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Sample records for adjuvant concurrent chemoradiation

  1. Concurrent chemoradiation for vaginal cancer.

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

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    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.

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

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    Baschnagel, Andrew; Shah, Chirag [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Margolis, Jeffrey; Nadeau, Laura [Department of Medical Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States); Stein, Julie; Jury, Robert [Department of Surgery, William Beaumont Hospital, Royal Oak, Michigan (United States); Robertson, John M., E-mail: jrobertson@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan (United States)

    2012-07-01

    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/m{sup 2} weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m{sup 2} 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

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

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    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

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

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    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.

  6. Case Report: En Bloc Resection of Pancoast Tumor with Adjuvant Aortic Endograft and Chemoradiation

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    Lu, Tony; Fischer, Uwe M.; Marco, Rex A.; Naoum, Joseph J.; Reardon, Michael J.; Lumsden, Alan B.; Blackmon, Shanda H.; Davies, Mark G.

    2015-01-01

    “Pancoast” tumors frequently require a multidisciplinary approach to therapy and are still associated with high morbidity and mortality. Due to their sensitive anatomic location, complex resections and chemoradiation regimens are typically required for treatment. Those with signs of aortic invasion pose an even greater challenge, given the added risks of cardiopulmonary bypass for aortic resection and interposition. Placement of an aortic endograft can facilitate resection if the tumor is in close proximity to or is invading the aorta. Prophylactic endografting to prevent radiation-associated aortic rupture has also been described. This case describes a 60-year-old female who presented with a stage IIIa left upper lobe undifferentiated non-small-cell carcinoma encasing the subclavian artery with thoracic aorta and bony invasion. Following carotid-subclavian bypass with Dacron, en bloc resection of the affected lung, ribs, and vertebral bodies was performed. The aorta was prophylactically reinforced with a Gore TAG thoracic endograft prior to adjuvant chemoradiation. The patient remains disease-free at more than 5 years follow-up after completing her treatment course. Endovascular stenting with subsequent chemoradiation may prove to be a viable alternative to palliation or open operative management and prevention of aortic injury during tumor resection and/or adjuvant therapy in select patients with aortic involvement. PMID:26306134

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

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    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.

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

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    Shen, Bing-Jie; Lin, Shih-Chiang; Shueng, Pei-Wei; Chou, Yueh-Hung; Tseng, Li-Ming; Hsieh, Chen-Hsi

    2013-01-01

    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 pseudomembranous colitis following concurrent chemoradiation therapy.

  9. Concurrent chemoradiation for unresectable advanced head and neck cancer

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    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)

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

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    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

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

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    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.

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

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    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.

  13. Clinical outcomes for gastric cancer following adjuvant chemoradiation utilizing intensity modulated versus three-dimensional conformal radiotherapy.

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    Gene-Fu F Liu

    Full Text Available PURPOSE/OBJECTIVES: To determine if intensity modulated radiation therapy (IMRT in the post-operative setting for gastric cancer was associated with reduced toxicity compared to 3D conformal radiation therapy (3DCRT. MATERIALS/METHODS: This retrospective study includes 24 patients with stage IB-IIIB gastric cancer consecutively treated from 2001-2010. All underwent surgery followed by adjuvant chemoradiation. Concurrent chemotherapy consisted of 5-FU/leucovorin (n = 21, epirubicin/cisplatin/5FU (n = 1, or none (n = 2. IMRT was utilized in 12 patients and 3DCRT in 12 patients. For both groups, the target volume included the tumor bed, anastomosis, gastric stump, and regional lymphatics. RESULTS: Median follow-up for the entire cohort was 19 months (range 0.4-8.5 years, and 49 months (0.5-8.5 years in surviving patients. The 3DCRT group received a median dose of 45 Gy, and the IMRT group received a median dose of 50.4 Gy (p = 0.0004. For the entire cohort, 3-year overall survival (OS was 40% and 3-year disease free survival (DFS was 41%. OS and DFS did not differ significantly between the groups. Acute toxicity was similar. Between 3DCRT and IMRT groups, during radiotherapy, median weight lost (3.2 vs. 3.3 kg, respectively; p = 0.47 and median percent weight loss were similar (5.0% vs. 4.3%, respectively; p = 0.43. Acute grade 2 toxicity was experienced by 8 patients receiving 3DCRT and 11 receiving IMRT (p = 0.32; acute grade 3 toxicity occurred in 1 patient receiving 3DCRT and none receiving IMRT (p = 1.0. No patients in either cohort experienced late grade 3 toxicity, including renal or gastrointestinal toxicity. At last follow up, the median increase in creatinine was 0.1 mg/dL in the IMRT group and 0.1 mg/dL in the 3DCRT group (p = 0.78. CONCLUSION: This study demonstrates that adjuvant chemoradiation for gastric cancer with IMRT to 50.4 Gy was well-tolerated and compared similarly in toxicity with 3DCRT to

  14. Concurrent Chemoradiation With Weekly Gemcitabine and Cisplatin in Locally Advanced Cervical Cancer

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    Esmati E

    2011-12-01

    Full Text Available Background: More than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard of treatment for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultaneously with radiation.Methods: Thirty Women with untreated invasive squamous-cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in Radiation Oncology department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty mg/m2 gemcitabine followed by 35 mg/m2 cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment.Results: The mean age of the participants was 58.13±11.83 (29-78 years. After 3 months of treatment, 73.3% had complete and 26.7% had partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients.Conclusion: According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation by gemcitabine in advanced cervical cancers.

  15. Role of concurrent chemoradiation in inoperable carcinoma esophagus: A prospective study

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    Virendra Bhandari

    2014-01-01

    Full Text Available Introduction: The treatment of choice in cancer esophagus is controversial. Radiation therapy oncology group, Eastern cooperative oncology group and Cochrane studies have shown superiority of concurrent chemoradiation in inoperable carcinoma esophagus. In these studies full dose cisplatin was given every 3 weeks along with radiotherapy and hence had some toxicity. So, we started treating inoperable carcinoma esophagus patients with low dose weekly cisplatin given concurrently with radiotherapy aiming at low toxicity and similar results. Materials and Methods: A total of 31 cases of inoperable cases of carcinoma esophagus were treated with once weekly cisplatin 30 mg/m 2 along with radiotherapy 60 Gy in 30 fractions in 6 weeks on Telecobalt/Linear accelerator. Results : w0 e could achieve lower toxicity with 80%, 35% and 19% with 1, 2, and 3 year′s survival with a median survival of 18 months. So, we conclude that this regimen is better than 3 weekly chemotherapy regimen as is better tolerated with less toxicity and similar outcome.

  16. Concurrent Chemoradiation with Low-Dose Weekly Cisplatin in Locally Advanced Stage IV Head and Neck Squamous Cell Carcinoma

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    Kang, Myoung Hee; Kang, Jung Hun; Song, Haa-Na; Jeong, Bae Kwon; Chai, Gyu Young; Kang, Kimun; Woo, Seung Hoon; Park, Jung Je; Kim, Jin Pyeong

    2014-01-01

    Purpose Concurrent chemoradiation (CRT) with 3-weekly doses of cisplatin is a standard treatment for loco-regionally advanced head and neck squamous cell carcinoma (HNSCC). However, treatment with 3-weekly doses of cisplatin is often associated with several adverse events. Therefore, we conducted this retrospective analysis to determine the efficacy and tolerance of CRT with a low weekly dose of cisplatin in stage IV HNSCC patients. Materials and Methods Medical records of patients who were d...

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

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    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.

  18. Pretreatment performance status and nutrition are associated with early mortality of locally advanced head and neck cancer patients undergoing concurrent chemoradiation.

    Science.gov (United States)

    Chang, Pei-Hung; Yeh, Kun-Yun; Huang, Jen-Seng; Lai, Chien-Hong; Wu, Tsung-Han; Lan, Yii-Jenq; Tsai, Jason Chien-Sheng; Chen, Eric Yen-Chao; Yang, Shih-Wei; Wang, Cheng-Hsu

    2013-05-01

    Unexpected fatal events in patients with head and neck cancers undergoing concurrent chemoradiation therapy are a clinical concern. Malnutrition, which is reported frequently in head and neck cancer patients, are associated with immunity derangement. The purpose of this study was to identify risk factors for early death of patients undergoing chemoradiation. We retrospectively analyzed the records of 194 stage III, IVA, and IVB head and neck cancer patients who were treated with chemoradiation between 2007 and 2009. We defined early death as death while receiving chemoradiation or within 60 days of treatment completion. Risk factors for early death were tested using univariate and multivariate analyses. Fourteen patients (7.2 %) experienced early death, 78.6 % of whom died of infection. Univariate analysis revealed significant correlations between early death and several pretreatment variables, including Eastern Cooperative Oncology Group performance status (PS) >1, hemoglobin total lymphocyte count 1, BMI total lymphocyte count malnutrition before chemoradiation independently predict early death in locally advanced head and neck cancer patients undergoing chemoradiation. Cautious management of head and neck cancer patients with these risk factors is required throughout chemoradiation period.

  19. Case Report: En Bloc Resection of Pancoast Tumor with Adjuvant Aortic Endograft and Chemoradiation

    OpenAIRE

    Lu, Tony; Fischer, Uwe M.; Rex A. Marco; Naoum, Joseph J.; Reardon, Michael J.; Lumsden, Alan B; Blackmon, Shanda H.; Davies, Mark G.

    2015-01-01

    “Pancoast” tumors frequently require a multidisciplinary approach to therapy and are still associated with high morbidity and mortality. Due to their sensitive anatomic location, complex resections and chemoradiation regimens are typically required for treatment. Those with signs of aortic invasion pose an even greater challenge, given the added risks of cardiopulmonary bypass for aortic resection and interposition. Placement of an aortic endograft can facilitate resection if the tumor is in ...

  20. Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward

    Science.gov (United States)

    Papadimitriou, Konstantinos; Antoniou, Georgios; Bronte, Giuseppe; Vassiliou, Vassilios; Papamichael, Demetris; Peeters, Marc; Kountourakis, Panteleimon

    2015-01-01

    Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targeting well-designed future approaches. PMID:26101524

  1. Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward

    Directory of Open Access Journals (Sweden)

    Konstantinos Papadimitriou

    2015-01-01

    Full Text Available Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targeting well-designed future approaches.

  2. The influence of number of high risk factors on clinical outcomes in patients with early-stage cervical cancer after radical hysterectomy and adjuvant chemoradiation

    Science.gov (United States)

    Lim, Soyi; Lee, Seok-Ho; Park, Chan-Yong

    2016-01-01

    Objective The purpose of this study was to evaluate the prognosis according to the number of high risk factors in patients with high risk factors after radical hysterectomy and adjuvant chemoradiation therapy for early stage cervical cancer. Methods Clinicopathological variables and clinical outcomes of patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB1 to IIA cervical cancer who had one or more high risk factors after radical hysterectomy and adjuvant chemoradiation therapy were retrospectively analyzed. Patients were divided into two groups according to the number of high risk factors (group 1, single high risk factor; group 2, two or more high risk factors). Results A total of 93 patients were enrolled in the present study. Forty nine out of 93 (52.7%) patients had a single high risk factor, and 44 (47.3%) had two or more high risk factors. Statistically significant differences in stage and stromal invasion were observed between group 1 and group 2. However, age, histology, tumor size, and lymphovascular space invasion did not differ significantly between the groups. Distant recurrence occurred more frequently in group 2, and the probability of recurrence and death was higher in group 2. Conclusion Patients with two or more high risk factors had worse prognosis in early stage cervical cancer. For these patients, consideration of new strategies to improve survival may be worthwhile. Conduct of further clinical trials is warranted for development of adjuvant treatment strategies individualized to each risk group. PMID:27200308

  3. Age dependent prognosis in concurrent chemo-radiation of locally advanced NSCLC

    DEFF Research Database (Denmark)

    Hansen, Olfred; Schytte, Tine; Nielsen, Morten;

    2015-01-01

    , the results might be due to selection bias, thus reports from a cohort of consecutively treated patients are warranted. The current single institution study reports on the influence of age on survival of locally advanced NSCLC patients treated with radiotherapy combined with or without concurrent chemotherapy....... Material and methods. Altogether, 478 patients completed radical radiotherapy in doses of 60-66 Gy/30-33 fractions from 1995 to June 2012; 137 of the patients had concurrent chemotherapy. The data was analyzed in age groups ... specific survival the hazard ratio was related to the use of concurrent chemotherapy was 0.49 (95% CI 0.29; 0.82), 0.68 (95% CI 0.48; 0.98) and 1.01 (95% CI 0.67; 1.51) for the age groups

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

    Energy Technology Data Exchange (ETDEWEB)

    Fraunholz, Ingeborg, E-mail: inge.fraunholz@kgu.de [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Rödel, Franz; Kohler, Daniela [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Diallo-Georgiopoulou, Margarita [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany); Department of Radiation Oncology, Klinikum Offenbach, Offenbach/Main (Germany); Distel, Luitpold [Department of Radiation Oncology, Friedrich Alexander University, Erlangen (Germany); Falk, Stefan [Pathology Associates, Frankfurt/Main (Germany); Rödel, Claus [Department of Radiotherapy and Oncology, Goethe University, Frankfurt/Main (Germany)

    2013-08-01

    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.

  5. Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy.

    Science.gov (United States)

    Wang, Xin Shelley; Shi, Qiuling; Williams, Loretta A; Mao, Li; Cleeland, Charles S; Komaki, Ritsuko R; Mobley, Gary M; Liao, Zhongxing

    2010-08-01

    Elevations in cancer treatment-induced circulating inflammatory cytokines may be partially responsible for the development of significant symptom burden (e.g., pain, fatigue, distress, disturbed sleep) during concurrent chemoradiation therapy (CXRT). Sixty-two patients undergoing CXRT for locally advanced non-small cell lung cancer (NSCLC) reported symptoms weekly for 15 weeks via the M. D. Anderson Symptom Inventory (MDASI). Serum inflammatory cytokines were assessed weekly during therapy via enzyme-linked immunosorbent assay. Dynamic changes in cytokines and associated symptom profiles were estimated using mixed-effect models. MDASI symptom severity increased gradually as CXRT dose accumulated and peaked at week 8. Serum concentrations of interleukin (IL)-6, IL-10, and serum soluble receptor 1 for tumor necrosis factor (sTNF-R1) increased significantly by week 8 (all ptreatment status, total radiotherapy dose, and CXRT delivery technique, an increase in sTNF-R1 was significantly related to an increase in the mean score for all 15 MDASI symptoms (estimate, 1.74; SE, 0.69; pcytokines in significant worsening of symptoms in NSCLC patients undergoing CXRT, and warrant further study to identify biological targets for ameliorating treatment-related symptom burden.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nam-Kyu; Min, Jin-Sik; Park, Jea-Kun; Yun, Seong-Hyun; Sung, Jin-Sil; Jung, Hyun-Chul; Roh, Jae-Kyung [Yonsei Univ., Seoul (Korea, Republic of). Coll. of Medicine

    2001-01-01

    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/m{sup 2}) and leucovorin (20 mg/m{sup 2}) were given for five consecutive days during the first and fifth weeks of radiation therapy (50.4 Gy) (n=14). Oral doxifluridine (700 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}) 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

  9. Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Feng-Ming [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan (China); Lee, Jang-Ming; Huang, Pei-Ming [Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Lee, Yung-Chie [Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Chia-Hsien Cheng, Jason, E-mail: jasoncheng@ntu.edu.tw [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan (China)

    2011-11-15

    Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal

  10. Management of advanced esophageal carcinoma potentially infiltrating to the adjacent organs. Usefulness of preoperative concurrent chemo-radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsujinaka, Toshimasa; Shiozaki, Hitoshi; Murata, Atsuo; Nishijima, Junichi; Inoue, Masatoshi; Tamura, Shigeyuki; Monden, Morito [Osaka Univ. (Japan). Faculty of Medicine

    1995-06-01

    A retrospective analysis was conducted to evaluate the prognostic benefit of various treatments for advanced esophageal carcinoma potentially infiltrating to the adjacent organs. In 77 enrolled patients, primary resection (11 cases, median survival time, MST: 281 days) and concurrent chemo (5FU CDDP)-radiation (FPRT) (23 cases, MST: 238 days) had prognostic advantages in comparison with palliative treatment (11 cases, MST: 94 days), but radiation therapy with daily rectal futraful administration (5 FURT) had no benefit (11 cases, MST: 169 days). In the primary resected cases, sufficient postoperative adjuvant therapies were feasible in 52%, and local and/or nodal recurrence was found in 61%. In FPRT cases, the local response rate was 79%, whereas the general response rate was 66% due to the association of distant metastasis in 5 cases. The resection rate after FPRT was 52%. Operative curability was superior in cases preceded by FPRT to those undergoing primary resection, and two year survival rates were 33% and 12%, respectively. FPRT is useful as a neoadjuvant therapy and subsequent curative resection may increase the chance for a long-term survival. (author).

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  12. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

    Science.gov (United States)

    Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

    2017-02-01

    Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

  13. Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

    Science.gov (United States)

    Takigawa, N; Kiura, K; Segawa, Y; Watanabe, Y; Kamei, H; Moritaka, T; Shibayama, T; Ueoka, H; Gemba, K; Yonei, T; Tabata, M; Shinkai, T; Hiraki, S; Takemoto, M; Kanazawa, S; Matsuo, K; Tanimoto, M

    2006-01-01

    Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0–4.9). PMID:17031394

  14. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. 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

    DEFF Research Database (Denmark)

    Sorensen, M.; Lassen, U.; Palshof, T.;

    2008-01-01

    of 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......: The combination of topotecan and cisplatin with concurrent twice-daily chemoradiation results in long-term survivors. As expected the incidence of severe esophagitis is high Udgivelsesdato: 2008/5...

  18. Sequential FDG-PET/CT reliably predicts response of locally advanced rectal cancer to neo-adjuvant chemo-radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Capirci, Carlo [Hospital, Division of Radiotherapy, Rovigo (Italy); Rampin, Lucia; Banti, Elena [Hospital, Nuclear Medicine and PET Service, Rovigo (Italy); Erba, Paola A.; Mariani, Giuliano [Regional Center of Nuclear Medicine, Univ. Pisa (Italy); Galeotti, Fabrizio [Hospital, Division of Surgery, Rovigo (Italy); Crepaldi, Giorgio [Hospital, Division of Oncology, Rovigo (Italy); Gava, Marcello [Hospital, Medical Physics Service, Rovigo (Italy); Fanti, Stefano [Politecnico Bologna (Italy). Dept. of Nuclear Medicine; Muzzio, Pier C. [Dept. of Radiology, Ist. Oncologico, Padova (Italy); Rubello, Domenico [Rovigo Hospital, Istituto Oncologico Veneto (IOV)-IRCCS, Nuclear Medicine Service, PET Unit, Rovigo (Italy)

    2007-10-15

    Prediction of rectal cancer response to preoperative, neo-adjuvant chemo-radiation therapy (CRT) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches. Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up, but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT, when restaging the patient before surgery. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising tool for monitoring the effect of anti-tumour therapy. The aim of this study was to prospectively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT. Forty-four consecutive patients with locally advanced (cT3-4) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospective study. Treatment consisted of external beam intensified radiotherapy, chemotherapy and, 8-10 weeks later, surgery with curative intent. All patients underwent FDG-PET/CT both before CRT and 5-6 weeks after completing CRT. One patient died before surgery because of acute myocardial infarction, and was therefore excluded from further analysis. Semi-quantitative measurements of FDG uptake (SUV{sub max}), absolute difference ({delta}SUV{sub max}) and percent SUV{sub max} difference (Response Index, RI) between pre- and post-CRT PET scans were considered. Results were correlated with pathological response, assessed both by histopathological staging of the surgical specimens (pTNM) and by the tumour regression grade (TRG) according to Mandard's criteria (patients with TRG1-2 being defined as responders and patients with TRG3-5 as non-responders). Following neo-adjuvant CRT, of the 45 patients submitted to surgery, 23 (51.1%) were classified as responders according to Mandard

  19. Pre-treatment diffusion-weighted MR imaging for predicting tumor recurrence in uterine cervical cancer treated with concurrent chemoradiation: Value of histogram analysis of apparent diffusion coefficients

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Suk Hee; Kim, Jin Woong; Lim, Hyo Soon; Jeong, Yong Yeon; Kang, Woo Dae; KIm, Seok Mo; Kang, Heong Keun [Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun (Korea, Republic of); Shin, Sang Soo [Chonnam National University Hospital, Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2013-08-15

    To evaluate the value of apparent diffusion coefficient (ADC) histogram analysis for predicting tumor recurrence in patients with uterine cervical cancer treated with chemoradiation therapy (CRT). Our institutional review board approved this retrospective study and waived informed consent from each patient. Forty-two patients (mean age, 56 ± 14 years) with biopsy-proven uterine cervical squamous cell carcinoma who underwent both pre-treatment pelvic magnetic resonance imaging with a 3.0 T magnetic resonance scanner and concurrent CRT were included. All patients were followed-up for more than 6 months (mean, 36.4 ± 11.9 months; range 9.0-52.8 months) after completion of CRT. Baseline ADC parameters (mean ADC, 25th percentile, 50th percentile, and 75th percentile ADC values) of tumors were calculated and compared between the recurrence and no recurrence groups. In the recurrence group, the mean ADC and 75th percentile ADC values of tumors were significantly higher than those of the no recurrence group (p = 0.043 and p = 0.008, respectively). In multivariate analysis, the 75th percentile ADC value of tumors was a significant predictor for tumor recurrence (p = 0.009; hazard ratio, 1.319). When the cut-off value of the 75th percentile ADC (0.936 x 10{sup -3} mm{sup 2}/sec) was used, the overall recurrence free survival rate above the cut-off value was significantly lower than that below the cut-off value (51.9% vs. 91.7%, p = 0.003, log-rank test). Pre-CRT ADC histogram analysis may serve as a biomarker for predicting tumor recurrence in patients with uterine cervical cancer treated with CRT.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

    Science.gov (United States)

    Noronha, Vanita; Prabhash, Kumar; Joshi, Amit; Patil, Vijay Maruti; Talole, Sanjay; Nakti, Dipti; Sahu, Arvind; Shah, Srushti; Ghosh-Laskar, Sarbani; Patil, Prachi S; Mehta, Shaesta A; Jambhekar, Nirmala; Mahajan, Abhishek; Purandare, Nilendu

    2016-01-01

    There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.].

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. 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

    Science.gov (United States)

    Showalter, Timothy N.; Winter, Kathryn A.; Berger, Adam C.; Regine, William F.; Abrams, Ross A.; Safran, Howard; Hoffman, John P.; Benson, Al B.; MacDonald, John S.; Willett, Christopher G.

    2010-01-01

    Purpose Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of 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. PMID:20934270

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

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dongryul [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Jeong Eun [Department of Radiation Oncology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Huh, Seung Jae, E-mail: sj5201.huh@samsung.com [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Won [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Nam, Heerim [Department of Radiation Oncology, Kangbuk Samsung Hospital, Seoul (Korea, Republic of); Choi, Joon Young; Kim, Byung-Tae [Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-11-01

    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 (ΔSUV{sub max}%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUV{sub max}% 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 SUV{sub max} 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, ΔSUV{sub max}% could predict CR response on post-CCRT PET/CT (P<.001, cutoff value of 59.7%). In all patients, the PFS rate was 71.9% at 2 years. Multivariate analysis showed that ΔSUV{sub max}% ≥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. ΔSUV{sub max}% ≥60% at 4 weeks of CCRT may predict CR response

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    ). Docetaxel and control treatment groups were compared by log-rank tests, and hazard ratios (HR) of DFS events were calculated by Cox modeling. All statistical tests were two-sided. RESULTS: Due to a lower-than-anticipated rate of relapse, this analysis was performed after 5 years with 732 events. Patients......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...... 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) concurrent...

  7. Study comparing sequential (neo-adjuvant) versus concurrent chemo-radiotherapy in patients with squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Okawa, Tomohiko; Karasawa, Kumiko; Kaneyasu, Yuko; Tanaka, Makiko; Kita-Okawa, Midori; Ishii, Tetsuo [Tokyo Women`s Medical Coll. (Japan)

    1994-11-01

    Radiotherapy combined with chemotherapy is still used for standard treatment in patients with locally advanced unresectable cancer. A study was undertaken to compare a sequential (neo-adjuvant) with a simultaneous (concurrent) chemotherapy and radiotherapy program. Neo-adjuvant chemotherapy with cisplatin (80 mg/m{sup 2} i.v. day 1) and 5FU (600 mg/m{sup 2} continuous i.v. day 1-5) every 3 weeks prior to definitive conventional radiotherapy (60-65 Gy), or cisplatin (20 mg/m{sup 2} i.v. day 1-5) and 5FU (250 mg/m{sup 2} continuous i.v. infusion. day 1-14) were given simultaneously for same radiotherapy. Complete response rate was 45% in the sequential treatment and 43% in the simultaneous arm. Leukopenia and other adverse effects were slightly more frequent in the simultaneous arm, but there were no significant differences. These results suggested that individualization of treatment planning and establishment of optimum treatment were most important for combination of chemotherapy and radiotherapy. (author).

  8. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

    Science.gov (United States)

    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  9. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

  12. Hypofractionated radiotherapy and stereotactic boost with concurrent and adjuvant temozolamide for glioblastoma in good performance status elderly patients – early results of a phase II trial.

    Directory of Open Access Journals (Sweden)

    Scott eFloyd

    2012-10-01

    Full Text Available Glioblastoma Multiforme (GBM is an aggressive primary brain neoplasm with dismal prognosis. Based on successful phase III trials, 60 Gy involved-field radiotherapy in 30 fractions over 6 weeks (Standard RT with concurrent and adjuvant temozolomide is currently the standard of care. In this disease, age and Karnofsky Performance Status (KPS are the most important prognostic factors. For elderly patients, clinical trials comparing standard RT with radiotherapy abbreviated to 40 Gy in 15 fractions over 3 weeks demonstrated similar outcomes, indicating shortened radiotherapy may be an appropriate option for elderly patients. However, these trials did not include temozolomide chemotherapy, and included patients with poor KPS, possibly obscuring benefits of more aggressive treatment for some elderly patients. We conducted a prospective Phase II trial to examine the efficacy of a hypofractionated radiation course followed by a stereotactic boost with concurrent and adjuvant temozolomide chemotherapy in elderly patients with good performance status. In this study, patients 65 years and older with a KPS >70 and histologically confirmed GBM received 40 Gy in 15 fractions with 3D conformal technique followed by a 1-3 fraction stereotactic boost to the enhancing tumor. All patients also received concurrent and adjuvant temozolomide. Patients were evaluated 1 month post-treatment and every 2 months thereafter. Between 2007 and 2010, 20 patients (9 males and 11 females were enrolled in this study. The median age was 75.4 years (range 65-87 years. At a median follow-up of 11 months (range 7-32 months, 12 patients progressed and 5 are alive. The median progression free survival was 11 months and the median overall survival was 13 months. There was no additional toxicity. These results indicate that elderly patients with good KPS can achieve outcomes comparable to the current standard of care using an abbreviated radiotherapy course, radiosurgery boost and

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

    Directory of Open Access Journals (Sweden)

    Sushma Agrawal

    2013-01-01

    Full Text Available 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 context of a developing country. We conclude that sequential chemoradiotherapy is better tolerated than concurrent chemoradiation in Indian patients with locally advanced non-small cell lung cancers. Patients with stage IIIa, normal weight or overweight, and adequate baseline pulmonary function should be offered concurrent chemoradiation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Primary transoral robotic surgery with concurrent neck dissection for early stage oropharyngeal squamous cell carcinoma implemented at a Danish head and neck cancer center

    DEFF Research Database (Denmark)

    Rubek, Niclas; Channir, Hani Ibrahim; Charabi, Birgitte Wittenborg

    2017-01-01

    (RT) with or without concomitant chemotherapy. This is the first study in Scandinavia from a head and neck cancer centre that aims to demonstrate the feasibility of performing primary transoral robotic surgery (TORS) and concurrent neck dissection for patients with early stage OPSCC. Between September...... bilateral neck dissection. Due to an upstaging following surgery, 13 patients were referred to adjuvant therapy. Four of these patients received RT and two patients received concomitant chemo-radiation (CCR) therapy. Seven patients declined the recommended adjuvant therapy one of whom later developed an N......-site recurrence and received salvage surgery with postoperative RT. In summary, 43% of the patients were referred to adjuvant therapy following primary surgery which was mainly due to N-site stage migration and ECE. Primary TORS and concurrent neck dissection is a safe and feasible procedure that may...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  18. The role of induction and adjuvant chemotherapy in combination with concurrent chemoradiotherapy for nasopharyngeal cancer: a Bayesian network meta-analysis of published randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Yu HL

    2016-01-01

    Full Text Available Hongliang Yu,1,* Dayong Gu,1,* Xia He,1 Xianshu Gao,2 Xiuhua Bian1 1Department of Radiation Oncology, Jiangsu Cancer Hospital affiliated with Nanjing Medical University, Nanjing, 2Department of Radiation Oncology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Whether the addition of induction chemotherapy (IC or adjuvant chemotherapy (AC to concurrent chemoradiotherapy (CCRT is superior to CCRT alone for locally advanced nasopharyngeal cancer is unknown. A Bayesian network meta-analysis was performed to investigate the efficacy of CCRT, IC + CCRT, and CCRT + AC on locally advanced nasopharyngeal cancer. The overall survival (OS with hazard ratios (HRs and locoregional recurrence rates (LRRs and distant metastasis rates (DMRs with risk ratios (RRs were investigated. After a comprehensive database search, eleven studies involving 2,626 assigned patients were included in this network meta-analysis. Compared with CCRT alone, IC + CCRT resulted in no significant improvement in OS or LRR and a marginal improvement in DMR (OS: HR =0.67, 95% credible interval (CrI 0.32–1.18; LRR: RR =1.79, 95% CrI 0.80–3.51; DMR: RR =1.79, 95% CrI 0.24–1.04 and CCRT + AC exhibited no beneficial effects on any of the endpoints of OS, LRR, or DMR (OS: HR =0.99, 95% CrI 0.64–1.43; LRR: RR =0.78, 95% CrI 0.43–1.32; DMR: RR =0.85, 95% CrI 0.57–1.24. As a conclusion, for locally advanced nasopharyngeal cancer, no significant differences in the treatment efficacies of CCRT, IC + CCRT, and CCRT + AC were found, with the exception of a marginally significant improvement in distant control observed following IC + CCRT compared with CCRT alone. Keywords: concurrent chemotherapy, induction chemotherapy, adjuvant chemotherapy, radiotherapy, nasopharyngeal cancer, network meta-analysis

  19. Relapse of herpes encephalitis induced by temozolomide-based chemoradiation in a patient with malignant glioma.

    Science.gov (United States)

    Okada, Masaki; Miyake, Keisuke; Shinomiya, Aya; Kawai, Nobuyuki; Tamiya, Takashi

    2013-02-01

    The authors report on a case of concurrent herpes simplex encephalitis (HSE) and malignant glioma. The co-occurrence of HSE and malignant glioma is very rare, but it can occur during glioma treatment. Both radiotherapy and chemoradiation with temozolomide can induce viral reactivation, leading to HSE relapse. Careful observation for HSE is necessary when administering chemoradiation to patients with a history of HSE. Antiviral therapy for HSE must be initiated immediately, and the chemoradiation for glioma should be stopped; however, it is not clear what antitumor therapy is optimal when HSE co-occurs during the treatment of glioma.

  20. Successful treatment of pituitary carcinoma with concurrent radiation, temozolomide, and bevacizumab after resection.

    Science.gov (United States)

    Touma, Waseem; Hoostal, Spencer; Peterson, Richard A; Wiernik, Andres; SantaCruz, Karen S; Lou, Emil

    2017-03-11

    The optimal treatment of pituitary carcinomas (PC) is unknown. Treatment includes surgical resection, radiation, and more recently, temozolomide (TMZ). Pituitary adenomas have relatively high expression of vascular endothelial growth factor; therefore, bevacizumab, an antiangiogenic agent, has been used in a small number of aggressive or malignant pituitary tumors after recurrence. However, it has not been administered concurrently with other chemotherapeutic agents or combined with radiation therapy in PC. We present a 63-year-old man with an adrenocorticotropic hormone (ACTH)-secreting PC, causing visual loss. It was resected transsphenoidally. There were several notable factors placing the patient at high risk for recurrence including distant metastasis in the form of a pulmonary nodule. Morphologically, his tumor was a pituitary neoplasm with malignant histopathologic features. It had abundant mitotic figures and zones of necrosis. Six weeks post-surgery, the patient started concurrent chemoradiation, using combination therapy with TMZ and bevacizumab. TMZ was continued for 12 cycles in the adjuvant setting. The ACTH was effective as a serum-based tumor marker and normalized during treatment. The patient is alive, five years after diagnosis, with no recurrence to date. This is the first case of pituitary carcinoma treated successfully with concurrent chemoradiation therapy that combined TMZ and bevacizumab with a long-term follow up.

  1. Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: a systematic literature review.

    Science.gov (United States)

    Ashby, Lynn S; Smith, Kris A; Stea, Baldassarre

    2016-08-24

    Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III

  2. 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

    DEFF Research Database (Denmark)

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

    2007-01-01

    of 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...

  3. PET/CT and Histopathologic Response to Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Charlotte; Loft, Annika; Berthelsen, Anne K

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locally...... advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral(R) (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared...... of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography....

  4. Preoperative chemoradiation and IOERT for unresectable or borderline resectable pancreas cancer

    Science.gov (United States)

    Moss, Adyr A.; Rule, William G.; Callister, Matthew G.; Reddy, K. Sudhakar; Mulligan, David C.; Collins, Joseph M.; De Petris, Giovanni; Gunderson, Leonard L.; Borad, Mitesh

    2013-01-01

    Background and objectives Pre-operative chemoradiation (preop CRT) plus intraoperative electron irradiation (IOERT) has been used in the multidisciplinary treatment for patients with locally advanced unresectable or borderline resectable pancreas cancer. This review was performed to evaluate survival, relapse patterns and prognostic factors in patients treated with curative intent. Methods Between January 2002 and December 2010, 48 patients with locally advanced pancreatic ductal adenocarcinoma received preop CRT prior to an attempt at resection and IOERT. 31/48 (65%) patients proceeded to curative-intent surgical resection. Resection status prior to preop CRT was locally unresectable (20 patients) and borderline resectable (11 patients). Preop CRT (45-50.4 Gy/25-28 Fx in 27/31) was delivered with concurrent 5FU or gemcitabine-based regimens. Subsequent gross total resection was achieved in 16 patients (R0, 11; R1, 5). IOERT was delivered in 28 patients (dose, 10-20 Gy). 16 patients also received adjuvant post-operative systemic chemotherapy. Outcomes evaluated include survival, local failure in the EBRT field (LF), central failure in the IOERT field (CF), and distant metastases. Results Resection status was predictive for survival and for patterns of relapse. For patients with at least a gross total resection after preop CRT (R0/R1; n=16) vs. no resection (n=15), both median and overall survival were improved (median 23 vs. 10 months; 2-year, 40% vs. 17%; 3-year, 40% vs. 0%; P=0.002). Liver or peritoneal relapse was documented in 22/31 patients (71%); LF/CF in 5/26 (16%). Conclusions Long term survival and disease control are achievable in select patients with borderline resectable or locally unresectable pancreas cancer when gross total surgical resection is achieved after preop CRT. Continued evaluation of curative-intent combined modality therapy is warranted in this high risk population, but additional strategies are needed to improve resectability and disease

  5. DNA hypermethylation biomarkers to predict response to cisplatin treatment, radiotherapy or chemoradiation : the present state of art

    NARCIS (Netherlands)

    Roossink, Frank; de Jong, Steven; Wisman, G Bea A; van der Zee, Ate G J; Schuuring, Ed

    2012-01-01

    BACKGROUND: Concurrent platinum-based chemoradiation significantly improved survival of advanced stage cervical patients over radiotherapy alone. However, the 5-year overall survival is still only 66%. Presently, no biomarkers are available to select those cervical cancer patients that might benefit

  6. 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

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    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

  7. 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

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    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.

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

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    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.

  9. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    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.

  10. Sphincter-preserving RO total mesorectal excision with resection of internal genitalia combined with pre- or postoperative chemoradiation for T4 rectal cancer in females

    Institute of Scientific and Technical Information of China (English)

    Bartlomiej Szynglarewicz; Rafal Matkowski; Piotr Kasprzak; Daniel Sydor; Jozef Forgacz; Marek Pudelko; Jan Kornafel

    2007-01-01

    AIM: To evaluate the impact of chemoradiation administered pre- or postoperatively on prognosis in females following RO extended resection with sphincterpreserving total mesorectal excision (TME) for locally advanced rectal cancer and to assess the association between chemoradiation and intra- and postoperative variables.METHODS: Twenty-one females were treated for locally advanced but preoperatively assessed as primarily resectable rectal cancer involving reproductive organs. Anterior resection with TME and excision of internal genitalia was combined with neo- or adjuvant chemoradiation. Two-year disease-free survival analysis was performed with the Kaplan-Meier method and logrank test. The association between chemoradiation and other variables was evaluated with the Fisher's exact test and Mann-Whitney test.RESULTS: Survival rate decreased in anaemic females (51.5% vs 57.4%), in patients older than 60 years (41.8% vs 66.7%) with poorly differentiated cancers (50.0% vs 55.6%) and tumors located ≤ 7 cm from the anal verge (42.9% vs 68.1%) but with the lack of importance. Patients with negative lymph nodes and women chemoradiated preoperatively had significantly favourable prognosis (85.7% vs 35.7%; P= 0.03 and 80.0% vs 27.3%; P = 0.01, respectively). Preoperative chemoradiation compared to adjuvant radiochemotherapy was not significantly associated with the duration of surgery, incidence of intraoperative bowel perforation and blood loss ≥ 1 L, rate of postoperative bladder and anorectal dysfunction, and minimal distal resection margin. It significantly influenced minimal radial margin (mean 4.2 mm vs 1.1 mm; P < 0.01).CONCLUSION: Despite involving internal genitalia, long-term disease-free survival and sphincter preservation may be achieved with combined-modality therapy for females with T4 locally advanced rectal carcinoma. Neoadjuvant chemoradiation does not compromise functional results and may significantly improve oncological outcomes probably due to

  11. Duodenal Toxicity After Fractionated Chemoradiation for Unresectable Pancreatic Cancer

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    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

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

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    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.

  13. Treatment of resectable distal rectal cancer with preoperative chemoradiation and sphincter saving surgery

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    Omrani Pour R

    2000-06-01

    Full Text Available To determine if pre-operative combined chemoradiation therapy increase sphincter preservation in the treatment of low-lying rectal cancer, 15 patients were treated with pre-operative chemoradiation: 5FU plus mitomycin C plus 4500-5000 Rad concurrent external beam radiotherapy between Jan 1997 and Jan 1999. There were 10 men and 5 women (Mean age: 49 y with the diagnosis of invasive resectable primary adenocarcinoma of distal rectum limited to pelvis. Median tumor distance from anal verge was 3.3 cm (Range 0-5 cm and half of the patients were absolute candidate for abdominoperineal resection. After 4-6 weeks, all patients were undergone proctectomy and eventually sphincter preservation surgery was done on 9 patients with colonal anastomosis. Function of sphincter was excellent in 6 of them (66% and good in 3 patients (33%. There was no case of incontinence. Complications of surgery were minimal: One case of stricture (10% and one case of partial rupture of anastomosis (10%. Complete pathologic response was achieved on one patient (6.6% and combined pre-operative chemoradiation has changed the plane of surgery from abdominoperineal resection to sphincter saving in 69.2% of patients.

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

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    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.

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

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    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. 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

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    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%).

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

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    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.

  18. Development and controversies of adjuvant therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES:A Medline database search was performed to identify relevant articles using the keywords"pancreatic neoplasm", and"adjuvant therapy". Additional papers were identiifed by a manual search of the references from the key articles. RESULTS:Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identiifed. The results for adjuvant regimens based on systemic 5-lfuorouracil with or without external radiotherapy were conlficting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS:Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

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

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    Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Garg, Madhur K. [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Aparo, Santiago; Kaubisch, Andreas [Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Tome, Wolfgang [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kennedy, Timothy J. [Department of Surgical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States); Kalnicki, Shalom; Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

    2013-06-01

    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.

  20. Impact of neoadjuvant chemoradiation therapy on the postoperative complication rate in rectal cancer

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    Kruschewski M

    2014-10-01

    Full Text Available Purpose: The impact of neoadjuvant chemoradiation therapy (CRT on the postoperative complication rate is discussed controversially. Thus the aim of this study was to evaluate the postoperative complication rate in our patient population. Methods: A retrospective analysis was performed to examine all patients documented online who had undergone conventionally fractionated adjuvant or neoadjuvant CRT from 2001 to 2009 in conjunction with curative resection (R0 for sporadic primary colorectal cancer in the middle or lower third. A total of 246 patients were included and analyzed. Two groups were formed: Group I, 2001-2004, adjuvant CRT, n=108, and Group II, 2005-2009, neoadjuvant CRT, n=138. Results: The two groups had comparable patient-, tumor- and therapy-related characteristics. No difference was found in the anastomotic leak rate (Group I vs. II: 10% vs. 11%. The rate of perineal wound healing problems differed significantly (Group I vs. II: 5% vs. 36%, p=0.016. While no patient died in Group I, lethality amounted to 1.5% (2/138 in Group II. Conclusions: Neoadjuvant CRT does not lead to a higher anastomotic leak rate or lethality in comparison to patients who were primarily operated and received adjuvant CRT in the further course. The rate of perineal wound healing problems is significantly increased.

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Role of chemoradiation in advanced cervical cancer

    Directory of Open Access Journals (Sweden)

    Singh T

    2003-01-01

    Full Text Available A prospective randomized study was conducted in our department of Radiotherapy, Regional Institute of Medical Sciences, Imphal to evaluating the role of chemoradiation in the management of advanced inoperable cervical cancer (stage IIB-IIIB taking only radiation treatment as control spanning the period 1996-1999. Of the fifty patients accumulated in the study group, three patients did not complete treatment, one expired due to other causes and three were lost to follow up. Likewise, of the forty-six patients in the control group, one patient did not complete treatment and 4 were lost to follow up. Thus only 43 and 41 patients were available for the result analysis for the study and control groups respectively. The early treatment response as assessed after two months of treatment conclusion were 79.1%, 13.9%, 93.0% and 58.5%, 31.7%, 90.2% as complete response (CR, partial response (PR, and total response (TR respectively for the study and control groups. Our patients included in this study had a median follow up of 35 months and 33 months for study and control groups respectively. For this follow up, the disease-free survival, survival with disease and overall survival were 67.4%, 7.0%, 74.4% and 43.9%, 12.2%, 56.1% for study and control groups respectively. There was an increase in early side-effects in the chemoradiation group but the difference was not significant. Because of the early side effects, treatment delays ensued in 7 patients (16.3% and in 3 patients (7.3% in the study and control groups respectively. There was no significant increase in the late treatment toxicities in both the groups.

  4. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management

    OpenAIRE

    SMITH, J. JOSHUA; Chow, Oliver S; Gollub, Marc J.; Nash, Garrett M.; Temple, Larissa K.; Weiser, Martin R.; Guillem, José G.; Paty, Philip B.; Avila, Karin; Garcia-Aguilar, Julio; ,

    2015-01-01

    Background Treatment of patients with non-metastatic, locally advanced rectal cancer (LARC) includes pre-operative chemoradiation, total mesorectal excision (TME) and post-operative adjuvant chemotherapy. This trimodality treatment provides local tumor control in most patients; but almost one-third ultimately die from distant metastasis. Most survivors experience significant impairment in quality of life (QoL), due primarily to removal of the rectum. A current challenge lies in identifying pa...

  5. Concurrent Collections

    OpenAIRE

    Zoran Budimlić; Michael Burke; Vincent Cavé; Kathleen Knobe; Geoff Lowney; Ryan Newton; Jens Palsberg; David Peixotto; Vivek Sarkar; Frank Schlimbach; Sağnak Taşırlar

    2010-01-01

    We introduce the Concurrent Collections (CnC) programming model. CnC supports flexible combinations of task and data parallelism while retaining determinism. CnC is implicitly parallel, with the user providing high-level operations along with semantic ordering constraints that together form a CnC graph. We formally describe the execution semantics of CnC and prove that the model guarantees deterministic computation. We evaluate the performance of CnC implementations on several applications an...

  6. Understanding molecular markers in recurrent oral squamous cell carcinoma treated with chemoradiation

    Directory of Open Access Journals (Sweden)

    Seema Gupta

    2016-12-01

    Conclusion: Our results signifies that tumors over expressing Cyclin D1, EGFR and p53 are resistant to chemoradiation and are associated with increased risk of locoregional recurrence and metastasis in OSCC patients undergoing chemoradiation.

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

    Directory of Open Access Journals (Sweden)

    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

  8. A randomized comparative study between neoadjuvant 5-fluorouracil and leukovorin versus 5-fluorouracil and cisplatin along with concurrent radiation in locally advanced carcinoma rectum

    Directory of Open Access Journals (Sweden)

    Priyanjit Kumar Kayal

    2014-01-01

    Full Text Available Context: Concurrent chemoradiotherapy (CCRT with cisplatin-5-fluorouracil (CDDP-5FU in rectal cancer is based on the concept of biochemical modulation. Aims: The study was designed to evaluate whether CCRT with CDDP and 5-FU is noninferior to CCRT with leukovorin (LV and 5FU in downstaging locally advanced rectal adenocarcinoma and to compare the toxicities between the two arms. Settings and Design : Single institutional, noninferiority, prospective, randomized study. Subjects and Methods : In control arm (N = 24 patients received chemotherapy. With bolus 5FU 350 mg/m 2 /day and LV 20 mg/m 2 /day for days 1-5 and 29-33. In study arm (N = 25, patients received chemotherapy with bolus 5 FU 350 mg/m 2 /day for days 1-5 and 29-33 and CDDP 100 mg/m 2 /day at days 1 and 29. Patients in both the arm received concurrent radiation (50.4 Gy in 28#, in conventional fractionation of 1.8 Gy per fraction. Six to eight weeks after concurrent chemoradiation patients underwent assessment and surgery. Postoperatively, adjuvant chemotherapy with m-FOLFO × 6 of 4 months was given to all patients. Statistical Analysis : The Chi-square test was used to compare categorical variables between the groups. Results: Response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST criteria was comparable between the two treatment arms (P = 0.9541. Pathological complete response rate of study arm was comparable to control arm (20 vs 20.83%, P = 0.7778 was not significant. Surgery with R0 resection was possible in 72% cases of study arm compared to 62.5% cases of control arm; P = 0.6861, not significant. Grade III toxicities were quite comparable between two treatment arms. Conclusions : In terms of pathologic complete response (pCR, R0 resection and toxicity profile of both the arms were comparable.

  9. Concurrent Collections

    Directory of Open Access Journals (Sweden)

    Zoran Budimlić

    2010-01-01

    Full Text Available We introduce the Concurrent Collections (CnC programming model. CnC supports flexible combinations of task and data parallelism while retaining determinism. CnC is implicitly parallel, with the user providing high-level operations along with semantic ordering constraints that together form a CnC graph. We formally describe the execution semantics of CnC and prove that the model guarantees deterministic computation. We evaluate the performance of CnC implementations on several applications and show that CnC offers performance and scalability equivalent to or better than that offered by lower-level parallel programming models.

  10. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Raquel Conde-Muíño

    2015-01-01

    Full Text Available There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile’s ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

  13. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    Science.gov (United States)

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

  14. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  15. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    DEFF Research Database (Denmark)

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per

    2015-01-01

    chemotherapy for patients already treated with preoperative (chemo) radiotherapy. For patients not treated preoperatively, several studies support the use of single agent 5-FU chemotherapy. Treatment guidelines seem to differ according to if preoperative chemoradiation is considered of importance for use......BACKGROUND: The use of postoperative adjuvant chemotherapy is controversial for rectal adenocarcinoma. Both international and national guidelines display a great span varying from recommending no adjuvant chemotherapy at all, over single drug 5-fluororuacil (5-FU), to combinations of 5-FU....../oxaliplatin. METHODS: A review of the literature was made identifying 24 randomized controlled trials on adjuvant treatment of rectal cancer based on about 10 000 patients. The trials were subdivided into a number of clinically relevant subgroups. RESULTS: As regards patients treated with preoperative (chemo...

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

    Science.gov (United States)

    Power, D G; Ilson, D H

    2009-11-01

    Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

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

    Energy Technology Data Exchange (ETDEWEB)

    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. Organ preservation with neoadjuvant chemoradiation in patients with orbit invasive sinonasal cancer otherwise requiring extenteration

    Energy Technology Data Exchange (ETDEWEB)

    Amsbaugh, Mark J.; Yusuf, Mehran; Silverman, Craig; Bumpous, Jeffery; Perez, Cesar A.; Potts, Keven; Tennant, Paul; Redman, Rebecca; Dunlap, Neal [University of Louisville, Louisville (United States)

    2016-09-15

    We sought to determine if organ preservation (OP) with neoadjuvant chemoradiation (CRT) was feasible in patients with sinonasal cancer determined to require exenteration. Twenty patients were determined to require exenteration for definitive treatment from 2005 to 2014. Fourteen patients underwent OP and 6 patients received exenteration with adjuvant CRT. Exenteration free survival (EFS), locoregional control (LRC), progression-free survival (PFS), and overall survival (OS) were estimated. Five patients (36%) receiving OP had complete disease response at time of surgery. With a median follow-up of 18.8 months, EFS was 62% at 2 years for patients undergoing OP. At 2 years, there were no significant differences in LRC, PFS or OS (all all p > 0.050) between the groups. Less grade 3 or greater toxicity was seen in patients undergoing OP (p = 0.003). Visual function was preserved in all patients undergoing OP. For patients with sinonasal cancer, OP may avoid exenteration, offering similar disease control and improved toxicity.

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

    Directory of Open Access Journals (Sweden)

    Tiffany A. Pompa

    2017-01-01

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

  20. Comparison of chemoradiation combined with hyperthermia therapy and chemoradiation therapy alone in invasive cervical cancer:a perspective randomized controlled study%深部热疗联合放化疗与单纯放化疗治疗中晚期子宫颈癌的随机对照研究

    Institute of Scientific and Technical Information of China (English)

    石兴源; 周同冲; 林晓丹; 张伟军

    2012-01-01

    目的 比较深部热疗加同步放化疗与单纯放化疗治疗中晚期子宫颈癌的临床疗效及不良反应.方法 80例Ⅱb~Ⅳa期子宫颈癌患者,随机均分为深部热疗加放化疗组(综合组)和放化疗组(对照组).对照组行适形放疗配合同期化疗,顺铂( DDP)40 mg/m2单药每周化疗,共6次,放疗结束后再行TP方案辅助化疗2周期,即多西他赛75 mg/m2 d1,DDP 35 mg/m2 d1-2,每4周为1周期.综合组放化疗方法同对照组,深部热疗每次治疗60分钟,每周1~2次,共8 ~12次.结果 综合组和对照组治疗结束后肿瘤完全缓解率、1年及2年无瘤生存率比较,差异有统计学意义(P<0.05).在Ⅲ~Ⅳa期患者中综合组治疗完全缓解率及1、2年无瘤生存率分别为80.0%、66.7%和60.0%,较对照组的35.3%、23.5%和17.6%明显增高,差异有统计学意义(P<0.05),两组不良反应比较,差异无统计学意义(P>0.05).结论 深部热疗联合放化疗治疗中晚期尤其是Ⅲ期以上子宫颈癌的疗效优于单纯放化疗,且无严重不良反应,值得临床进一步推广.%Objective To compare the short-term effect and acute toxicity of chemoradiation combined with hyperthermia therapy versus chemoradiation therapy alone in invasive cervical cancer. Methods Eighty women with invasive squamous cell carcinoma or adenocarcinoma of the cervix of stage Ⅱb, Ⅲ or Ⅳa were enrolled in the study. Patients were randomly assigned to receive hyperthermic chemoradiotherapy (HCRT) and chemoradiotherapy (CRT). The regimen for concurrent chemoradiotherapy:DDP 40 mg/ m2 dl/week for 6 cycles within radiotherapy; the regimen for adjuvant chemotherapy:Taxotere 75 mg/m2 dl, DDP 35 mg/m2 dl-2, every 4 weeks,2 cycles. In HCRT group patients also received 8 ~ 12 courses of radiofrequency hyperthermia therapy. Results The complete remission and 1- and 2-y disease-free survival rate was higher in HCRT group than that in CRT group (P<0.05) ; the difference was

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

    OpenAIRE

    2013-01-01

    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; 5...

  2. Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer.

    Science.gov (United States)

    Bhide, S A; Ahmed, M; Barbachano, Y; Newbold, K; Harrington, K J; Nutting, C M

    2008-07-08

    We describe a retrospective series of patients with advanced head-and-neck cancer who were treated with induction chemotherapy followed by radical chemo-radiation. Patients treated with two cycles of induction chemotherapy followed by definitive chemo-radiation for squamous cell carcinoma of the head-and-neck region, from 2001 - 2006 at the Royal Marsden Hospital, formed the basis of this study. Cisplatin (75 mg m(-2)) on day 1 and 5-FU (1000 mg m(-2)) day 1 - 4 was the standard regimen used for induction treatment. Cisplatin (100 mg m(-2)) on day 1 and day 29 was used for concomitant treatment. The radiation was delivered using conformal technique. Tissues containing macroscopic and microscopic disease were treated to doses of 65 Gray (Gy) in 30 fractions and 50 Gy in 25 fractions, respectively. Data on patterns of relapse and acute toxicity (NCICTCv.3.0) were collected. A total of 129 patients were included, median age was 58 (range: 27 - 78). The site of tumour was: oropharynx 70 (54%), larynx 30 (23%), hypopharynx 24 (19%) and other 5 (4%). The median follow-up was 19 months (range: 4 - 58). Local control, disease-specific survival and overall survival at 2 years were 71%, 68% and 63%, respectively. The distant recurrence rate at 2 years was 9%. Ten patients required dose reduction during induction chemotherapy due to toxicity. The dose of 5-FU was reduced in six patients and that of cisplatin in four patients. The incidence of grade 3/4 toxicity was: neutropenia 5%, thrombocytopenia 1%, nausea and vomiting 3%. One cycle of concurrent cisplatin was omitted in 23 patients due to toxicity. Full-dose radiotherapy was administered to 98% of patients. The incidence of grade 3/4 toxicity was: skin 20%, dysphagia 65%, mucositis 60%, neutropenia 3%, anaemia 1%, nausea and vomiting 4%, nephrotoxicity 1%. Induction chemotherapy followed by radical chemo-radiation is a safe and tolerable regimen in the treatment of advanced head-and-neck cancer. Distant recurrence rates

  3. A STUDY OF COX-2 INHIBITOR CELECOXIB AND CHEMORADIATION IN PATIENTS WITH LOCALLY ADVANCED CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    Kuppa Prakash

    2016-08-01

    Full Text Available AIMS AND OBJECTIVES To evaluate efficacy of concurrent oral Cox-2 Inhibitor (celecoxib and chemoradiation in locoregional control, distant control, disease free survival and/or overall survival in patients with locally advanced cervical cancer. To determine treatment related toxicity rates in patients with locally advanced cervical cancer treated by oral celecoxib, intravenous cisplatin and concurrent pelvic radiation therapy. MATERIALS AND METHODS Study was done for a period of 2 years in a tertiary care cancer hospital which caters to the cancer patients. Advanced squamous, adenocarcinoma or adenosquamous carcinoma of uterine cervix, Patients with age <70 years, ECOG performance status 0-2, Normal haematological investigations, Normal renal function test, Normal liver function test, No disease outside of pelvis. RESULTS This prospective study consisted 30 patients, 15 patients on either arm. Overall pooled mean age for both study and comparison group was 50.3 years with a probability value P=0.91 for age. 14 patients (93.33% in both the arms had a performance status of ECOG 0 or 1 and 1 patient in both arms had ECOG PS-2. Stage distribution of the patients in study arm was 3 in IB2, 2 in IIA, 5 in IIB, 4 in III and 1 in stage IVA. In control arm, out of the 15 patients 2 are in IB2, 2 in IIA, 5 in IIB, 5 in III and 1 in stage IVA. The mean probability value was P=0.65 for stage distribution. 15 patients in arm-A (study arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr after pelvic RT on an average of 1 week along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22 and Cox-2 inhibitor oral celecoxib 400 mg twice daily (800 mg/d starting from day 1 to throughout the duration of the chemoradiation. 15 patients in arm-B (Control arm received pelvic RT 50Gy 2Gy/Fr 5#/week followed by HDR –ICR 3 Fr. 700 cGy/Fr on an average of 1 week after pelvic RT along with weekly cisplatin 40 mg/m2 (50 mg (D1, D8, D15, D22

  4. Cardiovascular morbidity after radiotherapy or chemoradiation in patients with cervical cancer

    NARCIS (Netherlands)

    Maduro, John; den Dekker, Heleen; Pras, Elisabeth; de Vries, E.G.; van der Zee, A.G.; Klokman, W.J.; Reyners, A.K.; van Leeuwen, F.E.; Langendijk, J.A.; de Bock, G.H.; Gietema, J.A.

    2010-01-01

    PURPOSE: To evaluate the risk of cardiovascular events (CVE) in patients with cervical cancer treated with radiotherapy or chemoradiation. METHODS AND MATERIALS: The incidence of CVE in patients treated between 1989 and 2002 by radiotherapy or chemoradiation was compared with a Dutch reference popul

  5. Basic Concurrency Theory

    DEFF Research Database (Denmark)

    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....

  6. Comparison of efficacy of induction chemotherapy plus intensi-ty-modulated radiotherapy and concurrent chemo-radiotherapy plus adjuvant chemotherapy for patients with loco-regionally ad-vanced nasopharyngeal carcinoma%调强放疗结合诱导化疗或同期加辅助化疗治疗局部晚期鼻咽癌的疗效比较

    Institute of Scientific and Technical Information of China (English)

    丘文泽; 黄培钰; 施君理; 夏海群; 赵充; 曹卡加

    2015-01-01

    Objective: To compare the efficacy of induction chemotherapy (IC) plus intensity-modulated radiotherapy (IMRT) with that of concurrent chemo-radiotherapy (CCRT) plus adjuvant chemotherapy (AC) for patients with loco-regionally advanced naso-pharyngeal carcinoma (NPC). Methods:Data of 240 patients with loco-regionally advanced NPC were reviewed. These patients were admitted to the Sun Yat-sen University Cancer Center between January 2004 and December 2008. Among the 240 patients, 117 under-went the IC+IMRT and 123 were treated with the CCRT+AC. The IC+IMRT group received a regimen including cisplatin and 5-fluoro-uracil (5-FU). The CCRT+AC group received cisplatin concurrently with radiotherapy and subsequently received adjuvant cisplatin and 5-FU. The survival rates of the patients were assessed by Kaplan-Meier analysis, and the survival curves were compared by Log-rank test. Multivariate analysis was conducted using Cox proportional hazard regression model. Results:The 5-year overall survival (OS), disease-free survival, distant metastasis-free survival, local relapse-free survival, and the nodal relapse-free survival were 78.0%versus 78.7%, 68.9%versus 67.5%, 79.0%versus 77.0%, 91.6%versus 91.0%, and 95.3%versus 93.7%in the IC+IMRT and CCRT+AC groups, respectively. The survival between the two groups exhibited no significant differences. Higher rates of Grades 3 to 4 nau-sea-vomiting (8.1%vs. 1.7%, P=0.023) and leukopenia (9.7%vs. 0.9%, P=0.006) were observed in the CCRT+AC group. Multivariate analysis revealed that N stage and age were significant prognostic factors for the OS of the patients with loco-regionally advanced NPC. Conclusion:The treatment outcomes of IC+IMRT and CCRT+AC were similar. Distant metastasis remained as the predominant mode of treatment failure.%目的:比较诱导化疗加调强放疗和同期放化疗加辅助化疗治疗局部晚期鼻咽癌的疗效。方法:收集2004年1月至2008年12月中山大学肿瘤医院收治的经病

  7. Concurrent weighted logic

    DEFF Research Database (Denmark)

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Complete pathological responses in locally advanced rectal cancer after preoperative IMRT and integrated-boost chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Hernando-Requejo, Ovidio [Hospital Universitario Sanchinarro, Department of Radiation Oncology, Madrid (Spain); Hospital Universitario Sanchinarro, CEU San Pablo University, Madrid (Spain); HM Universitario Sanchinarro, Centro Integral Oncologico Clara Campal, Madrid (Spain); Lopez, Mercedes; Rodriguez, Almudena; Ciervide, Raquel; Valero, Jeannette; Sanchez, Emilio; Garcia-Aranda, Mariola; Potdevin, Guillermo [Hospital Universitario Sanchinarro, Department of Radiation Oncology, Madrid (Spain); Cubillo, Antonio; Rodriguez, Jesus [Hospital Universitario Sanchinarro, Department of Medical Oncology, Madrid (Spain); Hospital Universitario Sanchinarro, CEU San Pablo University, Madrid (Spain); Rubio, Carmen [Hospital Universitario Sanchinarro, Department of Radiation Oncology, Madrid (Spain); Hospital Universitario Sanchinarro, CEU San Pablo University, Madrid (Spain)

    2014-06-15

    To analyze the efficacy and safety of a new preoperative intensity-modulated radiotherapy (IMRT) and integrated-boost chemoradiation scheme. In all, 74 patients were treated with IMRT and concurrent standard dose capecitabine. The dose of the planning target volume (PTV) encompassing the tumor, mesorectum, and pelvic lymph nodes was 46 Gy in 23 fractions; the boost PTV, at a dose of 57.5 Gy in 23 fractions, included the macroscopic primary tumor and pathological lymph nodes. The patients underwent surgery 6-8 weeks after chemoradiation. The complete treatment data of 72 patients were analyzed. Tumor downstaging was achieved in 55 patients (76.38 %) and node downstaging in 34 (47.2 %). In 22 patients (30.6 %), there was complete pathological response (ypCR). The circumferential resection margin was free of tumor in 70 patients (97.2 %). The 3-year estimated overall survival and disease-free survival rates were 95.4 and 85.9 % respectively, and no local relapse was found; however, ten patients (13.8 %) developed distant metastases. High pathologic tumor (pT) downstaging was shown as a favorable prognostic factor for disease-free survival. No grade 4 acute radiotherapy-related toxicity was found. The IMRT and integrated-boost chemoradiation scheme offered higher rates of ypCR and pT downstaging, without a significant increase in toxicity. The circumferential margins were free of tumors in the majority of patients. Primary tumor regression was associated with better disease-free survival. (orig.) [German] Analyse von Wirksamkeit und Sicherheit eines neuen praeoperativen intensitaetsmodulierten Bestrahlungsschemas (IMRT) mit integriertem Boost. Insgesamt 74 Patienten wurden simultan mit IMRT und Capecitabin (Standarddosis) behandelt. Die Dosis des Planungszielvolumens (PTV) umfasste den Tumor, das Mesorektum sowie die Beckenlymphknoten und betrug 46 Gy in 23 Fraktionen. Das Boost-PTV betrug 57,5 Gy in 23 Fraktionen und umfasste den makroskopischen Primaertumor und die

  10. Measuring and modelling concurrency

    Directory of Open Access Journals (Sweden)

    Larry Sawers

    2013-02-01

    Full Text Available This article explores three critical topics discussed in the recent debate over concurrency (overlapping sexual partnerships: measurement of the prevalence of concurrency, mathematical modelling of concurrency and HIV epidemic dynamics, and measuring the correlation between HIV and concurrency. The focus of the article is the concurrency hypothesis – the proposition that presumed high prevalence of concurrency explains sub-Saharan Africa's exceptionally high HIV prevalence. Recent surveys using improved questionnaire design show reported concurrency ranging from 0.8% to 7.6% in the region. Even after adjusting for plausible levels of reporting errors, appropriately parameterized sexual network models of HIV epidemics do not generate sustainable epidemic trajectories (avoid epidemic extinction at levels of concurrency found in recent surveys in sub-Saharan Africa. Efforts to support the concurrency hypothesis with a statistical correlation between HIV incidence and concurrency prevalence are not yet successful. Two decades of efforts to find evidence in support of the concurrency hypothesis have failed to build a convincing case.

  11. Constraints meet concurrency

    CERN Document Server

    Mauro, Jacopo

    2014-01-01

    This book describes the benefits that emerge when the fields of constraint programming and concurrency meet. On the one hand, constraints can be used in concurrency theory to increase the conciseness and the expressive power of concurrent languages from a pragmatic point of view. On the other hand, problems modeled by using constraints can be solved faster and more efficiently using a concurrent system. Both directions are explored providing two separate lines of development. Firstly the expressive power of a concurrent language is studied, namely Constraint Handling Rules, that supports constraints as a primitive construct. The features of this language which make it Turing powerful are shown. Then a framework is proposed to solve constraint problems that is intended to be deployed on a concurrent system. For the development of this framework the concurrent language Jolie following the Service Oriented paradigm is used. Based on this experience, an extension to Service Oriented Languages is also proposed in ...

  12. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future.

  13. Towards Composable Concurrency Abstractions

    Directory of Open Access Journals (Sweden)

    Janwillem Swalens

    2014-06-01

    Full Text Available In the past decades, many different programming models for managing concurrency in applications have been proposed, such as the actor model, Communicating Sequential Processes, and Software Transactional Memory. The ubiquity of multi-core processors has made harnessing concurrency even more important. We observe that modern languages, such as Scala, Clojure, or F#, provide not one, but multiple concurrency models that help developers manage concurrency. Large end-user applications are rarely built using just a single concurrency model. Programmers need to manage a responsive UI, deal with file or network I/O, asynchronous workflows, and shared resources. Different concurrency models facilitate different requirements. This raises the issue of how these concurrency models interact, and whether they are composable. After all, combining different concurrency models may lead to subtle bugs or inconsistencies. In this paper, we perform an in-depth study of the concurrency abstractions provided by the Clojure language. We study all pairwise combinations of the abstractions, noting which ones compose without issues, and which do not. We make an attempt to abstract from the specifics of Clojure, identifying the general properties of concurrency models that facilitate or hinder composition.

  14. Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Fernando N Aguila; Taral Patel; Mark Knapp; XueQiang Zhu; XiLin Chen; Phillip D Price

    2016-01-01

    AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR) rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%) and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n = 16),the p CR rate was 47%(n = 8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n = 7) and 53%(n = 9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.

  15. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    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...... reflect the reactive interactions between concurrent constraint processes and their environment, as well as internal interactions between individual processes. Relationships between the suggested notions are studied, and they are all proved to be decidable for a substantial fragment of the calculus...

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

    Energy Technology Data Exchange (ETDEWEB)

    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%.

  17. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

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

    Institute of Scientific and Technical Information of China (English)

    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...

  19. The role of postoperative radiation and chemoradiation in Merkel Cell Carcinoma: A systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Shaakir eHasan

    2013-11-01

    Full Text Available Objective: A systematic review of the literature was undertaken to investigate whether adjuvant radiotherapy and/or chemotherapeutics offered any additional benefit than surgery alone in the treatment of Merkel Cell Carcinoma (MCC. Methods: A PubMed, MEDLINE search was conducted between 1995-2013, to identify reported cases of surgically treated MCC followed by either observation, radiation, or chemoradiation. Patient demographics and outcomes were recorded and compared in a systematic fashion. Results: Thirty-four studies (n = 4475 were included. The median age was 73 years, median follow-up was 36 months and there was a 1.5:1 ratio of men to women. All 4475 patients had surgery, 1975 had no further treatment, 1689 received postoperative RT, and 301 received postoperative chemoRT. The most common site was face/head/neck, 47.8%. Stage 1 was the most common clinical stage at diagnosis (57%. Three-year LC was 20% [median 10%] in the observation cohort, compared to 65% [62%] with postoperative RT and 67% [75%] with postoperative chemoRT; these findings were statistically significant (P

  20. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    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...

  1. Concurrent Software Engineering Project

    Science.gov (United States)

    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…

  2. Probabilistic Concurrent Kleene Algebra

    Directory of Open Access Journals (Sweden)

    Annabelle McIver

    2013-06-01

    Full Text Available We provide an extension of concurrent Kleene algebras to account for probabilistic properties. The algebra yields a unified framework containing nondeterminism, concurrency and probability and is sound with respect to the set of probabilistic automata modulo probabilistic simulation. We use the resulting algebra to generalise the algebraic formulation of a variant of Jones' rely/guarantee calculus.

  3. Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model

    OpenAIRE

    Lukianova-Hleb, Ekaterina Y; Kim, Yoo-Shin; Aryasomayajula, Bhawani; Boulikas, Teni; Phan, Jack; Hung, Mien-Chie; Torchilin, Vladimir P.; O’Neill, Brian E.; Lapotko, Dmitri O.

    2015-01-01

    Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard ch...

  4. Adjuvants for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe

    2012-10-01

    Allergen-specific immunotherapy is currently performed via either the subcutaneous or sublingual routes as a treatment for type I (IgE dependent) allergies. Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts in the absence of any immunopotentiator. Adjuvants to be included in the future in products for allergen specific immunotherapy should ideally enhance Th1 and CD4+ regulatory T cell responses. Imunomodulators impacting dendritic or T cell functions to induce IL10, IL12 and IFNγ production are being investigated in preclinical allergy models. Such candidate adjuvants encompass synthetic or biological immunopotentiators such as glucocorticoids, 1,25-dihydroxy vitamin D3, selected probiotic strains (e.g., Lactobacillus and Bifidobacterium species) as well as TLR2 (Pam3CSK4), TLR4 (monophosphoryl lipid A, synthetic lipid A analogs) or TLR9 (CpGs) ligands. Furthermore, the use of vector systems such as mucoadhesive particules, virus-like particles or liposomes are being considered to enhance allergen uptake by tolerogenic antigen presenting cells present in mucosal tissues.

  5. Pre-operative chemoradiation therapy with 5-fluorouracil and low-dose daily cisplatin for esophageal cancer. A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, Shouji; Konishi, Toshiro; Kawahara, Masaki; Ito, Akihiko; Hoji, Keiichi; Takeda, Yuichi; Oba, Hiroshi; Shimizu, Seiichiro [Showa General Hospital, Kodaira, Tokyo (Japan); Kaminishi, Michio

    1999-03-01

    A combination of chemotherapy and radiotherapy (chemoradiation therapy; CRT) has recently been developed to improve the survival of esophageal cancer patients. However, the optimal choice of chemotherapeutic agents and their doses, as well as chemotherapy and radiotherapy regimens, remain unclear. Based on recent advances in knowledge on the radiosensitizing and biochemical modulation effects of chemotherapeutic agents, we have recently developed concurrent CRT which consisted of continuous 5-fluorouracil (5FU) administration (600 mg/m{sup 2}/day, days 1-5) combined with a low dose of daily cisplatin administration (10 mg/m{sup 2}/day, days 1-5, and 5 or 10 mg/m{sup 2}/day, days 8-12 and 15-19) before each fraction of radiation (2 Gy each). To evaluate the efficacy and safety of our concurrent CRT, 10 esophageal cancer patients received one or one and a half courses of the CRT. All patients tolerated and completed a full course of the CRT. The effectiveness of the CRT on the primary tumor included pathologically or endoscopically complete responses in three patients (30%), partial response in five (50%), no response in two (20%) and tumoral downstaging (T-classification) in five (50%). Grade 2 and Grade 3 toxicity, seen in six patients, did not affect surgical operation. No patients showed CRT-related deaths. Eight patients (80%) underwent resection with no operative mortality. Of these, two patients (25%) showed pathologically or endoscopically complete responses, and four (50%) showed partial response. Three patients died of cancer after resection. The two inoperable patients showed a pathologically complete response and partial response, respectively. They were relieved of their cancer-related complaints and were living without hospitalization at the time of this analysis. These results suggest that the concurrent CRT based on the theoretical backgrounds is effective and has acceptable toxicities with maintaining its efficacy for the treatment of esophageal

  6. Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    Concurrent objects are named concurrent processes that interact by invoking each other's operations. We describe how such concurrent objects can be specified, how objects can be composed, and how it can be shown that one object refines another.First a model is defined, based on a transition...... relation over two objects and an event. In the model, objects can be composed by parallel composition, encapsulation, and hiding of operations. Refinement between objects is defined as fair trace inclusion.A specification language is presented where objects can be specified operationally by abstract...

  7. Building Safe Concurrency Abstractions

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    2014-01-01

    Concurrent object-oriented programming in Beta is based on semaphores and coroutines and the ability to define high-level concurrency abstractions like monitors, and rendezvous-based communication, and their associated schedulers. The coroutine mechanism of SIMULA has been generalized...... into the notions of concurrent and alternating objects. Alternating objects may be used to start a cooperative thread for each possible blocking communication and is thus an alternative to asynchronous messages and guarded commands. Beta like SIMULA, the first OO language, was designed as a language for modeling...... 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 introduce...

  8. Concurrent bisimulation algorithm

    OpenAIRE

    Kułakowski, Konrad

    2013-01-01

    The coarsest bisimulation-finding problem plays an important role in the formal analysis of concurrent systems. For example, solving this problem allows the behavior of different processes to be compared or specifications to be verified. Hence, in this paper an efficient concurrent bisimulation algorithm is presented. It is based on the sequential Paige and Tarjan algorithm and the concept of the state signatures. The original solution follows Hopcroft's principle "process the smaller half". ...

  9. Carbohydrate-based immune adjuvants

    Science.gov (United States)

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  10. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2011-01-01

    Full Text Available With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4 monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

  11. The role of surgery in locally advanced carcinoma of cervix after sub-optimal chemoradiation: Indian scenario

    Directory of Open Access Journals (Sweden)

    Rajshekar S Kundargi

    2013-01-01

    Full Text Available Background: Standard treatment of advanced cervical cancer is concurrent chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic external beam radiotherapy (EBRT with the concomitant platinum based chemotherapy followed by intracavitary brachytherapy (ICBT to boost central disease. Management of patients who are suboptimally treated, especially, after unsuccessful ICBT insertion is not well-defined. This study explores the role of hysterectomy in these patients. Materials and Methods: From January 2006 to December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT insertion was unsuccessful, were analyzed retrospectively. Operable patients with no parametrial involvement underwent hysterectomy and outcomes (recurrence free and overall survival were noted. Results: The major complications in post operative period were wound infection, paralytic ileus and bladder atony all of which were conservatively managed with no mortality. At median follow-up of 36 months (range 12-60 months there was no recurrence in patients with stage 1B2 and stage IIA, 25 out of 38 (65.8% were event free and the overall survival was 71%. Conclusion: Many patients in Indian scenario receive suboptimal therapy in locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra-fascial hysterectomy can be a good alternative for these patients.

  12. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    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.

  13. Channel's Concurrence and Quantum Teleportation

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. [Syndrome of inappropriate secretion of ADH following chemoradiation therapy].

    Science.gov (United States)

    Kikuchi, Norihiro; Masuda, Michiko; Tamura, Tomohiro; Nakazawa, Kensuke; Kanemoto, Koji; Iijima, Hiroaki; Ishikawa, Hirokazu; Sato, Shinya; Ishii, Yukio

    2012-11-01

    We report a 69-year-old female patient with pulmonary adenocarcinoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone(SIADH)following systemic chemotherapy with cisplatin(CDDP)and vinorelbine(VNR). She was admitted to our hospital for chemo-radiotherapy for advanced lung cancer, and became restless 4 hours after the administration of CDDP and VNR. Symptoms such as restlessness and incontinence were worsening despite the massive infusion that was completed. Laboratory examinations on day 6 after chemotherapy showed severe hyponatremia(107mEq/L)with decreased serum osmolarity(227mOsm/L)and increased urine osmolarity(452mOsm/L). The serum anti-diuretic hormone(ADH)level was elevated to 16. 7 pg/mL despite severe hyponatremia. She was diagnosed with SIADH and was treated with hypertonic saline infusion and fluid restriction. Her restlessness and other psychiatric symptoms were improved. The use of carboplatin and VNR in the subsequent course did not develop SIADH, indicating that the SIADH was induced by CDDP. Although SIADH following CDDP administration is rare, the electrolyte balance should be carefully monitored throughout the clinical course of chemo-radiation therapy, when psychiatric symptoms are found in patients with lung cancer.

  16. Changes in Cervical Cancer FDG Uptake During Chemoradiation and Association With Response

    Energy Technology Data Exchange (ETDEWEB)

    Kidd, Elizabeth A., E-mail: ekidd@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Thomas, Maria [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Siegel, Barry A.; Dehdashti, Farrokh [Alvin J. Siteman Cancer Center, St. Louis, Missouri (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri (United States); Grigsby, Perry W. [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Alvin J. Siteman Cancer Center, St. Louis, Missouri (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri (United States); Division of Gynecologic Oncology, Washington University School of Medicine, St. Louis, Missouri (United States)

    2013-01-01

    Purpose: Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUV{sub max}) and the variability of uptake (FDG{sub hetero}), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUV{sub max} and FDG{sub hetero} during concurrent chemoradiation for cervical cancer and their association with post-treatment response. Methods and Materials: Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUV{sub max}, FDG{sub hetero}, and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4 of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT. Results: For all patients, the average pretreatment SUV{sub max} was 17.8, MTV was 55.4 cm{sup 3}, and FDG{sub hetero} was -1.33. A similar decline in SUV{sub max} was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDG{sub hetero} decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUV{sub max} had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUV{sub max}, larger MTV, and greater heterogeneity at all 3 times. Week 4 SUV{sub max} (P=.037), week 4 FDG{sub hetero} (P=.005), pretreatment MTV (P=.008), and pretreatment FDG{sub hetero} (P=.008) were all significantly associated with post-treatment PET response. Conclusions: SUV{sub max} shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study

  17. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    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...

  18. Algebraic topology and concurrency

    DEFF Research Database (Denmark)

    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...

  19. ERM immersion vaccination and adjuvants

    DEFF Research Database (Denmark)

    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 commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Feature conversion for concurrent engineering

    NARCIS (Netherlands)

    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

  2. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    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...... with piecewise-smooth boundary. Our aim is to identify the equivalence classes with the critical points of a certain Morse function....

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  5. Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model.

    Science.gov (United States)

    Lukianova-Hleb, Ekaterina Y; Kim, Yoo-Shin; Aryasomayajula, Bhawani; Boulikas, Teni; Phan, Jack; Hung, Mien-Chie; Torchilin, Vladimir P; O'Neill, Brian E; Lapotko, Dmitri O

    2015-01-01

    Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near-infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5-fold, and reducing the side effects to a negligible level. In quadrapeutics, we observed an "inversion" of the drug efficacy of two standard drugs: doxorubicin, a low efficacy drug for the cancers studied, was two times more efficient than cisplatin, the first choice drug in clinic for HNSCC. The radical therapeutic gain of quadrapeutics resulted from the intracellular synergy of the four components employed which we administered in a specific sequence, while the reduction in the toxicity was due to the low doses of all four components. The biodistribution, safety and efficacy data for quadrapeutics in HNSCC ensure its high translational potential and justify the possibility of clinical trials.

  6. PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Kristiansen, C.; Loft, A.; Berthelsen, Anne Kiil;

    2008-01-01

    PURPOSE: The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. METHODS: The study included 30 patients with locall...

  7. Results of surgical treatment versus chemoradiation therapy in oropharyngeal early tumors

    Directory of Open Access Journals (Sweden)

    Chedid, Helma Maria

    2009-03-01

    Full Text Available Introduction: The epidermoid carcinoma of the upper aerodigestive tract is diagnosed in approximately 40% of the cases of advanced clinical stages. Objective: To evaluate the disease-free interval in patients with clinical stages I and II epidermoid carcinoma who were submitted to surgery or chemoradiation. Method: Retrospective study of the records of 139 patients treated for oropharyngeal epidermoid carcinoma submitted to treatment with curative intent. Among those patients, 38 were classified with early tumors clinical stages I and II. Twenty-seven (71.1% underwent surgical treatment whereas eleven (28.9% were treated with chemoradiation. The mean age was 56.4 years; 31 cases (81.6% were in men and seven (18.4% were in women. Results: Among the eleven patients who were submitted to chemoradiation, 72.7% obtained locoregional control of the disease and their disease-free survival was of 42%. Among the 27 patients operated, 19 remained in Clinical Stages I and II in the histological report and six underwent postoperative radiation therapy. The disease-free interval for two years was of 70%. Conclusion: The patients submitted to the surgery had a better disease-free interval as compared to those submitted to chemoradiation treatment.

  8. Reduction of heart volume during neoadjuvant chemoradiation in patients with resectable esophageal cancer

    NARCIS (Netherlands)

    Haj Mohammad, Nadia; Kamphuis, Martijn; Hulshof, Maarten C C M; Lutkenhaus, Lotte J; Gisbertz, Suzanne S; Bergman, Jacques J G H M; de Bruin-Bon, H A C M Rianne; Geijsen, Elisabeth D; Bel, Arjan; Boekholdt, S Mathijs; van Laarhoven, Hanneke W M

    2015-01-01

    BACKGROUND AND PURPOSE: Neoadjuvant chemoradiation (nCRT) followed by surgery is considered curative intent treatment for patients with resectable esophageal cancer. The aim was to establish hemodynamic aspects of changes in heart volume and to explore whether changes in heart volume resulted in cli

  9. A COX-2 inhibitor combined with chemoradiation of locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Mortensen, John Pløen; Bisgaard, Claus;

    2008-01-01

    BACKGROUND AND AIM: The aim of this study was to investigate the possible effect of a COX-2 inhibitor in addition to chemoradiation of locally advanced rectal cancer. MATERIALS AND METHODS: The study included 35 patients with rectal adenocarcinoma. All patients had a tumor localised....

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. How to define green adjuvants.

    Science.gov (United States)

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.

  12. Mastering concurrency in Go

    CERN Document Server

    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

  13. Fluorouracil Based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy Following Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the US Intergroup/RTOG 9704 Phase III Trial

    Science.gov (United States)

    Regine, William F.; Winter, K.A.; Abrams, R.; Safran, H.; Hoffman, J.P.; Konski, A.; Benson, A.B.; Macdonald, J.S.; Rich, T.A.; Willett, C.G.

    2011-01-01

    Background The impact of the addition of gemcitabine (G) to 5-FU chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. Methods Following resection of pancreatic adenocarcinoma patients were randomized to pre and post CRT 5-FU vs. pre and post CRT G. 5-FU = continuous (CI) at 250 mg/m2/day. G = 1000 mg/m2 weekly; both given over 3 weeks pre and 12 weeks post - CRT. CRT = 50.4 Gy with CI 5-FU. Primary endpoint was survival for all patients and for pancreatic head tumor patients. Results Four hundred and fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n=388) had a median survival and 5-year OS of 20.5 months and 22% with G vs. 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the G arm with pancreatic head tumors experienced a trend towards improved OS (p=0.08). First site of relapse local recurrence in 28% of patients vs. distant relapse in 73%. Conclusion(s) The sequencing of 5-FU CRT with G as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥ 70% of patients. These findings serve as the basis for the recently activated EORTC/US Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of G. PMID:21499862

  14. 胃癌的辅助治疗%Adjuvant therapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    曹雯; 赵爱光

    2009-01-01

    辅助化疗可改善日本胃癌患者的生存期;围手术期化疗给欧洲患者带来生存获益;辅助放化疗因其有效性和可行性成为美国胃癌根治术后患者的标准治疗方法;腹腔化疗亦在减少复发转移、延长生存期等方面起到了一定的作用,多在亚洲使用.%Adjuvant chemotherapy can improve the survival time of Japanese gastric cancer patients.Perioperative chemotherapy has extended the lives of European patients. Because of the effectiveness and feasi-bility, adjuvant chemoradiation has become the standard therapy scheme for American gastric cancer patients af-ter radical operation. Intraperitoneal chemotherapy, which is mainly applied in Asia, also plays its role in de-creasing recurrence and metastasis as well as extending survival time.

  15. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  16. Recursive Concurrent Stochastic Games

    CERN Document Server

    Etessami, Kousha

    2008-01-01

    We study Recursive Concurrent Stochastic Games (RCSGs), extending our recent analysis of recursive simple stochastic games [16,17] to a concurrent setting where the two players choose moves simultaneously and independently at each state. For multi-exit games, our earlier work already showed undecidability for basic questions like termination, thus we focus on the important case of single-exit RCSGs (1-RCSGs). We first characterize the value of a 1-RCSG termination game as the least fixed point solution of a system of nonlinear minimax functional equations, and use it to show PSPACE decidability for the quantitative termination problem. We then give a strategy improvement technique, which we use to show that player 1 (maximizer) has \\epsilon-optimal randomized Stackless & Memoryless (r-SM) strategies for all \\epsilon > 0, while player 2 (minimizer) has optimal r-SM strategies. Thus, such games are r-SM-determined. These results mirror and generalize in a strong sense the randomized memoryless determinacy r...

  17. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla;

    2007-01-01

    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes ...

  18. A Review and Prospect on Herbicide Adjuvants

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Concurrent engineering research center

    Science.gov (United States)

    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.

  20. Economic explanations for concurrent sourcing

    DEFF Research Database (Denmark)

    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....

  1. Definitive concurrent chemoradiotherapy in locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Comprehensive clinical study of concurrent chemotherapy breathing IMRT middle part of locally advanced esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jae Hong; Moon, Seong Kwon [Dept. of Radiation Oncology, College of Medicine, Soonchunhyang University , Asan (Korea, Republic of); Kim, Seung Chul [Dept. of Radiology, Songho College, Hoengseong (Korea, Republic of)

    2015-12-15

    The standard treatment of locally advanced type of mid-esophageal cancer is concurrent chemoradiation therapy (CRT). We evaluated the feasibility of chemotherapy with adding docetaxel to the classical basic regimens of cisplatin plus 5-fluorouracil (5-FU) and radiotherapy up to 70.2 Gy using dose escalations for esophageal cancer. It was possible to escalate radiation treatment dose up to 70.2 Gy by the respiratory-gated intensity- modulated radiotherapy (gated-IMRT) based on the 4DCT-simulation, with improving target coverage and normal tissue (ex., lung, heart, and spinal cord) sparing. This study suggested that the definitive chemo-radiotherapy with docetaxel, cisplatin, and 5-fluorouracil (i.e., DCF-R) and gating IMRT is tolerable and active in patients with locally advanced mid-esophageal cancer (AEC)

  3. Induction chemotherapy with carboplatin-paclitaxel followed by standard radiotherapy with concurrent daily low-dose cisplatin plus weekly paclitaxel for inoperable non-small-cell lung cancer.

    Science.gov (United States)

    Ardizzoni, Andrea; Scolaro, Tindaro; Mereu, Carlo; Cafferata, Mara Argenide; Tixi, Lucia; Bacigalupo, Almalina; Tiseo, Marcello; Monetti, Francesco; Rosso, Riccardo

    2005-02-01

    Both induction chemotherapy and concurrent platinating agents have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study investigated activity and feasibility of a novel chemoradiation regimen, including platinum and paclitaxel, both as induction chemotherapy and concurrently with thoracic radiotherapy. Previously untreated patients with histologically/cytologically proven unresectable stage I-III NSCLC were eligible. Induction chemotherapy consisted of 2 courses of 200 mg/m2 paclitaxel and carboplatin at AUC of 6 mg/mL/min every 3 weeks. From day 43, continuous thoracic irradiation (60 Gy in 30 fractions radiotherapy for 6 weeks) was given concurrently with daily cisplatin at a dose of 5 mg/m2 intravenously and weekly paclitaxel at a dose of 45 mg/m2 for 6 weeks. Fifteen patients were accrued in the first stage of the trial. According to the previous statistical considerations, accrual at the second stage of the study was halted as a result of the achievement an insufficient number of successes. Major toxicity of combined chemoradiation was grade III-IV esophagitis requiring hospitalization for artificial nutrition, which occurred in 58% of patients. Other toxicities included grade II-IV fatigue in 75% of patients and grade I-IV neuromuscular toxicity in 67%. Only 7 patients completed the treatment program as scheduled. Eight patients (53.3%; 95% confidence interval, 26.5-78.7%) had a major response (5 partial response, 3 complete response), 2 patients had disease progression, and 1 was stable at the end of treatment. Four patients died early. With a median follow up of 38 months, the median survival was 12 months. A combined chemoradiation program, including platinum and paclitaxel, appears difficult to deliver at full dose as a result of toxicity, mainly esophagitis. More active and less toxic combined modality treatments need to be developed for inoperable NSCLC.

  4. Rectum separation in patients with cervical cancer for treatment planning in primary chemo-radiation

    OpenAIRE

    Marnitz Simone; Budach Volker; Weißer Friederike; Burova Elena; Gebauer Bernhard; Vercellino Filiberto; Köhler Christhardt

    2012-01-01

    Abstract Purpose 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. Material and methods 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 pati...

  5. A Lower Bound on Concurrence

    Institute of Scientific and Technical Information of China (English)

    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.

  6. CRDTs: Consistency without concurrency control

    CERN Document Server

    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.

  7. Concurrent Validity and Holland's Theory

    Science.gov (United States)

    Gaffey, Robert L.; Walsh, W. Bruce

    1974-01-01

    This study was designed to explore two areas: (1) the concurrent validity of Holland's theory for employed men using four different operational definitions of vocational orientation, and (2) the relationships among all possible combinations of same named scales across the four inventories. Findings tend to support the concurrent validity of…

  8. Partnership concurrency and coital frequency.

    Science.gov (United States)

    Gaydosh, Lauren; Reniers, Georges; Helleringer, Stéphane

    2013-09-01

    National HIV prevalence estimates across sub-Saharan Africa range from less than 1 percent to over 25 percent. Recent research proposes several explanations for the observed variation, including prevalence of male circumcision, levels of condom use, presence of other sexually transmitted infections, and practice of multiple concurrent partnerships. However, the importance of partnership concurrency for HIV transmission may depend on how it affects coital frequency with each partner. The coital dilution hypothesis suggests that coital frequency within a partnership declines with the addition of concurrent partners. Using sexual behavior data from rural Malawi and urban Kenya, we investigate the relationship between partnership concurrency and coital frequency, and find partial support for the coital dilution hypothesis. We conclude the paper with a discussion of our findings in light of the current literature on concurrency.

  9. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kwint, Margriet [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Uyterlinde, Wilma [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Heuvel, Michel van den [Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Knegjens, Joost; Herk, Marcel van [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Belderbos, Jose, E-mail: j.belderbos@nki.nl [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

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

    Directory of Open Access Journals (Sweden)

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

    OpenAIRE

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

    2015-01-01

    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.

  12. Does Extending the Waiting Time of Low-Rectal Cancer Surgery after Neoadjuvant Chemoradiation Increase the Perioperative Complications?

    Science.gov (United States)

    Timudom, Kittinut; Phothong, Natthawut; Akaraviputh, Thawatchai; Chinswangwatanakul, Vitoon; Pongpaibul, Ananya; Petsuksiri, Janjira; Ithimakin, Suthinee

    2016-01-01

    Background. Traditionally, rectal cancer surgery is recommended 6 to 8 weeks after completing neoadjuvant chemoradiation. Extending the waiting time may increase the tumor response rate. However, the perioperative complication rate may increase. The purpose of this study was to determine the association between extending the waiting time of surgery after neoadjuvant chemoradiation and perioperative outcomes. Methods. Sixty patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiation followed by radical resection at Siriraj hospital between June 2012 and January 2015 were retrospectively analyzed. Demographic data and perioperative outcomes were compared between the two groups. Results. The two groups were comparable in term of demographic parameters. The mean time interval from neoadjuvant chemoradiation to surgery was 6.4 weeks in Group A and 11.7 weeks in Group B. The perioperative outcomes were not significantly different between Groups A and B. Pathologic examination showed a significantly higher rate of circumferential margin positivity in Group A than in Group B (30% versus 9.3%, resp.; P = 0.04). Conclusions. Extending the waiting to >8 weeks from neoadjuvant chemoradiation to surgery did not increase perioperative complications, whereas the rate of circumferential margin positivity decreased.

  13. New methods of concurrent checking

    CERN Document Server

    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. Expression of epidermal growth factor receptor (EGFR) and activated EGFR predict poor response to (chemo)radiation and survival in cervical cancer

    NARCIS (Netherlands)

    Noordhuis, M.G.; Eijsink, J.J.H.; ten Hoor, K.A.; Roossink, F.; Hollema, H.; Arts, H.J.G.; Pras, Elisabeth; Maduro, John; Reyners, A.K.L.; de Bock, G.H.; Wisman, G.B.A.; Schuuring, E.; van der Zee, A.G.J.

    2009-01-01

    PURPOSE: Activation of the epidermal growth factor receptor (EGFR) signaling pathway has been reported to induce resistance to (chemo)radiation in cancers, such as head and neck cancer, whereas EGFR-targeted agents in combination with (chemo)radiation seem to improve treatment efficacy. The aim of t

  15. A CAD MODEL FOR FUZZY CONCURRENT TOLERANCE

    Institute of Scientific and Technical Information of China (English)

    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.

  16. Mapping Patterns of Local Recurrence After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma: A New Approach to Adjuvant Radiation Field Design

    Energy Technology Data Exchange (ETDEWEB)

    Dholakia, Avani S.; Kumar, Rachit [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Raman, Siva P. [Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Moore, Joseph A.; Ellsworth, Susannah; McNutt, Todd [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Laheru, Daniel A.; Jaffee, Elizabeth [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Cameron, John L. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hobbs, Robert F. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Wolfgang, Christopher L. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

    2013-12-01

    Purpose: To generate a map of local recurrences after pancreaticoduodenectomy (PD) for patients with resectable pancreatic ductal adenocarcinoma (PDA) and to model an adjuvant radiation therapy planning treatment volume (PTV) that encompasses a majority of local recurrences. Methods and Materials: Consecutive patients with resectable PDA undergoing PD and 1 or more computed tomography (CT) scans more than 60 days after PD at our institution were reviewed. Patients were divided into 3 groups: no adjuvant treatment (NA), chemotherapy alone (CTA), or chemoradiation (CRT). Cross-sectional scans were centrally reviewed, and local recurrences were plotted to scale with respect to the celiac axis (CA), superior mesenteric artery (SMA), and renal veins on 1 CT scan of a template post-PD patient. An adjuvant clinical treatment volume comprising 90% of local failures based on standard expansions of the CA and SMA was created and simulated on 3 post-PD CT scans to assess the feasibility of this planning approach. Results: Of the 202 patients in the study, 40 (20%), 34 (17%), and 128 (63%) received NA, CTA, and CRT adjuvant therapy, respectively. The rate of margin-positive resections was greater in CRT patients than in CTA patients (28% vs 9%, P=.023). Local recurrence occurred in 90 of the 202 patients overall (45%) and in 19 (48%), 22 (65%), and 49 (38%) in the NA, CTA, and CRT groups, respectively. Ninety percent of recurrences were within a 3.0-cm right-lateral, 2.0-cm left-lateral, 1.5-cm anterior, 1.0-cm posterior, 1.0-cm superior, and 2.0-cm inferior expansion of the combined CA and SMA contours. Three simulated radiation treatment plans using these expansions with adjustments to avoid nearby structures were created to demonstrate the use of this treatment volume. Conclusions: Modified PTVs targeting high-risk areas may improve local control while minimizing toxicities, allowing dose escalation with intensity-modulated or stereotactic body radiation therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Effect of Suboptimal Chemotherapy on Preoperative Chemoradiation in Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hye; Kang, Hyun Cheol; Chie, Eui Kyu; Kang, Gyeong Hoon; Park, Jae Gahb; Oh, Do Youn; Im, Seock Ah; Kim, Tae You; Bang, Yung Jue; Ha, Sung Whan [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2009-06-15

    To examine the effect of suboptimal chemotherapy in patients undergoing preoperative chemoradiotherapy for the treatment of rectal cancer. The medical records of 43 patients who received preoperative concurrent chemoradiotherapy, followed by radical surgery for the treatment of pathologically proven adenocarcinoma of the rectum from April 2003 to April 2006 were retrospectively reviewed. The delivered radiation dose ranged from 41.4 to 50.4 Gy. The standard group consisted of patients receiving two cycles of a 5-FU bolus injection for three days on the first and fifth week of radiotherapy or twice daily with capecitabine. The standard group included six patients for each regimen. The non-standard group consisted of patients receiving one cycle of 5-FU bolus injection for three days on the first week of radiotherapy. The non-standard group included 31 patients. Radical surgery was performed at a median of 58 days after the end of radiotherapy. A low anterior resection was performed in 36 patients, whereas an abdominoperineal resection was performed in 7 patients. No significant difference was observed between the groups with respect to pathologic responses ranging from grades 3 to 5 (83.3% vs. 67.7%, p=0.456), downstaging (75.0% vs. 67.7%, p=0.727), and a radial resection margin greater than 2 mm (66.7% vs. 83.9%, p=0.237). The sphincter-saving surgery rate in low-lying rectal cancers was lower in the non-standard group (100% vs. 75%, p=0.068). There was no grade 3 or higher toxicity observed in all patients. Considering that the sphincter-saving surgery rate in low-lying rectal cancer was marginally lower for patients treated with non-standard, suboptimal chemotherapy, and that toxicity higher than grade 2 was not observed in the both groups, suboptimal chemotherapy should be avoided in this setting.

  19. Concurrent engineering: effective deployment strategies

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  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

    Energy Technology Data Exchange (ETDEWEB)

    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

  3. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  4. Adjuvant

    Directory of Open Access Journals (Sweden)

    Ramadan M. Nafae

    2013-07-01

    Conclusion: Adjunctive 7 day course of low dose hydrocortisone IV in patients with CAP hastens clinical recovery and prevents the development of sepsis-related complications with a significant reduction in the duration of mechanical ventilation, duration of IV antibiotics and length of hospital stay with the improvement in hospital outcome and weaning success from mechanical ventilation.

  5. Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer

    OpenAIRE

    Bhide, S A; M. Ahmed; Barbachano, Y; K Newbold; Harrington, K J; Nutting, C M

    2008-01-01

    We describe a retrospective series of patients with advanced head-and-neck cancer who were treated with induction chemotherapy followed by radical chemo-radiation. Patients treated with two cycles of induction chemotherapy followed by definitive chemo-radiation for squamous cell carcinoma of the head-and-neck region, from 2001 – 2006 at the Royal Marsden Hospital, formed the basis of this study. Cisplatin (75 mg m−2) on day 1 and 5-FU (1000 mg m−2) day 1 – 4 was the standard regimen used for ...

  6. Adjuvant chemoradiotherapy for adenocarcinoma of the stomach. A new progress?; Chimioradiotherapie dans le traitement adjuvant des adenocarcinomes gastriques: reelle avancee?

    Energy Technology Data Exchange (ETDEWEB)

    Mineur, L. [Institut Sainte Catherine, 84 - Avignon (France); Lacaine, F. [Hopital Tenon, 75 - Paris (France); Ychou, M. [Centre Regional de Lutte Contre le Cancer Val d' Aurelle, Service d' Oncologie, 34 - Montpellier (France); Bosset, J.F. [Centre Hospitalier Universitaire, Service de Radiotherapie, 25 - Besancon (France); Daban, A. [Centre Hospitalier Universitaire, Service de Radiotherapie, 86 - Poitiers (France)

    2002-11-01

    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)

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

    LENUS (Irish Health Repository)

    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

    Directory of Open Access Journals (Sweden)

    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. ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer.

    Directory of Open Access Journals (Sweden)

    Fumitaka Koga

    Full Text Available Radical cystectomy for muscle-invasive bladder cancer (MIBC patients frequently impairs their quality of life (QOL due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS were investigated. Of the 35 patients, 11 (31% achieved pathological CR, while tumors in the remaining 24 patients (69% were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014, 15.4 (P = 0.024 and 14.3 (P = 0.038. The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001. The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056 along with chemoradiation resistance (P = 0.003 and hydronephrosis (P = 0.018. The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with

  10. House dust extracts contain potent immunological adjuvants

    NARCIS (Netherlands)

    Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

    1987-01-01

    A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably endot

  11. Novel Adjuvants and Immunomodulators for Veterinary Vaccines

    DEFF Research Database (Denmark)

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  13. Electrophysiological correlates of information processing in breast-cancer patients treated with adjuvant chemotherapy.

    Science.gov (United States)

    Kreukels, Baudewijntje P C; Schagen, Sanne B; Ridderinkhof, K Richard; Boogerd, Willem; Hamburger, Hans L; van Dam, Frits S A M

    2005-11-01

    Cognitive deficits are found in a number of breast-cancer patients who have undergone adjuvant (Cyclophosphamide, Methotrexate, and 5-Fluorouracil (CMF)) chemotherapy, but the underlying mechanisms are still unclear. The objective of this study is to investigate information processing in these patients with concurrent registration of brain activity. Twenty-six breast-cancer patients treated with adjuvant CMF chemotherapy and a control group of 23 stage I breast-cancer patients not treated with chemotherapy were examined. Mean time since treatment for the CMF patients was 5.1 years after the last CMF course, and for the control patients 3.6 years after termination of radiotherapy. An information processing task was administered with concurrent EEG registration. Reaction times and the amplitudes and latencies of an Event Related Potential component (P3) in different task conditions related to input, central, and output processing of information were studied. Significant differences in latency and amplitude of the P3 component were found between the treatment groups with an earlier and reduced P3 in the chemotherapy group. Patients treated with chemotherapy had longer reaction times (although not significantly different) than the control group on all task conditions. Our data provide further evidence for long-term neurocognitive problems in breast-cancer patients treated with adjuvant (CMF) chemotherapy and offer new information regarding abnormalities in brain functioning in these patients.

  14. Adjuvants: Classification, Modus Operandi, and Licensing

    Science.gov (United States)

    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. PMID:27274998

  15. Adjuvants for single droplet application of glyphosate

    DEFF Research Database (Denmark)

    Mathiassen, Solvejg Kopp; Kudsk, Per; Lund, Ivar

    2016-01-01

    Retention and biological activity of droplets of glyphosate deposited onto plant leaves using a Drop on Demand inkjet printer application system, was examined on pot-grown Brassica napus, Solanum nigrum, Chenopodium album, Silene noctiflora and Echinocloa crus-galli plants. Retention was measured...... in admixture with the adjuvant Control was significantly higher on B. napus than with any of the other adjuvants, whereas on S. nigrum no difference was observed between Control and Bermocoll E 230 FQ. Only small differences among the adjuvants were observed on C. album, S. noctiflora and E. crus......-galli. The biological performance was not significantly influenced by the adjuvants except with C. album. However droplet volumes varied significantly with a minimum of 0.3 μl in admixture with Control and a maximum of 0.6 μl in combination with Adhere. In conclusion, retention could be optimized by adjuvant selection...

  16. Concurrent Engineering Research and Application

    Institute of Scientific and Technical Information of China (English)

    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.

  17. STU attractors from vanishing concurrence

    CERN Document Server

    Lévay, Péter

    2010-01-01

    Concurrence is an entanglement measure characterizing the {\\it mixed} state bipartite correlations inside of a pure state of an $n$-qubit system. We show that after organizing the charges and the moduli in the STU model of $N=2$, $d=4$ supergravity to a three-qubit state, for static extremal spherically symmetric BPS black hole solutions the vanishing condition for all of the bipartite concurrences on the horizon is equivalent to the attractor equations. As a result of this the macroscopic black hole entropy given by the three-tangle can be reinterpreted as a linear entropy characterizing the {\\it pure} state entanglement for an arbitrary bipartite split. Both for the BPS and non-BPS cases explicit expressions for the concurrences are obtained, with their vanishing on the horizon is demonstrated.

  18. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    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...... of 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...

  20. Fuzzy simulation in concurrent engineering

    Science.gov (United States)

    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.

  1. Prognostic cell biological markers in cervical cancer patients primarily treated with (chemo)radiation : a systematic review

    NARCIS (Netherlands)

    Noordhuis, Maartje G; Eijsink, Jasper J H; Roossink, Frank; de Graeff, Pauline; Pras, Elisabeth; Schuuring, Ed; Wisman, G Bea A; de Bock, Geertruida H; van der Zee, Ate G J

    2011-01-01

    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 b

  2. Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

    Science.gov (United States)

    Pérez, Oliver; Romeu, Belkis; Cabrera, Osmir; González, Elizabeth; Batista-Duharte, Alexander; Labrada, Alexis; Pérez, Rocmira; Reyes, Laura M.; Ramírez, Wendy; Sifontes, Sergio; Fernández, Nelson; Lastre, Miriam

    2013-01-01

    The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed. PMID:24348475

  3. Teaching Concurrency: Theory in Practice

    DEFF Research Database (Denmark)

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

    2009-01-01

    in 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...

  4. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    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 re...

  5. The composition of concurrent programs

    Science.gov (United States)

    Chandy, K. Mani; Taylor, Stephen

    1989-01-01

    A notation is presented for concurrent programs called program composition notation (PCN). The notation is being implemented at Caltech on multicomputers (a network of computers that communicate by sending and receiving messages). A fragment of this notation has been implemented on a data-parallel computer, the Connection Machine. The central ideas underlying PCN are discussed.

  6. A Model for Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    1996-01-01

    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 hid...

  7. Bisimulation for models in concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Clausen, Christian

    1994-01-01

    Recently, Joyal, Nielsen and Winskel suggested a categorical definition of bisimulation, applicable to a wide range of models in concurrency with an accompanying notion af observations. The definition is in terms of span of open maps, and it coincides with Park and Milner's strong bisimulation...

  8. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    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 se...... development has been verified correct in the Isabelle-HOL interactive theorem prover....

  9. Relationships between models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro; Winskel, Glynn

    1994-01-01

    Models for concurrency can be classified with respect to the 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....... The classifications are formalized through the medium of category theory....

  10. The system of concurrent engineering

    NARCIS (Netherlands)

    Wognum, Nel; Trienekens, Jacques

    2015-01-01

    Concurrent engineering (CE) has been a major theme in the 80s and 90s of the previous century in research and practice. Its main aim is to reduce time-tomarket, improve quality and reduce costs by taking into account downstream requirements and constraints already in the design phase. While start

  11. Visualization of Concurrent Program Executions

    Science.gov (United States)

    Artho, Cyrille; Havelund, Klaus; Honiden, Shinichi

    2007-01-01

    Various program analysis techniques are efficient at discovering failures and properties. However, it is often difficult to evaluate results, such as program traces. This calls for abstraction and visualization tools. We propose an approach based on UML sequence diagrams, addressing shortcomings of such diagrams for concurrency. The resulting visualization is expressive and provides all the necessary information at a glance.

  12. True Concurrency can be Traced

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik

    1990-01-01

    In this paper sets of labelled partial orders are employed as fundamental mathematical entities for modelling nondeterministic and concurrent processes thereby obtaining so-called noninterleaving semantics. Based on closures of sets of labelled partial orders, a simple algebraic language with ref...

  13. Safety of vaccine adjuvants: focus on autoimmunity.

    Science.gov (United States)

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed.

  14. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Charafeddine Maya

    2010-09-01

    Full Text Available Abstract Purpose/Objective This is a prospective comparison of weekly cisplatin to weekly paclitaxel as concurrent chemotherapy with standard radiotherapy for locally advanced cervical carcinoma. Materials/Methods 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. Results 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. Conclusions 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  18. Results of concomitant chemoradiation for cervical cancer using high dose rate intracavitary brachytherapy: Study of JROSG (Japan Radiation Oncology Study Group)

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, Koh-Ichi (Dept. of Radiology, Sapporo Medical Univ., School of Medicine, Sapporo (JP)); Sakurai, Hideyuki; Suzuki, Yoshiyuki (Dept. of Radiology and Radiation Oncology, Gunna Univ., School of Medicine, Gunna (JP)) (and others)

    2008-03-15

    The purpose of this study was to clarify outcome for concurrent chemoradiation (CT-RT) in locally advanced cervix cancer in Japan. This is a non-randomized retrospective analysis of 226 patients treated with definitive CT-RT or radiotherapy alone (RT alone) in nine institutions between 2001 and 2003. External irradiation consisted of whole pelvic irradiation and pelvic side wall boost irradiation, using a central shield during the latter half of the treatment with the anteroposterior parallel opposing technique. The external beam irradiation was performed with 1.8 or 2 Gy per fraction. High-dose-rate intracavitary brachytherapy (HDR) was performed in all cases. In chemotherapy, platinum based drugs were used alone or in combination with other drugs such as 5FU. Grade of late complications was scaled retrospectively with CTCv2.0. Overall survival rate at 50 months of stage Ib, II and III, IV was 82% and 66% in CR-RT and 81% and 43% in R alone, respectively. Disease-free survival rate at 50 months of stage Ib, II and III, IV was 74% and 59% in CR-RT and 76% and 52% in R alone, respectively. There was no significant difference between CT-RT and RT for overall survival and disease free survival. Univariate analysis suggested that loco-regional control was better with CT-RT, but multivariate analysis could not confirm this finding. Compared to RT alone, CT-RT caused significantly more acute and late complications. Thus, late complication (grade 3-4) free survival rate at 50 month was 69% for CT-RT and 86% for RT alone (p<0.01). The therapeutic window with concomitant radiochemotherapy and HDR brachytherapy may be narrow, necessitating a close control of dose volume parameters and adherence to systems for dose prescription

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. [Adjuvant dermato-cosmetic acne therapy].

    Science.gov (United States)

    Bayerl, Christiane; Degitz, Klaus; Meigel, Eva; Kerscher, Martina

    2010-03-01

    Adjuvant dermato-cosmetic therapy in acne is an essential part of the concept of treating acne after initiation and during maintenance therapy. Those are mechanical peeling, chemical peeling and its combination. It needs supervision by an experienced dermatologist.

  1. Adjuvants for spraying of fungicides in wheat

    OpenAIRE

    2014-01-01

    The foliar diseases and spike can markedly reduce the yield of wheat. Despite prevailing chemical control in the management of disease, studies with adjuvants to improve the performance of fungicides are still incipient. The aim of this study was to evaluate the effect of adding adjuvants to chemical fungicides to control leaf diseases and spike, as well as on the yield of wheat crop. The experimental design was a randomized block design with 05 treatments: control (no fungicide application i...

  2. Applications of nanomaterials as vaccine adjuvants.

    Science.gov (United States)

    Zhu, Motao; Wang, Rongfu; Nie, Guangjun

    2014-01-01

    Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials' physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants.

  3. 36 CFR 292.69 - Concurrent reclamation.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Concurrent reclamation. 292... reclamation. Plans of operations involving locatable minerals, operating plans involving outstanding mineral... practicable, that reclamation proceed concurrently with the mineral operation....

  4. Data refinement for true concurrency

    Directory of Open Access Journals (Sweden)

    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.

  5. Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

    Science.gov (United States)

    Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

    2016-04-02

    Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

  6. PyCSP - controlled concurrency

    DEFF Research Database (Denmark)

    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....

  7. PyCSP - controlled concurrency

    DEFF Research Database (Denmark)

    Vinter, Brian; Friborg, Rune Møllegaard; 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....

  8. Debugging Concurrent Software:Advances and Challenges

    Institute of Scientific and Technical Information of China (English)

    Jeff Huang; Charles Zhang

    2016-01-01

    Concurrency debugging is an extremely important yet challenging problem that has been hampering developer productivity and software reliability in the multicore era. We have worked on this problem in the past eight years and have developed several effective methods and automated tools for helping developers debugging shared memory concurrent programs. This article discusses challenges in concurrency debugging and summarizes our research contributions in four important directions: concurrency bug reproduction, detection, understanding, and fixing. It also discusses other recent advances in tackling these challenges.

  9. Molecular Imaging to Identify Tumor Recurrence following Chemoradiation in a Hostile Surgical Environment

    Directory of Open Access Journals (Sweden)

    Olugbenga T. Okusanya

    2015-01-01

    Full Text Available Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Simple concurrent garbage collection almost without synchronization

    NARCIS (Netherlands)

    Hesselink, Wim H.; Lali, M.I.

    2010-01-01

    We present two simple mark and sweep algorithms, A and B, for concurrent garbage collection by a single collector running concurrently with a number of mutators that concurrently modify shared data. Both algorithms are based on the ideas of Ben-Ari's classical algorithm for on-the-fly garbage collec

  12. Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Khalifa, J. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Tensaouti, F. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Chaltiel, L. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Biostatistics, Toulouse (France); Lotterie, J.A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Catalaa, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Radiology, Toulouse (France); Sunyach, M.P. [Centre Leon Berard, Department of Radiation Oncology, Lyon (France); Ibarrola, D. [CERMEP - Imagerie du Vivant, Lyon (France); Noel, G. [EA 3430, University of Strasbourg, Department of Radiation Oncology, Centre Paul Strauss, Strasbourg (France); Truc, G. [Centre Georges-Francois Leclerc, Department of Radiation Oncology, Dijon (France); Walker, P. [University of Burgundy, Laboratory of Electronics, Computer Science and Imaging (Le2I), UMR 6306 CNRS, Dijon (France); Magne, N. [Institut de cancerologie Lucien-Neuwirth, Department of Radiation Oncology, Saint-Priest-en-Jarez (France); Charissoux, M. [Department of Radiation Oncology, Institut du Cancer de Montpellier, Montpellier (France); Ken, S. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Medical Physics, Toulouse (France); Peran, P. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Berry, I. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (France); CHU Rangueil, Department of Nuclear Medicine, Toulouse (France); Universite Toulouse III Paul Sabatier, UMR 1214, Toulouse (France); Moyal, E.C. [Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (France); Universite Toulouse III Paul Sabatier, Toulouse (France); INSERM U1037, Centre de Recherches contre le Cancer de Toulouse, Toulouse (FR); Laprie, A. [INSERM UMR 1214, TONIC (TOulouse NeuroImaging Centre), Toulouse (FR); Institut Claudius Regaud/Institut Universitaire du Cancer de Toulouse - Oncopole, Department of Radiation Oncology, Toulouse (FR); Universite Toulouse III Paul Sabatier, Toulouse (FR)

    2016-11-15

    To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was t{sub end}; MR acquisitions performed at t{sub end-2M}, t{sub end-4M} and t{sub end-6M} (respectively 2, 4 and 6 months before t{sub end}) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∇B from t{sub end-4M} to t{sub end-2M} and ∇B from t{sub end-6M} to t{sub end-4M}. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. The fraction of hypoperfused tumor volume (F{sub h}P{sub g}) was a relevant biomarker. A ratio R(F{sub h}P{sub g}) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F{sub h}Pg) (≥0.61) was associated with more relapse at t{sub end} compared to low R(F{sub h}Pg) (75 % vs 12.5 %, p = 0.008). Iterative analysis of F{sub h}P{sub g} from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  15. Concurrent engineering teams. Volume 2: Annotated bibliography

    Science.gov (United States)

    Richter, Karen J.; Dierolf, David A.

    1990-11-01

    Specific concurrent engineering practices vary among organizations. There are, however, various management practices that appear to work well for most organizations. This paper presents the reader with specific, useful examples from several defense contractors illustrating how multifunctional concurrent engineering teams are being organized and managed and how concurrent engineering team meetings are conducted and supported. The types of computer support that could be used to enhance the efficiency and effectiveness of concurrent engineering team meetings are identified. The general findings are that there exists a direct relationship between total quality management (TQM) and concurrent engineering, and that many applications of computer-aided group problem solving are possible and practical today for the concurrent engineering team meetings. Areas identified for additional research are the documentation of the decision process and rationale during the product and process definition, the capturing of lessons learned during the implementation of concurrent engineering, and the performance evaluation and training of team members.

  16. (Neo)adjuvant systemic therapy for melanoma.

    Science.gov (United States)

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  17. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    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......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...

  18. A predictive genetic signature for response to fluoropyrimidine-based neoadjuvant chemoradiation in clinical Stage II and III rectal cancer

    Directory of Open Access Journals (Sweden)

    Jason eChan

    2013-11-01

    Full Text Available PurposePreoperative chemoradiation is currently the standard of care for patients with clinical stage II and III rectal cancer but only about 45% of patients achieve tumor downstaging and less than 20% of patients achieve a pathologic complete response. Better methods to stratify patients according to potential neoadjuvant treatment response are needed. We used microarray analysis to identify a genetic signature that correlates with a pathological complete response to neoadjuvant chemoradiation. We performed a gene network analysis to identify potential signaling pathways involved in determining response to neoadjuvant treatment.Patients and MethodsWe identified 31 T3-4 N0-1 rectal cancer patients who were treated with neoadjuvant fluorouracil-based chemoradiation. 8 patients were identified to have achieved a pathological complete response to treatment while 23 patients did not. mRNA expression was analyzed using cDNA microarrays. The correlation between mRNA expression and pathological complete response from pre-treatment tumor biopsies was determined. Gene network analysis was performed for the genes represented by the predictive signature.ResultsA genetic signature represented by expression levels of the 3 genes EHBP1, STAT1, and GAPDH was found to correlate with a pathological complete response to neoadjuvant treatment. The difference in expression levels between patients who achieved a pathological complete response and those who did not was greatest for EHBP1. Gene network analysis showed that the 3 genes can be connected by the gene UBC. ConclusionThis study identifies a 3-gene signature expressed in pre-treatment tumor biopsies that correlates with a pathological complete response to neoadjuvant chemoradiation in patients with clinical stage II and III rectal cancer. These 3 genes can be connected by the gene UBC, suggesting that ubiquination is a molecular mechanism involved in determining response to treatment. Validating this genet

  19. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer.

    Science.gov (United States)

    Cercek, Andrea; Goodman, Karyn A; Hajj, Carla; Weisberger, Emily; Segal, Neil H; Reidy-Lagunes, Diane L; Stadler, Zsofia K; Wu, Abraham J; Weiser, Martin R; Paty, Philip B; Guillem, Jose G; Nash, Garrett M; Temple, Larissa K; Garcia-Aguilar, Julio; Saltz, Leonard B

    2014-04-01

    Standard therapy for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy and postoperative chemotherapy. At Memorial Sloan-Kettering Cancer Center (MSKCC) the authors began offering FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as initial treatment for patients with high-risk LARC to target micrometastases while treating the primary tumor. The purpose of this study is to report the safety and efficacy of initial FOLFOX given before chemoradiotherapy on tumor downsizing and pathologic complete response (pathCR) in LARC. The records of patients with stage II/III rectal cancer treated at MSKCC between 2007 and 2012 were reviewed. Of approximately 300 patients with LARC treated at MSKCC, 61 received FOLFOX as initial therapy. Of these 61 patients, 57 received induction FOLFOX (median 7 cycles) followed by chemoradiation, and 4 experienced an excellent response, declined chemoradiation, and underwent total mesorectal excision (TME). Twelve of the 61 patients did not undergo TME: 9 had a complete clinical response (CCR), 1 declined despite persistent tumor, 1 declined because of comorbidities, and 1 developed metastatic disease. Among the 61 patients receiving initial FOLFOX, 22 (36%) had either a pathCR (n=13) or a CCR (n=9). Of the 49 patients who underwent TME, all had R0 resections and 23 (47%) had tumor response greater than 90%, including 13 (27%) who experienced a pathCR. Of the 28 patients who received all 8 cycles of FOLFOX, 8 experienced a pathCR (29%) and 3 a CCR (11%). No serious adverse events occurred that required a delay in treatment during FOLFOX or chemoradiation. FOLFOX and chemoradiation before planned TME results in tumor regression, a high rate of delivery of planned therapy, and a substantial rate of pathCRs, and offers a good platform for nonoperative management in select patients.

  20. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer.

    Science.gov (United States)

    Speicher, P J; Wang, X; Englum, B R; Ganapathi, A M; Yerokun, B; Hartwig, M G; D'Amico, T A; Berry, M F

    2015-01-01

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.

  1. Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dvorak, J.; Sirak, I.; Petera, J. [Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic). Dept. of Oncology and Radiotherapy; Sitorova, V.; Ryska, A.; Hatlova, J. [Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic). Dept. of Pathology; Richter, I. [Regional Hospital Liberec, Liberec (Czech Republic); Charles Univ. Medical School, Hradec Kralove (Czech Republic); Ferko, A. [Charles Univ. Medical School and Teaching Hospital, Hradec Kralove (Czech Republic). Dept. of Surgery; Melichar, B. [Palacky Univ. Medical School and Teaching Hospital, Olomouc (Czech Republic). Dept. of Oncology

    2012-09-15

    Purpose: The aim of the present study was to examine the effect of neoadjuvant chemoradiation on tumor epidermal growth factor receptor (EGFR) expression in patients with locally advanced rectal adenocarcinoma. Patients and methods: A total of 53 patients with rectal adenocarcinoma (clinical stages II and III) were studied. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4-6 weeks after the chemoradiation. EGFR expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. Results: Patients with an increase of EGFR expression during chemoradiation had significantly shorter disease-free survival (DFS; p = 0.003) and overall survival (OS; p = 0.005) compared to patients with either no change or decrease in EGFR expression. The 5-year DFS in patients with increased EGFR expression was only 29% compared to 61% in patients without an increase of EGFR expression. Similarly, the 5-year OS of the patients with increased EGFR expression was 29% compared to 66% in patients without an increase of EGFR expression. All recurrences in patients who had an increase of EGFR expression occurred within the first 2 years after the treatment. The increase in EGFR expression was the only significant predictor of DFS (p = 0.007) and OS (p = 0.04) using multivariate Cox regression analysis. Conclusion: An increase of EGFR expression during chemoradiation may be associated with significantly shorter DFS and OS. The increase of EGFR could identify a population of patients in whom the effect of the treatment with anti-EGFR therapy should be studied. (orig.)

  2. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    % of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast...... are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials...... adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours...

  4. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy

    Science.gov (United States)

    2017-01-01

    A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases. PMID:28261017

  7. Adjuvants and vector systems for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe; Lombardi, Vincent; Saint-Lu, Nathalie; Tourdot, Sophie; Bodo, Véronique; Mascarell, Laurent

    2011-05-01

    Allergen-specific immunotherapy represents a curative treatment of type I allergies. Subcutaneous immunotherapy is conducted with allergens adsorbed on aluminum hydroxide or calcium phosphate particles, whereas sublingual immunotherapy relies on high doses of soluble allergen without any immunopotentiator. There is a potential benefit of adjuvants enhancing regulatory and Th1 CD4+T cell responses during specific immunotherapy. Molecules affecting dendritic cells favor the induction of T regulatory cell and Th1 responses and represent valid candidate adjuvants for allergy vaccines. Furthermore, the interest in viruslike particles and mucoadhesive particulate vector systems, which may better address the allergen(s) to tolerogenic antigen-presenting cells, is documented.

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

    Energy Technology Data Exchange (ETDEWEB)

    Agoni, Lorenzo [Department of Pathology, Albert Einstein College of Medicine, Bronx, New York (United States); Basu, Indranil [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Gupta, Seema [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Biophysics Research Institute of America, North Miami Beach, Florida (United States); Alfieri, Alan [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Gambino, Angela [Department of Gynecologic Oncology, University of Brescia, Brescia (Italy); Goldberg, Gary L. [Department of Gynecologic Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Reddy, E. Premkumar [Department of Oncological Sciences, Mount Sinai School of Medicine, New York, New York (United States); Guha, Chandan, E-mail: cguha@montefiore.org [Department of Pathology, Albert Einstein College of Medicine, Bronx, New York (United States); Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States)

    2014-04-01

    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 G{sub 2}/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. Steps in Modular Specifications for Concurrent Modules

    DEFF Research Database (Denmark)

    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 modules......, 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....

  10. Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mohiuddin, Mohammed, E-mail: asemuddin@gmail.com [King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Paulus, Rebecca [RTOG Statistical Department, Philadelphia, Pennsylvania (United States); Mitchell, Edith [Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Hanna, Nader [Department of Surgical Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Yuen, Albert [Reading Hospital and Medical Center, Reading, Pennsylvania (United States); Nichols, Romaine [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Yalavarthi, Salochna [Ingalls Memorial Hospital, Harvey, Illinois (United States); Hayostek, Cherie [Santa Fe Cancer Center, Santa Fe, New Mexico (United States); Willett, Christopher [Duke University Medical Center, Durham, North Carolina (United States)

    2013-07-01

    Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m{sup 2} per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m{sup 2} per day, Monday to Friday, plus irinotecan, 50 mg/m{sup 2} once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.

  11. A Reference Framework for Concurrent Engineering

    Institute of Scientific and Technical Information of China (English)

    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.

  12. Concurrent Process Planning for Machined Parts

    Institute of Scientific and Technical Information of China (English)

    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.

  13. Gaps in knowledge and prospects for research of adjuvanted vaccines.

    Science.gov (United States)

    Seder, Robert; Reed, Steven G; O'Hagan, Derek; Malyala, Padma; D'Oro, Ugo; Laera, Donatello; Abrignani, Sergio; Cerundolo, Vincenzo; Steinman, Lawrence; Bertholet, Sylvie

    2015-06-08

    A panel of researchers working in different areas of adjuvanted vaccines deliberated over the topic, "Gaps in knowledge and prospects for research of adjuvanted vaccines" at, "Enhancing Vaccine Immunity and Value" conference held in July 2014. Several vaccine challenges and applications for new adjuvant technologies were discussed.

  14. Vitamins as influenza vaccine adjuvant components.

    Science.gov (United States)

    Quintilio, Wagner; de Freitas, Fábio Alessandro; Rodriguez, Dunia; Kubrusly, Flavia Saldanha; Yourtov, Dimitri; Miyaki, Cosue; de Cerqueira Leite, Luciana Cezar; Raw, Isaias

    2016-10-01

    A number of adjuvant formulations were assayed in mice immunized with 3.75 µg of A/California/7/2009 (H1N1) pdm09 influenza vaccine with vitamins A, D and/or E in emulsions or B2 and/or B9 combined with Bordetella pertussis MPLA and/or alum as adjuvants. Squalene was used as positive control, as well as MPLA with alum. The immune response was evaluated by a panel of tests, including a hemagglutination inhibition (HAI) test, ELISA for IgG, IgG1, and IgG2a and IFN-γ, IL-2, IL-6 and IL-10 quantification in splenocyte culture supernatant after stimulus with influenza antigen. Immunological memory was evaluated using a 1/10 dose booster 60 days after the first immunization followed by assessment of the response by HAI, IgG ELISA, and determination of the antibody affinity index. The highest increases in HAI, IgG1 and IgG2a titers were obtained with the adjuvant combinations containing vitamin E, or the hydrophilic combinations containing MPLA and alum or B2 and alum. The IgG1/IgG2a ratio indicates that the response to the combination of B2 with alum would have more Th2 character than the combination of MPLA with alum. In an assay to investigate the memory response, a significant increase in HAI titer was observed with a booster vaccine dose at 60 days after immunization with vaccines containing MPLA with alum or B2 with alum. Overall, of the 27 adjuvant combinations, MPLA with alum and B2 with alum were the most promising adjuvants to be evaluated in humans.

  15. Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes

    Science.gov (United States)

    Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel; Chen, Li; Kumar, Sameera; Shang, Yu; Huang, Chong; Johnson, Ellis L.; Stevens, Scott D.; Shelton, Brent J.; Yu, Guoqiang

    2016-08-01

    This study used a hybrid near-infrared diffuse optical instrument to monitor tumor hemodynamic responses to chemoradiation therapy for early prediction of treatment outcomes in patients with head and neck cancer. Forty-seven patients were measured once per week to evaluate the hemodynamic status of clinically involved cervical lymph nodes as surrogates for the primary tumor response. Patients were classified into two groups: complete response (CR) (n=29) and incomplete response (IR) (n=18). Tumor hemodynamic responses were found to be associated with clinical outcomes (CR/IR), wherein the associations differed depending on human papillomavirus (HPV-16) status. In HPV-16 positive patients, significantly lower levels in tumor oxygenated hemoglobin concentration ([HbO2]) at weeks 1 to 3, total hemoglobin concentration at week 3, and blood oxygen saturation (StO2) at week 3 were found in the IR group. In HPV-16 negative patients, significantly higher levels in tumor blood flow index and reduced scattering coefficient (μs‧) at week 3 were observed in the IR group. These hemodynamic parameters exhibited significantly high accuracy for early prediction of clinical outcomes, within the first three weeks of therapy, with the areas under the receiver operating characteristic curves (AUCs) ranging from 0.83 to 0.96.

  16. Safety and Efficacy of Stereotactic Radiosurgery and Adjuvant Bevacizumab in Patients With Recurrent Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Vredenburgh, James J.; Sampson, John H.; Reardon, David A.; Desjardins, Annick; Peters, Katherine B.; Friedman, Henry S. [Department of Surgery, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kirkpatrick, John P., E-mail: john.kirkpatrick@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States)

    2012-04-01

    Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. Methods and Materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant

  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

    Directory of Open Access Journals (Sweden)

    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. Petri nets and other models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro

    1998-01-01

    This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency.......This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency....

  19. How does concurrent sourcing affect performance?

    DEFF Research Database (Denmark)

    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...

  20. A Temporal Concurrent Constraint Programming Calculus

    DEFF Research Database (Denmark)

    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...

  1. New concurrent iterative methods with monotonic convergence

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Concurrent partnerships and HIV: an inconvenient truth

    Directory of Open Access Journals (Sweden)

    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.

  3. Lower Bounds of Concurrence for Multipartite States

    CERN Document Server

    Zhu, Xue-Na; Fei, Shao-Ming

    2012-01-01

    We study the entanglement of multipartite quantum states. Some lower bounds of the multipartite concurrence are reviewed. We further present more effective lower bounds for detecting and qualifying entanglement, by establishing functional relations between the concurrence and the generalized partial transpositions of the multipartite systems.

  4. Interval-based Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    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...

  5. Safety and Liveness in Concurrent Pointer Programs

    NARCIS (Netherlands)

    Distefano, Dino; Katoen, Joost-Pieter; Rensink, Arend; Boer, de Frank S.; Bonsangue, Marcello M.; Graf, Susanne; Roever, de Willem-Paul

    2006-01-01

    The incorrect use of pointers is one of the most common source of software errors. Concurrency has a similar characteristic. Proving the correctness of concurrent pointer manipulating programs, let alone algorithmically, is a highly non-trivial task. This paper proposes an automated verification tec

  6. Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Wenjin Yin

    Full Text Available BACKGROUND: Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors. METHODS: Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data. FINDINGS: With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001 from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018. Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001 but bore a higher incidence of CNS recurrence (P = 0.010, while statistical significance failed to be discerned for either overall survival (P = 0.069 or CNS metastasis (P = 0.374 between the sequential and observation arms. CONCLUSION: This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.

  7. Complete Response of Isolated Para-aortic Lymph Node Recurrence from Rectosigmoid Cancer Treated by Chemoradiation Therapy with Capecitabine/Oxaliplatin plus Bevacizumab: A Case Report.

    Science.gov (United States)

    Miyazawa, Tomonori; Ebe, Kazuyu; Koide, Norihiko; Fujita, Nobuhiro

    2012-05-01

    Para-aortic lymph node recurrence is a rare type of metastasis from colorectal cancer, and no treatment has yet been established. Here, we report on a case of isolated para-aortic lymph node metastasis from rectosigmoid cancer that showed complete response to chemoradiation therapy with capecitabine/oxaliplatin plus bevacizumab. A 58-year-old woman underwent high anterior resection for rectosigmoid cancer in 2009. Para-aortic lymph node recurrence occurred in 2011. She underwent radiation therapy (50 Gy) and 8 courses of capecitabine/oxaliplatin plus bevacizumab. Abdominal computed tomography and positron emission tomography with 18-fluorodeoxyglucose did not reveal any para-aortic lymph node recurrence after chemoradiation therapy. Hence, this case was interpreted as a complete response. No recurrence was noted 6 months after the complete response. Chemoradiation therapy with capecitabine/oxaliplatin plus bevacizumab is likely to be effective in treating patients with para-aortic lymph node recurrence.

  8. Complete Response of Isolated Para-aortic Lymph Node Recurrence from Rectosigmoid Cancer Treated by Chemoradiation Therapy with Capecitabine/Oxaliplatin plus Bevacizumab: A Case Report

    Directory of Open Access Journals (Sweden)

    Tomonori Miyazawa

    2012-05-01

    Full Text Available Para-aortic lymph node recurrence is a rare type of metastasis from colorectal cancer, and no treatment has yet been established. Here, we report on a case of isolated para-aortic lymph node metastasis from rectosigmoid cancer that showed complete response to chemoradiation therapy with capecitabine/oxaliplatin plus bevacizumab. A 58-year-old woman underwent high anterior resection for rectosigmoid cancer in 2009. Para-aortic lymph node recurrence occurred in 2011. She underwent radiation therapy (50 Gy and 8 courses of capecitabine/oxaliplatin plus bevacizumab. Abdominal computed tomography and positron emission tomography with 18-fluorodeoxyglucose did not reveal any para-aortic lymph node recurrence after chemoradiation therapy. Hence, this case was interpreted as a complete response. No recurrence was noted 6 months after the complete response. Chemoradiation therapy with capecitabine/oxaliplatin plus bevacizumab is likely to be effective in treating patients with para-aortic lymph node recurrence.

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

    Science.gov (United States)

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-08

    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.

  10. [Gastrointestinal surgeons should master the adjuvant therapy of colorectal cancer].

    Science.gov (United States)

    Gu, Jin; Chen, Pengju

    2015-10-01

    The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain. Unlike colon cancer, adjuvant therapy of rectal cancer is not evidence-based. Especially, the indication and duration of adjuvant chemotherapy for rectal cancer after neoadjuvant chemoradiotherapy remain controversial. Adjuvant therapy of colorectal cancer still needs further investigation.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Definitive Chemoradiation Therapy With Docetaxel, Cisplatin, and 5-Fluorouracil (DCF-R) in Advanced Esophageal Cancer: A Phase 2 Trial (KDOG 0501-P2)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Multiparty Compatibility for Concurrent Objects

    Directory of Open Access Journals (Sweden)

    Roly Perera

    2016-06-01

    Full Text Available Objects and actors are communicating state machines, offering and consuming different services at different points in their lifecycle. Two complementary challenges arise when programming such systems. When objects interact, their state machines must be "compatible", so that services are requested only when they are available. Dually, when objects refine other objects, their state machines must be "compliant", so that services are honoured whenever they are promised. In this paper we show how the idea of multiparty compatibility from the session types literature can be applied to both of these problems. We present an untyped language in which concurrent objects are checked automatically for compatibility and compliance. For simple objects, checking can be exhaustive and has the feel of a type system. More complex objects can be partially validated via test cases, leading to a methodology closer to continuous testing. Our proof-of-concept implementation is limited in some important respects, but demonstrates the potential value of the approach and the relationship to existing software development practices.

  14. Sensitization of Pancreatic Cancers to Gemcitabine Chemoradiation by WEE1 Kinase Inhibition Depends on Homologous Recombination Repair

    Directory of Open Access Journals (Sweden)

    Tasneem Kausar

    2015-10-01

    Full Text Available To improve the efficacy of chemoradiation therapy for locally advanced pancreatic cancer and begin to establish patient selection criteria, we investigated the combination of the WEE1 inhibitor AZD1775 with gemcitabine-radiation in homologous recombination (HR repair proficient and deficient pancreatic cancers. Sensitization to gemcitabine-radiation by AZD1775 was assessed in pancreatic cancer cells by clonogenic survival and in patient-derived xenografts by tumor growth. The contributions of HR repair inhibition and G2 checkpoint abrogation to sensitization were assessed by γH2AX, BRCA2 manipulation, and RAD51 focus formation and pHistone H3 flow cytometry, respectively. We found that AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type but not BRCA2 mutant pancreatic cancer cells. In all cells, AZD1775 caused inhibition of CDK1 phosphorylation and G2 checkpoint abrogation. However, sensitization by AZD1775 was associated with persistent γH2AX and inhibition of RAD51 focus formation. In HR-proficient (BRCA2 wild-type or -deficient (BRAC2 null isogenic cells, AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type, but not in BRCA2 null cells, despite significant G2 checkpoint abrogation. In patient-derived pancreatic tumor xenografts, AZD1775 significantly inhibited tumor growth and impaired RAD51 focus formation in response to gemcitabine-radiation. In conclusion, WEE1 inhibition by AZD1775 is an effective strategy for sensitizing pancreatic cancers to gemcitabine chemoradiation. Although this sensitization is accompanied by inhibition of CDK1 phosphorylation and G2 checkpoint abrogation, this mechanism is not sufficient for sensitization. Our findings demonstrate that sensitization to chemoradiation by WEE1 inhibition results from inhibition of HR repair and suggest that patient tumors without underlying HR defects would benefit most from this therapy.

  15. Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

    Directory of Open Access Journals (Sweden)

    Pablo Palma

    Full Text Available Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders. Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11 and non-responders (n = 16 to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029 gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with

  16. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    OpenAIRE

    2015-01-01

    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 bact...

  17. Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines.

    Science.gov (United States)

    Kashiwagi, Yasuyo; Maeda, Mika; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-06-05

    Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice. Aluminum-adjuvanted vaccines induced inflammatory nodules at the injection site, which expanded into the intra-muscular space without any muscle degeneration or necrosis, whereas non-adjuvanted vaccines did not. These nodules consisted of polymorph nuclear neutrophils with some eosinophils within the initial 48h, then monocytes/macrophages 1 month later. Inflammatory nodules were observed 6 months after IM, had decreased in size, and were absorbed 12 months after IM, which was earlier than that after SC. Cytokine production was examined in the injected muscular tissues and AS04 adjuvanted HPV induced higher IL-1β, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytokine profiles were observed to those induced by the other vaccines. Currently available vaccines did not induce muscular degeneration or fibrotic scar as observed with muscle contracture caused by multiple IMs of antibiotics in the past.

  18. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    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.

  19. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Narang, Amol K. [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Department of Hematology Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Reese, Jennifer B. [Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Gearhart, Susan L. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Azad, Nolifer S. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Chan, June; Olsen, Leah [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Efron, Jonathan E. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Lawrence, Theodore S.; Ben-Josef, Edgar [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  20. MO-F-CAMPUS-I-05: Quantitative ADC Measurement of Esophageal Cancer Before and After Chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yang, L [The University of Oklahoma, Tulsa, OK (United States); UT MD Anderson Cancer Center, Houston, TX (United States); Son, JB; Ma, J; Hazle, J; Carter, BW; Lin, S [UT MD Anderson Cancer Center, Houston, TX (United States); Cheng, S [The University of Oklahoma, Tulsa, OK (United States)

    2015-06-15

    Purpose: We investigated whether quantitative diffusion imaging can be used as an imaging biomarker for early prediction of treatment response of esophageal cancer. Methods: Eight patients with esophageal cancer underwent a baseline and an interim MRI studies during chemoradiation on a 3T whole body MRI scanner with an 8-channel torso phased array coil. Each MRI study contained two axial diffusion-weighted imaging (DWI) series with a conventional DWI sequence and a reduced field-of-view DWI sequence (FOCUS) of varying b-values. ADC maps with two b-values were computed from conventional DWI images using a mono-exponential model. For each of DWI sequences, separate ADCall was computed by fitting the signal intensity of images with all the b-values to a single exponential model. For the FOCUS sequence, a bi-exponential model was used to extract perfusion and diffusion coefficients (ADCperf and ADCdiff) and their contributions to the signal decay. A board-certified radiologist contoured the tumor region and mean ADC values and standard deviations of tumor and muscle ROIs were recorded from different ADC maps. Results: Our results showed that (1) the magnitude of ADCs from the same ROIs by the different analysis methods can be substantially different. (2) For a given method, the change between the baseline and interim muscle ADCs was relatively small (≤10%). In contrast, the change between the baseline and interim tumor ADCs was substantially larger, with the change in ADCdiff by FOCUS DWI showing the largest percentage change of 73.2%. (3) The range of the relative change of a specific parameter for different patients was also different. Conclusion: Presently, we do not have the final pathological confirmation of the treatment response for all the patients. However, for a few patients whose surgical specimen is available, the quantitative ADC changes have been found to be useful as a potential predictor for treatment response.

  1. Twenty-Five-Year Experience With Radical Chemoradiation for Anal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tomaszewski, Jonathan M., E-mail: jonathan.tomaszewski@petermac.org [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Link, Emma [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Leong, Trevor [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia); Heriot, Alexander [University of Melbourne, Parkville, Victoria (Australia); Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Vazquez, Melisa [Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Chander, Sarat; Chu, Julie; Foo, Marcus; Lee, Mark T. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Lynch, Craig A. [Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Mackay, John [University of Melbourne, Parkville, Victoria (Australia); Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Michael, Michael [University of Melbourne, Parkville, Victoria (Australia); Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Tran, Phillip [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Ngan, Samuel Y. [Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); University of Melbourne, Parkville, Victoria (Australia)

    2012-06-01

    Purpose: To evaluate the prognostic factors, patterns of failure, and late toxicity in patients treated with chemoradiation (CRT) for anal cancer. Methods and Materials: Consecutive patients with nonmetastatic squamous cell carcinoma of the anus treated by CRT with curative intent between February 1983 and March 2008 were identified through the institutional database. Chart review and telephone follow-up were undertaken to collect demographic data and outcome. Results: Two hundred eighty-four patients (34% male; median age 62 years) were identified. The stages at diagnosis were 23% Stage I, 48% Stage II, 10% Stage IIIA, and 18% Stage IIIB. The median radiotherapy dose to the primary site was 54 Gy. A complete clinical response to CRT was achieved in 89% of patients. With a median follow-up time of 5.3 years, the 5-year rates of locoregional control, distant control, colostomy-free survival, and overall survival were 83% (95% confidence interval [CI] 78-88), 92% (95% CI, 89-96), 73% (95% CI, 68-79), and 82% (95% CI, 77-87), respectively. Higher T stage and male sex predicted for locoregional failure, and higher N stage predicted for distant metastases. Locoregional failure occurred most commonly at the primary site. Omission of elective inguinal irradiation resulted in inguinal failure rates of 1.9% and 12.5% in T1N0 and T2N0 patients, respectively. Pelvic nodal failures were very uncommon. Late vaginal and bone toxicity was observed in addition to gastrointestinal toxicity. Conclusions: CRT is a highly effective approach in anal cancer. However, subgroups of patients fare relatively poorly, and novel approaches are needed. Elective inguinal irradiation can be safely omitted only in patients with Stage I disease. Vaginal toxicity and insufficiency fractures of the hip and pelvis are important late effects that require prospective evaluation.

  2. Effectiveness of Chemoradiation for Head and Neck Cancer in an Older Patient Population

    Energy Technology Data Exchange (ETDEWEB)

    VanderWalde, Noam A. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Meyer, Anne Marie; Deal, Allison M. [Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Layton, J. Bradley [Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Liu, Huan [Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Carpenter, William R. [Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Weissler, Mark C. [Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Hayes, David N. [Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Department of Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Fleming, Mary E. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); and others

    2014-05-01

    Purpose: The purpose of this study was to compare chemoradiation therapy (CRT) with radiation therapy (RT) only in an older patient population with head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2007), we identified a retrospective cohort of nonmetastatic HNSCC patients and divided them into treatment groups. Comparisons were made between CRT and RT cohorts. Propensity scores for CRT were estimated from covariates associated with receipt of treatment using multivariable logistic regression. Standardized mortality ratio weights (SMRW) were created from the propensity scores and used to balance groups on measured confounders. Multivariable and SMR-weighted Cox proportional hazard models were used to estimate the hazard ratio (HR) of death for receipt of CRT versus RT among the whole group and for separate patient and tumor categories. Results: The final cohort of 10,599 patients was 68% male and 89% white. Median age was 74 years. Seventy-four percent were treated with RT, 26% were treated with CRT. Median follow-up points for CRT and RT survivors were 4.6 and 6.3 years, respectively. On multivariable analysis, HR for death with CRT was 1.13 (95% confidence interval [CI]: 1.07-1.20; P<.01). Using the SMRW model, the HR for death with CRT was 1.08 (95% CI: 1.02-1.15; P=.01). Conclusions: Although the addition of chemotherapy to radiation has proven efficacious in many randomized controlled trials, it may be less effective in an older patient population treated outside of a controlled trial setting.

  3. The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

    Directory of Open Access Journals (Sweden)

    Gómez-Río Manuel

    2010-12-01

    Full Text Available Abstract Background We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT to predict the histopathologic response in locally advanced rectal cancer (LARC treated with preoperative chemoradiation (CRT. Methods The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders. Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR was investigated. Results Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%; This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accurately.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Mortensen, John P; Bisgaard, Claus

    2006-01-01

    PURPOSE: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. METHODS AND MATERIALS: The study included 50 patients with rectal adenocarcinoma. All patients had...

  6. Automatic and Hierarchical Verification for Concurrent Systems

    Institute of Scientific and Technical Information of China (English)

    赵旭东; 冯玉琳

    1990-01-01

    Proving correctness of concurrent systems is quite difficult because of the high level of nondeterminism,especially in large and complex ones.AMC is a model checking system for verifying asynchronous concurrent systems by using branching time temporal logic.This paper introduces the techniques of the modelling approach,especially how to construct models for large concurrent systems with the concept of hierarchy,which has been proved to be effective and practical in verifying large systems without a large growth of cost.

  7. Concurrent Manipulation of Expanded AVL Trees

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Comparing Concurrent Chemoradiotherapy to Chemotherapy Alone for Locally Advanced Unresectable Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Hoon; Kim, Woo Chul; Kim, Hun Jung; Gwak, Hee Keun [Inha University Hospital, Incheon (Korea, Republic of)

    2009-06-15

    Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced unresectable pancreatic cancer. However, the introduction of gemcitabine and the recognition of a benefit in patients with advanced disease stimulated the design of trials that compare chemotherapy alone to concurrent chemoradiation. Therefore, we evaluated role of CCRT for locally advanced unresectable pancreatic cancer. We carried out a retrospective analysis of treatment results for patients with locally advanced unresectable pancreatic cancer between January 2000 and January 2008. The radiation was delivered to the primary tumor and regional lymph nodes with a 1{approx}2 cm margin at a total dose of 36.0{approx}59.4 Gy (median: 54 Gy). The chemotherapeutic agent delivered with the radiation was 5-FU (500 mg/m{sup 2}). The patients who underwent chemotherapy alone received gemcitabine (1,000 mg/m{sup 2}) alone or gemcitabine with 5-FU. The follow-up period ranged from 2 to 38 months. The survival and prognostic factors were analyzed using Kaplan-Meier method and log-rank test, respectively. Thirty-four patients received concurrent chemoradiotherapy, whereas 21 patients received chemotherapy alone. The median survival time was 12 months for CCRT patients, compared to 11 months for chemotherapy alone patients (p=0.453). The median progression-free survival was 8 months for CCRT patients, compared to 5 months for chemotherapy alone patients (p=0.242). The overall response included 9 partial responses for CCRT and 1 partial response for chemotherapy alone. In total, 26% of patients from the CCRT group experienced grade 3{approx}4 bowel toxicity. In contract, no grade 3{approx}4 bowel toxicity was observed in the chemotherapy alone group. The significant prognostic factors of overall survival were lymph node status, high CA19-9, and tumor location. The response rate and progression-free survival were more favorable in the CCRT group, when compared with the chemotherapy alone group

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  10. CilkSpec: Optimistic Concurrency for Cilk

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Similarity based mixed transaction concurrency control protocol

    Institute of Scientific and Technical Information of China (English)

    PAN Yi; LU Yan-sheng

    2005-01-01

    Due to the various performance requirements and data access restrictions of different types of real-time transactions, concurrency control protocols which had been designed for the systems with single type of transactions are not sufficient for mixed real-time database systems (MRTDBS), where different types of real-time transactions coexist in the systems concurrently. In this paper, a new concurrency control protocol MRTT_CC for mixed real-time transactions is proposed. The new strategy integrates with different concurrency control protocols to meet the deadline requirements of different types of real-time transactions. The data similarity concept is also explored in the new protocol to reduce the blocking time of soft real-time transactions, which increases their chances to meet the deadlines. Simulation experiments show that the new protocol has gained good performance.

  12. 33 CFR 385.7 - Concurrency statements.

    Science.gov (United States)

    2010-07-01

    ... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.7 Concurrency statements. The administrative record of the programmatic regulations in this part..., Jacksonville District, 701 San Marco Blvd., Jacksonville, Florida 32207, or by accessing the...

  13. Abstract Diagnosis for Timed Concurrent Constraint programs

    CERN Document Server

    Comini, Marco; Villanueva, Alicia

    2011-01-01

    The Timed Concurrent Constraint Language (tccp in short) is a concurrent logic language based on the simple but powerful concurrent constraint paradigm of Saraswat. In this paradigm, the notion of store-as-value is replaced by the notion of store-as-constraint, which introduces some differences w.r.t. other approaches to concurrency. In this paper, we provide a general framework for the debugging of tccp programs. To this end, we first present a new compact, bottom-up semantics for the language that is well suited for debugging and verification purposes in the context of reactive systems. We also provide an abstract semantics that allows us to effectively implement debugging algorithms based on abstract interpretation. Given a tccp program and a behavior specification, our debugging approach automatically detects whether the program satisfies the specification. This differs from other semiautomatic approaches to debugging and avoids the need to provide symptoms in advance. We show the efficacy of our approach...

  14. Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer

    Science.gov (United States)

    Kim, Hwan-Ik; Noh, O Kyu; Oh, Young-Taek; Chun, Mison; Kim, Sang-Won; Cho, Oyeon; Heo, Jaesung

    2016-01-01

    Purpose Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. Materials and Methods From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4–60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. Results Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). Conclusion CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy. PMID:27730801

  15. Comparison of concurrent chemoradiotherapy versus sequential radiochemotherapy in patients with completely resected non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hwan Ik; Noh, O Kyu; Oh, Young Taek; Chun, Mi Son; Kim, Sang Won; Cho, O Yeon; Heo, Jae Sung [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2016-09-15

    Our institution has implemented two different adjuvant protocols in treating patients with non-small cell lung cancer (NSCLC): chemotherapy followed by concurrent chemoradiotherapy (CT-CCRT) and sequential postoperative radiotherapy (PORT) followed by postoperative chemotherapy (POCT). We aimed to compare the clinical outcomes between the two adjuvant protocols. From March 1997 to October 2012, 68 patients were treated with CT-CCRT (n = 25) and sequential PORT followed by POCT (RT-CT; n = 43). The CT-CCRT protocol consisted of 2 cycles of cisplatin-based POCT followed by PORT concurrently with 2 cycles of POCT. The RT-CT protocol consisted of PORT followed by 4 cycles of cisplatin-based POCT. PORT was administered using conventional fractionation with a dose of 50.4–60 Gy. We compared the outcomes between the two adjuvant protocols and analyzed the clinical factors affecting survivals. Median follow-up time was 43.9 months (range, 3.2 to 74.0 months), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 53.9%, 68.2%, and 51.0%, respectively. There were no significant differences in OS (p = 0.074), LRFS (p = 0.094), and DMFS (p = 0.490) between the two protocols. In multivariable analyses, adjuvant protocol remained as a significant prognostic factor for LRFS, favouring CT-CCRT (hazard ratio [HR] = 3.506, p = 0.046) over RT-CT, not for OS (HR = 0.647, p = 0.229). CT-CCRT protocol increased LRFS more than RT-CT protocol in patients with completely resected NSCLC, but not in OS. Further studies are warranted to evaluate the benefit of CCRT strategy compared with sequential strategy.

  16. From discovery to licensure, the Adjuvant System story

    Science.gov (United States)

    Garçon, Nathalie; Di Pasquale, Alberta

    2017-01-01

    ABSTRACT Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines. PMID:27636098

  17. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  18. Cardiac function after chemoradiation for esophageal cancer : comparison of heart dose-volume histogram parameters to multiple gated acquisition scan changes

    NARCIS (Netherlands)

    Tripp, P; Malhotra, H K; Javle, M; Shaukat, A; Russo, R; de Boer, Sietse; Podgorsak, M; Nava, H; Yang, G Y

    2005-01-01

    In this paper we determine if preoperative chemoradiation for locally advanced esophageal cancer leads to changes in cardiac ejection fraction. This is a retrospective review of 20 patients treated at our institution for esophageal cancer between 2000 and 2002. Multiple gated acquisition cardiac sca

  19. Characterizing Distributed Concurrent Engineering Teams: A Descriptive Framework for Aerospace Concurrent Engineering Design Teams

    Science.gov (United States)

    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.

  20. KRAS Mutation Status and Clinical Outcome of Preoperative Chemoradiation With Cetuximab in Locally Advanced Rectal Cancer: A Pooled Analysis of 2 Phase II Trials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Young; Shim, Eun Kyung [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Yeo, Hyun Yang [Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Hong, Yong Sang [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Dae Yong [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Tae Won [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jee Hyun [Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Im, Seock-Ah [Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Kyung Hae [Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Chang, Hee Jin, E-mail: heejincmd@yahoo.com [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Division of Translational and Clinical Research I, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2013-01-01

    Purpose: Cetuximab-containing chemotherapy is known to be effective for KRAS wild-type metastatic colorectal cancer; however, it is not clear whether cetuximab-based preoperative chemoradiation confers an additional benefit compared with chemoradiation without cetuximab in patients with locally advanced rectal cancer. Methods and Materials: We analyzed EGFR, KRAS, BRAF, and PIK3CA mutation status with direct sequencing and epidermal growth factor receptor (EGFR) and Phosphatase and tensin homolog (PTEN) expression status with immunohistochemistry in tumor samples of 82 patients with locally advanced rectal cancer who were enrolled in the IRIX trial (preoperative chemoradiation with irinotecan and capecitabine; n=44) or the ERBIRIX trial (preoperative chemoradiation with irinotecan and capecitabine plus cetuximab; n=38). Both trials were similarly designed except for the administration of cetuximab; radiation therapy was administered at a dose of 50.4 Gy/28 fractions and irinotecan and capecitabine were given at doses of 40 mg/m{sup 2} weekly and 1650 mg/m{sup 2}/day, respectively, for 5 days per week. In the ERBIRIX trial, cetuximab was additionally given with a loading dose of 400 mg/m{sup 2} on 1 week before radiation, and 250 mg/m{sup 2} weekly thereafter. Results: Baseline characteristics before chemoradiation were similar between the 2 trial cohorts. A KRAS mutation in codon 12, 13, and 61 was noted in 15 (34%) patients in the IRIX cohort and 5 (13%) in the ERBIRIX cohort (P=.028). Among 62 KRAS wild-type cancer patients, major pathologic response rate, disease-free survival and pathologic stage did not differ significantly between the 2 cohorts. No mutations were detected in BRAF exon 11 and 15, PIK3CA exon 9 and 20, or EGFR exon 18-24 in any of the 82 patients, and PTEN and EGFR expression were not predictive of clinical outcome. Conclusions: In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with

  1. Immunogenicity and immunization costs of adjuvanted versus non-adjuvanted hepatitis B vaccine in chronic kidney disease patients.

    Science.gov (United States)

    Vilajeliu, Alba; Sequera, Víctor-Guillermo; García-Basteiro, Alberto L; Sicuri, Elisa; Aldea, Marta; Velasco, César; Bayas, José M

    2016-09-01

    Hepatitis B virus (HBV) vaccination is recommended for all susceptible chronic pre-hemodialysis and hemodialysis patients. This study assessed the immunogenicity of HBV vaccines (adjuvanted and non-adjuvanted) in chronic kidney disease patients vaccinated at the Hospital Clinic of Barcelona (Spain) between January 2007 and July 2012. In addition, the costs for the health system were evaluated accor-ding to the proportion of vaccine responders after receiving either vaccine. Patients receiving 3 doses of hepatitis B adjuvanted vaccine were 3 times more likely to seroconvert than patients immunized with non-adjuvanted vaccines, OR 3.56 (95% CI 1.84-6.85). This resulted in fewer patients requiring a second course of HBV vaccination and fewer outpatient visits, saving more than €9,500 per 100 patients. The higher immunogenicity of the adjuvanted HBV vaccine would counterbalance the lower costs associated with the non-adjuvanted vaccine.

  2. Intratumoral Dendritic Cells and Chemoradiation for the Treatment of Murine Squamous Cell Carcinoma

    OpenAIRE

    Moyer, Jeffrey S.; Li, Ji; Wei, Shuang; Teitz-Tennenbaum, Seagal; Chang, Alfred E

    2008-01-01

    Dendritic cells are potent antigen presenting cells that have been shown to have significant antitumor effects in vitro and in vivo. However, the therapeutic efficacy of dendritic cells as an immunotherapeutic treatment has been limited by both immunologic tolerance and active immunosuppression in the tumor microenvironment. To address this problem, we examined the ability of concurrent systemic chemotherapy and local, fractionated radiation to augment intratumoral dendritic cell injections i...

  3. Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency Following Chemoradiation Treatment for Head and Neck Cancer

    Science.gov (United States)

    Rogus-Pulia, Nicole M.; Larson, Charles; Mittal, Bharat B; Pierce, Marge; Zecker, Steven; Kennelty, Korey; Kind, Amy; Connor, Nadine P.

    2016-01-01

    Purpose Patients treated with chemoradiation for head and neck cancer frequently develop dysphagia. Tissue damage to the oral tongue causing weakness and decreases in saliva production may contribute to dysphagia. Yet, effects of these variables on swallowing-related measures are unclear. The purpose of this study was (1) to determine effects of chemoradiation on tongue pressures, as a surrogate for strength, and salivary flow rates and (2) to elucidate relationships among tongue pressures, saliva production, and swallowing efficiency by bolus type. Methods and Materials 21 patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with 21 healthy control participants who did not receive chemoradiation. Each participant was given a questionnaire to rate dysphagia symptoms. Videofluoroscopic evaluation of swallowing was used to determine swallowing efficiency; the Saxon test measured salivary flow rate; and the Iowa Oral Performance Instrument (IOPI) was used for oral tongue maximum and endurance measures. Results Results revealed significantly lower tongue endurance measures for patients post-treatment as compared to controls (p=.012). Salivary flow rates also were lower compared to pre-treatment (p=.000) and controls (p=.000). Simple linear regression analyses showed that change in salivary flow rate was predictive of change in swallow efficiency measures from pre- to post-treatment for 1mL thin liquid (p=.017), 3mL nectar-thick liquid (p=.026), and 3mL standard barium pudding (p=.011) boluses. Conclusions Based on these findings, it appears that chemoradiation treatment affects tongue endurance and salivary flow rate and these changes may impact swallow efficiency. These factors should be considered when planning treatment for dysphagia. PMID:27492408

  4. Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Pei-Chun [Department of Statistics and Informatics Science, Providence University, Taiwan (China); Chen, Yen-Ching [Institute of Epidemiology Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Lai, Liang-Chuan [Graduate Institute of Physiology, National Taiwan University, Taiwan (China); Tsai, Mong-Hsun [Institute of Biotechnology, National Taiwan University, Taiwan (China); Chen, Shin-Kuang [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Yang, Pei-Wen; Lee, Yung-Chie [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Hsiao, Chuhsing K. [Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Lee, Jang-Ming, E-mail: jangming@ntuh.gov.tw [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Chuang, Eric Y., E-mail: chuangey@ntu.edu.tw [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taiwan (China)

    2012-04-01

    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.

  5. Theta oscillations accompanying concurrent auditory stream segregation.

    Science.gov (United States)

    Tóth, Brigitta; Kocsis, Zsuzsanna; Urbán, Gábor; Winkler, István

    2016-08-01

    The ability to isolate a single sound source among concurrent sources is crucial for veridical auditory perception. The present study investigated the event-related oscillations evoked by complex tones, which could be perceived as a single sound and tonal complexes with cues promoting the perception of two concurrent sounds by inharmonicity, onset asynchrony, and/or perceived source location difference of the components tones. In separate task conditions, participants performed a visual change detection task (visual control), watched a silent movie (passive listening) or reported for each tone whether they perceived one or two concurrent sounds (active listening). In two time windows, the amplitude of theta oscillation was modulated by the presence vs. absence of the cues: 60-350ms/6-8Hz (early) and 350-450ms/4-8Hz (late). The early response appeared both in the passive and the active listening conditions; it did not closely match the task performance; and it had a fronto-central scalp distribution. The late response was only elicited in the active listening condition; it closely matched the task performance; and it had a centro-parietal scalp distribution. The neural processes reflected by these responses are probably involved in the processing of concurrent sound segregation cues, in sound categorization, and response preparation and monitoring. The current results are compatible with the notion that theta oscillations mediate some of the processes involved in concurrent sound segregation.

  6. Establishment of a new quality control and vaccine safety test for influenza vaccines and adjuvants using gene expression profiling.

    Science.gov (United States)

    Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

    2015-01-01

    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.

  7. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.

  8. Comparative Efficacy of Cisplatin vs. Gemcitabine as Concurrent Chemotherapy for Untreated Locally Advanced Cervical Cancer: A Randomized Trail

    Directory of Open Access Journals (Sweden)

    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.

  9. Safety and Palliative Efficacy of Single-Dose 8-Gy Reirradiation for Painful Local Failure in Patients With Stage IV Non-Small Cell Lung Cancer Previously Treated With Radical Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Topkan, Erkan, E-mail: docdretopkan@gmail.com [Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana (Turkey); Yildirim, Berna Akkus; Guler, Ozan Cem; Parlak, Cem [Baskent Department of Radiation Oncology, University Adana Medical Faculty, Adana (Turkey); Pehlivan, Berrin [Koc University, School of Medicine, Department of Radiation Oncology, Istanbul, and American Hospital, University of Texas MD Anderson Radiation Treatment Center, Istanbul (Turkey); Selek, Ugur [Medstar Hospital, Department of Radiation Oncology, Antalya (Turkey)

    2015-03-15

    Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. Patients and Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of pain control. Secondary objectives were survival and prognostic factors. Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS. Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.

  10. Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer

    OpenAIRE

    Cleary, James M.; Mamon, Harvey J.; Szymonifka, Jackie; Bueno, Raphael; Choi, Noah; Donahue, Dean M.; Fidias, Panos M.; Gaissert, Henning A.; Jaklitsch, Michael T.; Kulke, Matthew H.; Lynch, Thomas P.; Mentzer, Steven J.; Meyerhardt, Jeffrey A.; Swanson, Richard S.; Wain, John

    2016-01-01

    Background: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. Methods...

  11. An Algorithm to Construct Concurrent Reachability Graph of Petri Nets

    Institute of Scientific and Technical Information of China (English)

    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.

  12. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber;

    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...

  13. Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: a systematic review of completed and ongoing studies.

    Science.gov (United States)

    Choy, Hak; Gerber, David E; Bradley, Jeffrey D; Iyengar, Puneeth; Monberg, Matthew; Treat, Joseph; Govindan, Ramaswamy; Koustensis, Andrew; Barker, Scott; Obasaju, Coleman

    2015-03-01

    Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0-16% and 0-23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed-cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.

  14. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    OpenAIRE

    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...

  15. Toxicity of combined treatment of adjuvant irradiation and interferon alpha2b in high-risk melanoma patients.

    Science.gov (United States)

    Conill, Carlos; Jorcano, Sandra; Domingo-Domènech, Josep; Marruecos, Jordi; Vilella, Ramón; Malvehy, Josep; Puig, Susana; Sánchez, Marcelo; Gallego, Rosa; Castel, Teresa

    2007-10-01

    Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) alpha2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of this combined therapy. Eighteen patients receiving adjuvant IFNalpha2b therapy during radiation therapy, or within 1 month of its completion, were reviewed retrospectively and analysed for outcome. Radiation was delivered at 600 cGy dose per fraction, in 16 out of 18 patients, twice a week, and at 200 cGy dose per fraction in two patients five times a week. Total radiation dose and number of fractions were as follows: 30 Gy/5 fr (n=8), 36 Gy/6 fr (n=8) and 50 Gy/25 fr (n=2). The percentage of disease-free patients, with no local recurrence, at 3 years was 88%. In 10 patients, IFNalpha2b was administered concurrently with radiotherapy; in three, within 30 days before or after radiation; and in five, more than 30 days after radiation. All the patients experienced acute skin reactions, grade I on the Radiation Therapy Oncology Group (RTOG) scale. Late radiation-related toxicity was seen in one patient with grade III (RTOG) skin reaction and two with grade IV (RTOG) radiation-induced myelitis. Concurrent use of adjuvant radiotherapy and IFNalpha2b might enhance radiation-induced toxicity, and special care should be taken when the spinal cord is included in the radiation field.

  16. Compositional Formal Analysis for Concurrent Object-Oriented Languages

    OpenAIRE

    Tran, Thi Mai Thuong

    2013-01-01

    Concurrency is a ubiquitous phenomenon in modern software ranging from distributed systems communicating over the Internet to communicating processes running on multi-core processors and multi-processors. Therefore modern programming languages offer ways to program concurrency effectively. Still, writing correct concurrent programs is notoriously difficult because of the complexity of possible interactions between concurrent processes and because concurrency-related errors are often subtle an...

  17. Immune adjuvant activity of the olive, soybean and corn oils

    Directory of Open Access Journals (Sweden)

    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.

  18. Micro-transactions for concurrent data structures

    DEFF Research Database (Denmark)

    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...... implementation of transactional memory that we call micro-transactions. In particular, we argue that hardware support for micro-transactions allows us to efficiently implement certain data structures. Those data structures are difficult to realize with the atomic operations provided by stock hardware and provide......, atomic instructions, and micro-transactions. Our results suggest that transactional memory is an interesting alternative to traditional concurrency control mechanisms....

  19. Concurrent Engineering in seafood product development

    DEFF Research Database (Denmark)

    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...

  20. Concurrent sourcing and external supplier opportunism

    DEFF Research Database (Denmark)

    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 expected...... costs of opportunism are determined as a product of four factors. The four factors are: likelihood of discovering supplier opportunism, buyer’s internalized quantity as reaction to supplier opportunism, asset specificity of external supplier’s investments, and multiplicator effects. Each...

  1. Authentic And Concurrent Evaluation-refining

    DEFF Research Database (Denmark)

    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. Models for concurrency: towards a classification

    DEFF Research Database (Denmark)

    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 category...

  3. Towards Interaction Reliability in Concurrent Applications

    Directory of Open Access Journals (Sweden)

    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.

  4. Concurrent Scheduling of Event-B Models

    CERN Document Server

    Boström, Pontus; Sere, Kaisa; Waldén, Marina; 10.4204/EPTCS.55.11

    2011-01-01

    Event-B is a refinement-based formal method that has been shown to be useful in developing concurrent and distributed programs. Large models can be decomposed into sub-models that can be refined semi-independently and executed in parallel. In this paper, we show how to introduce explicit control flow for the concurrent sub-models in the form of event schedules. We explore how schedules can be designed so that their application results in a correctness-preserving refinement step. For practical application, two patterns for schedule introduction are provided, together with their associated proof obligations. We demonstrate our method by applying it on the dining philosophers problem.

  5. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Directory of Open Access Journals (Sweden)

    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.

  7. Recurrence of paraneoplastic membranous glomerulonephritis following chemoradiation in a man with non-small-cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Kara Leonard

    2013-04-01

    Full Text Available Membranous glomerulonephritis can occur as a rare paraneoplastic complication of human cancers. In this case report, we describe a patient who presented acutely with symptoms of the nephrotic syndrome including heavy proteinuria and anasarca. He was subsequently diagnosed with membranous glomerulonephritis, and soon afterwards was found to have stage IIIB non-small cell lung cancer. Following chemoradiation therapy, both the patient’s cancer and membranous glomerulonephritis dramatically improved. However, approximately 14 months following his initial presentation, the patient was found to have a recurrence of his nephrotic-range proteinuria which corresponded temporally with recurrence of his cancer. We present details of the case and a review of the relevant scientific literature.

  8. Germline polymorphisms may act as predictors of response to preoperative chemoradiation in locally advanced T3 rectal tumors

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Nielsen, Jens N; Lindebjerg, Jan;

    2007-01-01

    with locally advanced T3 rectal tumors were analyzed for thymidylate synthase, epidermal growth factor receptor Sp1-216, and epidermal growth factor A61G gene polymorphisms by polymerase chain reaction. Treatment consisted of preoperative radiotherapy (total dose 65 Gy) and concomitant chemotherapy (Uftoral......PURPOSE: Patients with locally advanced T3 rectal tumors who present with complete pathologic response to preoperative chemoradiation have a low rate of local recurrence and an excellent prognosis. Predictive markers for complete pathologic response are needed with the perspective of improving...... individualized treatment of these patients. This study was designed to investigate the predictive value of a new combination of three gene polymorphisms: thymidylate synthase, epidermal growth factor receptor Sp1-216, and epidermal growth factor A61G. METHODS: Pretreatment blood samples from 60 patients...

  9. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

    Science.gov (United States)

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

    2014-04-01

    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 adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

  10. Dose-Volume Effects on Patient-Reported Acute Gastrointestinal Symptoms During Chemoradiation Therapy for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ronald C. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Mamon, Harvey J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Killoran, Joseph H. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Crowley, Elizabeth M. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Blaszkowsky, Lawrence S. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Wo, Jennifer Y. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ryan, David P. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Hong, Theodore S., E-mail: tshong1@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2012-07-15

    Purpose: Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. Methods and Materials: 66 patients treated at the Brigham and Women's Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearman's correlation. Potential associations between these parameters and individual GI symptoms were also explored. Results: The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. Conclusions: The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.

  11. Postoperative versus definitive chemoradiation in early-stage anal cancer. Results of a matched-pair analysis

    Energy Technology Data Exchange (ETDEWEB)

    Berger, B.; Menzel, M.; Bamberg, M.; Weinmann, M. [Tuebingen Univ. (Germany). Dept. of Radiation Oncology; Breucha, G. [Kreiskrankenhaus Hechingen, Tuebingen Univ. (Germany). Dept. of Surgery

    2012-07-15

    Background and purpose: The goal of the present study was to comparatively assess the results of definitive chemoradiation (CRT) with or without previous macroscopically complete resection in patients with early-stage node-negative (T1-2 N0) anal carcinoma. Patients and methods: A total of 20 patients with T1-2 N0 anal carcinoma who received radiotherapy (RT) with or without chemotherapy following incidental R0/1 tumor resection (S/CRT group) were selected. These were matched to 20 comparable patients who underwent definitive chemoradiation without previous surgery (CRT group). Major objectives of this analysis were treatment outcomes in terms of locoregional tumor control (LRC), overall survival (OS), colostomy-free survival, and toxicity. Results: Patients treated postoperatively received significantly lower RT doses (median 54.0 Gy vs. 59.7 Gy; p < 0.001) and less frequently concomitant chemotherapy than those treated definitely. The 5-year LRC and 5-year OS rates were 97.5% and 90.0%, respectively, without significant differences between the S/CRT and the CRT groups. The distribution of acute and late toxicities was comparable, and the 5-year colostomy-free survival was 95% in both groups. Conclusion: This matched-pair comparison of incidental R0/1 resection plus dose-reduced CRT with standard definitive CRT of early-stage anal cancer shows similar treatment results. Thus, dose-reduced RT with or without chemotherapy may be considered in R0/1 resected patients with T1-2 N0 anal carcinoma. (orig.)

  12. SU-E-J-268: Change of CT Number During the Course of Chemoradiation Therapy for Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X; Dalah, E; Liu, F; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States); Zhang, J [Department of Radiation Oncology, Qianfoshan Hospital Affiliated to Shandon, Jinan, Shandong (China)

    2015-06-15

    Purpose: It has been observed radiation can induce changes in CT number (CTN) inside tumor during the course of radiation therapy (RT) for several tumor sites including lung and head and neck, suggesting that the CTN change may be potentially used to assess RT response. In this study, we investigate the CTN changes inside tumor during the course of chemoradiation therapy (CRT) for pancreatic cancer. Methods: Daily diagnostic-quality CT data acquired during IGRT for 17 pancreatic head cancer patients using an in-room CT (CTVision, Siemens) were analyzed. All patients were treated with a radiation dose of 50.4 in 1.8 Gy per fraction. On each daily CT set, The contour of the pancreatic head, included in the treatment target, was generated by populating the pancreatic head contour from the planning CT or MRI using an auto-segmentation tool based on deformable registration (ABAS, Elekta) with manual editing if necessary. The CTN at each voxel in the pancreatic head contour was extracted and the 3D distribution of the CTNs was processed using MATLAB. The mean value of CTN distribution was used to quantify the daily CTN change in the pancreatic head. Results: Reduction of CTN in pancreatic head was observed during the CRT delivery in 14 out the 17 (82%) patients studied. Although the average reduction is only 3.5 Houncefield Unit (HU), this change is significant (p<0.01). Among them, there are 7 patients who had a CTN drop larger than 5 HU, ranging from 6.0 to 11.8 HU. In contrast to this trend, CTN was increased in 3 patients. Conclusion: Measurable changes in the CT number in tumor target were observed during the course of chemoradiation therapy for the pancreas cancer patients, indicating this radiation-induced CTN change may be used to assess treatment response.

  13. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience

    Science.gov (United States)

    Landry, Jerome C.

    2016-01-01

    Background Cholangiocarcinoma (CCA) is a bile duct tumor with a grim prognosis. The median survival after radiotherapy of unresectable disease is 9-12 months. The following is a review of our experience with neoadjuvant (NEO) chemoradiation followed by orthotopic liver transplantation (OLT) for CCA. Methods Ten patients with CCAs were selected as candidates for NEO-OLT between 2008-2011. Patients with unresectable CCA above the cystic duct without intra or extrahepatic metastases were eligible. Primary sclerosing cholangitis (PSC) patients were included due to their poor resection response. Patients initially received external-beam radiation [via conventional fields or volumetric-modulated arc therapy (VMAT)] plus capecitabine (XEL) or 5-fluorouracil (5-FU), followed by either Iridium192 (Ir192) brachytherapy high dose rate (HDR) or external boost. 5-FU or XEL was administered until OLT. Patients underwent periodic surveillance computed tomography (CT)/MRIs after OLT. Primary endpoints included actuarial rates (AR)/crude rates (CR) of overall survival (OS), and local control (LC) at 6, 12, and 24 months. Results Five males and five females were identified. Mean age was 58.3 years (range, 38-71 years). Mean composite radiation dose delivered was 59.0 Gy (range, 54-71.4 Gy). Forty percent of patients had an HDR boost. Fifty percent of patients received XEL during NEO. Two patients were excluded from the analysis as they did not go on to OLT due to metastases (n=1) and death due to GI bleed (n=1). Thirty-eight percent of the OLT patients had a pathological complete response (pCR) after NEO, while 25% required a Whipple due to positive margins. Median follow-up for the OLT group was 23 months (range, 6.5-37 months). Six, twelve, and twenty-four months LC AR was 100%. LC CR was 100% at longest interval (30 months). Six, twelve, and twenty-four months OS AR was 100%, 87.5%, and 87.5%, respectively. Mean OS AR was 30.2 months (95% CI: 22.8-37.7). OS CR was 75% at longest

  14. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

    Science.gov (United States)

    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.

  15. Designing CAF-adjuvanted dry powder vaccines: Spray drying preserves the adjuvant activity of CAF01

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis

    2013-01-01

    spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol......Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties...... remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6′-dibehenate (TDB) via...

  16. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    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....... RESULTS: The median observation period of the 740 patients included was 6.8 (range 5.4-7.9) years. A univariate analysis of all 740 patients and of the subgroup of 560 who underwent curative resection showed no significant effect of ranitidine on survival. Furthermore, ranitidine had no survival benefit...... in curatively resected patients who received a perioperative blood transfusion (n = 358), but it improved the survival of non-transfused patients (n = 202; hazard ratio (HR) 0.6 (95 per cent confidence interval (c.i.) 0.4 to 0.9), P = 0.02) and of non-transfused patients who did not develop postoperative...

  17. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    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......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...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

  18. On run-time exploitation of concurrency

    NARCIS (Netherlands)

    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

  19. Proceedings 8th Interaction and Concurrency Experience

    DEFF Research Database (Denmark)

    2015-01-01

    This volume contains the proceedings of ICE 2015, the 8th Interaction and Concurrency Experience, which was held in Grenoble, France on the 4th and 5th of June 2015 as a satellite event of DisCoTec 2015. The ICE procedure for paper selection allows PC members to interact, anonymously, with author...

  20. Nonlinear Inequalities and Entropy-Concurrence Plane

    CERN Document Server

    Bovino, F A

    2006-01-01

    Nonlinear inequalities based on the quadratic Renyi entropy for mixed two-qubit states are characterized on the Entropy-Concurrence plane. This class of inequalities is stronger than Clauser-Horne-Shimony-Holt (CHSH) inequalities and, in particular, are violated "in toto" by the set of Type I Maximally-Entangled-Mixture States (MEMS I).

  1. Concurrent Validity of a Pragmatic Protocol.

    Science.gov (United States)

    Duncan, Julie Condon; Perozzi, Joseph A.

    1987-01-01

    The scores of 11 non-handicapped kindergarten children on the Pragmatic Protocol (used in assessing language-handicapped children) were correlated with their ratings by five experienced judges on a 7-point equal-appearing interval scale of communicative competence. The concurrent validity of the Protocol and interobserver reliability were…

  2. Concurrent Meta-Evaluation: A Critique

    Science.gov (United States)

    Hanssen, Carl E.; Lawrenz, Frances; Dunet, Diane O.

    2008-01-01

    Meta-evaluations reported in the literature, although rare, often have focused on retrospective assessment of completed evaluations. Conducting a meta-evaluation concurrently with the evaluation modifies this approach. This method provides the opportunity for the meta-evaluators to advise the evaluators and provides the basis for a summative…

  3. Concurrent Engineering Design Using Intelligent Agents.

    Science.gov (United States)

    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…

  4. Concurrent Engineering in the 21st Century

    NARCIS (Netherlands)

    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

  5. Declarative interpretations of session-based concurrency

    DEFF Research Database (Denmark)

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

    2015-01-01

    Session-based concurrency is a type-based approach to the analysis of communication-intensive systems. Correct behavior in these systems may be specified in an operational or declarative style: the former defines how interactions are structured; the latter defines governing conditions. In this pa...

  6. CAPP Framework System for Concurrent Engineering

    Institute of Scientific and Technical Information of China (English)

    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.

  7. Logics and Games for True Concurrency

    CERN Document Server

    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...

  8. Integrated concurrent utilization quality review, Part one.

    Science.gov (United States)

    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.

  9. Adjuvants for veterinary vaccines--types and modes of action.

    Science.gov (United States)

    Gerdts, Volker

    2015-01-01

    Adjuvants are used to improve the immune response to vaccines. Formulation with adjuvants can result in an earlier onset of immunity, an overall stronger immune response, a specific type of immunity, or a longer duration of immunity to the vaccine. Adjuvants were discovered empirically, and for decades, have been used in both humans and animals without understanding the mechanisms of action. With an improved understanding of the immune system, and in particular the interplay between innate and adaptive immunity, we are now getting better insight into the function of adjuvants. As a result, new adjuvants are being developed that are safe and highly effective for common use in humans and animals, as well as for use in high risk populations such as immunocompromised animals, neonates or very old animals. Furthermore, adjuvants can help to reduce the amount of antigen needed in the vaccine, increase the stability of the vaccine and enable alternatiye administration routes such as needle-free delivery of the vaccine. Here, I will provide an over view of the existing adjuvant technologies for veterinary vaccines and provide an outlook into some of the new technologies in preclinical and clinical development.

  10. Progress in adjuvant chemotherapy for breast cancer: an overview.

    Science.gov (United States)

    Anampa, Jesus; Makower, Della; Sparano, Joseph A

    2015-01-01

    Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.

  11. The role of adjuvant in mediating antigen structure and stability.

    Science.gov (United States)

    Braun, Latoya Jones; Eldridge, Aimee M; Cummiskey, Jessica; Arthur, Kelly K; Wuttke, Deborah S

    2012-04-01

    The purpose of this study was to probe the fate of a model antigen, a cysteine-free mutant of bacteriophage T4 lysozyme, to the level of fine structural detail, as a consequence of its interaction with an aluminum (Al)-containing adjuvant. Fluorescence spectroscopy and differential scanning calorimetry were used to compare the thermal stability of the protein in solution versus adsorbed onto an Al-containing adjuvant. Differences in accessible hydrophobic surface areas were investigated using an extrinsic fluorescence probe, 8-Anilino-1-naphthalenesulfonic acid (ANS). As has been observed with other model antigens, the apparent thermal stability of the protein decreased following adsorption onto the adjuvant. ANS spectra suggested that adsorption onto the adjuvant caused an increase in exposure of hydrophobic regions of the protein. Electrostatic interactions drove the adsorption, and disruption of these interactions with high ionic strength buffers facilitated the collection of two-dimensional (15) N heteronuclear single quantum coherence nuclear magnetic resonance data of protein released from the adjuvant. Although the altered stability of the adsorbed protein suggested changes to the protein's structure, the fine structure of the desorbed protein was nearly identical to the protein's structure in the adjuvant-free formulation. Thus, the adjuvant-induced changes to the protein that were responsible for the reduced thermal stability were not observed upon desorption.

  12. Adjuvants for vaccines to drugs of abuse and addiction.

    Science.gov (United States)

    Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-09-22

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA.

  13. Functional Promoter Variant rs2868371 of HSPB1 Is Associated With Risk of Radiation Pneumonitis After Chemoradiation for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Qingsong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Department of Radiation Oncology and Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Wei, Qingyi [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Xu, Ting [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Yuan, Xianglin [Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan (China); Lopez Guerra, Jose Luis [Department of Medicine, Universitat Autònoma de Barcelona (Spain); Levy, Lawrence B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Liu, Zhensheng [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Zhuang, Yan [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center (United States); Wang, Li-E. [Department of Epidemiology, The University of Texas MD Anderson Cancer Center (United States); Mohan, Radhe [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center (United States); Komaki, Ritsuko [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center (United States)

    2013-04-01

    Purpose: To date, no biomarkers have been found to predict, before treatment, which patients will develop radiation pneumonitis (RP), a potentially fatal toxicity, after chemoradiation for lung cancer. We investigated potential associations between single nucleotide polymorphisms (SNPs) in HSPB1 and risk of RP after chemoradiation for non-small cell lung cancer (NSCLC). Methods and Materials: Subjects were patients with NSCLC treated with chemoradiation at 1 institution. The training data set comprised 146 patients treated from 1999 to July 2004; the validation data set was 125 patients treated from August 2004 to March 2010. We genotyped 2 functional SNPs of HSPB1 (rs2868370 and rs2868371) from all patients. We used Kaplan-Meier analysis to assess the risk of grade ≥2 or ≥3 RP in both data sets and a parametric log-logistic survival model to evaluate the association of HSPB1 genotypes with that risk. Results: Grade ≥3 RP was experienced by 13% of those with CG/GG and 29% of those with CC genotype of HSPB1 rs2868371 in the training data set (P=.028); corresponding rates in the validation data set were 2% CG/GG and 14% CC (P=.02). Univariate and multivariate analysis confirmed the association of CC of HSPB1 rs2868371 with higher risk of grade ≥3 RP than CG/GG after adjustment for sex, age, performance status, and lung mean dose. This association was validated both in the validation data set and with Harrell's C statistic. Conclusions: The CC genotype of HSPB1 rs2868371 was associated with severe RP after chemoradiation for NSCLC.

  14. Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

    Energy Technology Data Exchange (ETDEWEB)

    Park, Shin Hyung; Kim, Jae Chul [Dept. of Radiation Oncology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2016-06-15

    The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer.

  15. Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study

    Energy Technology Data Exchange (ETDEWEB)

    Morganti, Alessio G.; Picardi, Vincenzo; Ippolito, Edy; Massaccesi, Mariangela; Macchia, Gabriella; Deodato, Francesco (Radiotherapy Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy)), E-mail: gmacchia@rm.unicatt.it; Caravatta, Luciana; Tambaro, Rosa; Mignogna, Samantha (Palliative Therapies Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy)); Cellini, Numa; Valentini, Vincenzo; Mattiucci, Gian Carlo (Dept. of Radiotherapy, Policlinico Universitario ' A. Gemelli' , Catholic Univ., Rome (Italy)); Di Lullo, Liberato (Dept. of Oncology, ' F. Veneziale' General Hospital, Isernia (Italy)); Giglio, Gianfranco (Dept. of Oncology, ' A. Cardarelli' General Hospital Campobasso (Italy)); Caprino, Paola; Sofo, Luigi (Surgery Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy)); Ingrosso, Marcello (Endoscopy Unit, Dept. of Oncology, ' John Paul II' Center for High Technology Research and Education in Biomedical Sciences, Catholic Univ., Campobasso (Italy))

    2010-05-15

    The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. Material and methods. Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m2. Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. Results and discussion. Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m2) in patients with resected pancreatic carcinoma.

  16. Cardiac function after chemoradiation for esophageal cancer: comparison of heart dose-volume histogram parameters to multiple gated acquisition scan changes.

    Science.gov (United States)

    Tripp, P; Malhotra, H K; Javle, M; Shaukat, A; Russo, R; De Boer, S; Podgorsak, M; Nava, H; Yang, G Y

    2005-01-01

    In this paper we determine if preoperative chemoradiation for locally advanced esophageal cancer leads to changes in cardiac ejection fraction. This is a retrospective review of 20 patients treated at our institution for esophageal cancer between 2000 and 2002. Multiple gated acquisition cardiac scans were obtained before and after platinum-based chemoradiation (50.4 Gy). Dose-volume histograms for heart, left ventricle and left anterior descending artery were analyzed. Outcomes assessed included pre- and postchemoradiation ejection fraction ratio and percentage change in ejection fraction postchemoradiation. A statistically significant difference was found between median prechemoradiation ejection fraction (59%) and postchemoradiation ejection fraction (54%) (P = 0.01), but the magnitude of the difference was not clinically significant. Median percentage volume of heart receiving more than 20, 30 and 40 Gy were 61.5%, 58.5% and 53.5%, respectively. Our data showed a clinically insignificant decline in ejection fraction following chemoradiation for esophageal cancer. We did not observe statistically or clinically significant associations between radiation dose to heart, left ventricle or left anterior descending artery and postchemoradiation ejection fraction.

  17. A prospective dosimetric and clinical comparison of acute hematological toxicities in three-dimensional conformal radiation therapy and intensity modulated radiation therapy with concurrent chemotherapy in carcinoma cervix

    Directory of Open Access Journals (Sweden)

    H U Avinash

    2015-01-01

    Full Text Available Background and Objectives: Acute hematological toxicities are an important cause of morbidity in patients receiving concurrent chemoradiation to pelvis in carcinoma cervix. The objective of this study was to evaluate the role of intensity-modulated radiotherapy (IMRT in reducing the dose to the bone marrow as compared with three-dimensional conformal radiotherapy (3DCRT and hence its impact on reducing the acute hematological toxicities. Materials and Methods: Eleven consecutive patients treated with IMRT and 12 patients treated with 3DCRT to the whole pelvis along with concurrent chemotherapy were selected. Bone marrow was delineated. V10 Gy, V20 Gy, V95%, and Dmean of bone marrow were recorded. Weekly blood counts were recorded and graded as per Common Terminology Criteria version 4.0 for all the patients. Results: The dose to the bone marrow V20 Gy was 206.78 ± 57.10 cc (75% and 251.70 ± 40.45 cc (91% for IMRT and 3DCRT, respectively (P = 0.04 and V95% was 23.30 ± 8.34% and 46.76 ± 6.71% for IMRT and 3DCRT, respectively (P = 0.001. The grade of toxicities during each week did not show the difference in either arm. However, the total count and Neutrophil counts during the 2nd week showed statistical significance between IMRT and 3DCRT. Conclusion: IMRT significantly reduces the dose to the bone marrow as compared to 3DCRT. The reduction of the dose did not translate into a decrease in acute hematological toxicities. Concurrent platinum-based chemotherapy is the probable cause for the hematological toxicities.

  18. Preliminary Proceedings 15th International Workshop on Expressiveness in Concurrency

    DEFF Research Database (Denmark)

    The EXPRESS workshops aim at bringing together researchers interested in the relations between various formal systems, particularly in the field of Concurrency. More specifically, they focus on the comparison between programming concepts (such as concurrent, functional, imperative, logic and object...

  19. A Framework of Concurrent Mechanism Based on Java Multithread

    Directory of Open Access Journals (Sweden)

    Wuxue Jiang

    2013-09-01

    Full Text Available The continuously increased demand for paralleling multitask in domains such as grid computing and cloud computing has significantly promoted research on concurrent mechanism and concurrent programming. The Java programming language supports multithread mechanism for developing paralleling programs, however, it is difficult to apply Java concurrent primitives to specific problems. Thus, for the development of high reliable and qualitative Java concurrent programs, this paper analyses Java multithread mechanism and it’s realization, studies the concurrent mechanism based on Java synchronization and interactive communication mechanism , compares the concurrent structure based on operating system and based on Java multithread, sums up some concurrent programming rules and strategies to prevent deadlock. A frame instance based on entire synchronization is presented, which can help to develop concurrent programs quickly.  

  20. Aerospace concurrent engineering: a modern global approach

    Science.gov (United States)

    Imbert, Mariano; Li, Xiaoxing

    2009-12-01

    System engineering aspects, like concurrent engineering (CE) in the aerospace sector, has been studied by many authors. The change and evolution in this regard is continually influenced by the information technology advances. But global cooperation is only discussed by developed countries and high technology corporations. A review of CE and its ramifications in the aerospace industry is presented. Based on the current literature, the general lifecycle of a spacecraft and its phases are explained as well as the tools that are implemented in today's industry. In this paper we propose a new approach for the product development process in the spacecraft production industry the Aerospace Concurrent Engineering (ACE), which is mainly focused in the technology itself, its optimal design and environment impact rather than costs and marketing impact. And the potential of globally oriented research and implementation of space programs is discussed for its consideration.

  1. Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Barbara J., E-mail: barbara.fisher@lhsc.on.ca [London Regional Cancer Program, London, Ontario (Canada); Hu, Chen [Radiation Therapy Oncology Group-Statistical Center, Philadelphia, Pennsylvania (United States); Macdonald, David R. [London Regional Cancer Program, London, Ontario (Canada); Lesser, Glenn J. [Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina (United States); Coons, Stephen W. [Barrow Neurological Institute, Phoenix, Arizona (United States); Brachman, David G. [Arizona Oncology Services Foundation, Phoenix, Arizona (United States); Ryu, Samuel [Henry Ford Hospital, Detroit, Michigan (United States); Werner-Wasik, Maria [Thomas Jefferson University Hospital Center, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, Quebec (Canada); Liu, Junfeng [GCE Solutions, Inc., Bloomington, Illinois (United States); Chakravarti, Arnab [The Ohio State University, The James, Columbus, Ohio (United States); Mehta, Minesh [University of Maryland Medical Systems, Baltimore, Maryland (United States)

    2015-03-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.

  2. Mx bio adjuvant for enhancing immune responses against influenza virus

    Directory of Open Access Journals (Sweden)

    Sina Soleimani

    2015-06-01

    Conclusion: These data revealed that Mx1 as biological adjuvant was able to increase antibody titer and induction memory immune responses against influenza immunization without causing any side effects.

  3. Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

    Science.gov (United States)

    Meerwaldt, J H; Hoekstra, C J; van Putten, W L; Tjokrowardojo, A J; Koper, P C

    1990-02-01

    The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.

  4. Activity of glycated chitosan and other adjuvants to PDT vaccines

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  5. The Vaccine Formulation Laboratory: a platform for access to adjuvants.

    Science.gov (United States)

    Collin, Nicolas; Dubois, Patrice M

    2011-07-01

    Adjuvants are increasingly used by the vaccine research and development community, particularly for their ability to enhance immune responses and for their dose-sparing properties. However, they are not readily available to the majority of public sector vaccine research groups, and even those with access to suitable adjuvants may still fail in the development of their vaccines because of lack of knowledge on how to correctly formulate the adjuvants. This shortcoming led the World Health Organization to advocate for the establishment of the Vaccine Formulation Laboratory at the University of Lausanne, Switzerland. The primary mission of the laboratory is to transfer adjuvants and formulation technology free of intellectual property rights to academic institutions, small biotechnology companies and developing countries vaccine manufacturers. In this context, the transfer of an oil-in-water emulsion to Bio Farma, an Indonesian vaccine manufacturer, was initiated to increase domestic pandemic influenza vaccine production capacity as part of the national pandemic influenza preparedness plan.

  6. Concurrency Control Mechanism of Complex Objects

    Institute of Scientific and Technical Information of China (English)

    徐庆云; 王能斌

    1992-01-01

    A complex object is an abstraction and description of a complex entity of the real world.Many applications in such domains as CIMS,CAD and OA define and manipulate a complex object as a single unit.In this paper,a definition of the model of complex objects is given,and the concurrency control mechanism of complex objects in WHYMX object-oriented database system is described.

  7. Managing Asynchronous Data in ATLAS's Concurrent Framework

    CERN Document Server

    Leggett, Charles; The ATLAS collaboration

    2016-01-01

    In order to be able to make effective use of emerging hardware, where the amount of memory available to any CPU is rapidly decreasing as the core count continues to rise, ATLAS has begun a migration to a concurrent, multi-threaded software framework, known as AthenaMT. Significant progress has been made in implementing AthenaMT - we can currently run realistic Geant4 simulations on massively concurrent machines. the migration of realistic prototypes of reconstruction workflows is more difficult, given the large amounts of legacy code and the complexity and challenges of reconstruction software. These types of workflows, however, are the types that will most benefit from the memory reduction features of a multi-threaded framework. One of the challenges that we will report on in this paper is the re-design and implementation of several key asynchronous technologies whose behaviour is radically different in a concurrent environment than in a serial one, namely the management of Conditions data and the Detector D...

  8. Effect of Freund's adjuvant on standard dark and pastel mink.

    Science.gov (United States)

    Tabel, H; Ingram, D G

    1971-04-01

    Following a long series of injections of homologous immunoglobulin in complete and incomplete Freund's adjuvant into mink, a moderate elevation in the level of gammaglobulin in the serum was observed in a few animals. Relatively mild pathological changes also were seen in liver, spleen, lymph nodes, lungs and kidney. It is concluded that the injection of Freund's adjuvant, under the experimental conditions described, produced lesions which were readily distinguishable from the lesions characteristic of aleutian disease of mink.

  9. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle;

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  10. Learning impairment in honey bees caused by agricultural spray adjuvants.

    Directory of Open Access Journals (Sweden)

    Timothy J Ciarlo

    Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many

  11. Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

    Science.gov (United States)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

    2013-05-10

    Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations.

  12. Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera, Alvin R. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Cuneo, Kyle C. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Desjardins, Annick [Department of Surgery, Duke University, Durham, North Carolina (United States); Sampson, John H. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States); McSherry, Frances; Herndon, James E. [Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina (United States); Peters, Katherine B. [Department of Surgery, Duke University, Durham, North Carolina (United States); Allen, Karen [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Hoang, Jenny K. [Department of Radiology, Duke University, Durham, North Carolina (United States); Chang, Zheng; Craciunescu, Oana [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Vredenburgh, James J.; Friedman, Henry S. [Department of Surgery, Duke University, Durham, North Carolina (United States); Kirkpatrick, John P., E-mail: john.kirkpatrick@dm.duke.edu [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States)

    2013-08-01

    Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.

  13. Extended field chemoradiation for cervical cancer patients with histologically proven para-aortic lymph node metastases after laparoscopic lymphadenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Marnitz, Simone; Schram, Johanna; Budach, Volker [Charite University Medicine, Department of Radiation Oncology, Berlin (Germany); Sackerer, Irina [Technische Universitaet Muenchen, Department of Radiation Oncology, Muenchen (Germany); Vercellino, Giuseppe Filiberto [University Medicine Berlin, Department of Gynecology, Campus Benjamin Franklin, Berlin (Germany); Sehouli, Jalid [University Medicine Berlin, Department of Gynecology, Campus Benjamin Franklin and Virchow, Berlin (Germany); Koehler, Christhardt [ASKLEPIOS Clinic Hamburg-Harburg, Department of Specialized Surgical and Oncologic Gynecology, Hamburg (Germany)

    2015-05-01

    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.) [German] Ziel dieser Arbeit war es,die onkologischen Ergebnisse und die Toxizitaet der ''Extended-field''-Radiochemotherapie (EFRT) im

  14. Squalene and squalane emulsions as adjuvants.

    Science.gov (United States)

    Allison, A C

    1999-09-01

    Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen. Antigens are added after emulsification so that conformational epitopes are not lost by denaturation and to facilitate manufacture. A Pluronic block copolymer can be added to the squalane or squalene emulsion. Soluble antigens administered in such emulsions generate cytotoxic T lymphocytes able to lyse target cells expressing the antigen in a genetically restricted fashion. Optionally a relatively nontoxic analog of muramyl dipeptide (MDP) or another immunomodulator can be added; however, the dose of MDP must be restricted to avoid systemic side effects in humans. Squalene or squalane emulsions without copolymers or MDP have very little toxicity and elicit potent antibody responses to several antigens in nonhuman primates. They could be used to improve a wide range of vaccines. Squalene or squalane emulsions have been administered in human cancer vaccines, with mild side effects and evidence of efficacy, in terms of both immune responses and antitumor activity.

  15. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity

    Science.gov (United States)

    Watad, Abdulla; David, Paula; Brown, Stav; Shoenfeld, Yehuda

    2017-01-01

    The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto’s thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. PMID:28167927

  16. Radiation Therapy Oncology Group Protocol 02-29: A Phase II Trial of Neoadjuvant Therapy With Concurrent Chemotherapy and Full-Dose Radiation Therapy Followed by Surgical Resection and Consolidative Therapy for Locally Advanced Non-small Cell Carcinoma of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Suntharalingam, Mohan, E-mail: msuntha@umm.edu [Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Paulus, Rebecca [Radiation Therapy Oncology Group, Philadelphia, Pennsylvania (United States); Edelman, Martin J. [Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Krasna, Mark [Cancer Center at St. Joseph Medical Center, Towson, Maryland (United States); Burrows, Whitney [Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland (United States); Gore, Elizabeth [Dept of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wilson, Lynn D. [Dept of Radiation Oncology, Yale School of Medicine, New Haven, Connecticut (United States); Choy, Hak [Dept of Radiation Oncology, University of Texas Southwestern, Dallas, Texas (United States)

    2012-10-01

    Purpose: To evaluate mediastinal nodal clearance (MNC) rates after induction chemotherapy and concurrent, full-dose radiation therapy (RT) in a phase II trimodality trial (Radiation Therapy Oncology Group protocol 0229). Patients and Methods: Patients (n=57) with stage III non-small cell lung cancer (pathologically proven N2 or N3) were eligible. Induction chemotherapy consisted of weekly carboplatin (AUC = 2.0) and paclitaxel 50 mg/m{sup 2}. Concurrent RT was prescribed, with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease. The mediastinum was pathologically reassessed after completion of chemoradiation. The primary endpoint of the study was MNC, with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality. Results: The grade 3/4 toxicities included hematologic 35%, gastrointestinal 14%, and pulmonary 23%. Forty-three patients (75%) were evaluable for the primary endpoint. Twenty-seven patients achieved the primary endpoint of MNC (63%). Thirty-seven patients underwent resection. There was a 14% incidence of grade 3 postoperative pulmonary complications and 1 30-day, postoperative grade 5 toxicity (3%). With a median follow-up of 24 months for all patients, the 2-year overall survival rate was 54%, and the 2-year progression-free survival rate was 33%. The 2-year overall survival rate was 75% for those who achieved nodal clearance, 52% for those with residual nodal disease, and 23% for those who were not evaluable for the primary endpoint (P=.0002). Conclusions: This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease.

  17. TU-G-BRA-06: PET-Based Treatment Response Assessement for Neoadjuvent Chemoradiation for Pancreatic Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dalah, E; Tai, A; Oshima, K; Hall, W; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2015-06-15

    Purpose: To address the limitations of the conventional response evaluation criteria in solid tumors (RECIST), and validate PET response criteria in solid tumors (PERCIST1.0). We analyze the relationship between the pathological treatment response (PTR) and PERCIST1.0 for patients treated with neoadjuvent chemoradiation (nCR) for pancreatic adenocarcinoma. Methods: The pre- and post-nCR CT and PET data for a total of 8 patients with resectable, or borderline resectable pancreatic head adenocarcinoma treated with nCR were retrospectively analyzed. These data were compared with the PTR which were graded according to tumor cell destruction (cellularity), with Grade1, 2 or 3 (G1, G2 or G3) for good, moderate, and poor responses, respectively. RECIST-based PET (RECISTPET), and PERCIST1.0 were defined using lean body mass normalized SUV (nSUVlb). RECIST-based CT (RECISTCT) was defined by contouring the whole pancreas head (CTPH). Pre- and post-nSUVlb and SUVbw, PERCIST 1.0, were correlated with PTR using Pearson’s correlation coefficient test. Results: The average mean and SD in nSUVlb for all 8 patients analyzed were lower in post-nCR (1.35±0.34) compared to those at pre-nCR (1.38±0.20). Using PERCIST1.0, 5/8 patients showed stable metabolic disease (SMD), 2/8 partial metabolic response (PMR), and 1/8 progressive metabolic disease (PMD). Using RECISTPET 4/8 showed stable disease (STD), 4/8 partial response (PR), whereas 8/8 showed stable disease (STD) using RECISTCT. PTR were correlated with PERCIST1.0 (R=0.3780/P=0.6071). Pathological tumor size was correlated with RECISTCT (R=0.0727/P=0.8679), and RECISTPET, R=−0.3333/P=0.3798. Conclusion: Chemoradiation treatment response assessment based on metabolic tumor activities using PRECIST1.0 and RECISTPET appears to provide better agreement with pathological assessment as compared to the conventional CT-based assessment using RECISTCT. The integration of these additional radiographic metrics in assessing treatment

  18. Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dzhugashvili, Maia [Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia (Spain); Department of Radiation Oncology, Madrid Oncology Institute (Group IMO), Murcia (Spain); Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío [Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia (Spain); Conesa-Zamora, Pablo [Department of Pathology, University Hospital Santa Lucía, Cartagena (Spain); Escolar, Pedro Pablo [Department of Radiation Oncology, University Hospital Santa Lucía, Cartagena (Spain); Calvo, Felipe [Department of Radiation Oncology, University General Hospital Gregorio Marañón, Madrid (Spain); Vicente, Vicente [Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia (Spain); Ayala de la Peña, Francisco, E-mail: frayala@um.es [Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia (Spain)

    2014-11-01

    Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.

  19. Evidence-based adjuvant therapy for gliomas: Current concepts and newer developments

    Directory of Open Access Journals (Sweden)

    M K Khan

    2009-01-01

    Full Text Available The incidence of gliomas is increasing worldwide, including India. Of the 18,820 new cases of primary central nervous system (CNS tumors diagnosed annually in the United States, gliomas account for over 60% with 30-40% of them being glioblastoma multiforme (GBM, 10% being anaplastic astrocytoma (AA, and 10% being low grade gliomas (LGGs. This is in contrast to one study from West Bengal, India, in which only 7.9% of the brain tumors were GBMs, while 46.8% were astrocytomas. Of all adult primary CNS tumors, GBM is the most common and the most malignant with about 7,000 to 8,000 new cases annually in the United States. Given poor outcomes, a number of treatment approaches have been investigated. Common to these approaches is the use of adjuvant radiation therapy, even as surgery alone, with or without chemotherapy, may be the mainstay for some lower grade and low-risk gliomas. Today, treatment typically involves external beam radiation, with concurrent and adjuvant chemotherapy for more aggressive histologies. Although gliomas are relatively uncommon, active research is ongoing. Results of landmark trials along with some of the recently published trials are presented. These trials and management strategies as well as evolving concepts are found by reviewing over 200 articles in the National Library Medical (NLM database, PubMed, more than 60 of which are refrenced. Specifically, the database is searched using the following keywords, with various combinations: glioma, low-grade, anaplastic, astrocytoma, oligodendroglioma, oligoastrocytoma, glioblastoma multiforme, chemotherapy, radiation, new concepts, phase III, MGMT, CDX-110 (Celldex, temozolomide, 1p/19q deletion, and bevacizumab.

  20. Creating components object oriented, concurrent, and distributed computing in Java

    CERN Document Server

    Kann, Charles W

    2003-01-01

    INTRODUCTION TO CONCURRENT PROGRAMMING AND COMPONENTSChapter GoalsWhat is Concurrent Programming?ComponentsTypes of Concurrent ProgrammingTHREADS AND PROGRAM CONTEXTSWriting threads in JavaA Simple Execution ModelProgram SafetyDeadlockDESIGNING AND IMPLEMENTING CONCURRENT PROGRAMS WITH STATE DIAGRAMSBackgroundSteps to Create a Concurrent ProgramThe Producer/Consumer ProblemWhy Passive Objects are ComponentsGas Station Simulation ProblemIdentifiers, Variables, Objects, and Collection ClassesIdentifiers and VariablesJava Identifiers and VariablesPrimitivesObjectsCollection Classes in JavaPROGRAM

  1. Adjuvant postoperative radiochemotherapy for patients with gastric carcinoma: a single institution experience

    Institute of Scientific and Technical Information of China (English)

    Manal El-Baradie; Ola Khorshid; Ahmed Touny

    2012-01-01

    months, were 61.2%, 66.7% and 71%, respectively. At 3 and 5 years the corresponding values were: OS (42% and 28%), LRC (64% and 50.4%) and MFS (56.3% and 49%), respectively. Only stage and degree of nodal involvement had an adverse effect on all survival rates. Proximal lesion had poor OS rates. As regard LR control rate, mucinous cell type, and high grade had a bad effect. Although patients with less than D1 dissection had low OS and LRC rate, it didn't reach significant level. There was a significant improved 5-year OS rate for concurrent chemoradiotherapy (CCRTh, 55%) versus no or single adjuvant modality (27%), P = 0.035. A subgroup analysis according to CTH regimen showed a trend for all survival rates with ECF compared to bolus 5FU/LV. However, none was statistically significant. Conclusion: In oper-able gastric carcinoma, postoperative concomitant radiochemotherapy with 5FU and LV is feasible with acceptable toxicity with a significant increase of locoregional control. A well designed phase III clinical trial – with ECF regimen and conformal radiotherapy – is worth to start to increase local control and decrease toxicity.

  2. Concurrent conditional clustering of multiple networks: COCONETS.

    Directory of Open Access Journals (Sweden)

    Sabrina Kleessen

    Full Text Available The accumulation of high-throughput data from different experiments has facilitated the extraction of condition-specific networks over the same set of biological entities. Comparing and contrasting of such multiple biological networks is in the center of differential network biology, aiming at determining general and condition-specific responses captured in the network structure (i.e., included associations between the network components. We provide a novel way for comparison of multiple networks based on determining network clustering (i.e., partition into communities which is optimal across the set of networks with respect to a given cluster quality measure. To this end, we formulate the optimization-based problem of concurrent conditional clustering of multiple networks, termed COCONETS, based on the modularity. The solution to this problem is a clustering which depends on all considered networks and pinpoints their preserved substructures. We present theoretical results for special classes of networks to demonstrate the implications of conditionality captured by the COCONETS formulation. As the problem can be shown to be intractable, we extend an existing efficient greedy heuristic and applied it to determine concurrent conditional clusters on coexpression networks extracted from publically available time-resolved transcriptomics data of Escherichia coli under five stresses as well as on metabolite correlation networks from metabolomics data set from Arabidopsis thaliana exposed to eight environmental conditions. We demonstrate that the investigation of the differences between the clustering based on all networks with that obtained from a subset of networks can be used to quantify the specificity of biological responses. While a comparison of the Escherichia coli coexpression networks based on seminal properties does not pinpoint biologically relevant differences, the common network substructures extracted by COCONETS are supported by

  3. Enteral Feeding Tubes in Patients Undergoing Definitive Chemoradiation Therapy for Head-and-Neck Cancer: A Critical Review

    Energy Technology Data Exchange (ETDEWEB)

    Koyfman, Shlomo A., E-mail: koyfmas@ccf.org [Departments of Radiation and Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Adelstein, David J. [Departments of Radiation and Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States)

    2012-11-01

    Definitive chemoradiation therapy has evolved as the preferred organ preservation strategy in the treatment of locally advanced head-and-neck cancer (LA-HNC). Dry mouth and dysphagia are among the most common and most debilitating treatment-related toxicities that frequently necessitate the placement of enteral feeding tubes (FT) in these patients to help them meet their nutritional requirements. The use of either a percutaneous endoscopic gastrostomy tube or a nasogastric tube, the choice of using a prophylactic vs a reactive approach, and the effects of FTs on weight loss, hospitalization, quality of life, and long-term functional outcomes are areas of continued controversy. Considerable variations in practice patterns exist in the United States and abroad. This critical review synthesizes the current data for the use of enteral FTs in this patient population and clarifies the relative advantages of different types of FTs and the timing of their use. Recent developments in the biologic understanding and treatment approaches for LA-HNC appear to be favorably impacting the frequency and severity of treatment-related dysphagia and may reduce the need for enteral tube feeding in the future.

  4. Tumor microcirculation during a course of combined chemoradiation in patients with primary rectal carcinoma measured with dynamic T1 mapping

    Science.gov (United States)

    Kremser, Christian; Judmaier, Werner; De Vries, Alexander

    2003-05-01

    A recently introduced dynamic T1 mapping technique was used to investigate changes of tumor microcirculatory parameters in 16 patients with clinically staged T3) primary rectal carcinoma during a course of preoperative combined chemoradiation. For dynamic T1 mapping an ultra-fast snapshot FLASH T1 mapping sequence was implemented on a 1.5T whole body MR scanner. Acquiring a series of T1 maps contrast media (CM) uptake and washout over an examination time of 40 min was monitored. From the obtained series of T1-maps perfusion-indices (PI) were calculated as the ratio of maximum slope of the tumor CM curve and the maximum of the arterial CM curve. Using pathologic classification of the resected tumors after therapy the patient group could be divided into patients with and without response to therapy. It was found that mean pre-therapy PI values of tumors showing therapy-response were significantly lower than for tumors without no therapy-response. In addition a different behavior of PI distributions within tumors for both groups was observed. The presented study indicates that PI values and their distributions within a tumor seem to be of predictive value for therapy outcome of preoperative therapy in patients with primary rectal carcinoma.

  5. Concurrency-based approaches to parallel programming

    Science.gov (United States)

    Kale, L.V.; Chrisochoides, N.; Kohl, J.; Yelick, K.

    1995-01-01

    The inevitable transition to parallel programming can be facilitated by appropriate tools, including languages and libraries. After describing the needs of applications developers, this paper presents three specific approaches aimed at development of efficient and reusable parallel software for irregular and dynamic-structured problems. A salient feature of all three approaches in their exploitation of concurrency within a processor. Benefits of individual approaches such as these can be leveraged by an interoperability environment which permits modules written using different approaches to co-exist in single applications.

  6. Concurrent Kimura disease and lupus nephritis

    Science.gov (United States)

    Wang, Haitao; Fang, Fang; Sun, Ying; Wang, Songlan; Mao, Yonghui

    2016-01-01

    Abstract Background: Kimura disease is a rare chronic inflammatory disorder with peripheral eosinophilia and elevated serum IgE and is also frequently complicated by nephropathy. Methods: We report a rare case of Kimura disease concomitant with lupus nephritis in a 72-year old male patient with recurrent unexplained lymphadenopathy, renal lesions, and immunologic abnormalities. Results: The patient was successfully managed with gamma immunoglobulin, intravenous pulse methylprednisolone therapy, hydroxychloroquine, and prednisone. Conclusion: This is the first report of a case of Kimura disease concomitant with lupus nephritis and highlights the importance of considering lupus nephritis as a possible concurrent disease in patients with Kimura disease that have immunologic abnormalities. PMID:27741124

  7. Reliability-based concurrent subspace optimization method

    Institute of Scientific and Technical Information of China (English)

    FAN Hui; LI Wei-ji

    2008-01-01

    To avoid the high computational cost and much modification in the process of applying traditional re-liability-based design optimization method, a new reliability-based concurrent subspace optimization approach is proposed based on the comparison and analysis of the existing muhidisciplinary optimization techniques and reli-ability assessment methods. It is shown through a canard configuration optimization for a three-surface transport that the proposed method is computationally efficient and practical with the least modification to the current de-terministic optimization process.

  8. Concurrency control in distributed database systems

    CERN Document Server

    Cellary, W; Gelenbe, E

    1989-01-01

    Distributed Database Systems (DDBS) may be defined as integrated database systems composed of autonomous local databases, geographically distributed and interconnected by a computer network.The purpose of this monograph is to present DDBS concurrency control algorithms and their related performance issues. The most recent results have been taken into consideration. A detailed analysis and selection of these results has been made so as to include those which will promote applications and progress in the field. The application of the methods and algorithms presented is not limited to DDBSs but a

  9. Postoperative chemoradiation in patients with localized gastric adenocarcinoma: Single center experience

    Directory of Open Access Journals (Sweden)

    A Yoney

    2011-01-01

    Full Text Available Background : 5-Flourouracil (FU-based chemotherapy (CT and concurrent 45 Gy radiotherapy (RT is one of the standard postoperative approaches currently used in gastric carcinoma. The high toxicity rates of this treatment leads to interruption of treatment in the majority of patients. In our study, we investigated the rates of toxicity and treatment discontinuation observed during postoperative FU-based chemoradiotherapy (CRT; retrospectively evaluated the effect of CRT and the other prognostic factors on local and distant control and survival. Patients and Methods: A total of 160 patients consisting of 97 total and 63 subtotal gastrectomy receiving postoperative CRT, have been studied retrospectively. Results : Patients who had to discontinue the treatment for a median of 6 (range, 3-13 days experienced toxicity during treatment at a rate of 43%. During the 21 (range, 4-68 months of follow-up local recurrences were observed in 8 (5% patients and distant recurrences were observed in 41 (25.6% patients. While the 1-3 year overall survival (OS rates were 75% and 42%, 13-year disease-free survival (DFS rates were 63% and 42%, respectively. In the univariate analysis for OS and DFS demonstrated statistical significance for below those 60 years of age, D1-D2 dissection type, negative surgical margin, early treatment beginning, the absence of invasion, and early stage disease. D1D2 dissection type, early treatment begining, age below 60 years and early stage disease significantly improve OS and DFS in multivarite analysis. Conclusions: Survival is worse in patients older than 60 years, had late treatment begining, advanced stage and D0 dissection.

  10. Clinical Behaviors and Outcomes for Adenocarcinoma or Adenosquamous Carcinoma of Cervix Treated by Radical Hysterectomy and Adjuvant Radiotherapy or Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yi-Ting; Wang, Chun-Chieh; Tsai, Chien-Sheng [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China); Lai, Chyong-Huey; Chang, Ting-Chang; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Lee, Steve P. [Department of Radiation Oncology, University of California, Los Angeles School of Medicine, Los Angeles, CA (United States); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Lin-Kou, Chang Gung University, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan, Taiwan (China)

    2012-10-01

    Purpose: To compare clinical behaviors and treatment outcomes between patients with squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix treated with radical hysterectomy (RH) and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods and Materials: A total of 318 Stage IB-IIB cervical cancer patients, 202 (63.5%) with SCC and 116 (36.5%) with AC/ASC, treated by RH and adjuvant RT/CCRT, were included. The indications for RT/CCRT were deep stromal invasion, positive resection margin, parametrial invasion, or lymph node (LN) metastasis. Postoperative CCRT was administered in 65 SCC patients (32%) and 80 AC/ASC patients (69%). Patients with presence of parametrial invasion or LN metastasis were stratified into a high-risk group, and the rest into an intermediate-risk group. The patterns of failure and factors influencing survival were evaluated. Results: The treatment failed in 39 SCC patients (19.3%) and 39 AC/ASC patients (33.6%). The 5-year relapse-free survival rates for SCC and AC/ASC patients were 83.4% and 66.5%, respectively (p = 0.000). Distant metastasis was the major failure pattern in both groups. After multivariate analysis, prognostic factors for local recurrence included younger age, parametrial invasion, AC/ASC histology, and positive resection margin; for distant recurrence they included parametrial invasion, LN metastasis, and AC/ASC histology. Compared with SCC patients, those with AC/ASC had higher local relapse rates for the intermediate-risk group but a higher distant metastasis rate for the high-risk group. Postoperative CCRT tended to improve survival for intermediate-risk but not for high-risk AC/ASC patients. Conclusions: Adenocarcinoma/adenosquamous carcinoma is an independent prognostic factor for cervical cancer patients treated by RH and postoperative RT. Concurrent chemoradiotherapy could improve survival for intermediate-risk, but not necessarily high-risk, AC/ASC patients.

  11. Regulatory considerations on new adjuvants and delivery systems.

    Science.gov (United States)

    Sesardic, D

    2006-04-12

    New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

  12. Environmental adjuvants, apoptosis and the censorship over autoimmunity.

    Science.gov (United States)

    Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

    2005-11-01

    Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

  13. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    Directory of Open Access Journals (Sweden)

    Juliana De Souza Rebouças

    2012-01-01

    Full Text Available In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  14. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    Science.gov (United States)

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  15. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    Science.gov (United States)

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  16. Adjuvants for Clostridium tetani and Clostridium diphtheriae vaccines updating.

    Science.gov (United States)

    Alshanqiti, Fatimah M; Al-Masaudi, Saad B; Al-Hejin, Ahmed M; Redwan, Elrashdy M

    2017-01-01

    It's known that diphtheria and tetanus are a contagious lethal diseases over the years, they caused by pathogenic microbes corynebacterium diphtheria and Clostridium tetani, respectively. The diseases result from the production of bacterial toxin. Vaccination with bacterial toxoid vaccines adsorbed on particulates adjuvants still are the best way to prevent this epidemic diseases from spread. The particulate vaccines have been shown to be more efficient than soluble one for the induction of the immune responses. Nanoparticles can be engineered to enhance the immune responses. As well known the immune response to inactivate killed and subunit vaccine enhances by alum adjuvants. The adjuvants examined and tested after reducing its size to particle size, thus mimic size of viruses which is considered smallest units can derive the immune system. The major issue is minimizing the adjuvant particles, to gain insight of resulting immunity types and impact on immune response. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into antigen presenting cells.

  17. Concurrent bilateral ectopic pregnancy: a rarity

    Directory of Open Access Journals (Sweden)

    Prabhleen Kaur

    2015-08-01

    Full Text Available Bilateral ectopic pregnancy is a rare twin gestation with only a few cases reported in the literature. We report a 30 year old woman without any high risk factor for ectopic pregnancy, who had concurrent bilateral ectopic pregnancy. A 30 year old female presented to the Gynecology emergency department complaining of vaginal bleeding and abdominal pain. The presumptive diagnosis of ruptured left sided ectopic pregnancy was made on basis of clinical findings and ultrasound finings. An emergency laparotomy was done revealed a hemoperitoneum of 1.5 liters, a ruptured left tubal pregnancy with active bleeding and right tubal un-ruptured ectopic was found. A bilateral salpingectomy was performed. Histopathology confirmed presence of chorionic villi in both tubes. In theory, laparoscopic salpingostomy is the best surgical approach in bilateral tubal pregnancy. However, bilateral salpingectomy may be necessary when both tubes are extensively damaged or are actively bleeding. Successful pregnancies have been reported after conservative surgical treatment of bilateral ectopic, but the risk of recurrence is high. Our decision for an emergency laparotomy followed by bilateral salpingectomy was based on the fact that the patient presented with acute abdomen and was haemodynamically unstable and there was extensive bilateral tubal damage. As the incidence of ectopic pregnancies is increasing concurrently with the incidences of pelvic inflammatory disease and use of assisted fertility techniques; it may be that these and ldquo;rare ectopics and rdquo; will become less uncommon. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1197-1199

  18. Concurrent work with parents of adolescent patients.

    Science.gov (United States)

    Novick, Kerry Kelly; Novick, Jack

    2013-01-01

    Over the last ten years we have seen an increasing acceptance of the general idea of working with parents of child patients. What remains, however, as an area of controversy, conflict, and resistance, is the question of whether and how much therapists should or can work with the parents of adolescent patients. Questions cluster around how to maintain confidentiality and lead to the even larger issue of conceptualizing the developmental goals of the phase of adolescence. We see the major developmental tasks for both parents and adolescents as involving transformation of the self and the relationship, in the context of separateness rather than separation. If adolescent therapists work from the assumption that the goal of adolescence is transformation, concurrent work with parents and adolescents will move them all into a new level of relationship. Without concomitant change in parents, it is doubly hard for adolescents to progress into adulthood. In this paper we offer clinical material from five older adolescents and their parents to illustrate the techniques that follow from our model of dynamic concurrent parent work throughout the phases of treatment. Using the tasks of the therapeutic alliance as a conceptual framework, we describe working toward the dual goals of restoration to the path of progressive development and restoration of the parent-child relationship. We pay particular attention to the unfolding of conflicts between closed-system omnipotent functioning and open-system reality mastery, and the role offathers in late-adolescent development.

  19. Concurrent initialization for Bearing-Only SLAM.

    Science.gov (United States)

    Munguía, Rodrigo; Grau, Antoni

    2010-01-01

    Simultaneous Localization and Mapping (SLAM) is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range) cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras) in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes.

  20. Artificial concurrent catalytic processes involving enzymes.

    Science.gov (United States)

    Köhler, Valentin; Turner, Nicholas J

    2015-01-11

    The concurrent operation of multiple catalysts can lead to enhanced reaction features including (i) simultaneous linear multi-step transformations in a single reaction flask (ii) the control of intermediate equilibria (iii) stereoconvergent transformations (iv) rapid processing of labile reaction products. Enzymes occupy a prominent position for the development of such processes, due to their high potential compatibility with other biocatalysts. Genes for different enzymes can be co-expressed to reconstruct natural or construct artificial pathways and applied in the form of engineered whole cell biocatalysts to carry out complex transformations or, alternatively, the enzymes can be combined in vitro after isolation. Moreover, enzyme variants provide a wider substrate scope for a given reaction and often display altered selectivities and specificities. Man-made transition metal catalysts and engineered or artificial metalloenzymes also widen the range of reactivities and catalysed reactions that are potentially employable. Cascades for simultaneous cofactor or co-substrate regeneration or co-product removal are now firmly established. Many applications of more ambitious concurrent cascade catalysis are only just beginning to appear in the literature. The current review presents some of the most recent examples, with an emphasis on the combination of transition metal with enzymatic catalysis and aims to encourage researchers to contribute to this emerging field.

  1. Concurrent Initialization for Bearing-Only SLAM

    Directory of Open Access Journals (Sweden)

    Antoni Grau

    2010-03-01

    Full Text Available Simultaneous Localization and Mapping (SLAM is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes.

  2. Concurrent Engineering Working Group White Paper Distributed Collaborative Design: The Next Step in Aerospace Concurrent Engineering

    Science.gov (United States)

    Hihn, Jairus; Chattopadhyay, Debarati; Karpati, Gabriel; McGuire, Melissa; Panek, John; Warfield, Keith; Borden, Chester

    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 of performance, cost and schedule. To successfully accomplish these complex missions with limited funding, it is 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. The purpose of this white paper is to identify a near-term vision for the future of distributed collaborative concurrent engineering design for aerospace missions as well as discuss the challenges to achieving that vision. The white paper also documents the advantages of creating a working group to investigate how to engage the expertise of different teams in joint design sessions while enabling organizations to maintain their organizations competitive advantage.

  3. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chun-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China); Lai, Chyong-Huey [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Huang, Yi-Ting [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Chao, Angel; Chou, Hung-Hsueh [Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Hong, Ji-Hong, E-mail: jihong@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan (China); Department of Medical Imaging and Radiological Science, Chang Gung University, School of Medicine, Taoyuan, Taiwan (China)

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  4. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  5. Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

    Institute of Scientific and Technical Information of China (English)

    Yan-li LIU; Hai-ming LIN; Rong ZOU; Jun-chao WU; Rong HAN; Laurence N RAYMOND; Paul F REID; Zheng-hong QIN

    2009-01-01

    Aim:Cobratoxin (CTX),the long-chain α-neurotoxin from Thailand cobra venom,has been demonstrated to have analgesic action in rodent pain models.The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adju-vant arthritis (AA) in rats.Methods: Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats.Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration.Tumor necrosis factor-a (TNF-α),interleukin-1 (IL-1),interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA.Histopathological changes in synoviocytes were examined under a microscope.Involvement of the cholinergic system in the effects of CTX was examinedby pretreatment of animals with the α7 nicotinic receptor (α7-nAChR) antagonist methyllycaconitine (MLA).Results: CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal.The lev-els of TNF-α,IL-1 and IL-2 in the serum of AA rats were increased,whereas the level of IL-10 was decreased.Histopathologi-cal examination of synoviocytes showed pronounced inflammation and accumulation of collagen.The administration of CTX (17.0 μg/kg,ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia.CTX also reduced the produc-tion ofTNF-α,IL-1,and IL-2 but increased the production of IL-10 and altered pathohistological changes.The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg,sc).Conclusion: These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines,α7-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

  6. The immunobiology of aluminium adjuvants: how do they really work?

    Science.gov (United States)

    Exley, Christopher; Siesjö, Peter; Eriksson, Håkan

    2010-03-01

    Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.

  7. Simultaneous Integrated Boost Using Intensity-Modulated Radiotherapy Compared With Conventional Radiotherapy in Patients Treated With Concurrent Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Clavel, Sebastien, E-mail: sebastien.clavel@umontreal.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen, David H.A.; Fortin, Bernard [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Despres, Philippe [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Khaouam, Nader [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada); Donath, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Soulieres, Denis [Department of Medical Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Guertin, Louis [Department of Head and Neck Surgery, Centre Hospitalier de l' Universite de Montreal, Montreal, QC (Canada); Nguyen-Tan, Phuc Felix [Department of Radiation Oncology, Hopital Maisonneuve-Rosemont, Montreal, QC (Canada)

    2012-02-01

    Purpose: To compare, in a retrospective study, the toxicity and efficacy of simultaneous integrated boost using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) in patients treated with concomitant carboplatin and 5-fluorouracil for locally advanced oropharyngeal cancer. Methods and Materials: Between January 2000 and December 2007, 249 patients were treated with definitive chemoradiation. One hundred patients had 70 Gy in 33 fractions using IMRT, and 149 received CRT at 70 Gy in 35 fractions. Overall survival, disease-free survival, and locoregional control were estimated using the Kaplan-Meier method. Results: Median follow-up was 42 months. Three-year actuarial rates for locoregional control, disease-free survival, and overall survival were 95.1% vs. 84.4% (p = 0.005), 85.3% vs. 69.3% (p = 0.001), and 92.1% vs. 75.2% (p < 0.001) for IMRT and CRT, respectively. The benefit of the radiotherapy regimen on outcomes was also observed with a Cox multivariate analysis. Intensity-modulated radiotherapy was associated with less acute dermatitis and less xerostomia at 6, 12, 24, and 36 months. Conclusions: This study suggests that simultaneous integrated boost using IMRT is associated with favorable locoregional control and survival rates with less xerostomia and acute dermatitis than CRT when both are given concurrently with chemotherapy.

  8. Concurrent radiochemotherapy in advanced hypopharyngeal cancer

    Directory of Open Access Journals (Sweden)

    Lukarski Dusko

    2010-05-01

    Full Text Available Abstract Background Concurrent platinum-based radiochemotherapy has been recommended as a standard of care in patients with locally advanced squamous cell head and neck carcinomas. Unfortunately, there is a lack of level one evidence on best treatment approach for advanced hypopharyngeal cancer. This report aims to summarize the results of our study on concurrent radiochemotherapy in patients with advanced hypopharyngeal cancer. Methods A retrospective analysis of 41 patients with stage III-IV hypopharyngeal cancer was performed. All patients were treated with three dimensional conformal radiotherapy and received 70 Gy in 35 fractions (2 Gy per fraction, 5 fractions per week. In dependence of the period when radiotherapy was realized, two different treatment techniques were used. Concurrent chemotherapy consisted of cisplatin 30 mg/m2 given on a weekly basis. Results The median age was 52 years (range 29-70. Stage IV disease was recognized in 73.2% of the patients. Complete response rates at the primary site and at the metastatic neck lymph nodes were 68.3% and 36.6%, respectively. A complete composite response was present in 27 patients (65.9%. Median follow-up was 13 months (range 7-36. Distant metastases as initial failure occurred in 7 patients (46.7%. The 2-year local relapse-free survival and regional relapse-free survival rates were 55.2% and 75.8%, respectively. The 2-year locoregional relapse-free survival rate was 51.3%. The 2-year disease-free survival and overall survival rates were 29.3% and 32.8%, respectively. Confluent mucositis was developed in 46.3% of patients. Leucopenia grade 1 was the most frequent hematological toxicity. The median weight loss at the end of treatment was 12% (range 5-21. The worst grade of late toxicity was most commonly pronounced in the skin and in the subcutaneous tissue. Conclusions Based on unsatisfactory results in our study we suggest that the use of sequential radiochemotherapy or chemotherapy

  9. Modeling disease spread in populations with birth, death, and concurrency

    CERN Document Server

    Millera, Joel C

    2016-01-01

    The existence of sexual partnerships that overlap in time (concurrent relationships) is believed by some to be a significant contributing factor to the spread of HIV, although this is controversial. We derive an analytic model which allows us to investigate and compare disease spread in populations with and without concurrency. We can identify regions of parameter space in which its impact is negligible, and other regions in which it plays a major role. We also see that the impact of concurrency on the initial growth phase can be much larger than its impact on the equilibrium size. We see that the effect of concurrency saturates, which leads to the perhaps surprising conclusion that interventions targeting concurrency may be most effective in populations with low to moderate levels of concurrency.

  10. Correlation between Trichomonas vaginalis and Concurrency: An Ecological Study.

    Science.gov (United States)

    Kenyon, Chris R; Hamilton, Deven T

    2016-01-01

    Objective. There is a large variation in the prevalence of Trichomonas vaginalis (TV) between different countries and between racial groups within countries. Sexual partner concurrency may play a role. We investigate the correlation between the prevalence of sexual partner concurrency and TV prevalence. Methods. Spearman's correlation to assess relationship between TV prevalence in women and point prevalence of concurrency in men in (1) 11 countries with comparable data (concurrency data from WHO Survey and TV prevalence data from Global Burden of Disease estimates) and (2) three racial groups in the United States (Add Health Study). Results. The prevalence of TV and concurrency was positively correlated in the international (rho = 0.84, P = 0.001) and USA study (rho = 1.0, P < 0.001). Conclusion. Prospective longitudinal studies that include measures of partner behavior are required to definitively establish the role of concurrency in the spread of TV.

  11. Aluminium: a natural adjuvant in Leishmania transmission via sand flies?

    Science.gov (United States)

    Maingon, Rhayza; Khela, Amandeep; Sampson, Christopher; Ward, Richard; Walker, Karen; Exley, Christopher

    2008-11-01

    Genetically identical Leishmania chagasi/infantum parasites cause both atypical cutaneous leishmaniasis and visceral leishmaniasis. In this report we have tested the first part of a hypothesis that states that the form of this disease that is manifested depends upon the adjuvant-like activity of aluminium of dietary origin accumulated in the salivary gland of the sand fly vector. In sand flies fed aluminium-supplemented sucrose we have used histochemistry to qualitatively identify aluminium in their salivary glands and graphite furnace atomic absorption spectrometry to quantify the aluminium content of dissected salivary glands. Aluminium may be acting as a natural adjuvant in some forms of leishmaniasis.

  12. Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study

    DEFF Research Database (Denmark)

    Kirchheiner, Kathrin; Pötter, Richard; Tanderup, Kari

    2016-01-01

    Purpose This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study. Methods and Materials In total, 744...... patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during...

  13. Certifying Concurrent Programs Using Transactional Memory

    Institute of Scientific and Technical Information of China (English)

    Long Li; Yu Zhang; Yi-Yun Chen; Yong Li

    2009-01-01

    Transactional memory (TM) is a new promising concurrency-control mechanism that can avoid many of the pitfalls of the traditional lock-based techniques. TM systems handle data races between threads automatically so that programmers do not have to reason about the interaction of threads manually. TM provides a programming model that may make the development of multi-threaded programs easier. Much work has been done to explore the various implementation strategies of TM systems and to achieve better performance, but little has been done on how to formally reason about programs using TM and how to make sure that such reasoning is sound. In this paper, we focus on the semantics of transactional memory and present a proof-carrying code (PCC) system for reasoning about programs using TM . We formalize our reasoning with respect to the TM semantics, prove its soundness, and use examples to demonstrate its effectiveness.

  14. Mining Concurrent Topical Activity in Microblog Streams

    CERN Document Server

    Panisson, A; Quaggiotto, M; Cattuto, C

    2014-01-01

    Streams of user-generated content in social media exhibit patterns of collective attention across diverse topics, with temporal structures determined both by exogenous factors and endogenous factors. Teasing apart different topics and resolving their individual, concurrent, activity timelines is a key challenge in extracting knowledge from microblog streams. Facing this challenge requires the use of methods that expose latent signals by using term correlations across posts and over time. Here we focus on content posted to Twitter during the London 2012 Olympics, for which a detailed schedule of events is independently available and can be used for reference. We mine the temporal structure of topical activity by using two methods based on non-negative matrix factorization. We show that for events in the Olympics schedule that can be semantically matched to Twitter topics, the extracted Twitter activity timeline closely matches the known timeline from the schedule. Our results show that, given appropriate techn...

  15. Distributed Management of Concurrent Web Service Transactions

    DEFF Research Database (Denmark)

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

    2009-01-01

    Business processes involve dynamic compositions of interleaved tasks. Therefore, ensuring reliable transactional processing of Web services is crucial for the success of Web service-based B2B and B2C applications. But the inherent autonomy and heterogeneity of Web services render the applicability...... of conventional ACID transaction models for Web services far from being straightforward. Current Web service transaction models relax the isolation property and rely on compensation mechanisms to ensure atomicity of business transactions in the presence of service failures. However, ensuring 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...

  16. Concurrent Imitation Dynamics in Congestion Games

    CERN Document Server

    Ackermann, Heiner; Fischer, Simon; Hoefer, Martin

    2008-01-01

    Imitating successful behavior is a natural and frequently applied approach to trust in when facing scenarios for which we have little or no experience upon which we can base our decision. In this paper, we consider such behavior in atomic congestion games. We propose to study concurrent imitation dynamics that emerge when each player samples another player and possibly imitates this agents' strategy if the anticipated latency gain is sufficiently large. Our main focus is on convergence properties. Using a potential function argument, we how that our dynamics converge in a monotonic fashion to stable states. In such a state none of the players can improve its latency by imitating somebody else. As our main result, we show rapid convergence to approximate equilibria. At an approximate equilibrium only a small fraction of agents sustains a latency significantly above or below average. In particular, imitation dynamics behave like fully polynomial time approximation schemes (FPTAS). Fixing all other parameters, t...

  17. Concurrent remote entanglement with continuous variables

    Science.gov (United States)

    Zalys-Geller, E.; Narla, A.; Shankar, S.; Hatridge, M.; Silveri, M.; Sliwa, K. M.; Mundhada, S. O.; Girvin, S. M.; Devoret, M. H.

    A necessary ingredient for large scale quantum information processing is the ability to entangle distant qubits on demand. In the field of superconducting quantum information, this process can be achieved by entangling stationary superconducting qubits with flying coherent states of microwave light, which are then co-amplified by a Josephson Parametric Converter (JPC). The JPC also serves as a which-path information eraser, causing the probabilistic continuous measurement process to concurrently entangle the qubits. We discuss the sensitivity of the experiment to the loss of quantum information during the flight of the coherent states, as well as strategies to improve which-path information erasure and reduce information loss to the degree required for entanglement generation. Work supported by ARO, AFOSR, NSF, and YINQE.

  18. An Efficient Secure Real-Time Concurrency Control Protocol

    Institute of Scientific and Technical Information of China (English)

    XIAO Yingyuan; LIU Yunsheng; CHEN Xiangyang

    2006-01-01

    Secure real-time databases must simultaneously satisfy two requirements in guaranteeing data security and minimizing the missing deadlines ratio of transactions. However, these two requirements can conflict with each other and achieve one requirement is to sacrifice the other. This paper presents a secure real-time concurrency control protocol based on optimistic method. The concurrency control protocol incorporates security constraints in a real-time optimistic concurrency control protocol and makes a suitable tradeoff between security and real-time requirements by introducing secure influence factor and real-time influence factor. The experimental results show the concurrency control protocol achieves data security without degrading real-time performance significantly.

  19. Concurrence vectors for entanglement of high dimensional systems

    Institute of Scientific and Technical Information of China (English)

    You-quan LI; Guo-qiang ZHU

    2008-01-01

    The concurrence vectors are proposed by employing the fundamental representation of An Lie algebra,which provides a clear criterion to evaluate the entanglement of bipartite systems of arbitrary dimension.Accordingly,a state is separable if the norm of its concurrence vector vanishes.The state vectors related to SU(3)states and SO(3) states are discussed in detail.The sign situation of nonzero components of concurrence vectors of entangled bases presents a simple criterion to judge whether the whole Hilbert subspace spanned by those bases is entangled,or there exists an entanglement edge.This is illustrated in terms of the concurrence surfaces of several concrete examples.

  20. Four-Week Neoadjuvant Intensity-Modulated Radiation Therapy With Concurrent Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer Patients: A Validation Phase II Trial

    Energy Technology Data Exchange (ETDEWEB)

    Arbea, Leire, E-mail: larbea@unav.es [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Martinez-Monge, Rafael; Diaz-Gonzalez, Juan A.; Moreno, Marta; Rodriguez, Javier [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Hernandez, Jose Luis [Department of General Surgery, Clinica Universidad de Navarra, Navarra (Spain); Sola, Jesus Javier [Department of Pathology, Clinica Universidad de Navarra, Navarra (Spain); Ramos, Luis Isaac [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Subtil, Jose Carlos [Department of Gastroenterology, Clinica Universidad de Navarra, Navarra (Spain); Nunez, Jorge [Department of Preventive Medicine and Public Health, Clinica Universidad de Navarra, Navarra (Spain); Chopitea, Ana; Cambeiro, Mauricio; Gaztanaga, Miren; Garcia-Foncillas, Jesus; Aristu, Javier [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain)

    2012-06-01

    Purpose: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. Methods and Materials: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m{sup 2} b.i.d., Monday to Friday) and oxaliplatin (60 mg/m{sup 2} on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. Results: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. Conclusions: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.

  1. Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Varveris, H.; Kachris, S.; Lyraraki, E.; Petineli, E.; Varveris, A.; Fasoulaki, A. [Dept. of Radiotherapy and Oncology, Medical School of Crete Univ., Iraclion Univ. Hospital (Greece); Mazonakis, M.; Tzedakis, A. [Dept. of Medical Physics, Medical School of Crete Univ., Iraclion Univ. Hospital (Greece); Kouloulias, V. [Dept. of Radiotherapy and Oncology, Medical School of Athens Univ. (Greece); Zolindaki, A. [Dept. of Obstetrics and Gynecology, Medical School of Crete Univ., Iraclion Univ. Hospital (Greece); Vlachaki, M. [New York Univ. Medical Center, NY (United States)

    2006-03-15

    Background and Purpose: although the standard of care for patients with locally advanced uterine cervix carcinoma is cisplatin-(CDDP-)based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. Patients and Methods: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m{sup 2}/week was increased in 5-mg/m{sup 2} increments to two levels. The standard dose of CDDP was 20-25 mg/m{sup 2}/week. Results: concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m{sup 2}/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). Conclusion: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m{sup 2}/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising. (orig.)

  2. Phase I study of celecoxib with concurrent irinotecan, cisplatin, and radiation therapy for patients with unresectable locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ritsuko eKomaki

    2011-12-01

    Full Text Available Purpose: Preclinical findings suggest that adding targeted therapies to combination radiation-chemotherapy can enhance treatment efficacy; however, this approach may enhance normal tissue toxicity. We investigated the maximum tolerated dose, dose-limiting toxicities, and response rate when the selective cyclo-oxygenase-2 inhibitor celecoxib is added to concurrent irinotecan, cisplatin, and radiation therapy for patients with inoperable stage II-III non-small cell lung cancer. Methods and materials: Eighteen patients were analyzed in a phase I clinical dose-escalation trial. Celecoxib was given daily beginning 5 days before radiation followed by maintenance doses for 12 weeks. Toxicity was graded with the Common Terminology Criteria for Adverse Events V3.0 and response with the World Health Organization system. Primary endpoints were maximum tolerated dose of celecoxib and treatment toxicity; secondary endpoints were response and survival rates. Results: The maximum tolerated dose of celecoxib was not reached, in part owing to discontinuation of the drug supply. At doses of 200 or 400 mg/day, no patients experienced any dose-limiting toxicity (acute grade ≥4 esophagitis or pneumonitis, neutropenic fever or thrombocytopenia requiring transfusion, or acute grade ≥3 diarrhea. Grade 3 toxicities were leukopenia (5 patients, fatigue (3, pneumonitis (2, dyspnea (1, pain (1, and esophageal stricture (1. Interestingly, pulmonary fibrosis (a late toxicity was no more severe in the higher-dose (400-mg group and may have been less common than in the lower-dose group. The clinical response rate was 100% (8 complete, 10 partial. Two-year rates were: overall survival 65%; local-regional control 69%; distant metastasis-free survival 71%; and disease-free survival 64%. Conclusions: Although preliminary, our results suggest that adding celecoxib to concurrent chemoradiation for inoperable NSCLC is safe and can improve outcome without increasing normal tissue

  3. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  4. Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Ye J. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Chan W. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Seon A. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Cho, Dong H. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Park, Jong L.; Kim, Seon Y. [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Kim, Jong H. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun K. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Yong S., E-mail: yongsung@kribb.re.kr [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Jin C., E-mail: jckim@amc.seoul.kr [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

    2015-03-01

    Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.

  5. Novel Single-Nucleotide Polymorphism Markers Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin C., E-mail: jckim@amc.seoul.kr [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Ha, Ye J.; Roh, Seon A. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Cho, Dong H. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-do (Korea, Republic of); Choi, Eun Y. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Tae W. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Department of Internal Medicine, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Jong H. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kang, Tae W. [Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Kim, Seon Y. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Kim, Yong S., E-mail: yongsung@kribb.re.kr [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of)

    2013-06-01

    Purpose: Studies aimed at predicting individual responsiveness to preoperative chemoradiation therapy (CRT) are urgently needed, especially considering the risks associated with poorly responsive patients. Methods and Materials: A 3-step strategy for the determination of CRT sensitivity is proposed based on (1) the screening of a human genome-wide single-nucleotide polymorphism (SNP) array in correlation with histopathologic tumor regression grade (TRG); (2) clinical association analysis of 113 patients treated with preoperative CRT; and (3) a cell-based functional assay for biological validation. Results: Genome-wide screening identified 9 SNPs associated with preoperative CRT responses. Positive responses (TRG 1-3) were obtained more frequently in patients carrying the reference allele (C) of the SNP CORO2A rs1985859 than in those with the substitution allele (T) (P=.01). Downregulation of CORO2A was significantly associated with reduced early apoptosis by 27% (P=.048) and 39% (P=.023) in RKO and COLO320DM colorectal cancer cells, respectively, as determined by flow cytometry. Reduced radiosensitivity was confirmed by colony-forming assays in the 2 colorectal cancer cells (P=.034 and .015, respectively). The SNP FAM101A rs7955740 was not associated with radiosensitivity in the clinical association analysis. However, downregulation of FAM101A significantly reduced early apoptosis by 29% in RKO cells (P=.047), and it enhanced colony formation in RKO cells (P=.001) and COLO320DM cells (P=.002). Conclusion: CRT-sensitive SNP markers were identified using a novel 3-step process. The candidate marker CORO2A rs1985859 and the putative marker FAM101A rs7955740 may be of value for the prediction of radiosensitivity to preoperative CRT, although further validation is needed in large cohorts.

  6. Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Rischin, Danny [University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology, Melbourne (Australia); Fisher, Richard [Peter MacCallum Cancer Centre, Centre for Biostatistics and Clinical Trials, Melbourne (Australia); Binns, David [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); Scott, Andrew M. [Austin Hospital, Centre for PET, and Ludwig Institute for Cancer Research, Melbourne (Australia); Peters, Lester J. [Peter MacCallum Cancer Centre, Division of Radiation Oncology, Melbourne (Australia)

    2005-12-01

    The purpose of the study was to evaluate [{sup 18}F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [{sup 18}F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer. (orig.)

  7. FIVE-YEAR RESULTS OF ADJUVANT RADIOTHER

    Science.gov (United States)

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Kerimian, Maria Fenton; Goldberg, Judith D.; Formenti, Silvia C.

    2015-01-01

    Purpose/Objective A technique of prone breast radiotherapy delivered by a regimen of accelerated intensity modulated radiation therapy (IMRT) with a concurrent boost to the tumor bed, was developed at our institution. We report the five year results of this approach. Methods and Materials Between 2003–2006, 404 patients with Stage I–II breast cancer were prospectively enrolled into two consecutive protocols, institutional trials 03–30 and 05–181, that used the same regimen of 40.5Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5Gy (total dose=48Gy). All patients were treated after segmental mastectomy, had negative margins, and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine set-up attempted, and chosen if found to better spare these organs. Results 92% of patients were treated prone, 8% supine. 72% had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 –228.27cc, mean: 19.65cc. In-field heart volume for left breast cancer patients ranged from 0–21.24cc, mean: 1.59cc. There was no heart in the field for right breast cancer patients. At a median follow-up of five years, the five-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% CI: 0.65–1.04). The five-year cumulative incidence of regional recurrence was 0.53% (95% CI:0.41–0.69) and the five-year overall cumulative death rate was 1.28% (95% CI: 0.48–3.38). 82% (95% CI: 77–85) of patients judged their final cosmetic result as excellent/good. Conclusions Prone accelerated IMRT with a concomitant boost results in excellent local control, optimal sparing of heart and lung, with good cosmesis. RTOG 10–05, a phase III, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard six weeks radiotherapy with a sequential boost. PMID

  8. Comparative analysis of cisplatin-induced nephrotoxicity in head and neck cancer and carcinoma cervix during concurrent chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Puneet Kumar Bagri

    2014-01-01

    Full Text Available Background: Cisplatin is widely used as radio sensitizer in head and neck cancer (HNC and carcinoma cervix (CaCx. This study aims to see comparative nephrotoxicity of cisplatin in HNC and in CaCx without obstructive uropathy treated by concurrent chemoradiotherapy (CCRT. Materials and Methods: Fifty patients of HNC and 50 patients of CaCx stage II/III without obstructive uropathy were included in this study. Cisplatin 50 mg intravenous weekly was given before EBRT with adequate hydration and premedication in both groups. Before chemotherapy; blood urea, serum creatinine, and glomerular filtration rate (GFR were measured. GFR was measured using 99m Tc diethylene triamine pentacaetic acid (DTPA renogram study. Results: At the end of 4 th week, blood urea level 41-45 mg% was in 40 and 4% in HNC and CaCx, respectively (P = 0.018. At the end of 3 rd and 4 th week, blood urea level >45 mg% was 10 and 6% in HNC cases, respectively. At the end of 4 th week, serum creatinine level 1.1-1.5 mg% was 50 and 8% in HNC and CaCx, respectively (P = 0.047. Serum creatinine level >1.5 mg% was 6, 8, and 22% in HNC at the end of 2 nd , 3 rd , and 4 th week, respectively. GFR <80 ml/min at the end of 4 th week was 14% in HNC and only 2% in CaCx. GFR <100ml/min was significant at the end of 4 th week (P = 0.04. Univariate analysis showed significant relation between reduced oral fluid intake and reduced GFR (P < 0.001. Conclusion: In HNC, during concurrent chemoradiation, as the 3 rd -4 th week is reached, oral mucosal reactions increase and affect oral intake which further add to the cisplatin-induced nephrotoxicity. In CaCx without obstructive uropathy, renal function impairment is less severe as oral intake of water and liquid is not much impaired.

  9. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

    Directory of Open Access Journals (Sweden)

    Masayuki Hayashi

    2017-02-01

    Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  10. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.

    Science.gov (United States)

    Hayashi, Masayuki; Aoshi, Taiki; Haseda, Yasunari; Kobiyama, Kouji; Wijaya, Edward; Nakatsu, Noriyuki; Igarashi, Yoshinobu; Standley, Daron M; Yamada, Hiroshi; Honda-Okubo, Yoshikazu; Hara, Hiromitsu; Saito, Takashi; Takai, Toshiyuki; Coban, Cevayir; Petrovsky, Nikolai; Ishii, Ken J

    2017-02-01

    Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  11. 75 FR 66766 - NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development

    Science.gov (United States)

    2010-10-29

    ... discovery, development and clinical evaluation of adjuvants for use with preventive vaccines. NIAID has developed a draft Strategic Plan and Research Agenda for Adjuvant Discovery and Development, which... HUMAN SERVICES NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development Notice is...

  12. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    Licht, Peter B; Schytte, Tine; Jakobsen, Erik

    2014-01-01

    BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, ......BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single...... histopathology. A clinical oncologist, who was blinded to the surgical approach, reviewed all medical oncology charts for types of adjuvant chemotherapy, reasons for not initiating or stopping treatment, number of cycles delivered, and time interval from surgery to initial chemotherapy. RESULTS: During a 6-year...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p

  13. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    DEFF Research Database (Denmark)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky

    2012-01-01

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment...

  14. Persistent neurocognitive problems after adjuvant chemotherapy for breast cancer

    NARCIS (Netherlands)

    Kreukels, B.P.C.; van Dam, F.S.A.M.; Ridderinkhof, K.R.; Boogerd, W.; Schagen, S.B.

    2008-01-01

    Background: Neurocognitive problems have been observed in a number of women previously treated with adjuvant chemotherapy for breast cancer. The present study aims to combine the results of neuropsychological and electrophysiological techniques collected in patients with breast cancer treated with c

  15. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    2010-01-01

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA v

  16. Effects of 5-fluorouracil adjuvant treatment of colon cancer

    NARCIS (Netherlands)

    Kelder, Wendy; Hospers, Geke A. P.; Plukker, John T. M.

    2006-01-01

    Since the late 1980s and early 1990s, 5-fluorouracil-based chemotherapy has been the standard adjuvant treatment for Stage III colon cancer. After the initial introduction of 5-fluorouracil in standard treatment protocols, several changes have been made based on results of randomized studies on vari

  17. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy.

    Science.gov (United States)

    Kim, Su-Yeon; Joo, Hong-Gu

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant.

  18. Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yuan-Hong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Lin, Jun-Zhong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); An, Xin [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Luo, Jie-Lin [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); Cai, Mu-Yan [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou (China); Cai, Pei-Qiang [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou (China); Kong, Ling-Heng; Liu, Guo-Chen; Tang, Jing-Hua; Chen, Gong; Pan, Zhi-Zhong [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China); Ding, Pei-Rong, E-mail: dingpr@mail.sysu.edu.cn [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou (China)

    2014-12-01

    Purpose: Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. Methods and Materials: Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. Results: All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. Conclusions: Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen

  19. The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

    Directory of Open Access Journals (Sweden)

    Jessica A Hess

    2016-07-01

    Full Text Available In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses.Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2.The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.

  20. Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

    Science.gov (United States)

    Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

    2015-01-01

    Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

  1. Reasoning about Concurrent Actionsin Multi-Agent Systems

    Institute of Scientific and Technical Information of China (English)

    FAN Xiaocong; XU Dianxiang; HOU Jianmin; ZHENG Guoliang

    1999-01-01

    Concurrence is an important researcharea in collaborative problem solving.This paper offers a formaldefinition for cooperative sequences in multi-agentsystems, discussesthe different categories of concurrent actions, and proposes somerules forsituation revision and an algorithm used to generate resultingsituations.An example is also given to show how to solve concurrentproblems occurring inmulti-agent systems.

  2. Concurrent Lexicalized Dependency Parsing The ParseTalk Model

    CERN Document Server

    Broeker, N; Schacht, S; Broeker, Norbert; Hahn, Udo; Schacht, Susanne

    1994-01-01

    A grammar model for concurrent, object-oriented natural language parsing is introduced. Complete lexical distribution of grammatical knowledge is achieved building upon the head-oriented notions of valency and dependency, while inheritance mechanisms are used to capture lexical generalizations. The underlying concurrent computation model relies upon the actor paradigm. We consider message passing protocols for establishing dependency relations and ambiguity handling.

  3. 28 CFR 0.56 - Exclusive or concurrent jurisdiction.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exclusive or concurrent jurisdiction. 0.56 Section 0.56 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Criminal Division § 0.56 Exclusive or concurrent jurisdiction. The Assistant Attorney General...

  4. 术前放化疗并手术治疗局部晚期食管鳞癌的多中心随机对照临床研究%A multi-centered randomized controlled study of neo-adjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of esophagus:an interim analysis

    Institute of Scientific and Technical Information of China (English)

    杨弘; 毛伟敏; 郑晓; 朱成楚; 孔敏; 韩泳涛; 李涛; 傅剑华; 刘孟忠; 方文涛; 王家明; 陈于平; 陈志坚; 相加庆; 杨焕军

    2012-01-01

    Objective To evaluate the safety and validity of neo-adjuvant chemoradiotherapy followed by surgery for locally advanced esophageal carcinoma.Methods Patients with Ⅱ B,Ⅲ staged squamous cell carcinoma of thoracic esophagus were randomly allocated to either preoperative chemoradiotherapy followed by surgery ( arm A ) or surgery alone ( arm B ).In arm A,chemotherapy and radiotherapy were performed concurrently.Patients received two cycles of vinorelbine and cisplatin.Vinorelbine at 25 mg/m2 per day was administered as a bolus infusion at dl,d8,d22 and d29.Cisplatin at 75 mg/m2 was administered by an intravenous infusion at dl and d22( or 25 mg/m2 days 1 - 4 and 22 - 25 ).A total radiotherapeutic dose of 40 Gy was delivered in 20 daily fractions of 2.0 Gy each (5 d/wk for 4 weeks ).Three-incisioned esophagectomy was performed at Weeks 4 - 6 after chemoradiotherapy.Primary outcome was overall survival time.An interim analysis was performed in June 2011.Results From July 2007 to June 2011,123 eligible patients were randomly assigned at 7 cooperative cancer centers (54 cases in arm A vs 69 cases in arm B).In arm A,the clinical response rate of chemoradiotherapy was 90.7%.All patients finished the preoperative chemoradiotherapy. Forty-nine cases continued to receive esophagectomy.The pathological complete response rate was 29.6%.The rate of RO resection in arm A was significant higher than that in arm B (96.0% vs 85.5%,P =0.015 ).The most common grade 3/4 toxicity of chemoradiotherapy was leukopenia occurring in 33 cases (61.l% ).Vomiting and esophagitis were usually of Grade 1/2.No patient died or abandoned surgery because of chemoradiation toxicity.Between arms A and B,operative duration,blood loss,duration of chest tube drainage and length of postsurgical hospital stay were similar.The incidences of postoperative heart failure (2.0% vs 1.4%,P =1.000),anastomotic leakage(8.2% vs 11.6%,P =0.759)and hoarseness(6.1% vs 4.3%,P =0.691 )were not

  5. NEOSCOPE: a randomised Phase II study of induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin based chemoradiation as pre-operative regimen for resectable oesophageal adenocarcinoma

    NARCIS (Netherlands)

    Mukherjee, Somnath; Hurt, Christopher N; Gwynne, Sarah; Bateman, Andrew; Gollins, Simon; Radhakrishna, Ganesh; Hawkins, Maria; Canham, Jo; Lewis, Wyn; Grabsch, Heike I; Sharma, Ricky A; Wade, Wendy; Maggs, Rhydian; Tranter, Bethan; Roberts, Ashley; Sebag-Montefiore, David; Maughan, Timothy; Griffiths, Gareth; Crosby, Tom

    2015-01-01

    BACKGROUND Both oxaliplatin/capecitabine-based chemoradiation (OXCAP-RT) and carboplatin-paclitaxel based radiation (CarPac-RT) are active regimens in oesophageal adenocarcinoma, but no randomised study has compared their efficacy and toxicity. This randomised phase II "pick a winner" trial will ide

  6. EORTC 24051 : Unexpected side effects in a phase I study of TPF induction chemotherapy followed by chemoradiation with lapatinib, a dual EGFR/ErbB2 inhibitor, in patients with locally advanced resectable larynx and hypopharynx squamous cell carcinoma

    NARCIS (Netherlands)

    Lalami, Yassine; Specenier, Pol M.; Awada, Ahmad; Lacombe, Denis; Liberatoscioli, Cecilia; Fortpied, Catherine; El-Hariry, Iman; Bogaerts, Jan; Andry, Guy; Langendijk, J. A.; Vermorken, Jan B.

    2012-01-01

    Background: In this phase I/II study, the addition of lapatinib (LAP) was investigated in combination with the sequential use of both approaches TPF induction chemotherapy (ICT) followed by chemoradiation (CRT) in locally advanced larynx or hypopharynx squamous cell carcinoma. Patients and methods:

  7. Concurrent Object-Oriented Programming Based on MPI

    Institute of Scientific and Technical Information of China (English)

    鲁宏伟; 汪厚祥; 裴晓黎; 肖永玲

    2004-01-01

    Object-oriented model possesses inherent concurrency. Integration of concurrency and object-orientation is a promising new field. MPI is a message-passing standard and has been adopted by more and more systems. This paper proposes a novel approach to realize concurrent object-oriented programming based on Message-passing interface(MPI) in which future method communication is adopted between concurrent objects. A state behavior set is proposed to solve inheritance anomaly, and a bounded buffer is taken as an example to illustrate this proposal. The definition of ParaMPI class, which is the most important class in the concurrent class library,and implementation issues are briefly described.

  8. Proceedings Fourth Interaction and Concurrency Experience

    CERN Document Server

    Silva, Alexandra; Bruni, Roberto; Carbone, Marco; 10.4204/EPTCS.59

    2011-01-01

    This volume contains the pre-proceedings of ICE'11, the 4th Interaction and Concurrency Experience workshop, which was held in Reykjavik, Iceland on the 9th of June 2011 as a satellite event of DisCoTec'11. The topic of ICE'11 was Reliable and Contract-based Interaction. Reliable interactions are, e.g., those enjoying suitable logical, behavioural, or security properties, or adhering to certain QoS standards. Contract-based interactions are, e.g., those where the interacting entities are committed to give certain guarantees whenever certain assumptions are met by their operating environment. The ICE procedure for paper selection allows for PC members to interact, anonymously, with authors. During the review phase, each submitted paper is published on a Wiki and associated with a discussion forum whose access is restricted to the authors and to all the PC members not declaring a conflict of interests. The PC members post comments and questions that the authors reply to. Each paper was reviewed by four PC membe...

  9. Creatine and Caffeine: Considerations for Concurrent Supplementation.

    Science.gov (United States)

    Trexler, Eric T; Smith-Ryan, Abbie E

    2015-12-01

    Nutritional supplementation is a common practice among athletes, with creatine and caffeine among the most commonly used ergogenic aids. Hundreds of studies have investigated the ergogenic potential of creatine supplementation, with consistent improvements in strength and power reported for exercise bouts of short duration (≤ 30 s) and high intensity. Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance. Further, there is conflicting evidence from studies comparing the ergogenic effects of coffee and caffeine anhydrous supplementation. Previous research has identified independent mechanisms by which creatine and caffeine may improve strength and sprint performance, leading to the formulation of multi-ingredient supplements containing both ingredients. Although scarce, research has suggested that caffeine ingestion may blunt the ergogenic effect of creatine. While a pharmacokinetic interaction is unlikely, authors have suggested that this effect may be explained by opposing effects on muscle relaxation time or gastrointestinal side effects from simultaneous consumption. The current review aims to evaluate the ergogenic potential of creatine and caffeine in the context of high-intensity exercise. Research directly comparing coffee and caffeine anhydrous is discussed, along with previous studies evaluating the concurrent supplementation of creatine and caffeine.

  10. Chemoradiation for Ductal Pancreatic Carcinoma: Principles of Combining Chemotherapy with Radiation, Definition of Target Volume and Radiation Dose

    Directory of Open Access Journals (Sweden)

    Heinemann V

    2005-05-01

    Full Text Available Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

  11. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs.

    Science.gov (United States)

    Slot, A; Meerwaldt, J H; van Putten, W L; Treurniet-Donker, A D

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma (T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fractions in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial.

  12. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs

    Energy Technology Data Exchange (ETDEWEB)

    Slot, A.; Meerwaldt, J.H.; Treurniet-Donker, A.D. (Dr. Daniel Den Hoed Cancer Center, Rotteram (Netherlands). Department of Radiotherapy); Putten, W.L.J. van (Dr. Daniel Den Hoed Cancer Center, Rotterdam (Netherlands). Department of Statistics)

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma T{sub 3} or T{sub 4}, positive lymph nodes, positive resection line received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fraction in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m{sup 2}) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial. (author). 11 refs., 2 figs., 6 tabs.

  13. Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

    Science.gov (United States)

    Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

    2014-02-01

    The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

  14. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants

    Directory of Open Access Journals (Sweden)

    Marie-Ève Lebel

    2015-08-01

    Full Text Available Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease.

  15. Antifungal adjuvants: Preserving and extending the antifungal arsenal.

    Science.gov (United States)

    Butts, Arielle; Palmer, Glen E; Rogers, P David

    2017-02-17

    As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance.

  16. Transactions on Petri Nets and Other Models of Concurrency VI

    DEFF Research Database (Denmark)

    The sixth volume of ToPNoC includes revised versions of selected papers from workshops and tutorials held at the 32nd International Conference on Application and Theory of Petri Nets and Concurrency. It also contains a special section on Networks, Protocols, and Services, as well as a contributed...... paper submitted through the regular submission track of ToPNoC. The 14 papers cover a diverse range of topics including model checking and system verification, synthesis, foundational work on specific classes of Petri nets, and innovative applications of Petri nets and other models of concurrency. Thus...... this volume gives a good view of ongoing concurrent systems and Petri nets research....