced esophageal cancer treated with concurrent chemoradiotherapy at Keimyung University Dongsan Medical Center from June of 1999 to August of 2008. Seven patients with inappropriate data were excluded, and 43 patients were analyzed. There were 39 males and four female patients ranging in age from 43 to 78 years (median, 63 years). There were seven patients with stage IIA and 36 with stage III. Irradiation from 46 Gy to 63 Gy (median, 54 Gy) was carried out 5 days per week, 1.8 Gy once a day. There were eight patients with neo-adjuvant chemotherapy, and we mostly used 5-fluorouracil, cisplatin with 3 cycles for concurrent chemotherapy. The range of follow up periods was from 2 to 82 months (median, 15.5). There were nine patients that exhibited a complete response, 23 that exhibited a partial response, 9 that exhibited no response, and 2 that exhibited disease progression. The median survival time was 15 months. Two-year and 5-year survival rates were 36.5% and 17.3%, respectively. Two-year and 5-year disease-free survival rates were 32.4% and 16%, respectively. Treatment failure occurred in 22 patients (51.2%). Patterns of failure were categorized as local failure in 18 patients and distant metastasis in four patients. In a univariate analysis for prognostic factors related to overall survival and disease-free survival, the hemoglobin levels during chemoradiotherapy (≥12 vs. <12, p=0.02/p=0.1) and the response to the treatments (CR/PR vs. NR/PD, p=0.002/p <0.0001) were statistically significant. In a multivariate analysis, only response to the treatments was revealed to be statistically significant. There was no statistical significance associated with patient age, gender, disease stage, T-stage, smoking history, tumor location, or neo-adjuvant

  7. Concurrent engineering: effective deployment strategies

    Unny Menon; Michael Graham

    1996-01-01

    This paper provides a comprehensive insight into current trends and developments in Concurrent Engineering for integrated development of products and processes with the goal of completing the entire cycle in a shorter time, at lower overall cost and with fewer engineering design changes after product release. The evolution and definition of Concurrent Engineering are addressed first, followed by a concise review of the following elements of the concurrent engineering approach to product devel...

  8. Quantify entanglement by concurrence hierarchy

    Fan, Heng; Matsumoto, Keiji; Imai, Hiroshi

    2002-01-01

    We define the concurrence hierarchy as d-1 independent invariants under local unitary transformations in d-level quantum system. The first one is the original concurrence defined by Wootters et al in 2-level quantum system and generalized to d-level pure quantum states case. We propose to use this concurrence hierarchy as measurement of entanglement. This measurement does not increase under local quantum operations and classical communication.

  9. Concurrent engineering research center

    Callahan, John R.

    1995-01-01

    The projects undertaken by The Concurrent Engineering Research Center (CERC) at West Virginia University are reported and summarized. CERC's participation in the Department of Defense's Defense Advanced Research Project relating to technology needed to improve the product development process is described, particularly in the area of advanced weapon systems. The efforts committed to improving collaboration among the diverse and distributed health care providers are reported, along with the research activities for NASA in Independent Software Verification and Validation. CERC also takes part in the electronic respirator certification initiated by The National Institute for Occupational Safety and Health, as well as in the efforts to find a solution to the problem of producing environment-friendly end-products for product developers worldwide. The 3M Fiber Metal Matrix Composite Model Factory Program is discussed. CERC technologies, facilities,and personnel-related issues are described, along with its library and technical services and recent publications.

  10. A Review and Prospect on Herbicide Adjuvants

    2005-01-01

    The history, present status and future prospects of adjuvants application in herbicides were briefly reviewed. Adjuvants can be separated into two groups, activator adjuvants and utility adjuvants. The former directly enhances the efficacy of a herbicide through increasement of herbicide absorption, spreading, cuticular penetration, rainfastness and retention enhancement, and photodegradation of the herbicide can also be decreased. And the latter is utilized for improving application characteristics, behaviors and physical properties of herbicides and reducing or minimizing unwanted side effects on application.

  11. Economic explanations for concurrent sourcing

    Mols, Niels Peter

    2010-01-01

    Concurrent sourcing is a phenomenon where firms simultaneously make and buy the same good, i.e. they simultaneously use the governance modes of market and hierarchy. Though concurrent sourcing seems to be widespread, few studies of sourcing have focused on this phenomenon. This paper reviews diff...... different economic explanations for why firms use concurrent sourcing. The distinctive features of the explanations are compared, and it is discussed how they may serve as a springboard for research on concurrent sourcing. Managerial implications are also offered....

  12. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil; Han, Kwang Hyub; Kim, Soon Il

    2016-09-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  13. Preliminary results of chemoradiation as a primary treatment for vulvar carcinoma

    Purpose: To assess the role of chemoradiation as a primary treatment for vulvar carcinoma. Methods and Materials: Between December 1989 and August 1997, there were 14 patients with the diagnosis of squamous cell carcinoma of the vulva. Two patients were excluded from this study because of advanced stage at presentation. Key information about the remaining 12 patients was extracted from their charts. All patients had biopsy prior to treatment, and were treated with chemoradiation. Radiation was administered to the vulva only. Surgical biopsies from the vulva and inguinal nodal dissection were done 4-6 weeks after radiation treatment. All patients were followed for evaluation of response and clinical detection of recurrence. The period of follow-up ranged from 8 to 125 months. Mean follow-up period was 41 months. Results: All 12 patients showed complete response to the treatment. Only 1 patient (8.3%) developed local recurrence at 3 months posttreatment. Another patient (8.3%) developed nodal recurrence at 30 months posttreatment. Both patients were salvaged by surgical treatment and remained disease free. The actuarial 5-year disease-free survival was 43%. The actuarial 3-year disease-free survival was 84%. The majority of patients developed mild-to-moderate complications due to chemoradiation. These were well tolerated and responded to medical treatment. None of the patients developed late complications to chemoradiation treatment. Conclusions: Chemoradiation is an effective primary treatment for vulvar carcinoma as shown by these successfully managed cases

  14. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

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

  15. Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group

    Purpose: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T3 primary tumors, or the need for pelvic exenteration for patients with T4 primary tumors, not amenable to resection by standard radical vulvectomy. Methods and Materials: Seventy-three evaluable patients with clinical Stage III-IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal-femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior-posterior-anterior (AP-PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal-femoral and lower pelvic lymph nodes. Results: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and

  16. Chemoradiation in patients with isolated recurrent pancreatic cancer - therapeutical efficacy and probability of re-resection

    In the present retrospective analysis we analysed the therapeutic outcome of a set of patients, who were treated with chemoradiation (CRT) for recurrent pancreatic cancer (RPC) in a single institution. Forty-one patients had a history of primary resection for pancreatic cancer. In case of an unresectable recurrency patients were treated with CRT at our institution between 2002 and 2010 with a median dose of 48.4 Gy (range 39.6–54 Gy). Concurrent chemotherapy regimes included Gemcitabine (GEM) in 37/41 patients (90%) and Fluorouracil (FU) or Capecitabine (CAP) in 4/41 patients (10%). Patients were re-evaluated after CRT with computed tomography and/or explorative laparotomy. During re-resection or laparotomy 15 patients received an additional intraoperative radiotherapy (IORT) with a median dose of 15 Gy (range 12–15 Gy). Median age was 65 years (range 39–76 years) and there were 26 male and 15 female patients. The median overall survival (mOS), local control (LC) and progression-free survival (PFS) were 16.1, 13.8 and 6.9 months respectively for all patients after the first day of CRT. Re-resection was possible in five patients (12%) and a complete remission (CR) as defined by tumor-free biopsy was seen in 6 patients (15%). When re-resection could be achieved after CRT mOS was improved to 28.3 months (n = 5 patients, 95%-CI 10.2 – 46.3 months). Patients receiving IORT had a significantly improved mOS compared to no IORT (p = 0.034). Fifteen patients (37%) experienced a local tumour progression and main site of distant metastasis was the liver (11 patients, 27%).Overall treatment-related toxicity was mild, grade III hematologic toxicity was observed in 11 patients (27%). In summary we observed a good therapeutic response with mild to moderate toxicity levels for CRT in RPC. Overall survival and PFS were clearly improved in case of induction of a complete remission (tumor-free biopsies) or after achieving a re-resection, thus providing a curative intended

  17. Concurrent Product & Supply Chain Creation

    Gubi, Ebbe

    that product and supply chains should be created concurrently and integrated. The concept of Concurrent Product & Supply Chain Creation is introduced, and the two main components Focused Supply Chains and Design For Logistics are explained and exemplified by use of Bang & Olufsen....

  18. Feature conversion for concurrent engineering

    Kraker, J.K. de

    1998-01-01

    Feature conversion for concurrent engineering integrates two modern product development paradigms. Concurrent engineering is a product development paradigm in which multiple engineering disciplines participate. It optimizes a product with respect to available resources and product quality, for which it requires to communicate between the different engineering disciplines. Feature conversion is a feature modeling technique. The feature modeling paradigm combines geometric and functional produc...

  19. A Lower Bound on Concurrence

    LIU Li-Guo; TIAN Cheng-Lin; CHEN Ping-Xing; YUAN Nai-Chang

    2009-01-01

    We derive an analytical lower bound on the concurrence for bipartite quantum systems with an improved computable cross norm or realignment criterion and an improved positive partial transpose criterion respectively.Furthermore we demonstrate that our bound is better than that obtained from the local uncertainty relations criterion with optimal local orthogonal observables which is known as one of the best estimations of concurrence.

  20. CRDTs: Consistency without concurrency control

    Letia, Mihai; Shapiro, Marc

    2009-01-01

    A CRDT is a data type whose operations commute when they are concurrent. Replicas of a CRDT eventually converge without any complex concurrency control. As an existence proof, we exhibit a non-trivial CRDT: a shared edit buffer called Treedoc. We outline the design, implementation and performance of Treedoc. We discuss how the CRDT concept can be generalised, and its limitations.

  1. Impact of Adjuvant Therapy on Survival in Curatively Resected Gallbladder Carcinoma

    Asthana, Anupam Kumar

    2015-01-01

    Background Gallbladder carcinoma (GBC) has the propensity to fail at loco-regional (LR) and distant sites despite aggressive radical surgery. Adjuvant therapy in the form of radiotherapy (RT), systemic chemotherapy (CT) and chemoradiation (CRT) is the usual practice. Due to rarity of this disease, there is limited evidence to suggest the type of adjuvant treatment which should be offered to the patients. Aim The study was conducted to evaluate the impact of adjuvant treatment on curatively resected GBC patients. Settings and Design Histological proven patients of GBC registered between June, 2008 and July, 2014 were identified from our hospital database and retrospective analysis was done. Materials and Methods Patients of GBC who had curative resection followed by adjuvant treatment as RT alone, CT alone or CRT were included in the study. Statistical Analysis Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) and disease free survival (DFS) were evaluated using Cox Regression Method and Kaplan Meier plot. Results We identified 33 patients of which 23 were Stage I or II disease (Early disease) and the remaining 10 were Stage III or IV disease (Advanced disease). All except one patient had adenocarcinoma. A total of 5 patients were treated with RT alone while 16 patients received CT alone. The remaining 12 patients were treated with CRT. Median follow-up period was 8.5 months. At analysis 4 were alive while the remaining 29 were dead due to disease. With regard to “Early disease” patients who had RT alone, CT alone and CRT, the median OS was 22.3, 10.3 and 15.2 months respectively (p = .440). Cohort of patients with “Advanced disease” who were treated with CT alone and CRT the median OS was 7.5 and 7.0 months respectively (p = .643). On multivariate analysis none of the prognostic factors had an adverse impact on survival. Conclusion The impact of adjuvant treatment in the form of RT, CT or CRT after curative resection

  2. Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

    Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities

  3. Adjuvant and anti-inflammatory properties of cigarette smoke in murine allergic airway inflammation.

    Trimble, Nancy J; Botelho, Fernando M; Bauer, Carla M T; Fattouh, Ramzi; Stämpfli, Martin R

    2009-01-01

    The impact of cigarette smoke on allergic asthma remains controversial both clinically and experimentally. The objective of this study was to investigate, in a murine model, how cigarette smoke affects immune inflammatory processes elicited by a surrogate allergen. In our experimental design, mice were concurrently exposed to cigarette smoke and ovalbumin (OVA), an innocuous antigen that, unless introduced in the context of an adjuvant, induces inhalation tolerance. We show that cigarette smoke exposure has adjuvant properties, allowing for allergic mucosal sensitization to OVA. Specifically, concurrent exposure to cigarette smoke and OVA for 2 weeks led to airway eosinophilia and goblet cell hyperplasia. In vivo OVA recall challenge 1 month after the last smoke exposure showed that concurrent exposure to OVA and cigarette smoke induced antigen-specific memory. Robust eosinophilia and OVA-specific IgG1 and IgE characterized the ensuing inflammatory response. Mechanistically, allergic sensitization was, in part, granulocyte macrophage colony-stimulating factor (GM-CSF) dependent, as a significant reduction in BAL eosinophilia was observed in mice treated with an anti-GM-CSF antibody. Of note, continuous smoke exposure attenuated the OVA recall response; decreased airway eosinophilia was observed in mice continuously exposed to cigarette smoke compared with mice that ceased the smoke exposure protocol. In conclusion, we demonstrate experimentally that while cigarette smoke acts as an adjuvant allowing for allergic sensitization, it also attenuates the ensuing eosinophilic inflammatory response. PMID:18635815

  4. Short–term effects of neoadjuvant chemoradiation therapy on anorectal function in rectal cancer patients: a pilot study

    Neoadjuvant chemoradiation therapy followed by curative surgery has gained acceptance as the therapy of choice in locally advanced rectal cancer. However, deterioration of anorectal function after long-course neoadjuvant chemoradiation therapy combined with surgery for rectal cancer is poorly defined. The aim of this study was to evaluate the physiological and clinical change of anorectal function after neoadjuvant chemoradiation therapy for rectal cancer. We analyzed 30 patients on whom preoperative anorectal manometry data were available both before and after chemoradiation from October 2010 to September 2011. All patients underwent long-course neoadjuvant chemoradiation therapy. We compared manometric parameters between before and after neoadjuvant chemoradiation therapy. Of 30 patients, 20 were males and 10 females. The mean age was 64.9 ± 9.9 years (range, 48-82). Before nCRT, the rectal compliance was higher in patients with ulceroinfiltrative type (P = 0.035) and greater involvement of luminal circumference (P = 0.017). However, there was the tendency of increased rectal sensory threshold for desire to defecate when the patient had decreased circumferential ratio of the tumor (P = 0.099), down-graded T stage (P = 0.016), or reduced tumor volume (P = 0.063) after neoadjuvant chemoradiation. Neoadjuvant chemoradiation therapy did not significantly impair overall sphincter function before radical operation. The relationship between tumor response of chemoradiation and sensory threshold for desire to defecate may suggest that neoadjuvant chemoradiation may be helpful for defecatory function as well as local disease control, at least in the short-term period after the radiation in locally advanced rectal cancer patients

  5. Improving vaccine delivery using novel adjuvant systems.

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  6. VLSI architecture for concurrent data structures

    Concurrent data structures simplify the development of concurrent programs by encapsulating commonly used mechanisms for synchronization and communication into data structures. This thesis develops a notation for describing concurrent data structures, presents examples of concurrent data structures, and describes an architecture to support concurrent data structures. Concurrent Smalltalk (CST), a derivative of Smalltalk-80 with extensions for concurrency, is developed to describe concurrent data structures. CST allows the programmer to specify objects that are distributed over the nodes of a concurrent computer. These distributed objects have many constituent objects and thus can process many messages simultaneously. They are the foundation upon which concurrent data structures are built. Considering graphs as concurrent data structures, graph algorithms are presented for the shortest-path problem, the max-flow problem, and graph partitioning. These algorithms introduce new synchronization techniques to achieve better performance than existing algorithms. A message passing, concurrent architecture is developed that exploits the characteristics of VLSI technology to support concurrent data structures

  7. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Kwak, Yoo Kang; Lee, Jong Hoon; Lee, Myung Ah; Chun, Hoo Geun; Kim, Dong Goo; You, Young Kyoung; Hong, Tae Ho; Jang, Hong Seok [Seoul St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-15

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  8. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Survival outcome of locally advanced pancreatic cancer has been poor and little is known about prognostic factors of the disease, especially in locally advanced cases treated with concurrent chemoradiation. This study was to analyze overall survival and prognostic factors of patients treated with concurrent chemoradiotherapy (CCRT) in locally advanced pancreatic cancer. Medical records of 34 patients diagnosed with unresectable pancreatic cancer and treated with definitive CCRT, from December 2003 to December 2012, were reviewed. Median prescribed radiation dose was 50.4 Gy (range, 41.4 to 55.8 Gy), once daily, five times per week, 1.8 to 3 Gy per fraction. With a mean follow-up of 10 months (range, 0 to 49 months), median overall survival was 9 months. The 1- and 2-year survival rates were 40% and 10%, respectively. Median and mean time to progression were 5 and 7 months, respectively. Prognostic parameters related to overall survival were post-CCRT CA19-9 (p = 0.02), the Eastern Cooperative Oncology Group (ECOG) status (p < 0.01), and radiation dose (p = 0.04) according to univariate analysis. In multivariate analysis, post-CCRT CA19-9 value below 180 U/mL and ECOG status 0 or 1 were statistically significant independent prognostic factors associated with improved overall survival (p < 0.01 and p = 0.02, respectively). Overall treatment results in locally advanced pancreatic cancer are relatively poor and few improvements have been accomplished in the past decades. Post-treatment CA19-9 below 180 U/mL and ECOG performance status 0 and 1 were significantly associated with an improved overall survival.

  9. Concurrent Testicular and Bladder Cancer in a 57-year-old Man.

    Han, Esther; Stein, Daniel M; Shi, Dongping; Miocinovic, Ranko

    2015-09-01

    We present a rare finding of concurrent right testis non-seminomatous mixed germ cell tumor and muscle invasive urothelial carcinoma of the bladder in a 57-year-old homeless man. The socioeconomic factors and the disease presentation caused a treatment dilemma in terms of the appropriate type of neoadjuvant chemotherapy. The patient ultimately underwent upfront surgery with retroperitoneal lymph node dissection and radical cystoprostatectomy followed by adjuvant cisplatin-based chemotherapy. PMID:26793541

  10. Concurrent Testicular and Bladder Cancer in a 57-year-old Man

    Esther Han

    2015-09-01

    Full Text Available We present a rare finding of concurrent right testis non-seminomatous mixed germ cell tumor and muscle invasive urothelial carcinoma of the bladder in a 57-year-old homeless man. The socioeconomic factors and the disease presentation caused a treatment dilemma in terms of the appropriate type of neoadjuvant chemotherapy. The patient ultimately underwent upfront surgery with retroperitoneal lymph node dissection and radical cystoprostatectomy followed by adjuvant cisplatin-based chemotherapy.

  11. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer.

    Ferrari, Linda; Fichera, Alessandro

    2015-11-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15-27% patients with a pathological complete response (pCR)-defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5-6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  12. Quantify entanglement by concurrence hierarchy

    We define the concurrence hierarchy as d - 1 independent invariants under local unitary transformations in d-level quantum system. The first one is the original concurrence defined by Wootters (1998 Phys. Rev. Lett. 80 2245) and Hill and Wootters (1997 Phys. Rev. Lett. 78 5022) in a two-level quantum system and generalized to the d-level pure quantum state case. We propose to use this concurrence hierarchy as a measurement of entanglement. This measurement does not increase under local quantum operations and classical communication

  13. New methods of concurrent checking

    Goessel, Michael; Sogomonyan, Egor; Marienfeld, Daniel

    2008-01-01

    Written by a team of two leading experts and two very successful young former PhD students, New Methods of Concurrent Checking describes new methods of concurrent checking, such as partial duplication, use of output dependencies, complementary circuits, self-dual parity, self-dual duplication and others. A special chapter demonstrates how the new general methods of concurrent checking can be more specifically applied to regular structures to obtain optimum results. This is exemplified for all types of adders up to 64 bits with a level of detail never before presented in the literature. The cle

  14. Clinically Meaningful Differences in Patient-Reported Outcomes With Amifostine in Combination With Chemoradiation for Locally Advanced Non-Small-Cell Lung Cancer: An Analysis of RTOG 9801

    Purpose: The purpose of this study is to analyze changes in quality of life (QOL) and symptoms from pretreatment to 6 weeks posttreatment in a Phase III randomized study (Radiation Therapy Oncology Group 9801) of amifostine (AM) vs. no AM in patients with Stages II-III non-small-cell lung cancer receiving paclitaxel and carboplatin as induction and then concurrently with hyperfractionated radiation therapy (RT). Methods and Materials: One hundred thirty-eight patients with baseline and 6-week posttreatment QOL data were analyzed. There were no significant differences in baseline demographics between those who did and did not have QOL data. The QOL and symptoms were assessed by using the European Organization for Research and Treatment of Cancer (EORTC) Global QOL and Pain subscales and the EORTC-Lung Cancer-13 symptom tool. Clinically relevant changes in QOL were characterized by 10-point differences in individual scores pre/post treatment. A daily diary of patient-rated difficulty swallowing and a weekly physician-rated dysphagia log (using National Cancer Institute Common Toxicity Criteria) were completed during treatment. Weight loss was monitored. Differences in outcomes were examined according to smoking status, alcohol use, and sex. Results: Patients receiving AM reported significantly greater pain reduction after chemoradiation (34% vs. no AM, 21%), less difficulty swallowing during chemoradiation, and less weight loss than patients not receiving AM. However, physician-rated assessments of dysphagia were not significantly different by treatment arm. There were no other significant changes in QOL or symptoms according to treatment arm, smoking status, alcohol use, or sex. Conclusions: Patient evaluations of difficulty swallowing and pain suggest benefits from AM use that are distinct from clinician-rated assessments

  15. Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

    Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved

  16. Phase 2 Trial of Induction Gemcitabine, Oxaliplatin, and Cetuximab Followed by Selective Capecitabine-Based Chemoradiation in Patients With Borderline Resectable or Unresectable Locally Advanced Pancreatic Cancer

    Esnaola, Nestor F. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Chaudhary, Uzair B.; O' Brien, Paul [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Garrett-Mayer, Elizabeth [Division of Biostatistics and Epidemiology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Camp, E. Ramsay [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Thomas, Melanie B. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Cole, David J. [Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Montero, Alberto J. [Division of Hematology and Oncology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Hoffman, Brenda J.; Romagnuolo, Joseph [Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Orwat, Kelly P. [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States); Marshall, David T., E-mail: marshadt@musc.edu [Department of Radiation Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina (United States)

    2014-03-15

    Purpose: To evaluate, in a phase 2 study, the safety and efficacy of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer (BRPC or LAPC, respectively). Methods and Materials: Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles, combined with weekly cetuximab. Patients were then restaged; “downstaged” patients with resectable disease underwent attempted resection. Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy (54 Gy) and concurrent capecitabine; patients with borderline resectable disease or better at restaging underwent attempted resection. Results: A total of 39 patients were enrolled, of whom 37 were evaluable. Protocol treatment was generally well tolerated. Median follow-up for all patients was 11.9 months. Overall, 29.7% of patients underwent R0 surgical resection (69.2% of patients with BRPC; 8.3% of patients with LAPC). Overall 6-month progression-free survival (PFS) was 62%, and median PFS was 10.4 months. Median overall survival (OS) was 11.8 months. In patients with LAPC, median OS was 9.3 months; in patients with BRPC, median OS was 24.1 months. In the group of patients who underwent R0 resection (all of which were R0 resections), median survival had not yet been reached at the time of analysis. Conclusions: This regimen was well tolerated in patients with BRPC or LAPC, and almost one-third of patients underwent R0 resection. Although OS for the entire cohort was comparable to that in historical controls, PFS and OS in patients with BRPC and/or who underwent R0 resection was markedly improved.

  17. A CAD MODEL FOR FUZZY CONCURRENT TOLERANCE

    2000-01-01

    Research situation of concurrent tolerance design has been analyzed. As fuzzy factors are objective and unavoidable in concurrent tolerance design, fuzzy optimization theory is applied in the design. A new mathematical model of concurrent tolerance design is constructed.

  18. Clinical outcome of patients with primary gliosarcoma treated with concomitant and adjuvant temozolomide: A single institutional analysis of 27 cases

    G K Rath

    2015-01-01

    Full Text Available CONTEXT AND AIM: The prognosis of primary gliosarcoma (PGS remains dismal with current treatment modalities. We analyzed the outcome of PGS patients treated with concurrent and adjuvant temozolomide (TMZ. SETTINGS AND DESIGN: Retrospective single institutional analysis. MATERIALS AND METHODS: We retrospectively evaluated 27 patients of PGS treated with radiotherapy (RT and TMZ during 2007-2012. STATISTICAL ANALYSIS USED: Overall survival (OS was estimated by the use of Kaplan Meier method and toxicities were evaluate using common terminology criteria for adverse events version 2.0 (National Cancer Institute, USA. RESULTS: Median age at presentation and Karnofsky performance status was 45 years and 90 respectively and male: female ratio was 20:7. Patients received adjuvant RT to a total dose of 60 Gy at 2 Gy/fraction. All patients except 5 received adjuvant TMZ to a median number of 6 cycles. Grade 2 and 3 hematological toxicity was seen in 8% and 4% of patients respectively during concurrent RT. During adjuvant chemotherapy, 13.6% had Grade 3 thrombocytopenia and 9.5% had Grade 3 neutropenia. Median OS was 16.7 months (1 year and 2 year actuarial OS was 70.8% and 32.6% respectively. Adjuvant TMZ was associated with a better survival (median survival 21.21 vs. 11.93 months; P = 0.0046 on univariate analysis and also on multivariate analysis (hazard ratio 1.82, 95% confidence interval: 1.503-25.58; P = 0.012. CONCLUSIONS: The results of our study, largest series of patients with PGS treated with concurrent and adjuvant TMZ shows an impressive survival with acceptable toxicity. We suggest TMZ be included in the “standard of care” for this tumor.

  19. Concurrent Model Transformations with Linda

    Burgueño, Loli; Troya, Javier; Vallecillo, Antonio

    2013-01-01

    Nowadays, model transformations languages and engines use a sequential execution model. This is, only one execution thread deals with the whole transformation. However, model transformations dealing with very large models, such as those used in biology or aerospace applications, require concurrent solutions in order to speed up their performance. In this ongoing work we explore the use of Linda for implementing a set of basic mechanisms to enable concurrent model transformations, and prese...

  20. Concurrent engineering: effective deployment strategies

    Unny Menon

    1996-12-01

    Full Text Available This paper provides a comprehensive insight into current trends and developments in Concurrent Engineering for integrated development of products and processes with the goal of completing the entire cycle in a shorter time, at lower overall cost and with fewer engineering design changes after product release. The evolution and definition of Concurrent Engineering are addressed first, followed by a concise review of the following elements of the concurrent engineering approach to product development: Concept Development: The Front-End Process, identifying Customer Needs and Quality Function Deployment, Establishing Product Specifications, Concept Selection, Product Architecture, Design for Manufacturing, Effective Rapid Prototyping, and The Economics of Product Development. An outline of a computer-based tutorial developed by the authors and other graduate students funded by NASA ( accessible via the world-wide-web . is provided in this paper. A brief discussion of teamwork for successful concurrent engineering is included, t'ase histories of concurrent engineering implementation at North American and European companies are outlined with references to textbooks authored by Professor Menon and other writers. A comprehensive bibliography on concurrent engineering is included in the paper.

  1. Are we justified for concomitant chemo-radiation in advanced stage cancer cervix?

    the survival rates have achieved a plateau of 30-45% at five years. Over the last decade there have been studies on the use of chemo-radiotherapy in carcinoma cervix. Over 19 randomized trials have been published addressing the issue of chemo-radiotherapy. However, heterogeneous data, poor randomization, inadequate number of patients, sub-optimal radiotherapy, non-uniform use of chemotherapeutic drugs, its sequencing and poor documentation have not yet provided the evidence to substantially alter the practice. The Cochrane and Canadian meta-analyses have to a large extent tried to address the role of concomitant chemo-radiation, but carcinoma cervix stage III accounted for only 30?35%. Moreover, evaluation with optimal radiation schedules and comparison of late toxicities still remain unanswered. What is more important is that the cisplatin is relatively inexpensive and is available worldwide. This means that cisplatin-based chemo-radiation is affordable in the developing countries where carcinoma cervix still forms the major cancer. However, the role of chemo-radiation in carcinoma cervix stage IIIB in developing countries including India still remains unexplored. With an aim to evaluate the role and benefit of chemo-radiation in- patients with cervical cancer we proposed this randomized study

  2. Systemic adjuvant therapies in renal cell carcinoma

    Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...

  3. Cetuximab and chemoradiation for rectal cancer - is the water getting muddy?

    Glynne-Jones, Rob; Mawdsley, Suzy; Harrison, Mark (Mount Vernon Cancer Centre, Northwood, Middlesex (United Kingdom)), E-mail: Rob.glynnejones@nhs.net

    2010-04-15

    The epidermal growth factor receptor (EGFR) inhibitor cetuximab has been successfully combined with radical radiotherapy in head and neck cancer. In colorectal cancer, increased response rates are achieved by cetuximab and panitumumab within standard chemotherapy schedules, but not in chemoradiation regimens. This review examines the clinical evidence and potential mechanisms for an interaction when EGFR inhibitors are added to fluoropyrimidine-based chemoradiation in rectal adenocarcinoma. Methods. This review was compiled by searching PubMed and Medline for English language articles published until 2009 with established search strategies, supplemented by hand searching of abstracts from the proceedings of relevant international meetings. The primary outcome measure was pathological complete response (pCR). Results. Only 13 publications and three presentations in abstract of 13 phase I/II trials of preoperative chemoradiation with cetuximab in rectal cancer were identified. A total of 316 patients were identified who received cetuximab in combination with radiotherapy and 5-fluorouracil or capecitabine preoperatively. One hundred and thirty eight of these patients received either additional irinotecan or oxaliplatin. One study with panitumumab with safety but no efficacy results was identified, and two studies with gefinitib. The pCR rate ranged from 0-20%. The overall pooled pCR for cetuximab based chemoradiation was 9.1% (29/316). The rate of G3/G4 gastrointestinal toxicity, in terms of diarrhoea, varied from 5-30%, with an overall pooled rate of 47/313 (15%). Discussion. Potential reasons for the disappointing results of EGFR inhibition with fluoropyrimidine-based preoperative chemoradiation include a less critical role of repopulation in rectal adenocarcinoma using a non-curative radiation dose; or antagonistic effects on 5FU-based chemoradiation and oxaliplatin, if some cells arrest in G1 or G2-M and fail to pass through S phase. Conclusion. Cetuximab

  4. Adjuvant chemoradiotherapy for adenocarcinoma of the stomach. A new progress?

    Frequency of local and distant failures after gastrectomy has led to extended lymph nodes dissection to obtain a better locoregional control. However, five year survival rates were not significantly different between patients undergoing D2 and D1 lymphadenectomy, and higher morbidity and post operative deaths were reported in large randomized trials (respectively 25% vs 48% and 4 vs 13%). Additionally, several met-analysis failed to demonstrate a significant survival advantage with adjuvant chemotherapy. The results of the first trial demonstrating one advantage to adjuvant post-operative chemoradiotherapy should modify the standard care. Disease free and overall survival after surgery alone and after surgery and concurrent chemoradiotherapy were respectively 31% vs 48% and 41% vs 50%. The inter-group trial demonstrate that better local control improve survival if radiation fields include stamps, tumour bed, proximal nodal chains and nodes corresponding to D2 extended lymph nodes dissection. Treatment was feasible with few severe toxic effects (1%). Of the 281 patients, 17% stopped treatment because toxic effects. Technical modalities of radiotherapy and post-operative nutrition support which are critical points of interest for this treatment, are also discussed. (authors)

  5. Whole-Pelvis or Bladder-Only Chemoradiation for Lymph Node–Negative Invasive Bladder Cancer: Single-Institution Experience

    Purpose: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard bladder preserving option for patients with invasive bladder cancer. The standard practice is to treat elective pelvic lymph nodes, so our aim was to evaluate whether bladder-only (BO) CCRT leads to results similar to those obtained by standard WP-CCRT. Methods and Materials: Patient eligibility included histopathologically proven muscle-invasive bladder cancer, lymph nodes negative (T2–T4, N−) by radiology, and maximal transurethral resection of bladder tumor with normal hematologic, renal, and liver functions. Between March 2005 and May 2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120 patients) and BO-CCRT (110 patients). Data regarding the toxicity profile, compliance, initial complete response rates at 3 months, and occurrence of locoregional or distant failure were recorded. Results: With a median follow-up time of 5 years (range, 3–6), WP-CCRT was associated with a 5-year disease-free survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5). The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT, respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP-CCRT and 51% for BO-CCRT (p = 0.8). Conclusion: BO-CCRT showed similar rates of bladder preservation, disease-free survival, and overall survival rates as those of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node–negative bladder cancer to minimize the side effects of CCRT.

  6. A Phase II study of acute toxicity for CelebrexTM (celecoxib) and chemoradiation in patients with locally advanced cervical cancer: Primary endpoint analysis of RTOG 0128

    Purpose: To determine treatment-related acute toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, i.v. cisplatin and 5-FU, and concurrent pelvic radiation therapy. Methods and Materials: Eligible patients on this RTOG Phase I-II study for advanced cervix cancer included FIGO Stage IIB-IVA or patients with FIGO Stage IB through IIA with biopsy proven pelvic node metastases or tumor size ≥5 cm. Patients were treated with pelvic radiotherapy and brachytherapy. Celecoxib was prescribed at 400 mg twice daily beginning on day 1 for 1 year. Cisplatin (75 mg/m2) and 5-FU (1g/m2 for 4 days) were administered every 3 weeks times 3. The primary end point of the study was treatment related toxicity. Results: Between August 2001 and March 2004, 84 patients were accrued to the study and 77 patients were evaluable for toxicity. Regarding the primary end point, toxicities were observed in the following areas: blood/bone marrow (16), gastrointestinal (14), pain (7), renal/genitourinary (6), cardiovascular (3), hemorrhage (1), and neurologic (1). For the first 75 evaluable patients, a toxicity failure was identified in 36 patients for a rate of 48%. Conclusions: Celecoxib at 400 mg twice daily together with concurrent cisplatin and 5-FU and pelvic radiotherapy has a high incidence of acute toxicities. The most frequent toxicities were hematologic. Albeit, the toxicity was deemed excessive in this trial, the rate of toxicities was not too different compared to other recent experiences with concurrent chemoradiation for advanced cervix cancer

  7. Some Properties of D-Concurrence

    韦娜娜; 李愿

    2012-01-01

    In this note,we give a new lower bound for the concurrence,which is related to D-concurrence.For the Werner states,we compare that this D-concurrence bound with the other known bound.In addition,some of new upper and lower bounds of D-concurrence are given.

  8. Flow Java: declarative concurrency for Java.

    Drejhammar, Frej; Haridi, Seif; Brand, Per; Schulte, Christian

    2003-01-01

    Logic variables pioneered by (concurrent) logic and concurrent constraint programming are powerful mechanisms for automatically synchronizing concurrent computations. They support a declarative model of concurrency that avoids explicitly suspending and resuming computations. This paper presents Flow Java which conservatively extends Java with single assignment variables and futures as variants of logic variables. The extension is conservative with respect to object-orientation, types, paramet...

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

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

  10. Concurrent Engineering Research and Application

    1999-01-01

    Research and application of Concurrent Engineering have produced good results. A Chinese style concurrent engineering architecture and reference mode has been produced. A series of break thoughts in BPR (Business Process Reengineering) have been made with organization of the IPT (Integrated Product Development Team) and engineering support technologies. Several prototype tools were developed, including product development process modeling and management, QFD-based schema design and decision making, PDM-based concurrent design, STEP-based CAD/CAPP/CAM integration, design for assembly, design for manufacturing, computer aided fixture design, and machining process simulation. Finally, the research results were used in the development of two complex components in an aerospace application, and satisfactory results were obtained.

  11. Concurrency & Asynchrony in Declarative Workflows

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    concurrency in DCR Graphs admits asynchronous execution of declarative workflows both conceptually and by reporting on a prototype implementation of a distributed declarative workflow engine. Both the theoretical development and the implementation is supported by an extended example; moreover, the theoretical......Declarative or constraint-based business process and workflow notations have received increasing interest in the last decade as possible means of addressing the challenge of supporting at the same time flexibility in execution, adaptability and compliance. However, the definition of concurrent...... semantics, which is a necessary foundation for asynchronously executing distributed processes, is not obvious for declarative formalisms and is so far virtually unexplored. This is in stark contrast to the very successful Petri-net–based process languages, which have an inherent notion of concurrency. In...

  12. Novel Adjuvants and Immunomodulators for Veterinary Vaccines

    Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

    2016-01-01

    Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

  13. Concurrent Delay in Construction Disputes

    Cavaleri, Sylvie Cécile

    Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing the...... period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical...... solutions to the issue of concurrent delay in a comparative perspective between common and civil law systems, with an emphasis on Danish and English law....

  14. Object-oriented concurrent programming

    Yonezawa, A.; Tokoro, M.

    1986-01-01

    This book deals with a major theme of the Japanese Fifth Generation Project, which emphasizes logic programming, parallelism, and distributed systems. It presents a collection of tutorials and research papers on a new programming and design methodology in which the system to be constructed is modeled as a collection of abstract entities called ''objects'' and concurrent messages passing among objects. The book includes proposals for programming languages that support this methodology, as well as the applications of object-oriented concurrent programming to such areas as artificial intelligence, software engineering, music synthesis, office information systems, and system programming.

  15. Fuzzy simulation in concurrent engineering

    Kraslawski, A.; Nystrom, L.

    1992-01-01

    Concurrent engineering is becoming a very important practice in manufacturing. A problem in concurrent engineering is the uncertainty associated with the values of the input variables and operating conditions. The problem discussed in this paper concerns the simulation of processes where the raw materials and the operational parameters possess fuzzy characteristics. The processing of fuzzy input information is performed by the vertex method and the commercial simulation packages POLYMATH and GEMS. The examples are presented to illustrate the usefulness of the method in the simulation of chemical engineering processes.

  16. Adjuvants: Classification, Modus Operandi, and Licensing

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.

  17. Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS)

    Radical surgery is the cornerstone in the treatment of resectable gastric cancer. The Intergroup 0116 and MAGIC trials have shown benefit of postoperative chemoradiation and perioperative chemotherapy, respectively. Since these trials cannot be compared directly, both regimens are evaluated prospectively in the CRITICS trial. This study aims to obtain an improved overall survival for patients treated with preoperative chemotherapy and surgery by incorporating radiotherapy concurrently with chemotherapy postoperatively. In this phase III multicentre study, patients with resectable gastric cancer are treated with three cycles of preoperative ECC (epirubicin, cisplatin and capecitabine), followed by surgery with adequate lymph node dissection, and then either another three cycles of ECC or concurrent chemoradiation (45 Gy, cisplatin and capecitabine). Surgical, pathological, and radiotherapeutic quality control is performed. The primary endpoint is overall survival, secondary endpoints are disease-free survival (DFS), toxicity, health-related quality of life (HRQL), prediction of response, and recurrence risk assessed by genomic and expression profiling. Accrual for the CRITICS trial is from the Netherlands, Sweden, and Denmark, and more countries are invited to participate. Results of this study will demonstrate whether the combination of preoperative chemotherapy and postoperative chemoradiotherapy will improve the clinical outcome of the current European standard of perioperative chemotherapy, and will therefore play a key role in the future management of patients with resectable gastric cancer. clinicaltrials.gov http://www.clinicaltrials.gov/ct2/show/NCT00407186

  18. Efficacy Endpoints of Radiation Therapy Group Protocol 0247: A Randomized, Phase 2 Study of Neoadjuvant Radiation Therapy Plus Concurrent Capecitabine and Irinotecan or Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    Wong, Stuart J. [Medical College of Wisconsin, Madison, Wisconsin (United States); Moughan, Jennifer [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Meropol, Neal J., E-mail: Neal.Meropol@case.edu [University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio (United States); Anne, Pramila Rani [Department of Radiation Oncology and Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Kachnic, Lisa A. [Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts (United States); Rashid, Asif [Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Watson, James C. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Mitchell, Edith P. [Department of Radiation Oncology and Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Pollock, Jondavid [The Schiffler Cancer Center, Wheeling, West Virginia (United States); Lee, R. Jeffrey [Intermountain Medical Center, Murray, Utah (United States); Haddock, Michael [Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Erickson, Beth A. [Medical College of Wisconsin, Madison, Wisconsin (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2015-01-01

    Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m{sup 2}/d Monday-Friday) plus irinotecan (50 mg/m{sup 2}/wk × 4); and (2) capecitabine (1650 mg/m{sup 2}/d Monday-Friday) plus oxaliplatin (50 mg/m{sup 2}/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m{sup 2}; leucovorin 400 mg/m{sup 2}; 5-fluorouracil 400 mg/m{sup 2}; 5-fluorouracil 2400 mg/m{sup 2}) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local–regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an

  19. Efficacy Endpoints of Radiation Therapy Group Protocol 0247: A Randomized, Phase 2 Study of Neoadjuvant Radiation Therapy Plus Concurrent Capecitabine and Irinotecan or Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m2/d Monday-Friday) plus irinotecan (50 mg/m2/wk × 4); and (2) capecitabine (1650 mg/m2/d Monday-Friday) plus oxaliplatin (50 mg/m2/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2; 5-fluorouracil 2400 mg/m2) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local–regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival

  20. A Model for Concurrent Objects

    Sørensen, Morten U.

    We present a model for concurrent objects where obejcts interact by taking part in common events that are closely matched to form call-response pairs, resulting in resulting in rendez-vous like communications. Objects are built from primitive objects by parallel composition, encapsulation and...

  1. Teaching Concurrency: Theory in Practice

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand;

    2009-01-01

    mathematics. We report here on our experiences in teaching concurrency theory over the last twenty years or so to students ranging from mathsphobic bachelor students to sophisticated doctoral students. The contents of the courses, the material on which they are based and the pedagogical philosophy underlying...

  2. CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer

    This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation. Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m2 irinotecan weekly and 625 mg/m2 capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities. Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36

  3. The benefit of treatment intensification is age and histology-dependent in patients with locally advanced non-small cell lung cancer (NSCLC): a quality-adjusted survival analysis of radiation therapy oncology group (RTOG) chemoradiation studies

    Purpose: Currently, chemoradiation treatment strategies in locally advanced NSCLC are essentially the same irrespective of tumor histology or patient age. The purpose of this study is to analyze the impact of age, histology, Karnofsky performance status (KPS), and specific toxicities on the median survival time (MST) and quality-adjusted survival (QTime) for each treatment strategy. Methods and Materials: Nine hundred seventy-nine patients with Stage II-IIIB inoperable NSCLC were enrolled on 6 prospective Phase II and III studies from 1983 to 1995. Treatment regimens ranged from standard RT (SRT) to 60 Gy, hyperfractionated RT (HRT) to 69.6 Gy, induction chemotherapy (ICT) of cisplatin (CIS) and vinblastine (VBL) followed by SRT, ICT + concurrent CT (CCT) + SRT, and CCT + HRT; CCT consisted of etoposide or VBL + CIS. Toxicities assessed were skin, mucous membrane, lung, esophagus, neurologic, hematologic, and upper GI. QTime was calculated by weighting the time spent with a specific toxicity, as well as local or distant tumor progression. Each toxicity was weighted with increasing severity as the toxicity increased in grade. Results: As expected, patients with the worst KPS (50-70) had the lowest MST (7.8 months) and QTime (6.7 months). Patients 70 years achieved the best QTime with standard RT (SRT) alone. In patients with squamous cell carcinoma, those treated with ICT + CCT + SRT had dramatically improved MST (25.7 months) and QTime (21.8 months) compared to the other treatment regimens (11.7-12.8 and 10.7-12 months, respectively). Patients with adenocarcinoma, however, generally manifested incrementally better MST and QTime as the therapies intensified. Within the concurrent chemoradiation arms, the upper GI and lung toxicities had the greatest impact on QTime. Conclusion: This quality-adjusted survival analysis suggests that there is a critical relationship between the type of histology and its optimal treatment, age and the ability to tolerate intensive

  4. Preoperative chemoradiation and extended pelvic lymphadenectomy for rectal cancer: Two distinct principles

    Konishi, Tsuyoshi; Watanabe, Toshiaki; Nagawa, Hirokazu; Oya, Masatoshi; Ueno, Masashi; Kuroyanagi, Hiroya; Fujimoto, Yoshiya; Akiyoshi, Takashi; Yamaguchi, Toshiharu; Muto, Tetsuichiro

    2010-01-01

    Extended pelvic lymphadenectomy (EPL) with total mesorectal excision (TME) has been reported to provide oncological benefit in lower rectal cancer in Japan. In Western countries EPL is not widely accepted because of frequent morbidity but instead preoperative chemoradiation (CRT) followed by TME has been established as a standard treatment for decreasing local recurrence. Recently, several studies have focused on the comparison between these two distinct therapeutic approaches in Western coun...

  5. What does absence of lymph node in resected specimen mean after neoadjuvant chemoradiation for rectal cancer

    The effect of insufficient node sampling in patients with rectal cancer managed by neoadjuvant chemoradiation followed by surgery has not been clearly determined. We evalulated the impact of insufficient sampling or even abscence of lymph nodes in the specimen on survival in patients at high-risk (T3, T4 or node positive) for rectal cancer. We conducted a single institution, retrospective analysis of all patients who underwent surgical rectal resection following neoadjuvant chemoradiation for treatment of mid to lower rectal cancer between 1997 and 2009. ypNX was defined as the absence of lymph nodes retrieved in the resected specimen. A total of 132 patients underwent resection for treatment of rectal cancer following neoadjuvant chemoradiation. Ninety four patients (71.2%) were considered as having node-negative disease, including ypNx and ypN0. In 38 patients (28.8%), the primary tumor was associated with regional lymph node metastases (ypNpos). The mean number of retrieved nodes per specimen was 14.2, respectively. The five-year overall survival from initial operation for the ypNx group was 100%, respectively. The estimated five-year overall survival for ypN0 and ypNpos was 84.0% and 60.3%, respectively (P =0.001). No significant differences in overall survival were observed between the ypNx and ypN0 group (P =0.302). Absence of recovered LN in resected specimens after neoadjuvant chemoradiation was observed in 7.6% of specimens. Absence of LN should not be regarded as a risk factor for poor survival or as a sign of less radical surgery

  6. Neoadjuvant chemoradiation with capcitabine and celecoxib in stage II and III rectal adenocarcinoma

    Aghili M; Babaei M; Azmoodeh Ardalan F; Farhan F; Hadad P; Ganjalikhani M

    2010-01-01

    "nBackground: Colorectal cancer is the third common cancer world wide and the forth in Iran. Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. In this study we evaluate the efficacy a cox-2 inhibitor on pathologic response, sphincter preservation and acute toxicity during neoadjuvant chemoradiation."n "nMethods: Thirty-six patients that have adenocarcinoma of rectum was enrolled (up to 15 cm of anal verge). The patients were undergone E...

  7. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy

  8. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    Twu, Chih-Wen [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Wen-Yi [Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan (China); Chen, Chien-Chih [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Liang, Kai-Li; Jiang, Rong-San [Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wu, Ching-Te [Department of Radiation Oncology, Taichung Veterans General Hospital–Chiayi Branch, Chiayi, Taiwan (China); Shih, Yi-Ting [Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan (China); Lin, Po-Ju; Liu, Yi-Chun [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lin, Jin-Ching, E-mail: jclin@vghtc.gov.tw [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, China Medical University, Taichung, Taiwan (China)

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  9. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    WONDIM MELKAM

    2015-01-01

    Full Text Available Glucocorticoids (GCs, synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bacterial infection. This review, therefore, summarizes various bacterial infections for which glucocorticoids are reported to be used as adjuvant therapy, strategies for administration of glucocorticoids, and challenges of using glucocorticoids as adjuvant therapy.

  10. Durcissement de la concurrence et conventions de concurrence en France

    Christian Barrère

    2008-11-01

    Full Text Available Le texte s’intéresse au changement de régime de concurrence qui se manifeste en France au tournant des années 80. Si le durcissement des formes de concurrence s’explique in fine par les changements intervenus dans les formes d’accumulation il passe par des modifications dans les comportements micro-économiques des acteurs. Ceux-ci sont étudiés au moyen d’une formalisation en termes de jeux évolutionnaires qui met l’accent sur la prise en compte par les acteurs eux-mêmes de l’intensification de la rivalité inter-capitaliste et permet de montrer comment le système tend à s’enfermer dans une nouvelle convention de concurrence qui s’auto-renforce.The paper considers the breakdown of the competition convention which was dominant in the French post-war growth. The changes in the competition regime, from a soft competition, typical of the 50’s, 60’s and 70’s, to a new and harder one, is mainly related to changes in accumulation conditions. But the behaviours of the firms play a key role. Using an evolutionary game approach, we analyse the logic of the new competition convention and the lock-in effects that it creates.

  11. Neoadjuvant chemoradiation with IMRT in resectable and borderline resectable pancreatic cancer

    Purpose: Neoadjuvant chemoradiation is an alternative to the surgery-first approach for resectable pancreatic cancer (PDA) and represents the standard of care for borderline resectable (BLR). Materials and methods: All patients with resectable and BLR PDA treated with neoadjuvant chemoradiation using IMRT between 1/2009 and 11/2011 were reviewed. Patients were treated to a customized CTV which included the primary mass and regional vessels. Results: Neoadjuvant chemoradiation was completed in 69 patients (39 BLR and 30 resectable). Induction chemotherapy was used in 32 (82%) of the 39 patients with BLR disease prior to chemoXRT. All resectable patients were treated with chemoXRT alone. Following neoadjuvant treatment, 48 (70%) of the 69 patients underwent successful pancreatic resection with 47 (98%) being margin negative (RO). In 30 of the BLR patients who had arterial abutment or SMV occlusion, 19 (63%) were surgically resected and all had RO resections. The cumulative incidence of local failure at 1 and 2 years was 2% (95% CI 0–6%) and 9% (95% CI 0.6–17%) respectively. The median overall survival for all patients, patients undergoing resection, and patients without resection were 20, 26 and 11 months respectively. Sixteen (23%) of the 69 patients are alive without disease with a median follow-up of 47 months (36–60). Conclusion: Neoadjuvant chemoXRT can facilitate a margin negative resection in patients with localized PCa

  12. High survivin expression as a risk factor in patients with anal carcinoma treated with concurrent chemoradiotherapy

    To investigate the prognostic value of survivin expression in pretreatment specimens from patients with anal cancer treated with concurrent 5-FU and mitomycin C-based chemoradiation (CRT). Immunohistochemical staining for survivin was performed in pretreatment biopsies of 62 patients with anal carcinoma. Survivin expression was correlated with clinical and histopathological characteristics as well as local failure free- (LFFS), distant metastases free- (DMFS), cancer specific- (CSS), and overall survival (OS). Survivin staining intensity was weak in 10%, intermediate in 48% and intense in 42% of the patients. No association between survivin expression and clinicopathologic factors (tumor stage, age and HIV status) could be shown. In univariate analysis, the level of survivin staining was significantly correlated with DMFS (low survivin vs. high survivin: 94% vs. 74%, p = 0.04). T-stage, N-stage and the tumor grading were significantly associated with OS and CSS and with DMFS and LFFS, respectively. In multivariate analysis, survivin was confirmed as independent prognostic parameter for DMFS (RR, 0.04; p = 0.02) and for OS (RR, 0.27; p = 0.04). Our results demonstrated that the level of pretreatment survivin is correlated with the clinical outcome in patients with anal carcinoma treated with concurrent CRT. Further studies are warranted to elucidate the complex role of survivin for the oncologic treatment and to exploit the protein as a therapeutic target in combined modality treatment of anal cancer

  13. Strengthening Concurrent Enrollment through NACEP Accreditation

    Scheffel, Kent; McLemore, Yvette; Lowe, Adam

    2015-01-01

    This chapter describes how implementing the National Alliance of Concurrent Enrollment Partnerships' 17 accreditation standards strengthens a concurrent enrollment program, enhances secondary-postsecondary relations, and benefits students, their families, and secondary and postsecondary institutions.

  14. Efficacy of adjuvant therapy with procarbazine, MCNU, and vincristine for oligodendroglial tumors

    Wakabayashi, Toshihiko; Kajita, Yasukazu; Mizuno, Masaaki; Yoshida, Jun [Nagoya Univ. (Japan). School of Medicine; Nagasaka, Tetsurou

    2001-03-01

    An adjuvant chemotherapy regimen consisting of procarbazine, MCNU, and vincristine (PMV) was evaluated for the treatment of malignant oligodendroglial tumors. Ten patients with histologically proven oligodendroglial tumors were treated with PMV therapy and the effectiveness was assessed using magnetic resonance imaging. Four patients with primary tumors underwent PMV after radiation therapy, and six patients with recurrent tumors were treated using PMV only. Tumor response was defined as radiological evidence of mass size change after completion of three courses of PMV. Complete or partial responses (more than 50% reduction in tumor mass) were noted in six patients, and tumor growth stabilized in four patients. In particular, inhibition of tumor growth using PMV was achieved in three patients with recurrent oligodendroglial tumors, despite the initial response after chemoradiation therapy (interferon-{beta}, MCNU, radiation) or nitrosourea chemotherapy (ACNU, MCNU). This PMV regimen (a modified PCV regimen using drugs available in Japan) is effective for treating malignant oligodendroglial tumors despite recurrence after other initial treatment procedures. (author)

  15. Data refinement for true concurrency

    Brijesh Dongol

    2013-05-01

    Full Text Available The majority of modern systems exhibit sophisticated concurrent behaviour, where several system components modify and observe the system state with fine-grained atomicity. Many systems (e.g., multi-core processors, real-time controllers also exhibit truly concurrent behaviour, where multiple events can occur simultaneously. This paper presents data refinement defined in terms of an interval-based framework, which includes high-level operators that capture non-deterministic expression evaluation. By modifying the type of an interval, our theory may be specialised to cover data refinement of both discrete and continuous systems. We present an interval-based encoding of forward simulation, then prove that our forward simulation rule is sound with respect to our data refinement definition. A number of rules for decomposing forward simulation proofs over both sequential and parallel composition are developed.

  16. Modal abstractions of concurrent behavior

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well as...... supports the definition of a 3-valued modal logic for validating as well as refuting properties of systems. The construction is illustrated on a few examples, including the Ingemarsson-Tang-Wong key agreement protocol. © 2011 ACM....

  17. PyCSP - controlled concurrency

    Friborg, Rune Møllegaard; Vinter, Brian; Bjørndalen, John Markus

    Producing readable and correct programs while at the same time taking advantage of multi-core architectures is a challenge. PyCSP is an implementation of Communicating Sequential Processes algebra (CSP) for the Python programming language, taking advantage of CSP’s formal and verifiable approach to...... controlling concurrency and the readability of Python source code. We describe PyCSP, demonstrate it through examples and demonstrate how PyCSP compares to Pthreads using a benchmark....

  18. PyCSP - controlled concurrency

    Friborg, Rune Møllegaard; Vinter, Brian; Bjørndalen, John Markus

    2010-01-01

    Producing readable and correct programs while at the same time taking advantage of multi-core architectures is a challenge. PyCSP is an implementation of Communicating Sequential Processes algebra (CSP) for the Python programming language, that take advantage of CSP's formal and verifiable approach...... to controlling concurrency and the readability of Python source code. We describe PyCSP, demonstrate it through examples and demonstrate how PyCSP compares to Pthreads in a master-worker benchmark....

  19. Concurrent Lymphoma and Pancreatic Adenocarcinoma

    Jiun Miin Lai; Mehrdad Nikfarjam; Peter Crowley

    2011-01-01

    Context Retroperitoneal lymph node enlargement in patients with pancreatic cancer is sometimes treated as incurable disease. Nonmetastatic causes of lymphadenopathy should however be considered. Case reports Two cases of significant retroperitoneal lymphadenopathy in the setting of pancreatic cancer, treated by pancreaticoduodenectomy and lymph node dissection are described. Both cases had a final diagnosis of concurrent pancreatic cancer and lymphoma with no evidence of pancreatic lymph node...

  20. Adjuvant Bisphosphonates for Postmenopausal Breast Cancer

    A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.

  1. Integration-based cooperation in concurrent engineering

    Hillebrand, Gerd; Krakowski, Patricia; Lockemann, Peter C.; Posselt, Dietmar

    1998-01-01

    Motivated by global competition, rapid technological advance and shorter product life cycles, enterprises tend to restructure the traditionally sequential product development process into a collaborative, concurrent, and iterative effort called Concurrent Engineering. In Concurrent Engineering, design phases overlap and potentially incomplete results are exchanged between phases, facilitating early initiation of later stages and quick corrective feedback. ...

  2. Adjuvant interferon treatment for melanoma.

    Agarwala, S S; Kirkwood, J M

    1998-08-01

    After decades of research, the adjuvant therapy of patients with melanoma has recently shown significant survival and relapse-free interval benefit for the intravenous and subcutaneous administration of maximally tolerable dosages of recombinant IFN alpha 2b in a trial conducted by the ECOG (E1684). Despite the toxicity of this therapy, retrospective analyses of its impact upon quality-of-life using Q-TWiST methods and cost-efficacy analyses all argue for the benefit and utility of this intervention, especially for node-positive patients with resectable melanoma at highest risk of relapse. A confirmatory trial has been completed and will mature in the spring of 1998. The impact of lower dosages of IFN, apparent transiently during and for a period of time following treatment has not been sustained with longer follow-up in a number of trials. Current approaches in Europe and North America focus upon refinement of dose and duration of treatment with IFN and their potential interactions with, and comparison with, active specific immunotherapy with vaccines. A recently emerging area of research is the patient with stage IIA melanoma and the potential role of an abbreviated high-dose regimen of IFN alpha in this patient subset. PMID:9759581

  3. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic significance

  4. Prognostic Cell Biological Markers in Cervical Cancer Patients Primarily Treated With (Chemo)radiation: A Systematic Review

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in ≥50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1α). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients.

  5. A comparison of laparoscopic and open surgery following pre-operative chemoradiation therapy for locally advanced lower rectal cancer

    Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination. We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses. In total, 33 patients were enrolled (open surgery group, n=14; laparoscopic surgery group, n=19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra-operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group. This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery. (author)

  6. A pilot trial of hyperfractionated thoracic radiation therapy with concurrent cisplatin and oral etoposide for locally advanced inoperable non-small-cell lung cancer: a 5-year follow-up report

    Purpose: To improve the outcome of patients with locally advanced inoperable non-small cell lung cancer (NSCLC), we conducted a pilot trial of concurrent chemoradiation therapy using a cisplatin and oral etoposide regimen given concurrently with hyperfractionated radiation therapy. Methods and Materials: In this single-institution pilot trial, we enrolled 23 patients with inoperable Stage IIIa (4) and IIIb (19) NSCLC. Treatment consisted of two cycles of chemotherapy with oral etoposide 50 mg one day alternating with 50 mg b.i.d. (50 mg/day if BSA is 2) on days 1-21 and intravenous cisplatin (40 mg/m2) on days 1 and 8 of a 28-day cycle. Radiation therapy was given twice a day (1.2 Gy per fraction), 5 days a week, to a total dose of 69.6 Gy in 58 fractions over 6 weeks. Results: Overall, 18 (78%) of the 23 patients completed the chemotherapy as planned and 21 (91%) received thoracic irradiation per protocol. One patient died of radiation pneumonitis. Fourteen (78%) of 18 evaluable patients achieved objective responses. The median survival duration was 9.3 months for all patients and 20.2 months for 15 patients who had no more than 5% weight loss. After a minimum follow-up of 5 years, five patients (1 IIIa, 4 IIIb) are still alive and disease-free, which gives an actual 5-year survival rate of 22%. Four of the five 5-year survivors were among those who completed the treatment as planned. Conclusion: This long-term survival outcome compares favorably with that of other chemoradiation therapy trials and even with those reported in multimodality trials including surgery. These results suggest that intensive concurrent chemoradiation therapy is feasible, and some patients with locally advanced inoperable NSCLC may enjoy long-term survivorship following nonsurgical therapy

  7. A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer

    This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma. Between May 2000 and May 2004, 31 women with FIGO stage IB2-IVA cervical cancer or with postsurgical pelvic recurrence were enrolled into this phase II study and randomized to receive on a weekly basis either 40 mg/m2 Cisplatin (group I; 16 patients) or 50 mg/m2 paclitaxel (group II; 15 patients) concurrently with radiotherapy. Median total dose to point A was 74 Gy (range: 66-92 Gy) for group I and 66 Gy (range: 40-98 Gy) for group II. Median follow-up time was 46 months. Patient and tumor characteristics were similar in both groups. The mean number of chemotherapy cycles was also comparable with 87% and 80% of patients receiving at least 4 doses in groups I and II, respectively. Seven patients (44%) of group I and 8 patients (53%) of group II developed tumor recurrence. The Median Survival time was not reached for Group I and 53 months for group II. The proportion of patients surviving at 2 and 5 years was 78% and 54% for group I and 73% and 43% for group II respectively. This small prospective study shows that weekly paclitaxel does not provide any clinical advantage over weekly cisplatin for concurrent chemoradiation for advanced carcinoma of the cervix

  8. A Phase II Multi-institutional Trial of Chemoradiation Using Weekly Docetaxel and Erythropoietin for High-Risk Postoperative Head and Neck Cancer Patients

    Purpose: To determine efficacy and toxicities of postoperative concurrent chemoradiation using docetaxel in high-risk head and neck cancer. Methods and Materials: High-risk patients were enrolled 2-8 weeks after surgery. Treatment included 60 Gy for 6 weeks with weekly docetaxel 25 mg/m2 and erythropoietin alpha 40,000 U for hemoglobin ≤12 g/dL. Primary endpoints included locoregional control (LC), disease-free survival (DFS), and patterns of failure (POF). Secondary endpoints were toxicity and quality of life. Results: Eighteen patients were enrolled (14 male, 4 female), aged 24-70 years (median, 55 years). Primary site included oropharynx = 7, oral cavity 8, hypopharynx = 1, and larynx = 2. Pathologic American Joint Committee on Cancer Stage was III = 3 patients, IV = 15 patients. High-risk eligibility included ≥2 positive lymph nodes = 13, extracapsular extension = 10, positive margins = 8 (11 patients with two or more risk factors). Docetaxel was reduced to 20 mg/m2/week after 5 patients had prolonged Grade 3 or higher mucositis. Overall, number of doses delivered was 2 of 6 = 1, 3 of 6 2, 4 of 6 = 2, 5 of 6 = 4, 6 of 6 = 9 patients. With median follow-up of 30 months (range, 5-66), 10 (56%) patients are alive and have no evidence of disease (NED); POF: three local recurrences (two with distant) and 1 distant only. One-year survival was 76%, median PFS and DFS had not been reached. Three-year LC was 82%. No Grade 3 or higher late toxicities were observed, although a few cases of prolonged mucositis and taste loss (>3 months) were seen, particularly at 25 mg/m2/week. Conclusion: Postoperative radiation therapy with weekly docetaxel 20 or 25 mg/m2/week for high-risk postoperative head and neck cancer caused intolerable mucosal toxicity, prompting early study termination. Further studies should consider 15 mg/m2. Actuarial 3-year LC is 82%, similar to cisplatin-based chemoradiation regimens. Distant metastasis remains an important issue requiring additional

  9. c-Met Expression Is a Marker of Poor Prognosis in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Treated With Chemoradiation

    Baschnagel, Andrew M. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Williams, Lindsay [Department of Pathology, William Beaumont Hospital, Royal Oak, Michigan (United States); Hanna, Alaa; Chen, Peter Y.; Krauss, Daniel J. [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Pruetz, Barbara L. [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Akervall, Jan [Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States); Department of Otolaryngology, William Beaumont Hospital, Royal Oak, Michigan (United States); Wilson, George D., E-mail: George.Wilson@Beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Beaumont BioBank, William Beaumont Hospital, Royal Oak, Michigan (United States)

    2014-03-01

    Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16

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

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

    2014-09-25

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [German] Mehrere nichtrandomisierte Studien zeigten, dass eine neoadjuvante Therapie das Ueberleben bei Patienten mit Pankreaskarzinom verlaengert. Beim lokal fortgeschrittenen Rektumkarzinom gehoert die

  11. Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

    Palma, David A., E-mail: david.palma@uwo.ca [Department of Radiation Oncology, London Regional Cancer Program, London, Ontario (Canada); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Oberije, Cary [Department of Radiation Oncology (MAASTRO Clinic), GROW – School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Belderbos, Jose [Department of Radiation Oncology, The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Dios, Núria Rodríguez de [Department of Radiation Oncology, Parc de Salut Mar, Barcelona, Universidad Pompeu Fabra, Barcelona (Spain); Bradley, Jeffrey D. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Barriger, R. Bryan [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Moreno-Jiménez, Marta [Department of Oncology, Radiation Oncology Division, Clínica Universidad de Navarra, University of Navarra, Pamplona (Spain); Kim, Tae Hyun [Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi (Korea, Republic of); Ramella, Sara [Division of Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Everitt, Sarah [Radiation Therapy Services, Peter MacCallum Cancer Centre, Melbourne, Australia and Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University (Australia); Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina (United States); De Ruyck, Kim [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); and others

    2013-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors

  12. Predicting Esophagitis After Chemoradiation Therapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-Analysis

    Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors are statistically predictive of RE, the V60 alone provides the best

  13. Review: Adjuvant effects of saponins on animal immune responses

    RAJPUT Zahid Iqbal; HU Song-hua; XIAO Chen-wen; ARIJO Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines,ISCOMs (immunostimulating complexes), Freund's complete adjuvant, Freund's incomplete adjuvant, alums, bacterial toxins etc.,are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

  14. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  15. Chemoradiation in cervical cancer with cisplatin and high-dose rate brachytherapy combined with external beam radiotherapy. Results of a phase-II study

    Strauss, H.G.; Laban, C.; Puschmann, D.; Koelbl, H. [Dept. of Gynecology, Martin-Luther Univ. Halle-Wittenberg (Germany); Kuhnt, T.; Pigorsch, S.; Dunst, J.; Haensgen, G. [Dept. of Radiotherapy, Martin-Luther Univ. Halle-Wittenberg (Germany)

    2002-07-01

    Background: In 1999, five randomized studies demonstrated that chemoradiation with cisplatin and low-dose rate (LDR) brachytherapy has a benefit in locally advanced cervical cancer and for surgically treated patients in high-risk situations. We evaluated the safety and efficacy of concomitant chemoradiation with cisplatin and high-dose rate (HDR) brachytherapy in patients with cervical cancer. Patients and Method: 27 patients were included in our phase-II trial: 13 locally advanced cases (group A) and 14 adjuvant-therapy patients in high-risk situations (group B). A definitive radiotherapy was performed with 25 fractions of external beam therapy (1.8 Gy per fraction/middle shielded after eleven fractions). Brachytherapy was delivered at HDR schedules with 7 Gy in point A per fraction (total dose 35 Gy) in FIGO Stages IIB-IIIB. The total dose of external and brachytherapy was 70 Gy in point A and 52-54 Gy in point B. All patients in stage IVA were treated without brachytherapy. Adjuvant radiotherapy was performed with external beam radiotherapy of the pelvis with 1.8 Gy single-dose up to 50.4 Gy. Brachytherapy was delivered at HDR schedules with two fractions of 5 Gy only in patients with tumor-positive margins or tumor involvement of the upper vagina. The chemotherapeutic treatment schedule provided six courses of cisplatin 40 mg/m{sup 2} weekly recommended in the randomized studies GOG-120 and -123. Results: A total of 18/27 patients (66.7%) completed all six courses of chemotherapy. Discontinuation of radiotherapy due to therapy-related morbidity was not necessary in the whole study group. G3 leukopenia (29.6%) was the only relevant acute toxicity. There were no differences in toxicity between group A and B. Serious late morbidity occurred in 2/27 patients (7.4%). 12/13 patients (92.3%) with IIB-IVA cervical cancer showed a complete response (CR). 13/14 adjuvant cases (92.8%) are free of recurrence (median follow up: 19.1 months). Conclusion: Concomitant

  16. Concurrent analysis: a pragmatic justification.

    Snowden, Austyn; Atkinson, John

    2012-04-01

    Concurrent analysis (CA) is a process of synthesizing conceptually equivalent data for the purpose of producing a coherent and predictive model in social science. The process of CA is detailed. In short, CA uses Thagard's concept of coherence as a method of explicating links between mental representations. The product is a wide analysis of all pertinent data. This paper provides a philosophical justification for the need and function of CA. The paper is divided into three sections. The first section reviews some problems with the metasynthetic literature. The purpose of this is that CA can be initially understood as a branch of this type of synthesis. The second section links Risjord's post-paradigmatic position to Rorty's version of pragmatism in order to show the importance of the concept of coherence to these views. The reason for linking these issues is that CA is grounded in rejection of ontological priority. Instead it prioritises a pragmatic conception of coherence. The final section details the mechanics of CA. Concurrent analysis is presented as the most coherent method of synthesizing certain types of narrative evidence if pragmatism is prioritized over ontology. Examples are given from published studies using CA to illustrate the detail of the analysis and the practical value of the product. The examples show that CA appears useful under certain circumstances. These circumstances will be specified, and strengths and weaknesses of the method will be discussed. PMID:22405019

  17. Preparing HEP software for concurrency

    Clemencic, M.; Hegner, B.; Mato, P.; Piparo, D.

    2014-06-01

    The necessity for thread-safe experiment software has recently become very evident, largely driven by the evolution of CPU architectures towards exploiting increasing levels of parallelism. For high-energy physics this represents a real paradigm shift, as concurrent programming was previously only limited to special, well-defined domains like control software or software framework internals. This paradigm shift, however, falls into the middle of the successful LHC programme and many million lines of code have already been written without the need for parallel execution in mind. In this paper we have a closer look at the offline processing applications of the LHC experiments and their readiness for the many-core era. We review how previous design choices impact the move to concurrent programming. We present our findings on transforming parts of the LHC experiment reconstruction software to thread-safe code, and the main design patterns that have emerged during the process. A plethora of parallel-programming patterns are well known outside the HEP community, but only a few have turned out to be straightforward enough to be suited for non-expert physics programmers. Finally, we propose a potential strategy for the migration of existing HEP experiment software to the many-core era.

  18. Preparing HEP software for concurrency

    The necessity for thread-safe experiment software has recently become very evident, largely driven by the evolution of CPU architectures towards exploiting increasing levels of parallelism. For high-energy physics this represents a real paradigm shift, as concurrent programming was previously only limited to special, well-defined domains like control software or software framework internals. This paradigm shift, however, falls into the middle of the successful LHC programme and many million lines of code have already been written without the need for parallel execution in mind. In this paper we have a closer look at the offline processing applications of the LHC experiments and their readiness for the many-core era. We review how previous design choices impact the move to concurrent programming. We present our findings on transforming parts of the LHC experiment reconstruction software to thread-safe code, and the main design patterns that have emerged during the process. A plethora of parallel-programming patterns are well known outside the HEP community, but only a few have turned out to be straightforward enough to be suited for non-expert physics programmers. Finally, we propose a potential strategy for the migration of existing HEP experiment software to the many-core era.

  19. Beyond antigens and adjuvants: formulating future vaccines.

    Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J

    2016-03-01

    The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines. PMID:26928033

  20. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  1. Systemic adjuvant therapies in renal cell carcinoma.

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  2. Systemic adjuvant therapies in renal cell carcinoma

    Sebastiano Buti

    2012-10-01

    Full Text Available Renal cell carcinoma (RCC is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

  3. Rectal Cancer: Mucinous Carcinoma on Magnetic Resonance Imaging Indicates Poor Response to Neoadjuvant Chemoradiation

    Oberholzer, Katja, E-mail: oberholz@radiologie.klinik.uni-mainz.de [Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Mainz (Germany); Menig, Matthias [Department of Radiation Oncology, Johannes Gutenberg-University Mainz (Germany); Kreft, Andreas [Institute of Pathology, Johannes Gutenberg-University Mainz (Germany); Schneider, Astrid [Department of Medical Biometry, Epidemiology and Informatics, Johannes Gutenberg-University Mainz (Germany); Junginger, Theodor [Department of General and Abdominal Surgery, Johannes Gutenberg-University Mainz (Germany); Heintz, Achim [Department of General and Abdominal Surgery, St. Hildegardis Hospital, Mainz (Germany); Kreitner, Karl-Friedrich; Hoetker, Andreas M. [Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Mainz (Germany); Hansen, Torsten [Institute of Pathology, Johannes Gutenberg-University Mainz (Germany); Dueber, Christoph [Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Mainz (Germany); Schmidberger, Heinz [Department of Radiation Oncology, Johannes Gutenberg-University Mainz (Germany)

    2012-02-01

    Purpose: To assess response of locally advanced rectal carcinoma to chemoradiation with regard to mucinous status and local tumor invasion found at pretherapeutic magnetic resonance imaging (MRI). Methods and Materials: A total of 88 patients were included in this prospective study of patients with advanced mrT3 and mrT4 carcinomas. Carcinomas were categorized by MRI as mucinous (mucin proportion >50% within the tumor volume), and as nonmucinous. Patients received neoadjuvant chemoradiation consisting of 50.4 Gy (1.8 Gy/fraction) and 5-fluorouracil on Days 1 to 5 and Days 29 to 33. Therapy response was assessed by comparing pretherapeutic MRI with histopathology of surgical specimens (minimum distance between outer tumor edge and circumferential resection margin = CRM, T, and N category). Results: A mucinous carcinoma was found in 21 of 88 patients. Pretherapeutic mrCRM was 0 mm (median) in the mucinous and nonmucinous group. Of the 88 patients, 83 underwent surgery with tumor resection. The ypCRM (mm) at histopathology was significantly lower in mucinous carcinomas than in nonmucinous carcinomas (p {<=} 0.001). Positive resection margins (ypCRM {<=} 1 mm) were found more frequently in mucinous carcinomas than in nonmucinous ones (p {<=} 0.001). Treatment had less effect on local tumor stage in mucinous carcinomas than in nonmucinous carcinomas (for T downsizing, p = 0.012; for N downstaging, p = 0.007). Disease progression was observed only in patients with mucinous carcinomas (n = 5). Conclusion: Mucinous status at pretherapeutic MRI was associated with a noticeably worse response to chemoradiation and should be assessed by MRI in addition to local tumor staging to estimate response to treatment before it is initiated.

  4. Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

    The objectives of this study were to assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population. (author)

  5. Cyclooxygenase-2 (COX-2) expression in locally advanced cervical cancer patients undergoing chemoradiation plus surgery

    Purpose: To investigate whether cyclooxygenase-2 (COX-2) could be a marker of clinical outcome in cervical cancer patients undergoing concomitant chemoradiation plus surgery. Methods and Materials: The study included 33 locally advanced cervical cancer patients; all underwent neoadjuvant chemoradiation, and responsive patients underwent radical surgery. Immunohistochemistry was performed with rabbit antiserum against COX-2. Results: COX-2 integrated density values (IDVs) in the tumor component ranged from 1.4 to 72.3 (median 15.0); in stromal inflammatory cells, COX-2 IDVs ranged from 1.4 to 96.0 (median 16.0). A statistically significant inverse relation was found between the COX-2 IDVs of the tumor vs. the stromal inflammatory component (r=-0.52, p=0.0017). When the ratio between COX-2 IDV in the tumor vs. the stromal compartment was ≤1, it was considered to indicate cervical tumor with COX-2 expression in the tumor component lower or equivalent to COX-2 expression in the stroma. According to the chosen cutoff value, 17 (51.5%) of 33 were scored as having a high (>1) tumor/stroma COX-2 IDV ratio. Patients with a high tumor/stroma COX-2 IDV ratio had a shorter disease-free survival than did those with a low tumor/stroma COX-2 IDV ratio (p=0.030). Similarly, those with a high tumor/stroma COX-2 IDV ratio had a shorter overall survival (p=0.033). Conclusion: The assessment of COX-2 status in both the tumor and the stromal compartment could provide additional information in the prognostic characterization of cervical cancer patients administered concomitant chemoradiation plus surgery

  6. Predictive Factors of Tumor Response After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

    Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. Methods and Materials: From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Conclusions: Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5ng/ml, and use of capecitabine were associated with tumor downstaging.

  7. The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer.

    Abdul-Jalil, K I

    2014-01-01

    To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative.

  8. Unusual computed tomography findings of radionecrosis after chemoradiation of stage IV hypopharyngeal cancer: a case report

    Baba Yuh

    2011-01-01

    Full Text Available Abstract Introduction Radionecrosis (post-radiotherapy laryngeal submucosal inflammation and necrosis is a complication of (chemo radiotherapy for hypopharyngeal cancer that is difficult to differentiate from tumor recurrence. Case presentation A 67-year-old Japanese man presented with a condition extremely difficult to diagnose differentially as radionecrosis or tumor recurrence after radiotherapy for hypopharyngeal cancer. Although tumor recurrence was suspected from clinical conditions and computed tomography findings, pathologic analysis revealed no evidence of tumor recurrence, and successful therapy with steroids and antibiotics reduced the mucosal edema. Conclusion Our findings emphasize the wide spectrum of radiographic presentation of radionecrosis after chemoradiation of stage IV hypopharyngeal cancer.

  9. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  10. Does lipophilicity per se induce adjuvant effects?

    Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.;

    2007-01-01

    ) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al......Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL...

  11. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

    Sarma Nilendu

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.

  12. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu [Massachusetts General Hospital, Boston, Massachusetts (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Garofalo, Michael C. [University of Maryland School of Medicine, Baltimore, Maryland (United States); Bendell, Johanna [Sarah Cannon Research Institute, Nashville, Tennessee (United States); Berger, Adam C. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Oldenburg, Nicklas B.E. [North Main Radiation Oncology, Providence, Rhode Island (United States); Anne, Pramila Rani [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Perera, Francisco [London Regional Cancer Program/Western Ontario, London, Ontario (Canada); Lee, R. Jeffrey [Intermountain Medical Center, Salt Lake City, Utah (United States); Jabbour, Salma K. [Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Nowlan, Adam [Piedmont Hospital, Atlanta, Georgia (United States); DeNittis, Albert [Main Line Community Clinical Oncology Program, Wynnewood, Pennsylvania (United States); Crane, Christopher [University of Texas-MD Anderson Cancer Center, Houston, Texas (United States)

    2015-09-01

    Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

  13. The Balanced Cube: A Concurrent Data Structure

    Dally, William J.; Seitz, Charles L.

    1985-01-01

    This paper describee the balanced cube, a new data structure for implementing ordered seta. Conventional dats structures such as heaps, balanced trees and B-trees have root bottlenecks which limit their potential concurrency and make them unable to take advantage of the computing potential of concurrent machines. The balanced cube achieves greater concurrency by eliminating the root bottleneck; an operation in the balanced cube can be initiated from any node. The throughput of ...

  14. Steps in Modular Specifications for Concurrent Modules

    Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa

    2015-01-01

    The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent module......, in particular highlighting four key concepts: auxiliary state, interference abstraction, resource ownership and atomicity. We show how these concepts combine to provide powerful approaches to specifying concurrent modules....

  15. Concurrence, tangle and fully entangled fraction

    Li, Ming; Fei, Shao-Ming; Li-Jost, Xianqing

    2010-09-01

    We show that although we cannot distil a singlet from many pairs of bound entangled states, the concurrence and the tangle of two entangled quantum states are always strictly larger than those of one of them, even both entangled quantum states are bound entangled. We present a relation between the concurrence and the fidelity of optimal teleportation. We also give new upper and lower bounds for concurrence and tangle.

  16. Assessing Animals’ Preferences: Concurrent Schedules of Reinforcement

    Sumpter, Catherine E.; Foster, Mary T.; Temple, William

    2002-01-01

    Three methods of assessing animals’ preferences are outlined: free-access, two-choice (e.g., T maze), and concurrent-schedules. While all give indications of relative preference between the choices, freeaccess and discrete-trial procedures tend to give exclusive preference and so do not indicate the degree of preference. Concurrent schedules give at least ordinal measures of the degree of preference. Data from cows, hens, and brushtail possums are used to illustrate the use of concurrent sche...

  17. [Adjuvant chemotherapy of adults soft tissue sarcomas].

    Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M

    2010-06-01

    The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481

  18. Concurrent Process Planning for Machined Parts

    吴丹; 王先逵; 李志忠

    2002-01-01

    Detailed manufacturing information about the parts can help designers produce better designs. Detailed manufacturing information is conveyed to the designer through micro-circles within the concurrent design process for machined parts, focusing on instantaneous product design and process planning. The process has three key elements: a hierarchical architecture design of the concurrent process planning system, modeling and reengineering of the concurrent process planning, and modeling of information. The approach is successfully implemented and applied for concurrent design and process planning of some complicated parts.

  19. A Reference Framework for Concurrent Engineering

    2001-01-01

    Considering the diversity of methods and tools offered to concurrent engineering, the aspects playing important roles in the concurrent engineering c ontext have been pinpointed as being four core elements which are Activity, Meth od, Object and Information. Based on these four elements, a reference framework called AMOI is proposed to be the guideline for the systematic concurrent produc t design. Using the AMOI reference framework, concurrent product development sys tem can be structured into four function models (including the activity model, m ethod model, object model and information model) which are interconnected with e ach other.

  20. "STUDY OF CONCURRENT CISPLATIN AND EXTERNAL RADIOTHERAPY PRIOR TO RADICAL HYSTERECTOMY AND LYMPHADENECTOMY IN PATIENTS WITH STAGE IB-IIB CERVICAL CANCER"

    M. Modares Gilani

    2004-06-01

    Full Text Available The purpose of this study was to describe the feasibility of a combined preoperative chemoradiation program Ib-IIa, bulky and suspicious IIb by radical surgery in patients with stage Ib-IIb cervical cancer. From September 1999 to April 2002, 30 patients with carcinoma of the cervix were treated with preoperative external beam radiotherapy of 45 Gy in 5 weeks. Patients received concurrent continuous infusion of cisplatin 50 mg/m2 for one day in week during 5 weeks of radiation. Radical surgery was performed 4-6 weeks after completion of the preoperative treatment. Toxicity with chemoradiation was usually mild. Two patients developed vesicovaginal fistula, and four developed long-term hydronephrosis that needed ureteral stenting. Clinical response was observed in 100% of the patients (23.7% complete response. The analysis of the surgical specimens revealed complete pathological response in 43.3% of the cases and partial pathological response in 56.7%. The degree of pathological response was not predictable by the degree of clinical response. Thirty months disease-free survival and overall survival were 66.3% and 77.31%, respectively. Patients with complete and partial pathological response were not significantly different in terms of disease-free survival (p= 0.08 and overall survival (p= 0.3. Cisplatin in preoperative chemoradiation is effective and usually welltolerated in bulky cervical cancer and parametrial invasion, inducing a high rate of clinical and pathological complete responses. When this therapy is followed by radical surgery, disease-free and overall survival rates are higher. The latter may be possible only through extensive surgical resection with a parallel increase in complication rates.

  1. Review of Adjuvant Radiochemotherapy for Resected Pancreatic Cancer and Results From Mayo Clinic for the 5th JUCTS Symposium

    Purpose: To present an overview of Phase III trials in adjuvant therapy for pancreatic cancer and review outcomes at the Mayo Clinic after adjuvant radiochemotherapy (RT/CT) for resected pancreatic cancer. Methods and Materials: A literature review and a retrospective review of 472 patients who underwent an R0 resection for T1-3N0-1M0 invasive carcinoma of the pancreas from 1975 to 2005 at the Mayo Clinic, Rochester, MN. Patients with metastatic or unresectable disease at the time of surgery, positive surgical margins, or indolent tumors and those treated with intraoperative radiotherapy were excluded from the analysis. Median radiotherapy dose was 50.4Gy in 28 fractions, with 98% of patients receiving concurrent 5-fluorouracil- based chemotherapy. Results: Median follow-up was 2.7 years. Median overall survival (OS) was 1.8 years. Median OS after adjuvant RT/CT was 2.1 vs. 1.6 years for surgery alone (p = 0.001). The 2-y OS was 50% vs. 39%, and 5-y was 28% vs. 17% for patients receiving RT/CT vs. surgery alone. Univariate and multivariate analysis revealed that adverse prognostic factors were positive lymph nodes (risk ratio [RR] 1.3, p < 0.001) and high histologic grade (RR 1.2, p < 0.001). T3 tumor status was found significant on univariate analysis only (RR 1.1, p = 0.07). Conclusions: Results from recent clinical trials support the use of adjuvant chemotherapy in resected pancreatic cancer. The role of radiochemotherapy in adjuvant treatment of pancreatic cancer remains a topic of debate. Results from the Mayo Clinic suggest improved outcomes after the administration of adjuvant radiochemotherapy after a complete resection of invasive pancreatic malignancies.

  2. A Swedish study of chemoradiation in squamous cell carcinoma of the esophagus

    Stockeld, D.; Tennvall, J.; Wagenius, G.; Albertsson, Maria; Backman, L.; Brodin, O.; Cwikiel, M.; Granstroem, L.; Gustafsson, Gunnar; Gustavsson, Sven; Hambraeus, G.; Lewensohn, Rolf; Sjoestedt, S.; Strander, H.; Aaberg, B.; Fagerberg, J. [Danderyd Hospital, Stockholm (Sweden). Dept. of Surgery

    2001-07-01

    This multicenter study describes the development of a chemoradiation protocol for the treatment of non-metastatic squamous cell carcinoma of the esophagus. Eighty patients were treated with three courses of chemotherapy (cisplatinum and 5-fluorouracil) with concomitant radiotherapy (40 Gy) during the last two courses of chemotherapy. Esophagectomy was performed, when feasible. If no operation was performed, patients were planned to receive a target dose of 64 Gy. Toxicity was mainly attributable to hematological impairment and led to two adjustments of the treatment protocol (addition of filgrastim and lowering of the 5-fluorouracil dose). These changes made it possible to administer the planned treatment in a gradually higher proportion of patients (13/23 [57%] before changes of treatment compared with 30/36 [83%] after changes). Treatment-related mortality was 3.75% (3 patients, associated with leucopenic septicemia after chemotherapy). Fifty-four patients were resected. No per- or postoperative mortality was encountered. The complete response (pathological CR) rate in operated patients was 46% (27/59 patients) after chemoradiation. In the whole series the CR rate (including clinical CR for non-resected patients) was 44%. With a minimum follow-up of 37 months, the 3-year survival for the whole group was 31% compared with 57% for the CR patients. Total 5-year survival thus far (July 1999) is 26%.

  3. Restaging locally advanced rectal cancer by different imaging modalities after preoperative chemoradiation: a comparative study

    To compare the accuracy of different imaging modalities, alone and in combination in predicting findings at surgery after preoperative chemoradiation for locally advanced rectal cancer. Following chemoradiation, tumors were reclassified on the basis of findings on pelvic computed tomography (CT) (94 patients), endorectal ultrasonography (EUS) (138 patients) alone or by both CT and EUS (80 patients). The ability of the imaging modalities, to predict the pathologic T status, N status, and TNM stage at surgery was evaluated and compared. Mean age of the patients was 64.5 years (range 28–88 years); 55% were male. CT and EUS combined had a positive predictive value of 20% for pathologic pT1 stage, 29% for pT1, 29% for pT2, and 58% for pT3. Predictive values for the operative TNM stage were 50% for stage I, 45% for stage II, and 31% for stage III. These values did not exceed those for each modality alone. The performance of preoperative CT and EUS in predicting the T and TNM stage of rectal cancer at surgery is poor. Neither modality alone nor the two combined is sufficiently accurate to serve as the basis for decisions regarding treatment modification

  4. Approaches to chemoradiation therapy of patients with relapses and metastases of brain cancer

    A possibility and efficacy of chemoradiation therapy (CRT) in patients with relapses and metastases of breast cancer (BC) with the history of radical treatment (combination or chemoradiation therapy with hormone therapy) for local BC is shown. The treatment was differentiated depending of the disease localization. The patients with local relapses in the area of the breast were administered distance radiation therapy (DRT) and 4 courses of polychemotherapy (PCT) by TC protocol (Neotaxel 175 mg/m2 + Carboplatin 250-300 mg/m2). The patients with metastases to the brain were administered Temodal in radiomodifying dose of 75 mg/m2 per day during the course of DRT to the neurocranium, after 4 week break the patients were administered 6 courses of Temozolomide as monotherapy by the standard protocol. The patients with metastases to the skeleton were administered DRT with bisphonoites administration. The described techniques of CRT for relapses and metastases of breast cancer are moderately toxic and demonstrate a favorable profile of safety, which positively influences the quality of life of these patients.

  5. Gene Expression Profiling to Predict Outcome After Chemoradiation in Head and Neck Cancer

    Purpose: The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. Materials and Methods: We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling, we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. Results: Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Using Gene Set Enrichment analysis, several gene sets were found to be enriched in locoregional recurrences, although with high false-discovery rates. Previously published signatures for radiosensitivity, hypoxia, proliferation, 'wound,' stem cells, and chromosomal instability were not significantly correlated with outcome. However, a recently published signature for HNSCC defining a 'high-risk' group was shown to be predictive for locoregional control in our dataset. Conclusion: Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study

  6. Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study

    Background: In patients with loco-regionally advanced head and neck cancer conventionally fractionated radiotherapy alone results in poor loco-regional control and survival rates. Treatment intensification by simultaneous administration of cytotoxic drugs produces higher acute morbidity. Therefore chemical radioprotection of normal tissues may be of clinical benefit. Patients and Methods: In a pilot study patients with advanced nonresectable head neck cancer treated with conventionally fractionated radical radiotherapy (60 to 66 Gy total doses) and concomitantly given 5-fluorouracil as protracted venous infusion, 250 mg/sqm/24 h over the entire treatment period were given amifostine 300 mg absolutely before each fraction. Acute treatment related mobidity was scored according to CTC classification and loco-regional control and survival rates were estimated. Comparison was made with a historical control group of identical chemoradiation but without amifostine application. Results: Chemoradiation induced oral mucositis was delayed and showed significant lower degrees at all 10 Gy increments (p0.05). No significant toxicity was recorded with respect to blood pressure, serum calcium, potassium, hematologic parameters, emesis, nausea or body weight loss. Progression free survival and overall survival probability at 2 years were not statistically different in both cohorts. Conclusion: Amifostine given before each fraction of radiotherapy over 6 weeks has no cumulative toxicity, was well tolerated and may reduce treatment induced oral mucositis. No tumor protective effect was observed. (orig.)

  7. Artificial Neural Networks for Prediction of Response to Chemoradiation in HT29 Xenografts

    Purpose: To evaluate the feasibility of using neural networks for predicting treatment response by using longitudinal measurements of apparent diffusion coefficient (ADC) obtained from diffusion-weighted magnetic resonance imaging (DWMRI). Methods and Materials: Mice bearing HT29 xenografts were allocated to six treatment groups receiving different combinations of daily chemotherapy and/or radiation therapy for 2 weeks. T2-weighted and DWMR images were acquired before treatment, twice during fractionated chemoradiation (at days 4 and 11), and four times after treatment ended (at days 18, 25, 32, and 46). A tumor doubling growth delay (Tdelay) value was found for individual xenografts. ADC values and treatment groups (1-6) were used as input to a back propagation neural network (BPNN) to predict Tdelay. Results: When treatment group and ADC values from days 0, 4, 11, 18, 25, 32, and 46 were used as inputs to the BPNN, a strong correlation between measured and predicted Tdelay values was found (R = 0.731, p delay was 0.693 (p delay from tumor ADC values obtained from HT29 xenografts undergoing fractionated chemoradiation therapy.

  8. Tumour regression grading in patients with residual rectal cancer after preoperative chemoradiation

    Background and purpose: To explore the utility of tumour regression grading (TRG, the amount of residual tumour cells in relation to extension of fibrosis) after chemoradiation of rectal cancer. Materials and methods: Of 131 patients who received preoperative chemoradiation in the frame of the randomized trial, pathological complete response (pCR, TRG0), good regression (TRG1), moderate regression (TRG2), and poor regression (TRG3) were recorded in 17%, 31%, 31%, and 22% of patients, respectively. Results: The rates of ypN-positive category for TRG0, TRG1, TRG2, and TRG3 groups were 5%, 23%, 45%, and 46%, respectively, p = 0.001. When ypT-category and TRG were evaluated by the logistic regression analysis, only ypT-category remained significant for independent prediction of the risk for mesorectal nodal metastases, p = 0.006. The 4-year (median follow-up) disease-free survival (DFS) for TRG0, TRG1, TRG2, and TRG3 groups were 91%, 67%, 54%, and 47%. When patients with persistent disease (TRG1 vs. TRG2 vs. TRG3) were analyzed separately, TRG had no prognostic value for DFS, p = 0.402. Conclusions: TRG in patients with residual cancer had no prognostic value for the incidence of nodal disease and for DFS. Our findings and literature data question the need for the inclusion of TRG assessment into a routine pathological report.

  9. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    2010-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adjuvants for pesticide chemicals. 582.99...

  10. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    2010-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001 (c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide chemicals. 182.99...

  11. Effectiveness of spray adjuvants on reduction of spray drift

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  12. Residual tumor after neoadjuvant chemoradiation outside the radiation therapy target volume : a new prognostic factor for survival in esophageal cancer

    Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, Jannet C.; Mul, Veronique; van Dam, Go; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

    2014-01-01

    PURPOSE/OBJECTIVE(S): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. METHODS

  13. Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume : A New Prognostic Factor for Survival in Esophageal Cancer

    Muijs, Christina; Smit, Justin; Karrenbeld, Arend; Beukema, J.C.; Mul, Veronique; van Dam, Go; Hospers, Geke; Kluin, Phillip; Langendijk, Johannes; Plukker, John

    2014-01-01

    Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods

  14. Radiation dose does not influence anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation and transhiatal esophagectomy

    Neoadjuvant chemoradiation might increase anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. The aim of this study was to determine the influence of radiation dose on the incidence of leakage and stenosis. Fifty-three patients with esophageal cancer received neoadjuvant chemoradiation (23 × 1.8 Gy) (combined with Paclitaxel and Carboplatin) followed by a transhiatal esophagectomy between 2009 and 2011. On planning CT, the future anastomotic region was determined and the mean radiation dose, V20, V25, V30, V35 and V40 were calculated. Logistic regression analysis was conducted to examine determinants of anastomotic leakage and stenosis. Anastomotic leaks occurred in 13 of 53 patients (25.5%) and anastomotic stenosis occurred in 24 of 53 patients (45.3%). Median follow-up was 20 months. Logistic regression analysis showed that mean dose, V20-V40, age, co-morbidity, method of anastomosis, operating time and interval between last radiotherapy treatment and surgery were not predictors of anastomotic leakage and stenosis. A radiation dose of 23 × 1.8 Gy on the future anastomotic region has no influence on the occurrence of anastomotic leakage and stenosis in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by transhiatal esophagectomy

  15. Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Tod J Merkel

    2014-01-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax a...

  16. 37 CFR 2.42 - Concurrent use.

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Concurrent use. 2.42 Section... COMMERCE RULES OF PRACTICE IN TRADEMARK CASES The Written Application § 2.42 Concurrent use. An application..., and the mode of use for which applicant seeks registration; and also shall state, to the extent of...

  17. Declarative interpretations of session-based concurrency

    Cano, Mauricio; Rueda, Camilo; López-Acosta, Hugo-Andrés;

    2015-01-01

    paper, we investigate the relationship between operational and declarative models of session-based concurrency. We propose two interpretations of session π-calculus processes as declarative processes in linear concurrent constraint programming (lcc). They offer a basis on which both operational and...

  18. New concurrent iterative methods with monotonic convergence

    Yao, Qingchuan [Michigan State Univ., East Lansing, MI (United States)

    1996-12-31

    This paper proposes the new concurrent iterative methods without using any derivatives for finding all zeros of polynomials simultaneously. The new methods are of monotonic convergence for both simple and multiple real-zeros of polynomials and are quadratically convergent. The corresponding accelerated concurrent iterative methods are obtained too. The new methods are good candidates for the application in solving symmetric eigenproblems.

  19. An Approach to Concurrent TTCN Test Generation

    BI Jun; WU Jianping

    1999-01-01

    The basis of distributed system conformance testing is to test theconformance of each entity with its standard. This paper addresses theapproach to entity conformance testing based on concurrent TTCN. First apreliminary framework for entity conformance testing is introduced and aspecification model CEBE is presented. Then a test generation method,which could directly derive concurrent TTCN test suite from CEBE, isproposed.

  20. How does concurrent sourcing affect performance?

    Mols, Niels Peter

    2010-01-01

    Abstract Purpose – “Concurrent sourcing” is a term used by Parmigiani to describe the phenomenon where a firm simultaneously buys and makes the same good or service. The purpose of this paper is to develop propositions that suggest how concurrent sourcing affects performance. Design/methodology/a...

  1. Concurrent sourcing and external supplier opportunism

    Mols, Niels Peter

    When a firm simultaneously makes and buys the same components then the firm uses concurrent sourcing. This paper presents an agency model for explaining how and when concurrent sourcing reduces the likelihood of external supplier opportunism. In the proposed model, the external supplier’s expecte...

  2. A Temporal Concurrent Constraint Programming Calculus

    Palamidessi, Catuscia; Valencia Posso, Frank Darwin

    2001-01-01

    The tcc model is a formalism for reactive concurrent constraint programming. In this paper we propose a model of temporal concurrent constraint programming which adds to tcc the capability of modeling asynchronous and non-deterministic timed behavior. We call this tcc extension the ntcc calculus...

  3. Concurrent partnerships and HIV: an inconvenient truth.

    Epstein, Helen; Morris, Martina

    2011-01-01

    The strength of the evidence linking concurrency to HIV epidemic severity in southern and eastern Africa led the Joint United Nations Programme on HIV/AIDS and the Southern African Development Community in 2006 to conclude that high rates of concurrent sexual partnerships, combined with low rates of male circumcision and infrequent condom use, are major drivers of the AIDS epidemic in southern Africa. In a recent article in the Journal of the International AIDS Society, Larry Sawers and Eileen Stillwaggon attempt to challenge the evidence for the importance of concurrency and call for an end to research on the topic. However, their "systematic review of the evidence" is not an accurate summary of the research on concurrent partnerships and HIV, and it contains factual errors concerning the measurement and mathematical modelling of concurrency.Practical prevention-oriented research on concurrency is only just beginning. Most interventions to raise awareness about the risks of concurrency are less than two years old; few evaluations and no randomized-controlled trials of these programmes have been conducted. Determining whether these interventions can help people better assess their own risks and take steps to reduce them remains an important task for research. This kind of research is indeed the only way to obtain conclusive evidence on the role of concurrency, the programmes needed for effective prevention, the willingness of people to change behaviour, and the obstacles to change. PMID:21406080

  4. Concurrent partnerships and HIV: an inconvenient truth

    Epstein Helen

    2011-03-01

    Full Text Available Abstract The strength of the evidence linking concurrency to HIV epidemic severity in southern and eastern Africa led the Joint United Nations Programme on HIV/AIDS and the Southern African Development Community in 2006 to conclude that high rates of concurrent sexual partnerships, combined with low rates of male circumcision and infrequent condom use, are major drivers of the AIDS epidemic in southern Africa. In a recent article in the Journal of the International AIDS Society, Larry Sawers and Eileen Stillwaggon attempt to challenge the evidence for the importance of concurrency and call for an end to research on the topic. However, their "systematic review of the evidence" is not an accurate summary of the research on concurrent partnerships and HIV, and it contains factual errors concerning the measurement and mathematical modelling of concurrency. Practical prevention-oriented research on concurrency is only just beginning. Most interventions to raise awareness about the risks of concurrency are less than two years old; few evaluations and no randomized-controlled trials of these programmes have been conducted. Determining whether these interventions can help people better assess their own risks and take steps to reduce them remains an important task for research. This kind of research is indeed the only way to obtain conclusive evidence on the role of concurrency, the programmes needed for effective prevention, the willingness of people to change behaviour, and the obstacles to change.

  5. Interval-based Specification of Concurrent Objects

    Løvengreen, Hans Henrik; Sørensen, Morten U.

    1998-01-01

    We propose a logic for specifying the behaviour of concurrent objects, ie. concurrent entities that invoke operation of each other. The logic is an interval logic whith operation invocatins as primitive formulas. The strengths and deficiencies of the logic are illustrated by specifying a variety of...

  6. Updates of Adjuvant Therapy in Pancreatic Cancer: Where Are We and Where Are We Going? Highlights from the '2010 ASCO Annual Meeting'. Chicago, IL, USA. June 4-8, 2010

    Jia Li

    2010-07-01

    Full Text Available Pancreatic cancer represents the 4th leading cause of cancer deaths in the United States. Surgical resection remains the only potential curative approach. Current standard adjuvant therapy is gemcitabine monotherapy for 6 months. This year several trials investigated other combinations with or without molecular target agents, with or without concurrent radiation attempting to optimize adjuvant therapy. Several abstracts presented at the 2010 American Society of Clinical Oncology (ASCO Annual Meeting are highlighted here and will be further discussed in this review article. Abstracts #4012, #4059, and TPS226 added immunotherapy to adjuvant treatment. Abstract #4034 demonstrated lack of efficacy by adding either cetuximab or bevacizumab to known adjuvant therapies. Abstract e14625 combined S-1 to gemcitabine and abstract #4113 demonstrated a positive correlation between symptoms and CA 19-9 levels with the length of survival

  7. Administration of Concurrent Vaginal Brachytherapy During Chemotherapy for Treatment of Endometrial Cancer

    Nagar, Himanshu; Boothe, Dustin; Parikh, Amar; Yondorf, Menachem; Parashar, Bhupesh [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Gupta, Divya; Holcomb, Kevin; Caputo, Thomas [Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Chao, K. S. Clifford; Nori, Dattatreyudu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9006@med.cornell.edu [Department of Radiation Oncology, Weill Cornell Medical College of Cornell University, New York, New York (United States)

    2013-11-15

    Purpose: To evaluate the tolerability and toxicity of administering vaginal brachytherapy (VB) concurrently during chemotherapy compared with the sequential approach for patients with endometrial cancer. Methods and Materials: A retrospective analysis of 372 surgically staged patients with endometrial cancer American Joint Committee on Cancer 2009 stages I to IV treated with adjuvant postoperative radiation therapy (RT) at our institution from 2001 to 2012 was conducted. All patients received VB + external beam RT (EBRT) + 6 cycles of adjuvant carboplatin- and paclitaxel-based chemotherapy. The VB mean dose was 15.08 Gy (range, 15-20 Gy), with 3 to 4 weekly applications, and the EBRT mean dose was 45 Gy delivered with 3-dimensional or intensity modulated RT techniques. Hematologic, gastrointestinal (GI), and genitourinary (GU) toxicities were assessed by Common Toxicity Criteria (CTC) and compared between sequential and concurrent chemotherapy and VB schedules. Results: Among patients who received RT and adjuvant chemotherapy, 180 of 372 patients (48%) received RT sandwiched between cycles 3 and 4 of chemotherapy. A separate group of 192 patients (52%) were treated with VB during the first 3 cycles of chemotherapy, with a weekly application on nonchemotherapy days, and received the EBRT portion in a sandwiched fashion. Patients treated with VB during chemotherapy had a decreased overall treatment time by 4 weeks (P<.001; 95% confidence interval: 3.99-4.02) and sustained no difference in CTC-graded acute hematologic, GI, or GU toxicities in comparison with the patients treated with VB and chemotherapy in a sequential manner (P>.05). CTC grade 3 or 4 hematologic, GI, and GU toxicities were zero. Conclusions: VB during chemotherapy is well tolerated, decreases overall treatment time, and does not render more toxicity than the sequential regimen.

  8. Gene Expression Changes in Cervical Squamous Cell Carcinoma After Initiation of Chemoradiation and Correlation With Clinical Outcome

    Purpose: The purpose of this study was to investigate early gene expression changes after chemoradiation in a human solid tumor, allowing identification of chemoradiation-induced gene expression changes in the tumor as well as the tumor microenvironment. In addition we aimed to identify a gene expression profile that was associated with clinical outcome. Methods and Materials: Microarray experiments were performed on cervical cancer specimens obtained before and 48 h after chemoradiation from 12 patients with Stage IB2 to IIIB squamous cell carcinoma of the cervix treated between April 2001 and August 2002. Results: A total of 262 genes were identified that were significantly changed after chemoradiation. Genes involved in DNA repair were identified including DDB2, ERCC4, GADD45A, and XPC. In addition, significantly regulated cell-to-cell signaling pathways included insulin-like growth factor-1 (IGF-1), interferon, and vascular endothelial growth factor signaling. At a median follow-up of 41 months, 5 of 12 patients had experienced either local or distant failure. Supervised clustering analysis identified a 58-gene set from the pretreatment samples that were differentially expressed between patients with and without recurrence. Genes involved in integrin signaling and apoptosis pathways were identified in this gene set. Immortalization-upregulated protein (IMUP), IGF-2, and ARHD had particularly marked differences in expression between patients with and without recurrence. Conclusions: Genetic profiling identified genes regulated by chemoradiation including DNA damage and cell-to-cell signaling pathways. Genes associated with recurrence were identified that will require validation in an independent patient data set to determine whether the 58-gene set associated with clinical outcome could be useful as a prognostic assay

  9. A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

    Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m2/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m2. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC

  10. An evaluation of three dimensional conformal radiation therapy versus intensity modulated radiation therapy in radical chemoradiation of esophageal cancer: A dosimetric study

    Soumik Ghosh

    2012-01-01

    Full Text Available Aims: To evaluate the feasibility whether intensity-modulated radiotherapy (IMRT can be used to reduce doses to normal thoracic structures than three-dimensional conformal radiotherapy (3DCRT in treating esophageal cancer and to compare normal tissue complication probability (NTCP for lung between two treatment plans. Materials and Methods: A prospective study was carried out from 2009 to 2011, in which 15 inoperable patients of esophageal cancer who were suitable for radical chemoradiation were enrolled. All patients were treated with 3DCRT. In first phase, patients were treated with external beam radiation therapy (EBRT dose of 36Gy in 20 fractions in 4 weeks, along with concurrent weekly chemotherapy with cisplatinum and 5-fluorouracil (5 FU. In second phase, boost dose of 18Gy in 10 fractions in 2 weeks was given. An IMRT plan was generated for each patient. Plan sum of both the 3D CRT and IMRT plans were compared. Doses to critical structures and NTCP for lung were compared between 3DCRT and IMRT plans. Results: The mean lung dose and volumes of lung receiving 20 Gy, 10 Gy, and 5 Gy (V20, V10, and V5 were significantly lower with 3DCRT plans as compared to IMRT plans. The mean dose to heart and spinal cord was higher in 3DCRT arm. There was no difference in dose distribution to the liver between the 3D CRT and IMRT techniques. The NTCP for lung was lower with 3D CRT than IMRT. Conclusion: IMRT technique needs further dosimetric study as well as further clinical trials before implication of this technique replacing 3D CRT technique with escalated dose for the treatment of esophageal cancer in our setup. IMRT using seven fields provided no improvement over 3DCRT.

  11. A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

    Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan); Sagawa, Tamotsu [Division of Gastroenterology, Hokkaido Cancer Center, Sapporo (Japan); Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi [Department of Radiology, Sapporo Medical University School of Medicine, Sapporo (Japan); Takayama, Tetsuji [Department of Gastroenterology and Oncology, University of Tokushima, Tokushima (Japan); Kato, Junji, E-mail: jkato@sapmed.ac.jp [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan)

    2015-10-01

    Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m{sup 2}) and nedaplatin (50 mg/m{sup 2}) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m{sup 2}. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

  12. Gaudi components for concurrency: Concurrency for existing and future experiments

    Clemencic, M.; Funke, D.; Hegner, B.; Mato, P.; Piparo, D.; Shapoval, I.

    2015-05-01

    HEP experiments produce enormous data sets at an ever-growing rate. To cope with the challenge posed by these data sets, experiments’ software needs to embrace all capabilities modern CPUs offer. With decreasing memory/core ratio, the one-process-per-core approach of recent years becomes less feasible. Instead, multi-threading with fine-grained parallelism needs to be exploited to benefit from memory sharing among threads. Gaudi is an experiment-independent data processing framework, used for instance by the ATLAS and LHCbexperiments at CERN's Large Hadron Collider. It has originally been designed with only sequential processing in mind. In a recent effort, the frame work has been extended to allow for multi-threaded processing. This includes components for concurrent scheduling of several algorithms - either processingthe same or multiple events, thread-safe data store access and resource management. In the sequential case, the relationships between algorithms are encoded implicitly in their pre-determined execution order. For parallel processing, these relationships need to be expressed explicitly, in order for the scheduler to be able to exploit maximum parallelism while respecting dependencies between algorithms. Therefore, means to express and automatically track these dependencies need to be provided by the framework. In this paper, we present components introduced to express and track dependencies of algorithms to deduce a precedence-constrained directed acyclic graph, which serves as basis for our algorithmically sophisticated scheduling approach for tasks with dynamic priorities. We introduce an incremental migration path for existing experiments towards parallel processing and highlight the benefits of explicit dependencies even in the sequential case, such as sanity checks and sequence optimization by graph analysis.

  13. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    Cho, Hanbyoul [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, Byung-Ho [Cancer Biostatistics Branch, Research Institute for National Cancer Control and Evaluation, National Cancer Center, Goyang (Korea, Republic of); Kim, Seok Mo [Department of Obstetrics and Gynecology, Chonnam National University School of Medicine, Gwangju (Korea, Republic of); Cho, Chi-Heum [Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu (Korea, Republic of); Kim, Byoung Gie [Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ryu, Hee-Sug [Department of Obstetrics and Gynecology, Ajou University School of Medicine, Suwon (Korea, Republic of); Kang, Soon Beom [Department of Obstetrics and Gynecology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Kim, Jae-Hoon, E-mail: jaehoonkim@yuhs.ac [Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Institute of Women' s Life Medical Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-09-01

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m{sup 2} was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study.

  14. A Phase 2 Trial of Radiation Therapy With Concurrent Paclitaxel Chemotherapy After Surgery in Patients With High-Risk Endometrial Cancer: A Korean Gynecologic Oncologic Group Study

    Purpose: A phase 2 study was completed by the Korean Gynecologic Oncologic Group to evaluate the efficacy and toxicity of concurrent chemoradiation with weekly paclitaxel in patients with high-risk endometrial cancer. Methods and Materials: Pathologic requirements included endometrial endometrioid adenocarcinoma stages III and IV. Radiation therapy consisted of a total dose of 4500 to 5040 cGy in 5 fractions per week for 6 weeks. Paclitaxel 60 mg/m2 was administered once weekly for 5 weeks during radiation therapy. Results: Fifty-seven patients were enrolled between January 2006 and March 2008. The median follow-up time was 60.0 months (95% confidence interval [CI], 51.0-58.2). All grade 3/4 toxicities were hematologic and usually self-limited. There was no life-threatening toxicity. The cumulative incidence of intrapelvic recurrence sites was 1.9% (1/52), and the cumulative incidence of extrapelvic recurrence sites was 34.6% (18/52). The estimated 5-year disease-free and overall survival rates were 63.5% (95% CI, 50.4-76.5) and 82.7% (95% CI, 72.4-92.9), respectively. Conclusions: Concurrent chemoradiation with weekly paclitaxel is well tolerated and seems to be effective for high-risk endometrioid endometrial cancers. This approach appears reasonable to be tested for efficacy in a prospective, randomized controlled study

  15. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction ch...

  16. New generation adjuvants--from empiricism to rational design.

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-01

    Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. PMID:26022561

  17. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    Mentha Gilles

    2011-06-01

    Full Text Available Abstract Background Extrahepatic biliary duct cancers (EBDC are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT in a series of patients treated in one institution. Methods Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma received 3D conformal external beam RT to a median total dose of 50.4Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%. Surgical margins were negative in 11 patients (48%, narrow in 2 (9%, and microscopically involved in 8 (35%. Eleven patients (55% had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98. Results Acute gastrointestinal grade 2 toxicity (RTOG scale was recorded in 2 patients (9%. Nausea or vomiting grade 1 and 2 was observed in 8 (35% and 2 patients (9% respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung. No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p = 0.04. The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p = 0.07. Conclusions Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor

  18. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98). Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p = 0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p = 0.07). Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location

  19. Nanoparticle-Based Brachytherapy Spacers for Delivery of Localized Combined Chemoradiation Therapy

    Kumar, Rajiv, E-mail: r.kumar@neu.edu [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Belz, Jodi [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Markovic, Stacey [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Jadhav, Tej; Fowle, William [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Niedre, Mark [Department of Electrical and Computer Engineering, Northeastern University, Boston, Massachusetts (United States); Cormack, Robert; Makrigiorgos, Mike G. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States); Sridhar, Srinivas [Nanomedicine Science and Technology Center, Northeastern University, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts (United States)

    2015-02-01

    Purpose: In radiation therapy (RT), brachytherapy-inert source spacers are commonly used in clinical practice to achieve high spatial accuracy. These implanted devices are critical technical components of precise radiation delivery but provide no direct therapeutic benefits. Methods and Materials: Here we have fabricated implantable nanoplatforms or chemoradiation therapy (INCeRT) spacers loaded with silica nanoparticles (SNPs) conjugated containing a drug, to act as a slow-release drug depot for simultaneous localized chemoradiation therapy. The spacers are made of poly(lactic-co-glycolic) acid (PLGA) as matrix and are physically identical in size to the commercially available brachytherapy spacers (5 mm × 0.8 mm). The silica nanoparticles, 250 nm in diameter, were conjugated with near infrared fluorophore Cy7.5 as a model drug, and the INCeRT spacers were characterized in terms of size, morphology, and composition using different instrumentation techniques. The spacers were further doped with an anticancer drug, docetaxel. We evaluated the in vivo stability, biocompatibility, and biodegradation of these spacers in live mouse tissues. Results: The electron microscopy studies showed that nanoparticles were distributed throughout the spacers. These INCeRT spacers remained stable and can be tracked by the use of optical fluorescence. In vivo optical imaging studies showed a slow diffusion of nanoparticles from the spacer to the adjacent tissue in contrast to the control Cy7.5-PLGA spacer, which showed rapid disintegration in a few days with a burst release of Cy7.5. The docetaxel spacers showed suppression of tumor growth in contrast to control mice over 16 days. Conclusions: The imaging with the Cy7.5 spacer and therapeutic efficacy with docetaxel spacers supports the hypothesis that INCeRT spacers can be used for delivering the drugs in a slow, sustained manner in conjunction with brachytherapy, in contrast to the rapid clearance of the drugs when

  20. Chemoradiation of unresectable pancreatic carcinoma: impact of pretreatment hemoglobin level on patterns of failure

    Aim: To evaluate, in patients with locally advanced pancreatic carcinoma undergoing concomitant chemoradiation, the impact of pretreatment hemoglobin (Hb) concentration on the outcome in terms of clinical response, local control, metastasis-free survival, disease-free survival, and overall survival. Patients and Methods: 30 patients undergoing concomitant chemoradiation (5-fluorouracil [5-FU], 1,000 mg/m2/day, continuous i.v. infusion days 1-4 of radiotherapy) and external beam radiotherapy (50.4-59.4 Gy) were divided into two groups based on pretreatment median Hb value (11.5 g/dl). The potential prognostic factors examined besides Hb concentration were: tumor site (head vs body-tail), sex (female vs male), cN (cN0 vs cN1), dose of external beam radiotherapy (50.4 Gy vs 59.4 Gy), presence of jaundice at diagnosis (yes vs no), weight loss at diagnosis (≥ 5 kg vs 11.5 g/dl. Metastasis-free survival was 5.1 months in patients with an Hb ≤ 11.5 g/dl and 10.7 months in patients with an Hb > 11.5 g/dl (p = 0.010). Median actuarial disease-free survival was 5.1 and 10.2 months in patients with an Hb ≤ 11.5 and > 11.5 g/dl, respectively (p = 0.026). Median actuarial overall survival was 7.5 and 10.3 months in patients with an Hb ≤ 11.5 and > 11.5 g/dl, respectively (p = 0.039). On multivariate analysis, Hb concentration at diagnosis was the only factor prognostically correlated with metastasis-free survival (p = 0.026), disease-free survival (p = 0.032), and overall survival (p = 0.048). Conclusion: In a group of patients with locally advanced pancreatic carcinoma treated with chemoradiation, a significant correlation was observed between pretreatment Hb levels and metastasis-free survival, disease-free survival, and overall survival. (orig.)

  1. Concurrent chemo-radiotherapy in the treatment of early breast cancer: Current status

    Nabil Ismaili

    2013-01-01

    Full Text Available Concurrent chemo-radiotherapy (CCRT in early breast cancer was investigated by few authors and remains controversial. This treatment is more commonly used for locally advanced breast cancer and showed high rate of complete pathological response. A search of articles published in English literature, between 1980 and November 2012, was conducted on Medline using the following terms: "breast cancer", "chemotherapy", "concurrent radiotherapy", and "Trastuzumab". We identified five phase I/II trials and three randomized phase three trials evaluating concurrent chemoradiotherapy in the adjuvant of breast cancer. In patients with early breast cancer having positive lymph nodes, phases III clinical trials showed that CCRT improved local control after conservative breast surgery. However, these randomized trials used non-standard regimen: Cyclophosphamide, methotrexate and fluorouracil (CMF or fluorouracil, mitoxantrone and cyclophosphamide (FNC. In addition, in phases II clinical trials, concurrent use of taxanes and anthracycline with standard whole-breast irradiation showed high rate of toxicity: Pulmonary toxicity with taxane; and cardiac and skin toxicity with anthracycline. Consequentely, CCRT is not be used in practice because of concerns of toxicity with the standard drugs (anthracyclines and taxanes and radiation. Anthracyclines with partial breast irradiation (PBI was feasible according to one phase I clinical trial, and should be investigated in randomized clinical trials. Concurrent Trastuzumab plus radiotherapy is safe and can be used in HER2-positive breast cancer; in this case, cardiac volume sparing and patient selections for internal mammary chain irradiation are highly recommended. The present paper aimed to review the current data evaluating the efficacy and safety of CCRT in early breast cancer.

  2. Concurrent Manipulation of Expanded AVL Trees

    章寅; 许卓群

    1998-01-01

    The concurrent manipulation of an expanded AVL tree(EAVL tree)s considered in this paper.The presented system can support any number of concurrent processes which perform searching,insertion and deletion on the tree.Simulation results indicate the high performance of the system.Elaborate techniques are used to achieve such a system unavailable based on any known algorithms.Methods developed in this paper may provide new insights into other problems in the area of concurrent search structure manipulation.

  3. Distributed Management of Concurrent Web Service Transactions

    Alrifai, Mohammad; Dolog, Peter; Balke, Wolf-Tilo;

    2009-01-01

    consistency in the open and dynamic environment of Web services, where interleaving business transactions enter and exit the system independently, remains an open issue. In this paper, we address this problem and propose an architecture that supports concurrency control on the Web services level. An extension...... to the standard framework for Web service transactions is proposed to enable detecting and handling transactional dependencies between concurrent business transactions. We also present an optimistic protocol for concurrency control that can be deployed in a fully distributed fashion within the...

  4. 17-Week Delay Surgery after Chemoradiation in Rectal Cancer with Complete Pathological Response

    Marisa D. Santos

    2015-01-01

    Full Text Available Neoadjuvant chemoradiation (CRT followed by curative surgery still remains the standard of care for locally advanced rectal cancer (LARC. The main purpose of this multimodal treatment is to achieve a complete pathological tumor response (ypCR, with better survival. The surgery delay after CRT completion seems to increase tumor response and ypCR rate. Usually, time intervals range from 8 to 12 weeks, but the maximum tumor regression may not be seen in rectal adenocarcinomas until several months after CRT. About this issue, we report a case of a 52-year-old man with LARC treated with neoadjuvant CRT who developed, one month after RT completion, an acute myocardial infarction. The need to increase the interval between CRT and surgery for 17 weeks allowed a curative surgery without morbidity and an unexpected complete tumor response in the resected specimen (given the parameters presented in pelvic magnetic resonance imaging (MRI performed 11 weeks after radiotherapy completion.

  5. Modern radiation therapy and potential fertility preservation strategies in patients with cervical cancer undergoing chemoradiation

    Young patients with cervical cancer who undergo chemoradiation might be interested in fertility preservation, not only dependent upon the use of a gestational carrier as maybe achieved by the use of ovarian transposition and cryo-conservation of oocytes or ovarian tissue, but may prefer to carry pregnancy to term after cancer treatment. The latter approach is a non-established concept needing both modern radiation therapy approaches as well as modifications -if at all possible- in current recommendations for target volume delineation to spare dose to the unaffected uterus. Future strategies to serve selected patients in this respect should only be conducted in prospective clinical evaluations and are critically discussed in this article

  6. The effect of chemoradiation therapy on pituitary-thyroid system function in children suffering Hodgkin's disease

    The functional status of the thyroid gland was evaluated in 63 children with Hodgkin's disease, aged 4-15 years, before, in the course of and 5 years after chemoradiation therapy. Thyroxin (T4), triiodothyronine (T) and thyroid-stimulating hormone (TSH) in the blood were assayed. The disease was shown to disrupt the pituitary-thyroid system leading to hypothyroidism development which progressed as the disease advanced. While chemotherapy brought the balance between the peripheral thyroid hormone levels and TSH back to normal, thyroid function decrease again following radiotherapy of the neck. The most pronounced and persistent failure of the pituitary-thyroid system was registered with the total target dose of 30 Gy and higher. Irradiation in a dose of 20 Gy caused less disruption and the function was spontaneously restored within 12 months after the treatment

  7. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.;

    2013-01-01

    external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of......Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we...... estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of...

  8. Rigosertib Is a More Effective Radiosensitizer Than Cisplatin in Concurrent Chemoradiation Treatment of Cervical Carcinoma, In Vitro and In Vivo

    Purpose: To compare rigosertib versus cisplatin as an effective radiosensitizing agent for cervical malignancies. Methods and Materials: Rigosertib and cisplatin were tested in cervical cancer cell lines, HeLa and C33A. A 24-hour incubation with rigosertib and cisplatin, before irradiation (2-8 Gy), was used for clonogenic survival assays. Cell cycle analysis (propidium iodide staining) and DNA damage (γ-H2AX expression) were evaluated by fluorescence-activated cell sorter cytometry. Rigosertib was also tested in vivo in tumor growth experiments on cervical cancer xenografts. Results: Rigosertib was demonstrated to induce a G2/M block in cancer cells. Survival curve comparison revealed a dose modification factor, as index of radiosensitization effect, of 1.1-1.3 for cisplatin and 1.4-2.2 for rigosertib. With 6-Gy irradiation, an increase in DNA damage of 15%-25% was achieved in both HeLa and C33A cells with cisplatin pretreatment, and a 71-108% increase with rigosertib pretreatment. In vivo tumor growth studies demonstrated higher performance of rigosertib when compared with cisplatin, with 53% longer tumor growth delay. Conclusions: Rigosertib was more effective than cisplatin when combined with radiation and caused minimal toxicity. These data support the need for clinical trials with rigosertib in combination therapy for patients with cervical carcinoma

  9. Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

    Purpose: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. Methods and Materials: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. Results: At a median follow-up time of 52.6 months (95% CI 46.1–56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Conclusions: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic

  10. Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era

    Amini, Arya [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); UC Irvine School of Medicine, Irvine, California (United States); Xiao Lianchun [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Suzuki, Akihiro; Hayashi, Yuki [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hofstetter, Wayne [Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Bhutani, Manoop S.; Lee, Jeffrey H.; Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2012-06-01

    Purpose: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. Methods and Materials: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. Results: At a median follow-up time of 52.6 months (95% CI 46.1-56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. Conclusions: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic treatment

  11. Rectum separation in patients with cervical cancer for treatment planning in primary chemo-radiation

    To proof feasibility of hydrogel application in patients with advanced cervical cancer undergoing chemo-radiation in order to reduce rectal toxicity from external beam radiation as well as brachytherapy. Under transrectal sonographic guidance five patients with proven cervical cancer underwent hydro gel (20 cc) instillation into the tip of rectovaginal septum adherent to posterior part of the visible cervical tumor. Five days after this procedure all patients underwent T2 weighted transversal and sagittal MRI for brachytherapy planning. MRI protocol included T2 weighted fast spin echo (FSE) imaging in sagittal, coronal and para-axial orientation using an 1.5 Tesla MRI. Separation of anterior rectal wall and cervix was documented. Hydrogel application was uneventful in all patients and no toxicity was reported. Separation ranged from 7 to 26 mm in width (median 10 mm). The length of the separation varied between 18 and 38 mm (median 32 mm). In all patients displacement was seen in the posterior vaginal fornix, and/or at the deepest part of uterine cervix depending on the extension of the cul-de-sac in correlation to the posterior wall of the uterus. In patients with bulky tumor and/or deep (vaginal) extend of peritoneal cavity tumour was seen mainly cranial from the rectovaginal space and therefore above the hydrogeI application. Only in the extra-peritoneal (lower) part of the cervix a good separation could be achieved between the rectum and cervix. Hydrgel instillation in patients with cervial cancer undergoing chemoradiation is safe and feasible. Because of the loose tissue of the cul-de-sac and its intra- and extraperitoneal part, hydrogel instillation of 20 cc did not result in a sufficient separation of the cervix from anterior wall

  12. The adjuvancy of silicones: dependency on compartmentalization.

    Klykken, P C; White, K L

    1996-01-01

    Studies have been conducted in mice (B6C3F1) and rats (Sprague Dawley, Fischer 344) to investigate the adjuvancy potential of silicone mammary gel and the low molecular weight silicone fluid, octamethylcyclotetrasiloxane (D4). Dependent on the experimental conditions employed, a divergent data profile emerges. If the antigen (bovine serum albumin, BSA) is emulsified with either the gel or the D4 prior to intramuscular immunization, an amplified anti-BSA IgG antibody response, as measured by multipoint ELISA methodology, is noted over the 8 week measurement period. In parallel studies, a variety of non-silicone personal care ingredients (lanolin, white mineral oil, isopropyl palmitate) were also capable of amplifying this humoral response relative to the non-adjuvant phosphate buffered saline control. These observations are consistent with the empirical knowledge that hydrophobic substances tend to augment immune responses. However, under conditions in which the antigen is not blended with the silicone prior to immunization, normal immune responses are noted. In short (10 day) and long (180 day) term gel implant studies, the optimal IgM and IgG antibody responses, as determined in the antibody forming cell assay, were equivalent between the gel implanted and control animals. Moreover, under similar exposure conditions, no adjuvancy was noted in the three Host Resistance models (B16F10 Melanoma, Listeria monocytogenes, and Streptococcus pneumoniae) tested. Antibody forming cell studies conducted after 28 days of oral or inhalation exposure to D4 have also yielded responses similar to the non-silicone exposed vehicle controls. Collectively, these data suggest that in the absence of premixing the antigen with the silicone test material, there does not appear to be any silicone induced adjuvant response. PMID:8565549

  13. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes "standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  14. Impact of adjuvant chemotherapy for gliomatosis cerebri

    Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC

  15. Chitosan as an adjuvant for poliovaccine.

    Ghendon, Y; Markushin, S; Akopova, I; Koptiaeva, I; Krivtsov, G

    2011-05-01

    The use of inactivated poliomyelitis vaccine is very important for eradicating poliomyelitis. However, this vaccine is not available readily in underdeveloped countries due to the high cost. Adjuvants can improve the immunogenicity of a vaccine and reduce the antigen dose required for vaccination, thus lowering the cost of the vaccine. Chitosan glutamate solution and a chitosan sulfate micro/nanoparticle suspension were tested as adjuvants for Imovax-inactivated poliovaccine and for inactivated monovalent poliovirus type 1, 2, and 3 vaccines obtained by inactivation of the attenuated Sabin poliovirus strains. Inactivated vaccines admixed with either chitosan glutamate or chitosan sulfate micro/nanoparticles and administered to mice showed significantly enhanced immunogenicity to poliovirus type 1, 2, and 3 strains compared to the respective vaccines administered without chitosan. Chitosan preparations increased the immunogenicity of 1:2 and 1:4 diluted inactivated Sabin strain preparations in mice 8- to 16-fold, so that the neutralizing antibody titers after vaccination with adjuvanted diluted vaccine were equal to those obtained after vaccination with undiluted vaccine administered without chitosan. Neutralizing antibodies could be detected in sera of rats vaccinated with undiluted, 1:10, and 1:100 diluted Imovax vaccine admixed with chitosan sulfate micro/nanoparticles, although in the control group, vaccination only with the undiluted vaccine resulted in antibody production. These results show that the chitosan glutamate solution and chitosan sulfate micro/nanoparticle suspension can significantly improve the immunogenicity of various poliovaccines, and reduce the effective antigen dose. PMID:21412793

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

    Purpose: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). Methods and Materials: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m2 plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. Results: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. Conclusions: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

  17. Prospective randomized trial to compare accelerated (six fractions a week radiotherapy against concurrent chemoradiotherapy (using conventional fractionation in locally advanced head and neck cancers

    Manoj Gupta

    2015-01-01

    Full Text Available Background: Concurrent chemoradiation (CCRT is currently considered to be the standard of care in locally advanced head and neck cancer. The optimum radiotherapy schedule for best local control and acceptable toxicity is not yet clear. We aimed at shortening of treatment time by using accelerated radiation, thereby comparing the disease response, loco-regional tumor control and tolerability of accelerated radiation (six fractions per week against CCRT in locally advanced head and neck cancer. Materials and Methods: We conducted the prospective randomized study for a period of 2 years from June 2011 to May 2013 in 133 untreated patients of histologically confirmed squamous cell carcinoma of head and neck. Study group (66 patients received accelerated radiotherapy with 6 fractions per week (66Gy/33#/5½ weeks. Control group (67 patients received CCRT with 5 fractions per week radiation (66 Gy/33#/6½ weeks along with intravenous cisplatin 30 mg/m 2 weekly. Tumor control, survival, acute and late toxicities were assessed. Results: Median overall treatment time was 38 days and 45 days in the accelerated radiotherapy and concurrent chemoradiation arm, respectively. At a median follow up of 12 months, 41 patients (62.1% in the accelerated radiotherapy arm and 47 patients (70.1% in the CCRT arm were disease free (P = 0.402. Local disease control was comparable in both the arms. Acute toxicities were significantly higher in the CCRT arm as compared with accelerated radiotherapy arm. There was no difference in late toxicities between the two arms. Conclusion: We can achieve, same or near to the same local control, with lower toxicities with accelerated six fractions per week radiation compared with CCRT especially for Indian population.

  18. CilkSpec: Optimistic Concurrency for Cilk

    Aga, Shaizeen D.; Krishnamoorthy, Sriram; Narayanasamy, Satish

    2015-11-15

    Recursive parallel programming models such as Cilk strive to simplify the task of parallel programming by enabling a simple divide-and-conquer model of programming. This model is effective in re- cursively partitioning work into smaller parts and combining their results. However, recursive work partitioning can impose additional constraints on concurrency than is implied by the true dependences in a program. In this paper, we present a speculation-based approach to alleviate the concurrency constraints imposed by such recursive parallel programs. We design a runtime infrastructure that supports speculative execution and a predictor to accurately learn and identify opportunities to relax extraneous concurrency constraints. Experimental evaluation demonstrates that speculative relaxation of concurrency constraints can deliver gains of up to 1.6× on 30 cores over baseline Cilk.

  19. Mining sequential patterns to explain concurrent counterexamples

    Leue, Stefan; Tabaei Befrouei, Mitra

    2013-01-01

    Concurrent systems are often modeled using an interleaving semantics. Since system designers tend to think sequentially, it is highly probable that they do not foresee some interleavings that their model encompasses. As a consequence, one of the main sources of failure in concurrent systems is unforeseen interleavings. In this paper, we devise an automated method for revealing unforeseen interleavings in the form of sequences of actions derived from counterexamples obtained by explicit state ...

  20. Flow Java: Declarative Concurrency for Java

    Drejhammar, Frej

    2005-01-01

    This thesis presents the design, implementation, and evaluation of Flow Java, a programming language for the implementation of concurrent programs. Flow Java adds powerful programming abstractions for automatic synchronization of concurrent programs to Java. The abstractions added are single assignment variables (logic variables) and futures (read-only views of logic variables). The added abstractions conservatively extend Java with respect to types, parameter passing, a...

  1. Constraint Solving for Diagnosing Concurrency Bugs

    Khoshnood, Sepideh

    2015-01-01

    Programmers often have to spend a significant amount of time inspecting the software code and execution traces to identify the root cause of a software bug. For a multithreaded program, debugging is even more challenging due to the subtle interactions between concurrent threads and the often astronomical number of possible interleavings. In this work, we propose a logical constraint-based symbolic analysis method to aid in the diagnosis of concurrency bugs and find their root causes, which ca...

  2. Proving correctness of Timed Concurrent Constraint Programs

    de Boer, F.S.; Gabbrielli, M.; Meo, M.C.

    2002-01-01

    A temporal logic is presented for reasoning about the correctness of timed concurrent constraint programs. The logic is based on modalities which allow one to specify what a process produces as a reaction to what its environment inputs. These modalities provide an assumption/commitment style of specification which allows a sound and complete compositional axiomatization of the reactive behavior of timed concurrent constraint programs.

  3. Parallelism Via Concurrency at Multiple Levels

    Latif, Kamran

    2014-01-01

    In this paper we examine the key elements determining the best performance of computing by increasing the frequency of a single chip and to get the minimum latency during execution of the programs to achieve best possible output. It is not enough to provide concurrent improvements in the hardware as Software also have to introduce concurrency in order to exploit the parallelism. The software parallelism is defined by the control and data dependency of programs whereas Hardware refers to the t...

  4. Concurrent planning and execution for autonomous robots

    Simmons, Reid G.

    1992-01-01

    The Task Control Architecture (TCA) provides communication and coordination facilities to construct distributed, concurrent robotic systems. The use of TCA in a system that walks a legged robot through rugged terrain is described. The walking system, as originally implemented, had a sequential sense-plan-act control cycle. Utilizing TCA features for task sequencing and monitoring, the system was modified to concurrently plan and execute steps. Walking speed improved by over 30 percent, with only a relatively modest conversion effort.

  5. Templet: a Markup Language for Concurrent Programming

    Vostokin, Sergey

    2014-01-01

    In this paper we propose a new approach to the description of a network of interacting processes in a traditional programming language. Special programming languages or extensions to sequential languages are usually designed to express the semantics of concurrent execution. Using libraries in C++, Java, C#, and other languages is more practical way of concurrent programming. However, this method leads to an increase in workload of a manual coding. Besides, stock compilers can not detect seman...

  6. Concurrent partnerships and HIV: an inconvenient truth

    Epstein Helen; Morris Martina

    2011-01-01

    Abstract The strength of the evidence linking concurrency to HIV epidemic severity in southern and eastern Africa led the Joint United Nations Programme on HIV/AIDS and the Southern African Development Community in 2006 to conclude that high rates of concurrent sexual partnerships, combined with low rates of male circumcision and infrequent condom use, are major drivers of the AIDS epidemic in southern Africa. In a recent article in the Journal of the International AIDS Society, Larry Sawers ...

  7. SACO: Static analyzer for concurrent objects

    Albert Albiol, Elvira; Arenas Sánchez, Purificación; Flores Montoya, A.; Genaim, Samir; Gómez-Zamalloa Gil, Miguel; Martín Martín, Enrique; Puebla, G.; Román Díez, Guillermo

    2014-01-01

    We present the main concepts, usage and implementation of SACO, a static analyzer for concurrent objects. Interestingly, SACO is able to infer both liveness(namely termination and resource boundedness) and safety properties (namely deadlock freedom) of programs based on concurrent objects. The system integrates auxiliary analyses such as points-to and may-happen-in-parallel, which are essential for increasing the accuracy of the aforementioned more complex properties. SACO provides accurate ...

  8. Micro-transactions for concurrent data structures

    Meawad, Fadi; Iyer, Karthik; Schoeberl, Martin;

    2013-01-01

    Transactional memory is a promising technique for enforcing disciplined access to shared data in a multiprocessor system. Transactional memory simplifies the implementation of a variety of concurrent data structures. In this paper, we study the benefits of a modest, real-time aware, hardware......, atomic instructions, and micro-transactions. Our results suggest that transactional memory is an interesting alternative to traditional concurrency control mechanisms....

  9. Concurrent Design of Embedded Control Software

    Groothuis, Marcel; Frijns, Raymond; Voeten, Jeroen; Broenink, Jan; Margaria, T.; Padberg, J. (Jan); Taentzer, G.; Levendovszky, T.; Lengyel, L.; Karsai, G.; Hardebolle, C.

    2009-01-01

    Embedded software design for mechatronic systems is becoming an increasingly time-consuming and error-prone task. In order to cope with the heterogeneity and complexity, a systematic model-driven design approach is needed, where several parts of the system can be designed concurrently. There is however a trade-off between concurrency efficiency and integration efficiency. In this paper, we present a case study on the development of the embedded control software for a real-world mechatronic sy...

  10. Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience.

    Cao, Jeffrey Q; Fisher, Barbara J; Bauman, Glenn S; Megyesi, Joseph F; Watling, Christopher J; Macdonald, David R

    2012-04-01

    The landmark Stupp study demonstrated a survival advantage with concomitant and adjuvant temozolomide (TMZ) with standard radiotherapy (RT) in glioblastoma multiforme (GBM) patients but excluded those older than 70 years. The prospective Roa study of older GBM patients treated with hypofractionated 3-week course RT demonstrated equivalence to standard 6-week course RT. Taken together, these trials suggest hypofractionated RT with TMZ may be a reasonable treatment option for elderly GBM patients. We conducted a retrospective review of GBM patients (age ≥60 years) treated with hypofractionated RT and temozolomide at our institution between 2000 and 2010. We identified 112 patients who received hypofractionated RT, with 57 receiving concurrent and adjuvant TMZ and 55 without concurrent chemotherapy. Of the 55 patients who received hypofractionated RT alone initially, 24 subsequently received TMZ as salvage treatment at time of progression. Among the concurrent RT + TMZ patients, mean age was 70 years (range 60-86), median KPS was 80 (range 30-100) and 24/57 (42%) received prior debulking surgery. Median overall survival (OS) among the RT + TMZ patients was 6.9 months (95% CI, 4.5-8.6). Patients without concurrent chemotherapy were similar in demographics (age, sex, corticosteroid use, KPS) except 34/55 (62%) were debulked (P-value 0.045.) Median OS was 9.3 months (95% CI, 5.9-11.8) (P-value 0.351). Sub-group analysis revealed patients treated with initial hypofractionated radiation with salvage TMZ had increased median OS of 13.3 months (95% CI, 9.9-19.3) (P-value 0.012). Our results suggest concurrent and adjuvant TMZ does not confer a survival benefit in elderly GBM patients. A sequential approach may be a more effective and efficient strategy by selecting responding patients who may benefit most from subsequent salvage chemotherapy. PMID:22105851

  11. Clinical outcomes of adjuvant radiation therapy and prognostic factors in early stage uterine cervical cancer

    Kim, Hyun Ju; Rhee, Woo Joong; Choi, Seo Hee; Kim, Gwi Eon; Kim, Yong Bae [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Nam, EunJi; Kim, Sang Wun; Kim, Sung Hoon [Dept. of Radiation Oncology, Obstetrics and Gynecology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To evaluate the outcomes of adjuvant radiotherapy (RT) and to analyze prognostic factors of survival in the International Federation of Gynecology and Obstetrics (FIGO) IB-IIA uterine cervical cancer. We retrospectively reviewed the medical records of 148 patients with FIGO IB-IIA uterine cervical cancer who underwent surgery followed by adjuvant RT at the Yonsei Cancer Center between June 1997 and December 2011. Adjuvant radiotherapy was delivered to the whole pelvis or an extended field with or without brachytherapy. Among all patients, 57 (38.5%) received adjuvant chemotherapy either concurrently or sequentially. To analyze prognostic factors, we assessed clinicopathologic variables and metabolic parameters measured on preoperative {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). To evaluate the predictive performance of metabolic parameters, receiver operating characteristic curve analysis was used. Overall survival (OS) and disease-free survival (DFS) were analyzed by the Kaplan-Meier method. The median follow-up period was 63.2 months (range, 2.7 to 206.8 months). Locoregional recurrence alone occurred in 6 patients, while distant metastasis was present in 16 patients, including 2 patients with simultaneous regional failure. The 5-year and 10-year OSs were 87.0% and 85.4%, respectively. The 5-year and 10-year DFSs were 83.8% and 82.5%, respectively. In multivariate analysis, pathologic type and tumor size were shown to be significant prognostic factors associated with both DFS and OS. In subset analysis of 40 patients who underwent preoperative PET/CT, total lesion glycolysis was shown to be the most significant prognostic factor among the clinicopathologic variables and metabolic parameters for DFS. Our results demonstrated that adjuvant RT following hysterectomy effectively improves local control. From the subset analysis of preoperative PET/CT, we can consider that metabolic parameters may hold prognostic

  12. Disparities in receipt of modern concurrent chemoradiotherapy in glioblastoma.

    Rhome, Ryan; Fisher, Rebecca; Hormigo, Adília; Parikh, Rahul R

    2016-06-01

    Temozolomide given concurrently with radiation after resection/biopsy improves survival in glioblastoma (GBM). The disparities in receipt of adjuvant single-agent chemotherapy and their association with outcome have not been well established. Observational study of a prospectively collected database, the National Cancer Database (NCDB), from 1998 to 2012 with median follow-up 12.4 months. Among the 114,979 patients in the NCDB with GBM, 44,531 patients were analyzed for disparities, and 28,279 patients were analyzed for overall survival (OS). Associations were assessed in a multivariable Cox proportional hazards regression model. Survival was estimated using the Kaplan-Meier method. Median age was 58 years. Chemotherapy use was associated with male gender, white race, younger age (≤50), higher performance status (≥70), more extensive surgery, insurance status, higher income/education, and treatment at academic centers (all p < 0.05). We found improved OS associated with type of insurance (private insurance HR 0.91, 95 % CI 0.85-0.96 and Medicare HR 1.24, 95 % CI 1.16-1.33, both p < 0.01 compared to uninsured) and treatment at academic programs (HR 0.86; p < 0.01). MGMT methylation status predicted improved OS (HR 0.54; 95 % CI 0.41-0.70, p < 0.01). 1-year OS for patients receiving chemotherapy was 55.9 % versus 35.3 % for those without (p < 0.0001). After adjustment for confounders, chemotherapy use remained associated with improved OS (HR 0.64, 95 % CI 0.63-0.66, p < 0.01). Chemotherapy utilization increased from 26.9 to 93.3 % during the study period. We have identified specific disparities in the use of chemotherapy that may be targeted to improve patient access to care. Widespread adoption of adjuvant chemoradiotherapy after resection or biopsy for GBM appears to improve OS. PMID:26970981

  13. A Phase 1/2 and Biomarker Study of Preoperative Short Course Chemoradiation With Proton Beam Therapy and Capecitabine Followed By Early Surgery for Resectable Pancreatic Ductal Adenocarcinoma

    Hong, Theodore S., E-mail: tshong1@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ryan, David P.; Borger, Darrell R.; Blaszkowsky, Lawrence S.; Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Deshpande, Vikram; Shinagare, Shweta [Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Wo, Jennifer Y.; Boucher, Yves [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Wadlow, Raymond C.; Kwak, Eunice L.; Allen, Jill N.; Clark, Jeffrey W.; Zhu, Andrew X. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ferrone, Cristina R. [Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Mamon, Harvey J. [Department of Radiation Oncology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Adams, Judith; Winrich, Barbara; Grillo, Tarin [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); and others

    2014-07-15

    Purpose: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients. Methods and Materials: Patients with radiographically resectable, biopsy-proven PDAC were treated with neoadjuvant short-course (2-week) proton-based radiation with capecitabine, followed by surgery and adjuvant gemcitabine. The primary objective was to demonstrate a rate of toxicity grade ≥3 of <20%. Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood. Results: The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled, of whom 35 patients were treated in the phase 2 portion. There were no grade 4 or 5 toxicities, and only 2 of 35 patients (4.1%) experienced a grade 3 toxicity event (chest wall pain grade 1, colitis grade 1). Of 48 patients eligible for analysis, 37 underwent pancreaticoduodenectomy. Thirty of 37 (81%) had positive nodes. Locoregional failure occurred in 6 of 37 resected patients (16.2%), and distant recurrence occurred in 35 of 48 patients (72.9%). With median follow-up of 38 months, the median progression-free survival for the entire group was 10 months, and overall survival was 17 months. Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12, stromal CXCR7 expression, and circulating biomarkers CEA, CA19-9, and HGF (all, P<.05). Conclusions: This study met the primary endpoint by showing a rate of 4.1% grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation. Treatment was associated with favorable local control. In exploratory analyses, KRAS{sup G12D} status and high CXCR7 expression and circulating CEA, CA19-9, and HGF levels were associated with poor survival.

  14. Characterizing Distributed Concurrent Engineering Teams: A Descriptive Framework for Aerospace Concurrent Engineering Design Teams

    Chattopadhyay, Debarati; Hihn, Jairus; Warfield, Keith

    2011-01-01

    As aerospace missions grow larger and more technically complex in the face of ever tighter budgets, it will become increasingly important to use concurrent engineering methods in the development of early conceptual designs because of their ability to facilitate rapid assessments and trades in a cost-efficient manner. To successfully accomplish these complex missions with limited funding, it is also essential to effectively leverage the strengths of individuals and teams across government, industry, academia, and international agencies by increased cooperation between organizations. As a result, the existing concurrent engineering teams will need to increasingly engage in distributed collaborative concurrent design. This paper is an extension of a recent white paper written by the Concurrent Engineering Working Group, which details the unique challenges of distributed collaborative concurrent engineering. This paper includes a short history of aerospace concurrent engineering, and defines the terms 'concurrent', 'collaborative' and 'distributed' in the context of aerospace concurrent engineering. In addition, a model for the levels of complexity of concurrent engineering teams is presented to provide a way to conceptualize information and data flow within these types of teams.

  15. Efficacy of concurrent chemoradiotherapy with superselective intra-arterial docetaxel-nedaplatin for metastatic cervical lymph nodes in oral cancers

    The purpose of this study was to evaluate the efficacy of concurrent chemoradiation with intra-arterial docetaxel-nedaplatin infusion to metastatic cervical lymph nodes in oral cancers. Sixteen patients with advanced oral cancer accompanied by cervical lymph node metastasis were treated between 2003 and 2009 at Hirosaki University Hospital. A total of 66 Gy of external beam irradiation concurrent with 2 to 3 courses of intra-arterial chemotherapy infusion via the femoral artery with a combination of docetaxel (40 mg/m2) and nedaplatin (80 mg/m2) was conducted. Amongst the 16 patients, 6 received a total anticancer drug delivery to the primary tumor and 10 received a partial delivery to the nodal disease. The feeding artery to the nodal disease was the facial artery in 3 patients and the occipital artery in 3 patients. The remaining 4 patients received anticancer drug infusion to the external carotid artery with arterial redistribution technique where embolization was applied in order to achieve an antitumor effect due to a high local concentration. Treatment effect was evaluated by computed tomography (CT), magnetic resonance imaging and positron emission tomography-CT (PET-CT). Metastatic cervical lymph nodes disappeared in 15 out of the 16 patients (93.8%) post-treatment. Neck dissection was performed for the patient with residual nodal disease. One patient had neck recurrence at level V in ipsilateral neck. The three-year overall survival rate was 74.6% with a median follow-up duration of 27 months. Intra-arterial docetaxel-nedaplatin infusion concurrent with radiotherapy is an effective treatment not only for primary disease but also for metastatic cervical lymph nodes. (author)

  16. A case of esophageal cancer with septic disseminated intravascular coagulation treated with recombinant human soluble thrombomodulin during chemoradiation therapy

    A 70-year-old woman was diagnosed with synchronous advanced esophageal cancer and early renal cancer. During chemo-radiation therapy for the esophageal cancer, she suffered from septic shock due to pneumonia. She got worse despite the administration of antibiotics and γglobulin. On the following day, she was diagnosed with septic disseminated intravascular coagulation (DIC) on the basis of the diagnostic criterion for acute DIC. Recombinant human soluble thrombomodulin (rTM) was administered to treat the DIC. The patient responded promptly to rTM treatment and recovered from the DIC in just 1 day. rTM is thought to be an effective drug for sepsis-induced DIC during chemoradiation therapy. (author)

  17. Adjuvant Therapy of Colon Cancer: Current Status and Future Developments

    Morse, Michael A.

    2005-01-01

    Options for the adjuvant therapy of resected stage III colon cancer have expanded beyond the previously well-accepted standard of 5-fluorouracil (5-FU) combined with leucovorin. The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) study confirmed that capecitabine (Xeloda) is at least as effective and is less toxic than a bolus 5-FU and leucovorin regimen for patients with stage III colon cancer. This study, in addition to National Surgical Adjuvant Breast and Bowel Project (NSABP) C-06, which...

  18. Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer

    Background and purpose: Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation. Patients and methods: One hundred and twenty-five consecutive patients with newly diagnosed inoperable stage III and IV head and neck cancer were enrolled for intra-arterial chemoradiation. There were 28 women (22%) and 97 men (78%) and the mean age was 55 years (range 30-80). One hundred and nine patients had stage IV disease (87%), 16 patients (13%) had stage III disease. Statistical analyses were performed to identify an association between factors and acute/late toxicity. Results: There were eight treatment-related deaths (6%). Severe acute toxicity (grade 3-4), mainly mucositis and dysphagia as categorized by the RTOG toxicity criteria, was recorded in 51% of the patients. Leucopenia (grade 3-4) occurred in 39% and aspiration pneumonia in 20% of patients. Tracheotomy was necessary in 15 (12%) patients. Neurological complications during treatment occurred in 3 (2%) patients. Severe late toxicity occurred in 34% of the patients. The most important of these were pneumonia (14%), osteoradionecrosis (9%) and swallowing problems with permanent percutaneous gastrostomy (20%). Statistical analysis did show a significant association between site and severe acute mucositis (p = 0.007), site and osteoradionecrosis (p = 0.014) and age and xerostomia (p = 0.004). Conclusions: Chemoradiation is frequently associated with serious toxicity. Oral cavity tumours and older age are related to acute mucositis/osteoradionecrosis and xerostomia, respectively

  19. [Recent advance in adjuvant therapy for breast cancer].

    Shimizu, Chikako; Watanabe, Toru

    2002-12-01

    Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467

  20. Concurrent cisplatin and radiotherapy for inoperable bladder cancer: long term results and prognostic predictors of local control and survival

    Therapeutic strategies for muscle invasive bladder cancer are currently evolving. A recent European randomized study has shown that neo-adjuvant chemotherapy does not improve the chance of cure or of conservative treatment. Concurrent chemotherapy and radiotherapy would provide better results but these is a need to identify by prognostic factors patients who may benefit from such a conservative strategy. Concurrent cisplatin and radiation therapy is a potentially locally curative treatment for 43 % of patients with muscle-invasive bladder cancer not candidates for radical surgery. Clinical T-stage and hydronephrosis have a significant and independent prognostic value on local control but appears not discriminant enough to select patients for conservative treatment. (authors)

  1. Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-Fu, and VP-16 for advanced esophageal cancer

    Mukaida, Hidenori; Hirai, Toshihiro; Yamashita, Yoshinori; Yoshida, Kazuhiro; Hihara, Jun; Kuwahara, Masaki; Inoue, Hideki; Toge, Tetsuya [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

    1998-01-01

    The aim of this study was to evaluate the efficacy of adjuvant chemoradiotherapy following surgery in patients with advanced esophageal cancer. We followed the cases of 57 such patients treated at our hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who received radiotherapy alone (R group), and 19 who did received neither (N group). In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP), 5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3 weeks after esophagectomy. CDDP at 50 mg/m{sup 2} was administered on days 1 and 7.5-FU at 500 mg/m{sup 2} and VP-16 at 60 mg/m{sup 2} were administered on days 3, 4, and 5. Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy combined with radiation. Side-effects of severe anorexia (grade 3) and leukocytopenia (<1900/{mu}l) were observed in 47% and 39% of the patients, respectively. However no treatment-related death was observed. The 5-year-survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group, respectively. The recurrence rate was 66.7% in the CR group, which was higher than in the matched control groups (46.2% in the N group and 54.5% in the R group), but with no significant difference. These results suggested that adjuvant chemoradiotherapy did not contribute to improvement in prognosis for these patients with advanced esophageal cancer. (author)

  2. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine & Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland

    Fox, Christopher B.

    2013-01-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characte...

  3. CpG ODN and ISCOMATRIX Adjuvant: A Synergistic Adjuvant Combination Inducing Strong T-Cell IFN-γ Responses

    Michael J. McCluskie; Weeratna, Risini D.; Evans, Dana M.; Shawn Makinen; Debbie Drane; Heather L. Davis

    2013-01-01

    For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG), and ISCOMATRIX adjuvant (ISCOMATRIX), composed of saponin, phospholipid, and cholesterol, which possesses both immunostim...

  4. The Role of Dual-Time Combined 18-Fluorideoxyglucose Positron Emission Tomography and Computed Tomography in the Staging and Restaging Workup of Locally Advanced Rectal Cancer, Treated With Preoperative Chemoradiation Therapy and Radical Surgery

    Purpose: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. Methods and Materials: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300mg/m2/day) followed 8-10 weeks later by surgery. All patients underwent [18F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUVmax), and percentage of SUVmax difference (Response Index = RI) between pre- and post-CRT [18F]FDG-PET scans were evaluated. Results: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUVmax was significantly higher than post-CRT (15.8, vs 5.9; p 18F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.

  5. 14 CFR 221.141 - Method of revoking concurrence.

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Method of revoking concurrence. 221.141... PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS Giving and Revoking Concurrences to Carriers § 221.141 Method of revoking concurrence. (a) A concurrence may be revoked by filing with the Department a Notice of...

  6. Acute toxicity of chemoradiation for rectal cancer; Akuttoxizitaet der simultanen Radiochemotherapie des Rektumkarzinoms

    Roedel, C. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Fietkau, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Keilholz, L. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Grabenbauer, G.G. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Kessler, H. [Erlangen-Nuernberg Univ., Erlangen (Germany). Chirurgische Klinik; Martus, P. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizinische Statistik und Dokumentation; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik

    1997-08-01

    Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41,4 to 56 Gy) {+-} 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m{sup 2}/d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. Results: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p = 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p = 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0,04; grade 2 to 3-nausea/emesis: 21% vs 8% in men, p = 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p = 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. (orig./AJ) [Deutsch] Von 1987 bis 1995 wurde bei 120 Patienten mit Rektumkarzinom (73 Primaertumoren, 47 Rezidivtumoren) eine simultane Radiochemotherapie durchgefuehrt. 56 Patienten wurden praeoperativ, 64 Patienten postoperativ behandelt. Die Bestrahlung erfolgte ueber eine Vier-Felder-Technik mit 6- bis 10-MV-Photonen. Die Einzeldosis betrug 1,8 Gy im Referenzpunkt (Isozentrum, ICRU 50

  7. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  8. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    Paximadis, Peter, E-mail: ppaximad@med.wayne.edu [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States); Yoo, George; Lin, Ho-Sheng; Jacobs, John [Department of Otolaryngology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Sukari, Ammar [Department of Medical Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Dyson, Greg [Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Christensen, Michael; Kim, Harold [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States)

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  9. An Algorithm to Construct Concurrent Reachability Graph of Petri Nets

    张金泉; 倪丽娜; 蒋昌俊

    2004-01-01

    Reachability graph is a very important tool to analyze the dynamic properties of Petri nets, but the concurrent relation of transitions in Petri nets cannot be represented by reachability graph. Petri net is a concurrent system, while reachability graph is a serial one. However, concurrency is a kind of property which is not only very significant but also difficult to be analyzed and controlled. This paper presents the concepts of concurrent reachable marking and concurrent reachable graph in order to represent and analyze the concurrent system. The algorithm constructing concurrent reachable marking set and concurrent reachability graph is also shown so that we can study the response problems among services in a network computing environment and analyze the throughput of the system. The Dining Philosophers Problem, which is a classic problem of describing the management of concurrent resources, is given as an example to illustrate the significance of concurrent reachability graph.

  10. Establishment of a new quality control and vaccine safety test for influenza vaccines and adjuvants using gene expression profiling.

    Haruka Momose

    Full Text Available We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine.

  11. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  12. Integration of filgrastim into chemoradiation for limited small cell lung cancer: a phase I study

    Purpose: Recent studies document the value of early combined modality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. Methods and Materials: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) ± filgrastim (5 μg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. Results: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1-3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete). Conclusions: Despite

  13. Concurrent exposure to microbial products and food antigens triggers initiation of food allergy

    Ping-Chang Yang

    2009-06-01

    Full Text Available It is estimated that as much as 6-8% population suffers from food allergy or food antigen-related disorders. The prevalence keeps rising. So far we do not have identified remedy to treat food allergy. Avoidance of the offending food is the only effective method currently. Skewed T helper 2 polarization is one of the major feature in the pathogenesis of food allergy. However, the causative mechanism in the initiation of food allergy remains to be further understood. Research in food allergy has got giant advance in recent years. Several animal models have been established and used in food allergy study. One of the common features of these food allergy animal models is that most of them require using microbial products as adjuvant to sensitize animals. This review documents the recent advance in the mechanistic study on concurrent use of microbial products and food antigens to study food allergy.

  14. Adjuvant chemotherapy for soft tissue sarcoma.

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  15. Mucosal adjuvants to improve wildlife rabies vaccination.

    Fry, Tricia; Van Dalen, Kaci; Hurley, Jerome; Nash, Paul

    2012-10-01

    RABORAL V-RG(®)a is a recombinant vaccine used in oral rabies vaccination (ORV) programs for wildlife in the United States. Vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. Research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. We evaluated the possibility of using two benign compounds, chitosan and N,N,N-trimethylated chitosan (TMC), to increase the viscosity of the vaccine and potentially act as adjuvants to improve the immune response in raccoons (Procyon lotor). Forty mildly sedated raccoons were orally vaccinated via needleless syringe with either RABORAL V-RG (n = 12), chitosan+RABORAL V-RG (n = 12), TMC+ RABORAL V-RG (n = 12), or no vaccine (n = 4), on day 0 and again on day 90. We collected sera every 2-4 wk for 4 mo and evaluated rabies virus-neutralizing antibodies (rVNA). Raccoons were considered responders if rVNA titers were ≥ 0.1 IU/mL. Eleven of 12 raccoons vaccinated with TMC+RABORAL V-RG responded after one dose of vaccine, as did eight of 12 vaccinated with RABORAL V-RG, and three of 12 vaccinated with chitosan+ RABORAL V-RG. Our results suggest that the inclusion of an adjuvant, such as TMC, could increase vaccine efficacy to aid in controlling rabies virus spread in wildlife reservoirs. PMID:23060506

  16. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  17. Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

    Paul H. Sugarbaker

    2012-01-01

    Full Text Available Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement.

  18. Towards Interaction Reliability in Concurrent Applications

    A. Silva

    2012-01-01

    Full Text Available Developing trustworthy concurrent applications is a seemingly never ending quest, which is necessary but difficult. It is necessary because mainstream systems and applications are inherently concurrent and they are pervasive to our daily life activities. It is difficult because such systems are inherently interactive and heterogeneous, so that boundaries can hardly be established for studying subsystems in isolation. Formal methods are a key instrument in resolving ambiguities and design reliable applications in a rigorous way. The authors overview major problems in the application of formal methods and outline how they are tackled by the papers collected in this volume.

  19. Models for concurrency: towards a classification

    Sassone, Vladimiro; Nielsen, Mogens; Winskel, Glynn

    1996-01-01

    Models for concurrency can be classified with respect to three relevant parameters: behaviour/ system, interleaving/noninterleaving, linear/branching time. When modelling a process, a choice concerning such parameters corresponds to choosing the level of abstraction of the resulting semantics. In...... this paper, we move a step towards a classification of models for concurrency based on the parameters above. Formally, we choose a representative of any of the eight classes of models obtained by varying the three parameters, and we study the formal relationships between them using the language of...

  20. Concurrent Engineering in seafood product development

    Jonsdottir, Stella; Vesterager, Johan; Børresen, Torger

    1998-01-01

    Concurrent Engineering (CE) can provide an improved approach to product development for extending the lines of seafood products. Information technology support tools based on product models can provide an integrated and simultaneous approach for specifying new recipes. The seafood industry can...... benefit from the CE approach which can support product developers to provide concurrent specifications for raw materials, ingredients, packaging, and production methods. The approach involves the use of product models from which line extensions are more easily generated than by use of customary stepwise...

  1. Authentic And Concurrent Evaluation-refining

    Eriksson, Carina Ihlström; Åkesson, Maria; Kautz, Karlheinz

    2011-01-01

    This paper addresses the need for more detailed accounts for evaluation in design science research literature. By revisiting a design project regarding the future e-newspaper we give detailed descriptions of its authentic and concurrent evaluation approach by illustrating the what, why and how...... as well as decisions on strategic levels. We emphasize a holistic and concurrent approach to evaluation compared to the general design science research thinking and argue that reflecting on how to seek authenticity is important. By authenticity we refer to the notion of how closely an evaluation captures...

  2. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bi...

  3. Vaccine Adjuvants: from 1920 to 2015 and Beyond.

    Pasquale, Alberta Di; Preiss, Scott; Silva, Fernanda Tavares Da; Garçon, Nathalie

    2015-01-01

    The concept of stimulating the body's immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

  4. Spray characteristics affected by physical properties of adjuvants

    Four drift adjuvants, Array, In-Place, Vector and Control, were tested and physical properties and spray spectrum parameters measured. Array had the highest conductivity, indicating a good potential for the electrostatic charging, and the highest shear viscosity. All adjuvants had very similar neut...

  5. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber; Christensen, Dennis; Foged, Camilla

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  6. In vitro interactions between macrophages and aluminum-containing adjuvants.

    Rimaniol, Anne-Cécile; Gras, Gabriel; Clayette, Pascal

    2007-09-17

    Intramuscular administration of aluminum-adjuvanted vaccines induces an infiltration of aluminum-containing macrophages between muscle fibers. In vitro stimulation of human monocyte-derived macrophages with aluminum hydroxide (AlOOH) induces similar intracellular crystalline inclusions as well as phenotypical and functional modifications. We compared in this study the ability of other adjuvants to exert similar changes in macrophages in vitro. All mineral salts, i.e. aluminic (AlOOH, AlPO(4)) and non-aluminic mineral adjuvants (CaPO(4), FePO(4)) but not emulsion were able to increase macrophages capacity to potentiate autologous memory T lymphocyte proliferation, while only aluminic adjuvants induced CD83 expression and increased CD86 on macrophages. All together, this suggests that aluminic and non-aluminic adjuvants exerted their immunoactivities by distinct mechanisms on macrophages. PMID:17689842

  7. Adjuvants in micro- to nanoscale: current state and future direction.

    Gupta, Ankur; Das, Soumen; Schanen, Brian; Seal, Sudipta

    2016-01-01

    Adjuvants have been used in vaccines for over 70 years to promote long-lived and sterilizing immunity. Since then, various adjuvant systems were developed by combining nanotechnology with natural and/or synthetic immunomodulatory molecules. These systems are biocompatible, immunogenic, and possess higher antigen carrying capacity. This article showcases advancements made in the adjuvant systems formulations, their synthesis routes, and the improvement of these adjuvants have brought in response to combat against ongoing global health threats such as malaria, hepatitis C, universal influenza, and human immunodeficiency virus. This review also highlights the interaction of adjuvants with the delivery of antigens to cells and unfolds mechanism of actions. In addition, this review discusses the physicochemical factors responsible for the efficient interaction of nanoadjuvants with antigen receptors to develop more effective, less reactogenic, and multifunctional systems for the next generation vaccines. PMID:26053286

  8. Immune adjuvant activity of the olive, soybean and corn oils

    Ana Claudia Marinho da Silva

    2016-08-01

    Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

  9. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  10. Preoperative gemcitabine-based chemoradiation therapy for T3/T4 pancreatic cancer

    A total of 250 patients with T3 · T4 (JPS) pancreatic cancer received preoperative gemcitabine-based chemoradiation therapy (CRT). Patients were classified into the following three groups based on the locoregional tumor extension: T3-R (n=64), tumors without extension to the adjacent vasculature systems; T4-R (n=125), tumors with extension to the adjacent vasculature system except SMA, CHA, and CA: T4-BR (n=61), tumors showing abutment to 180deg of the circumference of the SMA and/or CHA and/or CA. We evaluated the followings in comparisons among patients with T3-R, T4-R and T4-BR: resection rate, rate of margin-negative resection, survival, and frequency of local recurrence. Resection rates of T3-R, T4-R, and T4-BR patients were 92%, 85%, and 74%, respectively. Pathological margin-negative resection was achieved in 98%, 100%, and 98% in those patients groups, respectively. The 5-year postoperative survival rates of T3-R, T4-R, and T4-BR patients were 70%, 52%, and 37%, respectively. The 5-year cumulative incidence of local recurrence was comparable in the three groups (10%, 17%, and 15%, respectively). In the resected cases, locoregional control was comparable regardless of the degree of locoregional tumor extension in the setting of preoperative CRT strategy. However, the resection rate and postoperative survival rate were lower in the patients with more locally advanced tumors. (author)

  11. Two cases of superficial esophageal cancer after chemoradiation treatment for lung cancer

    We report two cases of superficial esophageal cancer after chemoradiation treatment (CRT) for lung cancer. A 74-year-old man had a type 0-IIc cancer of the upper thoracic esophagus 12 years after CRT, including 45-Gy irradiation, for left lung small cell cancer. Transthoracic esophagectomy was performed, and pathological examination revealed that the tumor was squamous cell carcinoma invading the submucosal layer (SM3) without nodal metastasis. He has had no recurrence of esophageal cancer for more than 3.5 years since the operation. A 61-year-old man had a type 0-IIc cancer of the upper thoracic esophagus 20 years after CRT, including 60-Gy irradiation, for left lung small cell cancer. Transthoracic esophagectomy was performed, and pathological examination revealed that the tumor was squamous cell carcinoma invading the submucosal layer (SM2) without nodal metastasis. He has had no recurrence of esophageal cancer for more than 2 years. A possible causal relationship between the previous CRT and the two esophageal cancers was suspected. The treatment strategy for patients after CRT should be carefully decided based on the patient's general status. In surgery, scarring and blood circulation disorders of the organs in the irradiated field should be taken into consideration. (author)

  12. Quality of life and tumor control after short split-course chemoradiation for anal canal carcinoma

    To evaluate quality of life (QOL) and outcome of patients with anal carcinoma treated with short split-course chemoradiation (CRT). From 1991 to 2005, 58 patients with anal cancer were curatively treated with CRT. External beam radiotherapy (52 Gy/26 fractions) with elective groin irradiation (24 Gy) was applied in 2 series divided by a median gap of 12 days. Chemotherapy including fluorouracil and Mitomycin-C was delivered in two sequences. Long-term QOL was assessed using the site-specific EORTC QLQ-CR29 and the global QLQ-C30 questionnaires. Five-year local control, colostomy-free survival, and overall survival were 78%, 94% and 80%, respectively. The global QOL score according to the QLQ-C30 was good with 70 out of 100. The QLQ-CR29 questionnaire revealed that 77% of patients were mostly satisfied with their body image. Significant anal pain or fecal incontinence was infrequently reported. Skin toxicity grade 3 or 4 was present in 76% of patients and erectile dysfunction was reported in 100% of male patients. Short split-course CRT for anal carcinoma seems to be associated with good local control, survival and long-term global QOL. However, it is also associated with severe acute skin toxicity and sexual dysfunction. Implementation of modern techniques such as intensity-modulated radiation therapy (IMRT) might be considered to reduce toxicity

  13. Logics and Games for True Concurrency

    Gutierrez, Julian

    2010-01-01

    We study the underlying mathematical properties of various partial order models of concurrency based on transition systems, Petri nets, and event structures, and show that the concurrent behaviour of these systems can be captured in a uniform way by two simple and general dualities of local behaviour. Such dualities are used to define new mu-calculi and logic games for the analysis of concurrent systems with partial order semantics. Some results of this work are: the definition of a number of mu-calculi which, in some classes of systems, induce the same identifications as some of the best known bisimulation equivalences for concurrency; and the definition of (infinite) higher-order logic games for bisimulation and model-checking, where the players of the games are given (local) monadic second-order power on the sets of elements they are allowed to play. More specifically, we show that our games are sound and complete, and therefore, determined; moreover, they are decidable in the finite case and underpin nove...

  14. Teaching Teamwork and Problem Solving Concurrently

    Goltz, Sonia M.; Hietapelto, Amy B.; Reinsch, Roger W.; Tyrell, Sharon K.

    2008-01-01

    Teamwork and problem-solving skills have frequently been identified by business leaders as being key competencies; thus, teaching methods such as problem-based learning and team-based learning have been developed. However, the focus of these methods has been on teaching one skill or the other. A key argument for teaching the skills concurrently is…

  15. Integrated concurrent utilization quality review, Part one.

    Caterinicchio, R P

    1987-01-01

    This article is the first of a two-part series which argues for the concurrent management of the appropriateness, necessity, and quality of patient care. Intensifying scrutiny by the credentialing groups, the PROs and all third-party payors underscores the vital need to implement cost-effective information systems which integrate the departmentalized functions of patient-physician profiling, DRG case-mix analyses, length of stay monitoring, pre-admission/admission and continued stay review, discharge planning, risk management, incident reporting and quality review. In the domain of physician performance regarding admitting and practice patterns, the ability to exercise concurrent utilization-quality review means early detection and prevention of events which would otherwise result in denials of payment and/or compromised patient care. Concurrent utilization-quality review must, by definition, be managerially invasive and focused; hence, it is integral to maintaining the integrity of the services and product lines offered by the provider. In fact, if PPO status is a marketing agenda, then the institutional objectives of cost-effectiveness, productivity, value, and competitiveness can only be achieved through concurrent utilization-quality review. PMID:10291443

  16. Concurrent Engineering Design Using Intelligent Agents.

    Parkinson, Brian

    1998-01-01

    Describes Design Builder, interactive multimedia software that was developed to enable undergraduate engineers to experience working in a concurrent environment without direct and specialized teaching-staff support, and to provide an interactive and intelligent simulation environment from which users may develop a culture that introduces…

  17. CAPP Framework System for Concurrent Engineering

    1999-01-01

    Difficulty in generalizing and lack of adaptability are important factors that hamper a computer aided process planning (CAPP) system from being popular and practical. New manufacturing philosophies such as Concurrent Engineering require special characteristic of a CAPP system. Proposed in this paper is a CAPP framework system for Concurrent Engineering (CAPPFS-CE) which can meet the requirements of Concurrent Engineering and whose information models, function models and decision logic can be customized by users to form various CAPP application systems. Its function requirements are discussed broadly. An architecture for CAPPFS-CE is presented. It is based on abstract information models (AIMs) and abstract function models (AFMs). The kernel is formed by customization interpretation, internal process control and decision engine. A new information modeling and system development method, information element method (IEM), is introduced to build up AIMs, decision engine, and AFMs and then realize a CAPPFS-CE. THCAPP-SHELL, a CAPPFS-CE developed by IEM, is demonstrated. A CAPP system produced by customizing THCAPP-SHELL for complex structural parts in a concurrent engineering environment is shown.

  18. Concurrent Engineering in the 21st Century

    Stjepandic, Josip; Wognum, P.M.; Verhagen, Wim

    2015-01-01

    Presenting the gradual evolution of the concept of Concurrent Engineering (CE), and the technical, social methods and tools that have been developed, including the many theoretical and practical challenges that still exist, this book serves to summarize the achievements and current challenges of CE

  19. On run-time exploitation of concurrency

    Hölzenspies, Philip Kaj Ferdinand

    2010-01-01

    The `free' speed-up stemming from ever increasing processor speed is over. Performance increase in computer systems can now only be achieved through parallelism. One of the biggest challenges in computer science is how to map applications onto parallel computers. Concurrency, seen as the set of v

  20. Pancreatic Neuroendocrine Tumors With Involved Surgical Margins: Prognostic Factors and the Role of Adjuvant Radiotherapy

    Purpose: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized. Methods and Materials: We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS). Results: Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%–77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21–11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01–1.04; p = 0.007) were associated with decreased OS. Conclusions: Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further

  1. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1–3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  2. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    Sher, David J., E-mail: dsher@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Thotakura, Vijaya [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Balboni, Tracy A. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States); Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen [Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Goguen, Laura A.; Annino, Donald J. [Department of Surgery, Division of Otolaryngology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  3. Pancreatic Neuroendocrine Tumors With Involved Surgical Margins: Prognostic Factors and the Role of Adjuvant Radiotherapy

    Arvold, Nils D. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Fernandez-del Castillo, Carlos [Department of Surgery, Massachusetts General Hospital, Boston, MA (United States); Ryan, David P. [Department of Medicine, Massachusetts General Hospital, Boston, MA (United States); Ferrone, Cristina R. [Department of Surgery, Massachusetts General Hospital, Boston, MA (United States); Clark, Jeffrey W.; Blaszkowsky, Lawrence S. [Department of Medicine, Massachusetts General Hospital, Boston, MA (United States); Deshpande, Vikram [Department of Pathology, Massachusetts General Hospital, Boston, MA (United States); Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Allen, Jill N.; Kwak, Eunice L.; Wadlow, Raymond C.; Zhu, Andrew X. [Department of Medicine, Massachusetts General Hospital, Boston, MA (United States); Warshaw, Andrew L. [Department of Surgery, Massachusetts General Hospital, Boston, MA (United States); Hong, Theodore S., E-mail: Tshong1@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-07-01

    Purpose: Pancreatic neuroendocrine tumors (pNET) are rare neoplasms associated with poor outcomes without resection, and involved surgical margins are associated with a worse prognosis. The role of adjuvant radiotherapy (RT) in these patients has not been characterized. Methods and Materials: We retrospectively evaluated 46 consecutive patients with positive or close (<1 mm) margins after pNET resection, treated from 1983 to 2010, 16 of whom received adjuvant RT. Median RT dose was 50.4 Gy in 1.8-Gy fractions; half the patients received concurrent chemotherapy with 5-fluorouracil or capecitabine. No patients received adjuvant chemotherapy. Cox multivariate analysis (MVA) was used to analyze factors associated with overall survival (OS). Results: Median age at diagnosis was 56 years, and 52% of patients were female. Median tumor size was 38 mm, 57% of patients were node-positive, and 11% had a resected solitary liver metastasis. Patients who received RT were more likely to have larger tumors (median, 54 mm vs. 30 mm, respectively, p = 0.002) and node positivity (81% vs. 33%, respectively, p = 0.002) than those not receiving RT. Median follow-up was 39 months. Actuarial 5-year OS was 62% (95% confidence interval [CI], 41%-77%). In the group that did not receive RT, 3 patients (10%) experienced local recurrence (LR) and 5 patients (18%) developed new distant metastases, while in the RT group, 1 patient (6%) experienced LR and 5 patients (38%) developed distant metastases. Of all recurrences, 29% were LR. On MVA, male gender (adjusted hazard ratio [AHR] = 3.81; 95% CI, 1.21-11.92; p = 0.02) and increasing tumor size (AHR = 1.02; 95% CI, 1.01-1.04; p = 0.007) were associated with decreased OS. Conclusions: Long-term survival is common among patients with involved-margin pNET. Despite significantly worse pathologic features among patients receiving adjuvant RT, rates of LR between groups were similar, suggesting that RT might aid local control, and merits further

  4. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m2) and cisplatin (40 mg/m2) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m2/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R

  5. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    Higuchi, Katsuhiko, E-mail: k.higu@kitasato-u.ac.jp [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Komori, Shouko [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Tanabe, Satoshi [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Chikatoshi [Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Azuma, Mizutomo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Ishiyama, Hiromichi [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Sasaki, Tohru; Ishido, Kenji [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan); Katada, Natsuya [Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Hayakawa, Kazushige [Department of Radiology and Radiation Oncology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan); Koizumi, Wasaburo [Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Kanagawa (Japan)

    2014-07-15

    Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m{sup 2}) and cisplatin (40 mg/m{sup 2}) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R.

  6. Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

    Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62–10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57–10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

  7. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

    Fox, Christopher B

    2013-09-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted. PMID:23787558

  8. Ranitidine as adjuvant treatment in colorectal cancer

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance with the...... postoperative infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had...

  9. Quadrantectomy and adjuvant radiotherapy for breast cancer

    The conservative treatment of early breast cancer always requires irradiation of residual mammary tissue. The preliminary results obtained in 45 early breast cancer patients, who received quadrantectomy plus axillary dissection, followed by radiation of residual breast are reported. Radiation was performed by the two opposed field technique. In some cases the residual breast tissue was compressed using a special accessory provided with the Theratron 780. In addition to the tumor dose of 50 GY, 10 GY boots was added to the surgical scar using 7 MeV electrons. The 6 patients with positive axillary nodes received 6 courses of adjuvant chemotherapy (CMF) after radiotherapy. All patients are currently alive and free of disease. The 64% (29 patients) were followed up for at least 5 years, and 36% (16 patients) for at least 3 years. Only 2 cases of local recurrence were encountered (4,4%). The esthetic result was satisfactory in all cases. No side effects due to treatment were noted

  10. Comparative Efficacy of Cisplatin vs. Gemcitabine as Concurrent Chemotherapy for Untreated Locally Advanced Cervical Cancer: A Randomized Trail

    Dr. Manoj Srivastava

    2007-01-01

    Full Text Available Cisplatin based chemo-radiation is considered the standard of care for most patients with locally advanced cervical cancer. Gemcitabine is a new pyrimidire analogue with high radio sensitizing potency in vitro. This study was undertaken to compare the anti-tumor activity and toxicity of the two drugs. It is a prospective randomized study of 60 patients histologically confirmed locally advanced cervical cancer, FIGO stage IIB - IIIB with no previous treatment. Patients were randomized to receive either weekly Cisplatin 40mg/m2 intravenously or Gemcitabine 100mg/m2 intravenously for 5 cycles concurrent with external beam radiation therapy 50Gy/25# as 5# / weeks, followed by single application of medium does rate intracavitory brachytherapy to deliver 20 Gy at point A, 2 weeks after completion of external beam radiation therapy (EBRT. Toxicity was graded according to WHO criteria. Both subjective and objective responses were measured six weeks after completion of treatment. In Cisplatin arm 28/30 (93.33% patients showed complete clinical regression of tumor whereas in Gemcitabine arm only 21/30 (70% patients showed complete clinical response. Thus immediate response was significantly higher in the cisplatin group as compared to the gemcitabine group (p=0.01. All toxicities except nausea and vomiting were more common and severe in patients receiving Gemcitabine with radiation. To conclude, Cisplatin appears to be better than Gemcitabine when used as a radio sensitizer for untreated locally advanced cervical cancer in terms of response and toxicity.

  11. Adjuvant radiation for vulvar carcinoma: improved local control

    Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and

  12. Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis

    It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes. From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation. Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15). Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients. (orig.)

  13. Extended field chemoradiation for cervical cancer patients with histologically proven para-aortic lymph node metastases after laparoscopic lymphadenectomy

    The purpose of this work was to evaluate the use of extended-field chemoradiation (EFRT) with concomitant chemotherapy in patients with histologically confirmed para-aortic metastases after laparoscopic para-aortic and pelvic lymphadenectomy (LAE) with regard to oncologic results and treatment-related toxicity. A total of 44 women with squamous cell carcinoma (82 %) and adenocarcinoma (18 %) of the cervix in FIGO stages IIA (n = 3), IIB (n = 29); IIIB (n = 9), and IVA (n = 3) and histologically proven para-aortic metastases underwent EFRT and chemotherapy. Laparoscopic LAE was performed in 40 patients. Patients underwent chemoradiation with conventional fractionation of 1.8-50.4 Gy to the para-aortic and pelvic region. In addition, MRI-guided brachytherapy was performed to the cervix with 5-6 single doses of 5 Gy for a total dose of 25-30 Gy. The mean number of harvested lymph nodes was 17 in the pelvic as well as para-aortic regions, respectively. Laparoscopic intervention did not delay chemoradiation. Follow-up was 6-76 months (mean 25.1 months). There was no grade 4 or 5 acute radiation toxicity. In all, 8, 4, and 11 % grade 1, 2, and 3 gastrointestinal late toxicities and 7, 11, and 19 % grade 1, 2 and 3 genitourinary late toxicities were recorded. Despite the excellent locoregional (pelvic) control rates of 89.1 and 82.8 % after 2 and 5 years, respectively, the overall survival rates were 68.4 and 54.1 % after 2 and 5 years, respectively. Of the 44 patients, 43 remained tumor free in the para-aortic region. In patients with proven para-aortic disease, excellent pelvic and para-aortic control could be achieved by laparoscopic LAE followed by EFRT. More than half of the patients were long-term survivors. The high risk of distant metastases should be addressed by further improving systemic treatment. (orig.)

  14. Concurrent exposure to microbial products and food antigens triggers initiation of food allergy

    Xiao Chen

    2009-01-01

    Full Text Available It is estimated that as much as 6-8% population suffers from food allergy or food antigen-related disorders. The prevalence keeps rising. So far we do not have identified remedy to treat food allergy. Avoidance of the offending food is the only effective method currently. Skewed T helper 2 polarization is one of the major feature in the pathogenesis of food allergy. However, the causative mechanism in the initiation of food allergy remains to be further understood. Research in food allergy has got giant advance in recent years. Several animal models have been established and used in food allergy study. One of the common features of these food allergy animal models is that most of them require using microbial products as adjuvant to sensitize animals. This review documents the recent advance in the mechanistic study on concurrent use of microbial products and food antigens to study food allergy. (Chen X, Yang PC. Concurrent exposure to microbial products and food antigens triggers initiation of food allergy.

  15. Radiologic response to radiation therapy concurrent with temozolomide for progressive simple dysembryoplastic neuroepithelial tumor.

    Morr, Simon; Qiu, Jingxin; Prasad, Dheerendra; Mechtler, Laszlo L; Fenstermaker, Robert A

    2016-07-01

    Dysembryoplastic neuroepithelial tumors (DNETs) are low-grade neuroglial tumors that are traditionally considered to be benign hamartoma-like mass lesions. Malignant transformation and disease progression have been reported in complex DNETs. We report a case of a simple DNET with disease progression following subtotal resection. A 34-year-old woman underwent craniotomy with subtotal resection of a large nonenhancing right temporal lobe and insular mass. Histopathological analysis revealed a simple DNET. Magnetic resonance imaging obtained 6 months after surgery demonstrated disease progression with no enhancement or change in signal characteristics. Following concurrent therapy with temozolomide and external beam radiation therapy, a significant radiologic response was observed. Progressive DNET with malignant transformation exhibits predominantly glial transformation and occurs predominantly in complex DNETs. The histological classification of DNETs into simple, complex, and nonspecific are reviewed. Contrast-enhancing regions are more frequently seen in complex tumors, with nonenhancing regions having fewer complex histologic features. Close clinical and radiographic follow-up is important in all cases of DNET. Following tumor progression, radiation therapy with concurrent and adjuvant temozolomide chemotherapy may be an effective treatment. PMID:27181792

  16. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp [Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba (Japan); Ioka, Tatsuya [Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ito, Yoshinori [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Yonemoto, Naohiro [Department of Epidemiology and Biostatistics, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo (Japan); Nagase, Michitaka [Department of Clinical Oncology, Jichi Medical University, Tochigi (Japan); Yamao, Kenji [Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya (Japan); Miyakawa, Hiroyuki [Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo (Japan); Ishii, Hiroshi [Hepatobiliary and Pancreatic Division, Cancer Institute Hospital, Tokyo (Japan); Furuse, Junji [Department of Internal Medicine, Medical Oncology School of Medicine, Kyorin University, Tokyo (Japan); Sato, Keiko [Kyoto Unit Center, Japan Environment and Children' s Study, Kyoto University Graduate School of Medicine, Kyoto (Japan); Sato, Tosiya [Department of Biostatistics, Kyoto University School of Public Health, Kyoto (Japan); Okusaka, Takuji [Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo (Japan)

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  17. A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

    McCormack, M; Kadalayil, L; Hackshaw, A; Hall-Craggs, M A; Symonds, R P; Warwick, V; Simonds, H.; Fernando, I.; Hammond, M.; James, L.; Feeney, A.; Ledermann, J. A.

    2013-01-01