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Sample records for chemoradiation therapy ccrt

  1. 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.

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

    International Nuclear Information System (INIS)

    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.

  3. 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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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.

  6. 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.

  7. Preoperative chemoradiation therapy for lower rectal cancer

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

    1996-09-01

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

  8. Chemoradiation therapy for anal cancer

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  13. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer

    International Nuclear Information System (INIS)

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

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  17. Oral surgery in patients undergoing chemoradiation therapy.

    Science.gov (United States)

    Demian, Nagi M; Shum, Jonathan W; Kessel, Ivan L; Eid, Ahmed

    2014-05-01

    Oral health care in patients undergoing chemotherapy and/or radiation therapy can be complex. Care delivered by a multidisciplinary approach is timely and streamlines the allocation of resources to provide prompt care and to attain favorable outcomes. A hospital dentist, oral and maxillofacial surgeon, and a maxillofacial prosthodontist must be involved early to prevent avoidable oral complications. Prevention and thorough preparation are vital before the start of chemotherapy and radiation therapy. Oral complications must be addressed immediately and, even with the best management, can cause delays and interruption in treatment, with serious consequences for the outcome and prognosis. PMID:24794266

  18. 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

    International Nuclear Information System (INIS)

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

  19. 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

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    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.

  20. 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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-02-15

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Kim, Jung Ho; Han, Sang Hoon

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Ferrari, Linda; Fichera, Alessandro

    2015-11-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Zhou Jessica

    2011-09-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

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

  14. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  20. 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

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

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

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

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

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

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

  4. Changes of symptoms and depression in oral cavity cancer patients receiving radiation therapy.

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    Chen, Shu-Ching; Lai, Yeur-Hur; Liao, Chun-Ta; Lin, Chia-Chin; Chang, Joseph Tung-Chien

    2010-07-01

    The purposes of this study were to (1) examine changes in symptom severity and depression within 3 months of first undergoing radiation therapy (RT) or concurrent chemoradiation therapy (CCRT), and (2) identify factors involved in changes in symptom severity in newly diagnosed oral cavity cancer patients undergoing post-operative RT or CCRT. A prospective panel survey was conducted to assess changes in symptoms, depression, and disease- or treatment-related characteristics within 3 months of beginning RT or CCRT (pre-treatment and 1, 2, and 3 months from first receiving RT). A total of 76 eligible oral cavity cancer patients were recruited from the outpatient radiation department of a medical center in northern Taiwan. The results showed mild-to-moderate overall symptom and depression levels during treatment, with the five most distressing symptoms being swallowing difficulty, poor appetite, oral mucositis, pain, and fatigue. The severity of symptoms and depression peaked at approximately 2 months from beginning RT or CCRT (T3). Changes in overall symptom severity were found to be significantly related to patients' radiation dose and depression level. These results can help advance understanding of changes in symptoms and facilitate prevention and management of symptoms associated with RT or CCRT. Psychological distress, particularly, depression, requires careful monitoring and management in oral cavity cancer patients undergoing RT or CCRT. PMID:20308004

  5. A role of FDG-PET on assessment of chemoradiation therapy for pancratic cancer

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    Usefulness of fluorodeoxyglucose-positron emission tomography (FDG-PET) was retrospectively evaluated by FDG accumulation in unresectable pancreatic cancer before and after its chemoradiation therapy (CRT). Subjects were 31 patients with the cancer at stage IIa (2 cases), IIb (2), III (19) and IV (8) and underwent chemotherapy (11 cases) or CRT (20). Tumor diameters were measured by the contrast CT to be 14-52 mm. CRT was conducted with hyper-fractionated accelerated RT (1.25 Gy x 2/day x 5/week, total 50 Gy) and with TS-1 (tegafur/gimeracil/oteracil potassium) 80 mg/m2/day before and after RT. FDG-PET was done with intravenous 3.7 MBq/kg FDG before and 3-6 months after the therapy, and standardized uptake value (SUV) of the lesion was calculated to compare with the evaluation by the guideline response evaluation criteria in solid tumors (RECIST), 2009. Results were: no significant relationships of SUV before therapy with that after or with survival curve; significant decrease of SUV after therapy; decreased or unchanged SUV in cases of partial response (PR), 15 cases and stable disease (SD), 10 after therapy but increased in 4/6 progressive disease (PD); significant relationships between the change of SUV and RECIST after therapy and between change rates of SUV and of carcinoembryonic antigen (CEA)/tumor diameter. Thus, the change of SUV in FDG-PET was suggested to be useful for evaluation of therapeutic efficacy as an aid of diagnosis. (T.T.)

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

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    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-therapy

  7. A case of esophageal cancer with septic disseminated intravascular coagulation treated with recombinant human soluble thrombomodulin during chemoradiation therapy

    International Nuclear Information System (INIS)

    A 70-year-old woman was diagnosed with synchronous advanced esophageal cancer and early renal cancer. During chemo-radiation therapy for the esophageal cancer, she suffered from septic shock due to pneumonia. She got worse despite the administration of antibiotics and γglobulin. On the following day, she was diagnosed with septic disseminated intravascular coagulation (DIC) on the basis of the diagnostic criterion for acute DIC. Recombinant human soluble thrombomodulin (rTM) was administered to treat the DIC. The patient responded promptly to rTM treatment and recovered from the DIC in just 1 day. rTM is thought to be an effective drug for sepsis-induced DIC during chemoradiation therapy. (author)

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

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    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

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

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

  10. Effects of Treatment Duration During Concomitant Chemoradiation Therapy for Cervical Cancer

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    Purpose: To determine whether extended treatment duration (TD) impacts in-field relapse and survival in the setting of concomitant chemoradiation therapy (CRT) for cervical cancer. Methods and Materials: A total of 480 consecutive cervical cancer patients treated with radiation therapy (RT) alone or concomitant CRT for curative intent were retrospectively analyzed. Relapse was defined as in-field with respect to external beam radiation therapy fields. The effects of TD on in-field relapse, disease-free survival (DFS), and overall survival (OS) rates were assessed continuously and categorically within the separate RT and CRT cohorts. Covariates included age, histology, stage, and cumulative dose to point A. In-field relapse, DFS, and OS rates were estimated with Kaplan-Meier analysis; comparisons used log–rank statistic. Multivariate analysis used the Cox proportional hazards model. Results: A total of 372 patients (RT n=206, CRT n=166) were evaluable, with a median follow-up for relapse-free patients of 4.2 years (RT 4.4 years, CRT 4.2 years; P=.807). Treatment duration was longer in the RT cohort (median 55 days; range 35-99 days) versus the CRT cohort (median 51 days; range 35-92 days) (P=.001). In the RT cohort, TD ≥62 days trended to significance for predicting inferior DFS (hazard ratio 1.42, 95% confidence interval 0.86-1.98, P=.086). However, in the CRT cohort, TD assessed continuously or categorically across multiple cutoff thresholds did not predict for in-field relapse, DFS, or OS. Conclusion: With RT alone, extended TD ≥62 days may adversely impact treatment efficacy. With the addition of concomitant chemotherapy to RT, however, extended TD has no effect on treatment efficacy

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

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    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%.

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

    International Nuclear Information System (INIS)

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

  13. Preoperative gemcitabine-based chemoradiation therapy for T3/T4 pancreatic cancer

    International Nuclear Information System (INIS)

    A total of 250 patients with T3 · T4 (JPS) pancreatic cancer received preoperative gemcitabine-based chemoradiation therapy (CRT). Patients were classified into the following three groups based on the locoregional tumor extension: T3-R (n=64), tumors without extension to the adjacent vasculature systems; T4-R (n=125), tumors with extension to the adjacent vasculature system except SMA, CHA, and CA: T4-BR (n=61), tumors showing abutment to 180deg of the circumference of the SMA and/or CHA and/or CA. We evaluated the followings in comparisons among patients with T3-R, T4-R and T4-BR: resection rate, rate of margin-negative resection, survival, and frequency of local recurrence. Resection rates of T3-R, T4-R, and T4-BR patients were 92%, 85%, and 74%, respectively. Pathological margin-negative resection was achieved in 98%, 100%, and 98% in those patients groups, respectively. The 5-year postoperative survival rates of T3-R, T4-R, and T4-BR patients were 70%, 52%, and 37%, respectively. The 5-year cumulative incidence of local recurrence was comparable in the three groups (10%, 17%, and 15%, respectively). In the resected cases, locoregional control was comparable regardless of the degree of locoregional tumor extension in the setting of preoperative CRT strategy. However, the resection rate and postoperative survival rate were lower in the patients with more locally advanced tumors. (author)

  14. Examination of resectable and borderline pancreatic cancer treated with neoadjuvant chemoradiation therapy

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    The purpose of this study was to determine the effect of neoadjuvant chemotherapy (NAC) and chemoradiation therapy (NAC-RT) for the treatment of potentially resectable (PR) and borderline resectable (BR) pancreatic cancer. Patients with PR (n=14) and BR (n=13) pancreatic cancer who received NAC (n=15) or NAC-RT (n=12) were enrolled in our study. NAC comprised 2 cycles of S-1 or S-1 plus gemcitabine, and NAC-RT comprised hyperaccelerated radiation therapy and S-1 chemotherapy. According to the Response Evaluation Criteria in Solid Tumors (RECIST), partial response was observed in 10 patients (37%); stable disease (SD), in 11 patients (41%); and progressive disease (PD), in 6 patients (22%). The rates of curative surgery in patients with PR and BR pancreatic cancer were 57% and 38%, respectively. Curative surgery was performed in 8 patients with PR pancreatic cancer. Downstaging was observed in 3 patients and upstaging was observed in 1 patient. During the postoperative course, peritoneal dissemination was detected in 2 patients at 4 months after surgery. One patient survived for more than 3 years. Curative surgery was performed in 5 patients with BR pancreatic cancer. Downstaging was observed in 4 patients, and upstaging was observed in 1 patient. During the postoperative course, recurrence was detected in 3 patients and the remaining 2 patients survived with a recurrence-free status. The results of the present study indicate that NAC-RT may be useful for the treatment of patients with PR or BR pancreatic cancer. However, this protocol has disadvantages in that the possibility of resectability might be compromised and early recurrence might occur, Thus, this protocol warrants further evaluation. (author)

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

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

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

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

  17. Can MRI-derived factors predict the survival in glioblastoma patients treated with postoperative chemoradiation therapy?

    International Nuclear Information System (INIS)

    Background: Advanced diagnostic and therapeutic developments may yield novel prognostic factors in patients with glioblastoma multiforme (GBM). Purpose: To validate the predictive values of pretreatment quantitative diffusion-weighted (DW) magnetic resonance imaging (MRI) and MRI performed within 72 h after surgery in patients with GBM. Material and Methods: Between January 2000 and September 2009, 138 patients with GBM underwent postoperative chemoradiation therapy (chemo-RT) and longitudinal MRI before surgery, in the early postoperative period, and at 1-month intervals thereafter. The role of the patient age, Karnofsky performance scale (KPS) score, minimum apparent diffusion coefficient (ADC) on pretreatment DW-MRI, and gross residual tumor on early postoperative MRI were assessed by factor analysis of overall survival (OS). Survival curves were calculated using the Kaplan-Meier method; the multivariate Cox's proportional hazards model was used to adjust for the influence of prognostic factors. Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) criteria were used to validate the predictive value of the MRI-derived factors. Results: Substantial independent prognostic factors were the KPS score (hazard ratio [HR], 1.812), minimum ADC (HR, 2.365), and gross residual tumor (HR, 1.777). Based on MRI-derived factors, we assigned the patients to different prognostic groups in the RTOG-RPA classification and grouped them according to the level of risk, i.e. a high-risk group with low minimum ADCs (-3 mm2/s) with gross residual tumor and a low-risk group with high minimum ADCs (≥0.93 X 10-3 mm2/s) without gross residual tumor; the other patients were assigned to the intermediate-risk group. Median OS for the low-, intermediate-, and high-risk groups were 28.2, 14.7, and 10.8 months, respectively (P < 0.001). Conclusion: The minimum ADC on pretreatment DW-MRI and gross residual tumor on early postoperative MRI can predict the survival in GBM

  18. Can MRI-derived factors predict the survival in glioblastoma patients treated with postoperative chemoradiation therapy?

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    Hideo Nakamura, Hideo [Dept. of Neurosurgery, Faculty of Life Sciences, Kumamoto Univ., Kumamoto, (Japan); Murakami, Ryuji [Dept. of Medical Imaging, Faculty of Life Sciences, Kumamoto Univ., Kumamoto (Japan)], e-mail: murakami@kumamoto-u.ac.jp; Hirai, Toshinori; Kitajima, Mika; Yamashita, Yasuyuki [Dept. of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto Univ., Kumamoto (Japan)

    2013-03-15

    Background: Advanced diagnostic and therapeutic developments may yield novel prognostic factors in patients with glioblastoma multiforme (GBM). Purpose: To validate the predictive values of pretreatment quantitative diffusion-weighted (DW) magnetic resonance imaging (MRI) and MRI performed within 72 h after surgery in patients with GBM. Material and Methods: Between January 2000 and September 2009, 138 patients with GBM underwent postoperative chemoradiation therapy (chemo-RT) and longitudinal MRI before surgery, in the early postoperative period, and at 1-month intervals thereafter. The role of the patient age, Karnofsky performance scale (KPS) score, minimum apparent diffusion coefficient (ADC) on pretreatment DW-MRI, and gross residual tumor on early postoperative MRI were assessed by factor analysis of overall survival (OS). Survival curves were calculated using the Kaplan-Meier method; the multivariate Cox's proportional hazards model was used to adjust for the influence of prognostic factors. Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) criteria were used to validate the predictive value of the MRI-derived factors. Results: Substantial independent prognostic factors were the KPS score (hazard ratio [HR], 1.812), minimum ADC (HR, 2.365), and gross residual tumor (HR, 1.777). Based on MRI-derived factors, we assigned the patients to different prognostic groups in the RTOG-RPA classification and grouped them according to the level of risk, i.e. a high-risk group with low minimum ADCs (<0.93 X 10{sup -3} mm{sup 2}/s) with gross residual tumor and a low-risk group with high minimum ADCs ({>=}0.93 X 10{sup -}3 mm{sup 2}/s) without gross residual tumor; the other patients were assigned to the intermediate-risk group. Median OS for the low-, intermediate-, and high-risk groups were 28.2, 14.7, and 10.8 months, respectively (P < 0.001). Conclusion: The minimum ADC on pretreatment DW-MRI and gross residual tumor on early

  19. 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.

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

    Science.gov (United States)

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

  2. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    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® 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.

  6. 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.

  7. Prediction of therapeutic efficacy and prognosis in the setting of preoperative chemoradiation therapy for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    The prediction in the title is explained on authors' experience of the chemoradiation therapy (CRT) at 4 stages around the resection of locally advanced pancreatic cancer (PC). CRT is conducted by the full-dose gemcitabine/12 weeks + 3D conformal radiation therapy with 50-60 Gy/25 fractions/2 months. Authors have found that PC cells overexpressing antiapoptic a regenerating islet-derived protein 4 (REG4) are resistant to gamma ray in vitro and that the preoperative CRT efficacy can be predicted to be low in patients with the elevated serum REG4 level. The efficacy is found good in patients exerting a rapid fall of the tumor marker carbohydrate antigen (CA) 19-9 level during the CRT therapy even if it was high before. At the completion of CRT, the resectability is evaluated by imaging diagnosis like the thin slice CT, but the tumor viability is rather obscure. Authors have retrospectively compared the standard uptake value (SUV) change of the primary PC lesion in 18F-deoxyglucose (FDG) PET before and after CRT, with post-surgical histopathologic features, to divide the CRT responders (histological tumor breakdown >50%) and non-responders. The efficacy is suggested significant in patients (responders) with the high pre-operative SUV and rate (1 minus SUV ratio post-/pre-operation), suggesting the usefulness of PET to see the viability after CRT. In cases undergone CRT and then resection, the local postoperative histopathological features are found to be not an independent prognostic factor, but the metastasis to lymph nodes and perineural infiltration are the factors. This means that the disease should be handled mostly as subclinical, systemic one. (T.T.)

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

    International Nuclear Information System (INIS)

    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

  9. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

  10. Comparison between preoperative imaging and postoperative histopathological findings of vascular invasion after neoadjuvant chemoradiation therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Outcomes of neoadjuvant chemoradiation therapy (NACRT) of the borderline resectable (BR) pancreatic cancer (PC) conducted in authors' facility are reported to discuss about the assessment of its efficacy by comparison of imaging and pathological findings in the title. Subjects were 28 patients with BR-PC preoperatively complicated with the invasion in superior mesenteric artery (SMA) (10 cases), common hepatic artery (CHA) (7), SMA + CHA (1), portal vein (PV) and superior mesenteric vein (SMV) (10). NACRT was conducted with S-1 (80 mg/m2/2 weeks then with 1 week holiday x 2) + radiation 50.4 Gy (1.8 Gy x 28 fractions) with multi-gate irradiation to the primary site before resection. NARCT resulted in the complete response 0 cases, partial response 3, steady disease 22 and progressive disease 3, of which 4 cases were excluded from the operation because of their rejection or newly found hepatic metastasis. Fourteen cases with preoperative images of arterial invasions gave post-operative pathologic finding of absence of PC cells at the ablated arterial stump; and in 10 with PV + SMV, only 1 case pre-operatively gave the disappearance of the invasion and 4 cases gave post-operative pathological findings of PV + SMV invasion, but PC cells were negative at the ablated end in all cases. Thus the discrepancy was observed between CT images after pre-operative NACRT and post-operative histopathologic findings, which suggesting the necessity of celiotomy for indication of resection. (T.T.)

  11. 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.

  12. 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.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    2016-09-01

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

  15. 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

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

    International Nuclear Information System (INIS)

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

  17. 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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

  20. 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.

  1. 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

  2. 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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

  7. Impact of institutional experience on survival outcome of patients undergoing combined chemoradiation therapy for inoperable non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: Clinical experience of both physicians and institutions has been shown to significantly influence the outcome of patients. We conducted this retrospective cohort study to examine its impact on the outcome of patients undergoing combined chemoradiation therapy for the treatment of locally advanced inoperable non-small-cell lung cancer. Methods and Materials: We compared the clinical data from 239 patients who were enrolled in two consecutive Radiation Therapy Oncology Group (RTOG) trials (RTOG 91-06, RTOG 92-04) according to the number of patients enrolled from each institution in either trial alone or the two trials combined. Results: Overall, patients treated at the institutions that enrolled ≥5 patients survived longer than those treated at the institutions that enrolled <5 patients (median survival 20.5 vs. 13.4 months, p=0.0006) with a more than doubling of the 2- and 3-year survival rates (45% and 31% vs. 20% and 13%, respectively). Multivariate analyses confirmed that the number of patients enrolled from each institution was an important prognostic factor for the entire group (p=0.001) and also for RTOG 91-06 (p=0.05) and RTOG 92-04 (p=0.004) when the data were analyzed separately. Conclusion: Institutional experience has a significant impact on the survival outcome of patients undergoing combined chemoradiation therapy for inoperable non-small cell lung cancer

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

    International Nuclear Information System (INIS)

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

  9. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer

    Directory of Open Access Journals (Sweden)

    Tatsuhiro Shibata

    2011-09-01

    Full Text Available Esophageal squamous cancer (ESC is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22% in advanced ESC tumors and ESC cell lines (3/10. The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT.

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

    Directory of Open Access Journals (Sweden)

    Honsoul Kim

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    International Nuclear Information System (INIS)

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

  13. Clinical complete responders to definite chemoradiation or radiation therapy for oesophageal cancer: predictors of outcome

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    To identify predictors of long-term outcome for patients with clinical complete response (cCR) after definite chemoradiotherapy (CRT) or radiation therapy (RT) for oesophageal cancer (EC). In this retrospective study, we reviewed the files of all patients from our institution that underwent definitive RCT or RT for EC, from January 1998 to December 2003. Among 402 consecutive patients with EC, 110 cCR responses were observed, i.e. without evidence of tumour on morphological examination of the biopsy specimens, 8 to 10 weeks after radiation. Baseline patient and tumour characteristics were as follows: male = 98/110, median age = 60, squamous histology = 103/110, tumour site (upper/middle/lower third) = 41/50/19, weight loss none/<10%/≥10% = 36/45/29, dysphagia grade 1/2/≥3 = 30/14/66. Patients were staged according to endosonography and/or computed tomography. There were 9 stage I, 31 stage IIA, 15 stage IIB, 41 stage III, 6 stage IV. Post treatment nutritional characteristics were as follows: weight loss during treatment none/<10% ≥ 10% = 35/38/37, remaining dysphagia grade 1/2/≥3 = 54/24/32. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. During follow up (median: 6 [0.4–9.8] years), 16 patients had salvage surgery. Median OS was 2.5 years, and 5-year OS was 33.5%. Histological type, stage, age, gender, and treatment characteristics had no significant impact on outcome. The risk of death was increased two-fold for patients with grade ≥ 3 dysphagia after treament (HR = 1.9 [1.2–3.1], p = 0.007). Weight loss ≥10% during treatment also negatively affected outcome (HR = 1.8 [1.0–3.2], p = 0.040). One EC patient among 3 with cCR after definite CRT/RT is still alive at 5 years. Variables related to reduced OS were: remaining significant dysphagia after treatment and weight loss ≥10% during treatment

  14. Preoperative Chemoradiation Therapy With Capecitabine/Oxaliplatin and Cetuximab in Rectal Cancer: Long-Term Results of a Prospective Phase 1/2 Study

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    Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Conradi, Lena [Department of General Surgery, University Medical Center of Göttingen (Germany); Weiss, Christian [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sprenger, Thilo [Department of General Surgery, University Medical Center of Göttingen (Germany); Middel, Peter [Institute for Pathology, University Medical Center, Göttingen (Germany); Rau, Tillman [Institute of Pathology, University Hospital Erlangen, Erlangen (Germany); Dellas, Kathrin [Department of Radiotherapy, Lübeck University (Germany); Kitz, Julia [Institute for Pathology, University Medical Center, Göttingen (Germany); Rödel, Franz [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Sauer, Rolf [Department of Radiation Oncology, University of Erlangen (Germany); Rüschoff, Josef [Targos Molecular Pathology, Kassel (Germany); Beissbarth, Tim [Department of Medical Statistics, University Medical Center of Göttingen (Germany); Arnold, Dirk [Tumor Biology Center Freiburg, University of Freiburg (Germany); Ghadimi, B. Michael [Department of General Surgery, University Medical Center of Göttingen (Germany); Rödel, Claus [Department of Radiation Therapy and Oncology, University of Frankfurt (Germany); Liersch, Torsten [Department of General Surgery, University Medical Center of Göttingen (Germany)

    2013-12-01

    Purpose: We have previously shown that the addition of cetuximab to chemoradiation therapy failed to improve complete response rates (pCR) in rectal cancer. Here we report the long-term results of the cetuximab added to preoperative radiation therapy with capecitabine and oxaliplatin (CET-CAPOX-RT) phase 1/2 study that evaluated preoperative chemoradiation with cetuximab, capecitabine, and oxaliplatin in patients with rectal cancer. Methods and Materials: The median follow-up was 63 months (range, 5-73 months). Sixty patients were enrolled; 3 patients were excluded due to protocol violation, and 4 died before surgery. Total mesorectal excision was performed in 53 patients, in 85% (n=45) with curative intention (M0-status). Secondary end points including overall survival (OS) disease-free survival (DFS) and cancer-specific survival (CSS) were calculated. The prognostic value of KRAS mutation status was also assessed. Results: Histopathological examination confirmed ypUICC stages 0 (n=4; pCR), I (n=17), II (n=10), III (n=14), and IV (n=8). For patients who underwent surgery (n=53), OS at 1, 3, and 5 years was 88.7%, 83%, and 75.5%, respectively, whereas CSS rates were 94.1%, 88.1%, and 78.1%, respectively. In the 45 patients who were treated with curative intent (M0), the OS rates at 1, 3, and 5 years were 91.1%, 88.9%, and 86.7%, respectively; whereas CSS rates were 97.6%, 95.2%, and 90.3%, respectively; and DFS rates were 90.7%, 88.3%, and 88.3%, respectively. We did not find any locoregional failure in patients with M0-status (n=45). Chronic toxicity was rare. KRAS mutations, as detected in 33.3%, showed no correlation with the clinicopathological parameters nor significance for either OS (P=.112), CSS (P=.264), or DFS (P=.565). Conclusions: Taken together, chemoradiation therapy combined with cetuximab is safe, feasible, and offers excellent survival rates. KRAS mutation status was not a predictive factor. Importantly, lack of improvement in pCR rate did not

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

    Directory of Open Access Journals (Sweden)

    Soumik Ghosh

    2012-01-01

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

  16. 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

  17. 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

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    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.

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

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

    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.

  20. 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.

  1. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

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    Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States); Seder, Christopher W.; Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Koshy, Matthew [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

    2015-06-01

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  2. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

    International Nuclear Information System (INIS)

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  3. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    International Nuclear Information System (INIS)

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation

  4. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

    Energy Technology Data Exchange (ETDEWEB)

    Habr-Gama, Angelita, E-mail: gamange@uol.com.br [Angelita and Joaquim Gama Institute, São Paulo (Brazil); University of São Paulo School of Medicine, São Paulo (Brazil); Gama-Rodrigues, Joaquim [Angelita and Joaquim Gama Institute, São Paulo (Brazil); University of São Paulo School of Medicine, São Paulo (Brazil); São Julião, Guilherme P. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Colorectal Surgery Division, University of São Paulo School of Medicine, São Paulo (Brazil); Proscurshim, Igor; Sabbagh, Charles; Lynn, Patricio B. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Perez, Rodrigo O. [Angelita and Joaquim Gama Institute, São Paulo (Brazil); Ludwig Institute for Cancer Research, São Paulo Branch (Brazil)

    2014-03-15

    Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). When early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.

  5. Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

    Energy Technology Data Exchange (ETDEWEB)

    Parlak, Cem, E-mail: cemparlak@gmail.com [Department of Radiation Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey); Mertsoylu, Hüseyin [Department of Medical Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey); Güler, Ozan Cem; Onal, Cem; Topkan, Erkan [Department of Radiation Oncology, Baskent University, Adana Medical Faculty, Adana (Turkey)

    2014-03-15

    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM.

  6. Definitive Chemoradiation Therapy Following Surgical Resection or Radiosurgery Plus Whole-Brain Radiation Therapy in Non-Small Cell Lung Cancer Patients With Synchronous Solitary Brain Metastasis: A Curative Approach

    International Nuclear Information System (INIS)

    Purpose/Objectives: The aim of this study was to evaluate the impact of definitive thoracic chemoradiation therapy following surgery or stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) on the outcomes of patients with non-small cell lung cancer (NSCLC) with synchronous solitary brain metastasis (SSBM). Methods and Materials: A total of 63 NSCLC patients with SSBM were retrospectively evaluated. Patients were staged using positron emission tomography-computed tomography in addition to conventional staging tools. Thoracic radiation therapy (TRT) with a total dose of 66 Gy in 2 Gy fractions was delivered along with 2 cycles of cisplatin-based chemotherapy following either surgery plus 30 Gy of WBRT (n=33) or SRS plus 30 Gy of WBRT (n=30) for BM. Results: Overall, the treatment was well tolerated. All patients received planned TRT, and 57 patients (90.5%) were also able to receive 2 cycles of chemotherapy. At a median follow-up of 25.3 months (7.1-52.1 months), the median months of overall, locoregional progression-free, neurological progression-free, and progression-free survival were 28.6, 17.7, 26.4, and 14.6, respectively. Both univariate and multivariate analyses revealed that patients with a T1-T2 thoracic disease burden (P=.001), a nodal stage of N0-N1 (P=.003), and no weight loss (P=.008) exhibited superior survival. Conclusions: In the present series, surgical and radiosurgical treatments directed toward SSBM in NSCLC patients were equally effective. The similarities between the present survival outcomes and those reported in other studies for locally advanced NSCLC patients indicate the potentially curative role of definitive chemoradiation therapy for highly selected patients with SSBM

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-01

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

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-01

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

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

    International Nuclear Information System (INIS)

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

  12. Locally advanced rectal cancer: is diffusion weighted MRI helpful for the identification of complete responders (ypT0N0) after neoadjuvant chemoradiation therapy?

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    Sassen, S.; Booij, M. de; Vliegen, R. [Atrium Medical Center Parkstad, Department of Radiology, P.O. Box 4446, Heerlen (Netherlands); Sosef, M. [Atrium Medical Center Parkstad, Department of General Surgery, P.O. Box 4446, Heerlen (Netherlands); Berendsen, R. [Atrium Medical Center Parkstad, Department of Clinical Physics, P.O. Box 4446, Heerlen (Netherlands); Lammering, G. [MAASTRO Clinic, Department of Radiation Oncology, P.O. Box 3035, Maastricht (Netherlands); Clarijs, R. [Atrium Medical Center Parkstad, Department of Pathology, P.O. Box 4446, Heerlen (Netherlands); Bakker, M. [Atrium Medical Center Parkstad, Department of Gastroenterology and Hepatology, P.O. Box 4446, Heerlen (Netherlands); Beets-Tan, R. [Maastricht University Medical Center, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Warmerdam, F. [Atrium Medical Center Parkstad, Department of Internal Medicine/Oncology, P.O. Box 4446, Heerlen (Netherlands)

    2013-12-15

    To determine retrospectively the additional value of DWI-MRI toT2-MRI for predicting complete response (ypT0N0 = CR) after chemoradiation-therapy (CRT) in locally advanced rectal cancer. Seventy locally advanced rectal cancer patients underwent CRT followed by restaging MRI and resection. Two readers with different experience levels independently scored T2 images for CR and, in a second reading, combined T2 and DWI. A 5-point confidence-level score was used to generate ROC curves. Areas under the ROC curves (AUC) and interobserver agreement were compared for both readings. Histology served as reference standard. The interobserver agreement increased after addition of DWI from 0.35 to 0.58 but the AUC improved only for the experienced reader (0.77 to 0.89, p = 0.005 vs. 0.74 to 0.70, p > 0.05). Sensitivity and NPV improved from 20-30 % to 40-70 %, respectively 88 % to 91-95 %. Specificity and PPV improved only for the experienced reader (87 to 93 % respectively 27 to 63 %). Adding DWI to T2-MRI improves consistency between readers and has potential to improve readers' accuracy dependent on his/her experience. DWI could be of additional value, particularly in ruling out CR (high NPV), but considering the sub-optimal PPV one should be cautious about relying solely on MRI for the clinical decision to offer a wait-and-see strategy. (orig.)

  13. Locally advanced rectal cancer: is diffusion weighted MRI helpful for the identification of complete responders (ypT0N0) after neoadjuvant chemoradiation therapy?

    International Nuclear Information System (INIS)

    To determine retrospectively the additional value of DWI-MRI toT2-MRI for predicting complete response (ypT0N0 = CR) after chemoradiation-therapy (CRT) in locally advanced rectal cancer. Seventy locally advanced rectal cancer patients underwent CRT followed by restaging MRI and resection. Two readers with different experience levels independently scored T2 images for CR and, in a second reading, combined T2 and DWI. A 5-point confidence-level score was used to generate ROC curves. Areas under the ROC curves (AUC) and interobserver agreement were compared for both readings. Histology served as reference standard. The interobserver agreement increased after addition of DWI from 0.35 to 0.58 but the AUC improved only for the experienced reader (0.77 to 0.89, p = 0.005 vs. 0.74 to 0.70, p > 0.05). Sensitivity and NPV improved from 20-30 % to 40-70 %, respectively 88 % to 91-95 %. Specificity and PPV improved only for the experienced reader (87 to 93 % respectively 27 to 63 %). Adding DWI to T2-MRI improves consistency between readers and has potential to improve readers' accuracy dependent on his/her experience. DWI could be of additional value, particularly in ruling out CR (high NPV), but considering the sub-optimal PPV one should be cautious about relying solely on MRI for the clinical decision to offer a wait-and-see strategy. (orig.)

  14. Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

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    Balermpas, Panagiotis [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Michel, Yvonne [Senckenberg Institute of Pathology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Wagenblast, Jens [Department of Otorhinolaryngology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Seitz, Oliver [Department of Maxillofacial Surgery, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Sipek, Florian; Rödel, Franz; Rödel, Claus [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany)

    2013-07-15

    Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

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

    International Nuclear Information System (INIS)

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

  16. 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.

  17. Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-01

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

  20. Cancer stem cells and chemoradiation resistance

    International Nuclear Information System (INIS)

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

  1. 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

  2. Low miR-187 expression promotes resistance to chemoradiation therapy in vitro and correlates with treatment failure in patients with esophageal adenocarcinoma.

    Science.gov (United States)

    Lynam-Lennon, Niamh; Bibby, Becky A; Mongan, Ann Marie; Marignol, Laure; Paxton, Christian N; Geiersbach, Katherine; Bronner, Mary P; O'Sullivan, Jacintha; Reynolds, John; Maher, Stephen G

    2016-01-01

    Esophageal adenocarcinoma (EAC) has a poor prognosis and is increasing in incidence in many western populations. Neoadjuvant chemoradiation therapy (CRT) followed by surgery is increasingly the standard of care for locally advanced EAC; however, resistance to treatment is a significant clinical problem. The identification of both novel biomarkers predicting response to treatment and novel therapeutic targets to enhance the efficacy of CRT are key to improving survival rates in EAC. In this study we performed global microRNA (miRNA) profiling of pre-treatment EAC biopsies and identified 67 miRNA significantly altered in patients who are resistant to CRT. One of these miRNA, miR-187, was significantly decreased in pre-treatment EAC tumors from patients having a poor response to neoadjuvant CRT, highlighting downregulation of miR-187 as a potential mechanism of treatment resistance in EAC. In vitro, miR-187 was demonstrated to play a functional role in modulating sensitivity to X-ray radiation and cisplatin in EAC and its dysregulation was demonstrated to be due to chromosomal alterations. In vitro, miR-187 altered expression of a diverse array of pathways, including the immune regulator complement component 3 (C3), serum levels of which we have previously demonstrated to predict patient response to CRT. In vivo, expression of C3 was significantly increased in tumors from patients having a poor response to CRT. This study highlights for the first time a role for miR-187 as a novel biomarker of response to CRT and a potential therapeutic target for enhancing the efficacy of CRT in EAC. PMID:27254108

  3. 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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    Purpose: A previous phase 1 study suggested that definitive chemoradiation therapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) is tolerable and active in patients with advanced esophageal cancer (AEC). This phase 2 study was designed to confirm the efficacy and toxicity of DCF-R in AEC. Methods and Materials: Patients with previously untreated thoracic AEC who had T4 tumors or M1 lymph node metastasis (M1 LYM), or both, received intravenous infusions of docetaxel (35 mg/m2) and cisplatin (40 mg/m2) on day 1 and a continuous intravenous infusion of 5-fluorouracil (400 mg/m2/day) on days 1 to 5, every 2 weeks, plus concurrent radiation. The total radiation dose was initially 61.2 Gy but was lowered to multiple-field irradiation with 50.4 Gy to decrease esophagitis and late toxicity. Consequently, the number of cycles of DCF administered during radiation therapy was reduced from 4 to 3. The primary endpoint was the clinical complete response (cCR) rate. Results: Characteristics of the 42 subjects were: median age, 62 years; performance status, 0 in 14, 1 in 25, 2 in 3; TNM classification, T4M0 in 20, non-T4M1LYM in 12, T4M1LYM in 10; total scheduled radiation dose: 61.2 Gy in 12, 50.4 Gy in 30. The cCR rate was 52.4% (95% confidence interval [CI]: 37.3%-67.5%) overall, 33.3% in the 61.2-Gy group, and 60.0% in the 50.4-Gy group. The median progression-free survival was 11.1 months, and the median survival was 29.0 months with a survival rate of 43.9% at 3 years. Grade 3 or higher major toxicity consisted of leukopenia (71.4%), neutropenia (57.2%), anemia (16.7%), febrile neutropenia (38.1%), anorexia (31.0%), and esophagitis (28.6%). Conclusions: DCF-R frequently caused myelosuppression and esophagitis but was highly active and suggested to be a promising regimen in AEC. On the basis of efficacy and safety, a radiation dose of 50.4 Gy is recommended for further studies of DCF-R

  6. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hao [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Tan, Shan [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Department of Control Science and Engineering, Huazhong University of Science and Technology, Wuhan (China); Chen, Wengen; Kligerman, Seth [Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland (United States); Kim, Grace; D' Souza, Warren D.; Suntharalingam, Mohan [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Lu, Wei, E-mail: wlu@umm.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States)

    2014-01-01

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher

  7. 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.

  8. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Kim, Sinae [Division of Biometrics, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Biostatistics, School of Public Health, Rutgers University, New Brunswick, New Jersey (United States); Haider, Syed A. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Xu, Xiaoting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Wu, Alson [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Surakanti, Sujani; Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Langenfeld, John [Division of Surgery, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Yue, Ning J.; Haffty, Bruce G.; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States)

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  9. Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal 18F-FDG PET Features, Clinical Parameters, and Demographics

    International Nuclear Information System (INIS)

    Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]max, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than

  10. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes

  11. Bax to Bcl-2 ratio and Ki-67 index are useful predictors of neoadjuvant chemoradiation therapy in bladder cancer

    International Nuclear Information System (INIS)

    In this study, locally advanced bladder cancer was treated by radiation combined with cisplatin therapy and a retrospective analysis was conducted to predict the clinical response to chemoradiotherapy (CRT) based on the immunohistochemistry of apoptosis-related proteins. Sixty-two patients (median age, 68 years; range, 45-89 years) with transitional cell carcinoma of the bladder (pT1G3-pT4M0) treated with CRT (median dose: 40.5 Gy of radiation and 230 mg of cisplatin) were studied. Mucosal biopsy was performed before and after CRT. Paraffin-embedded tumor specimens were examined with TdT-mediated dUTP-biotin nick end-labeling (TUNEL) and were immunostained for Ki-67, p53, Bcl-2 and Bax; the Bax/Bcl-2 ratio and apoptosis index (AI) were calculated. Clinical features of the patients and response to CRT were compared with data obtained from examination of the tumors. The 62 patients had a median follow-up period of 34 months (range, 3-84 months). Responses to CRT were as follows: complete response (CR), 34%; partial response (PR), 45%; no change (NC), 21%. The survival rate of patients with Ki-67-positive tumors was significantly lower than those of patients with Ki-67-negative tumors (P<0.05). No significant correlation was observed between the expression of any protein, the AI and the clinical response. However, the Bax/Bcl-2 ratio showed a significant association with the CR rate (P=0.0289). The results of this study suggest that the combined assessment of Bcl-2 and Bax protein expression may be used to predict a clinical response to CRT based on the Bax/Bcl-2 ratio determined before therapy. The Ki-67 index may be a useful predictor of prognosis in patients treated by CRT. (author)

  12. The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

    International Nuclear Information System (INIS)

    Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on

  13. SU-C-BRA-04: Use of Esophageal Wall Thickness in Evaluation of the Response to Chemoradiation Therapy for Esophageal Cancer

    International Nuclear Information System (INIS)

    Purpose: To quantitatively evaluate the esophageal cancer response to chemoradiation therapy (CRT) by measuring the esophageal wall thickness in CT. Method: Two datasets were used in this study. The first dataset is composed of CT scans of 15 esophageal cancer patients and 15 normal controls. The second dataset is composed of 20 esophageal cancer patients who underwent PET/CT scans before (Pre-CRT) and after CRT (Post-CRT). We first segmented the esophagus using a multi-atlas-based algorithm. The esophageal wall thickness was then computed, on each slice, as the equivalent circle radius of the segmented esophagus excluding the lumen. To evaluate the changes of wall thickness, we computed the standard deviation (SD), coefficient of variation (COV, SD/Mean), and flatness [(Max–Min)/Mean] of wall thickness along the entire esophagus. Results: For the first dataset, the mean wall thickness of cancer patients and normal controls were 6.35 mm and 6.03 mm, respectively. The mean SD, COV, and flatness of the wall thickness were 2.59, 0.21, and 1.27 for the cancer patients and 1.99, 0.16, and 1.13 for normal controls. Statistically significant differences (p < 0.05) were identified in SD and flatness. For the second dataset, the mean wall thickness of pre-CRT and post-CRT patients was 7.13 mm and 6.84 mm, respectively. The mean SD, COV, and flatness were 1.81, 0.26, and 1.06 for pre-CRT and 1.69, 0.26, and 1.06 for post-CRT. Statistically significant difference was not identified for these measurements. Current results are based on the entire esophagus. We believe significant differences between pre- and post-CRT scans could be obtained, if we conduct the measurements at tumor sites. Conclusion: Results show thicker wall thickness in pre-CRT scans and differences in wall thickness changes between normal and abnormal esophagus. This demonstrated the potential of esophageal wall thickness as a marker in the tumor CRT response evaluation. This work was supported in part by

  14. Gender-based analysis of esophageal cancer patients undergoing preoperative chemoradiation: differences in presentation and therapy outcome.

    Science.gov (United States)

    Rohatgi, P R; Correa, A M; Swisher, S G; Wu, T T; Liao, Z; Komaki, R; Walsh, G L; Vaporciyan, A A; Lee, J H; Rice, D C; Roth, J A; Ajani, J A

    2006-01-01

    The purpose of this study was to identify gender-dependent differences in presentation at baseline and therapy outcome in esophageal carcinoma patients treated with preoperative chemoradiotherapy (CTRT). We stratified patients according to gender and statistically compared pretreatment clinical stage, post-CTRT effect on carcinoma in the resected specimen, overall survival (OS), and patterns of failure. Of the 235 patients who underwent preoperative CTRT, 203 were men and 32 were women. Carcinomas in women correlated significantly with clinical stage II classification (78%vs. 55%) while cancers in men correlated significantly with clinical stage III classification (39%vs. 16%; P = 0.02). Carcinomas in women also correlated significantly with lower clinical N classification; more women had cN0 (52%) compared to men (28%; P = 0.01). Similarly, in the surgical specimens, more women had pN0 (78%) compared to men (64%; P = 0.06). At a median follow-up of 37 months, 10% more women than men remain alive (63%vs. 53%; P = 0.3). Distant metastases-free survival time was longer for women than men. Our results suggest that localized esophageal carcinoma is diagnosed in more advanced stages in men than in women. The reasons for these differences remain unclear and further expansion of these observations and study of biologic differences that might exist are warranted. PMID:16722991

  15. Clinical outcomes in elderly patients with human papillomavirus–positive squamous cell carcinoma of the oropharynx treated with definitive chemoradiation therapy

    Science.gov (United States)

    Hanasoge, Sheela; Magliocca, Kelly R.; Switchenko, Jeffrey M.; Saba, Nabil F.; Wadsworth, J. Trad; El-Deiry, Mark W.; Shin, Dong M.; Khuri, Fadlo; Beitler, Jonathan J.; Higgins, Kristin A.

    2016-01-01

    Background The benefit of combined chemoradiation in elderly patients with human papillomavirus (HPV)-positive locally advanced oropharyngeal squamous cell carcinoma (SCC) must be balanced with the potential for higher toxicity rates. We performed a retrospective review of our institutional experience. Methods Patients 70 years or older with p16-positive oropharyngeal SCC treated with definitive chemoradiation from 2005 to 2013 were evaluated. Overall survival (OS), disease-free survival (DFS), and locoregional failure–free survival were calculated. Results Twenty-one eligible patients had a follow-up of 22.4 months. Estimated 5-year OS, DFS, and locoregional failure–free survival were 76.0%, 40%, and 95%, respectively. There was 1 death from acute toxicity, and 50% had unplanned hospitalizations. Sixty percent had late toxicity, and 6-month feeding tube dependence was 25%. Conclusion Elderly patients with HPV-positive locally advanced SCC of the oropharynx treated with definitive chemoradiation had good OS but high rates of acute and long-term toxicity. PMID:25899391

  16. Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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%

  19. 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%.

  20. The Role of Dual-Time Combined 18-Fluorideoxyglucose Positron Emission Tomography and Computed Tomography in the Staging and Restaging Workup of Locally Advanced Rectal Cancer, Treated With Preoperative Chemoradiation Therapy and Radical Surgery

    International Nuclear Information System (INIS)

    Purpose: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. Methods and Materials: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300mg/m2/day) followed 8-10 weeks later by surgery. All patients underwent [18F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUVmax), and percentage of SUVmax difference (Response Index = RI) between pre- and post-CRT [18F]FDG-PET scans were evaluated. Results: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUVmax was significantly higher than post-CRT (15.8, vs 5.9; p 18F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.

  1. Chemoradiation for adenocarcinoma of the anus

    International Nuclear Information System (INIS)

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

  2. Concurrent chemoradiation for vaginal cancer.

    Directory of Open Access Journals (Sweden)

    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.

  3. Combined Chemoradiation Therapy With Twice-Weekly Gemcitabine and Cisplatin for Organ Preservation in Muscle-Invasive Bladder Cancer: Long-Term Results of a Phase 1 Trial

    International Nuclear Information System (INIS)

    Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabine twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing

  4. Investigation of the pharmacokinetics of 3'-deoxy-3'-[{sup 18}F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer

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    Menda, Yusuf [Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States)], E-mail: yusuf-menda@uiowa.edu; Boles Ponto, Laura L. [Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Dornfeld, Kenneth J. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Tewson, Timothy J.; Watkins, G. Leonard [Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Gupta, Anjali K.; Anderson, Carryn; McGuire, Sarah [Department of Radiation Oncology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Schultz, Michael K.; Sunderland, John J.; Graham, Michael M. [Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Buatti, John M. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States)

    2010-05-15

    Introduction: The kinetics of the bone marrow uptake of 3'-deoxy-3'-[{sup 18}F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K{sub FLT}) and the Patlak constant (K{sub Patlak}) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08{+-}0.66, K{sub FLT}=0.045{+-}0.016 min{sup -1} and K{sub Patlak}=0.039{+-}0.013 min{sup -1}. After treatment, these values were SUV=0.74{+-}0.19, K{sub FLT}=0.011{+-}0.005 min{sup -1} and K{sub Patlak}=0.005{+-}0.002 min{sup -1}. Compartmental analysis revealed a significant drop in k{sub 3} in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT.

  5. [{sup 18}F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Elicin, Olgun [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland); Callaway, Sharon [Velocity Medical Solutions, Atlanta, Georgia (United States); Prior, John O. [Department of Nuclear Medicine, Lausanne University Hospital, Lausanne (Switzerland); Bourhis, Jean [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland); Ozsahin, Mahmut, E-mail: mahmut.ozsahin@chuv.ch [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland); Herrera, Fernanda G., E-mail: fernanda.herrera@chuv.ch [Department of Radiation Oncology, Lausanne University Hospital, Lausanne (Switzerland)

    2014-12-01

    Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using {sup 18}F-labeled fluorodeoxyglucose positron emission tomography [{sup 18}F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [{sup 18}F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BM{sub TOT}). Active bone marrow (BM{sub ACT}) was contoured based on SUV greater than the mean SUV of BM{sub TOT}. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V{sub 10}, V{sub 20}, V{sub 30}, and V{sub 40}, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BM{sub TOT} and BM{sub ACT} were 27% and 38%, respectively. BM{sub ACT} volume was significantly reduced after treatment (from 651.5 to 231.6 cm{sup 3}, respectively; P<.0001). BM{sub ACT} V{sub 30} was significantly correlated with a reduction in BM{sub ACT} SUV (R{sup 2}, 0.14; P<.001). The reduction in BM{sub ACT} SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R{sup 2}, 0.27; P=.04) and at last follow-up (R{sup 2}, 0.25; P=.04). Different dosimetric parameters of BM{sub TOT} and BM{sub ACT} correlated with long-term hematological outcome. Conclusions: The volumes of BM

  6. [18F]FDG-PET Standard Uptake Value as a Metabolic Predictor of Bone Marrow Response to Radiation: Impact on Acute and Late Hematological Toxicity in Cervical Cancer Patients Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To quantify the relationship between bone marrow (BM) response to radiation and radiation dose by using 18F-labeled fluorodeoxyglucose positron emission tomography [18F]FDG-PET standard uptake values (SUV) and to correlate these findings with hematological toxicity (HT) in cervical cancer (CC) patients treated with chemoradiation therapy (CRT). Methods and Materials: Seventeen women with a diagnosis of CC were treated with standard doses of CRT. All patients underwent pre- and post-therapy [18F]FDG-PET/computed tomography (CT). Hemograms were obtained before and during treatment and 3 months after treatment and at last follow-up. Pelvic bone was autosegmented as total bone marrow (BMTOT). Active bone marrow (BMACT) was contoured based on SUV greater than the mean SUV of BMTOT. The volumes (V) of each region receiving 10, 20, 30, and 40 Gy (V10, V20, V30, and V40, respectively) were calculated. Metabolic volume histograms and voxel SUV map response graphs were created. Relative changes in SUV before and after therapy were calculated by separating SUV voxels into radiation therapy dose ranges of 5 Gy. The relationships among SUV decrease, radiation dose, and HT were investigated using multiple regression models. Results: Mean relative pre-post-therapy SUV reductions in BMTOT and BMACT were 27% and 38%, respectively. BMACT volume was significantly reduced after treatment (from 651.5 to 231.6 cm3, respectively; P<.0001). BMACT V30 was significantly correlated with a reduction in BMACT SUV (R2, 0.14; P<.001). The reduction in BMACT SUV significantly correlated with reduction in white blood cells (WBCs) at 3 months post-treatment (R2, 0.27; P=.04) and at last follow-up (R2, 0.25; P=.04). Different dosimetric parameters of BMTOT and BMACT correlated with long-term hematological outcome. Conclusions: The volumes of BMTOT and BMACT that are exposed to even relatively low doses of radiation are associated with a decrease in WBC counts following CRT. The loss in

  7. Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC

  8. 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

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    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.

  9. Circulating Cell-Free DNA in Plasma of Locally Advanced Rectal Cancer Patients Undergoing Preoperative Chemoradiation: A Potential Diagnostic Tool for Therapy Monitoring

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    Matthias Zitt

    2008-01-01

    Full Text Available Circulating cell-free DNA opens up an interesting field for therapy monitoring, in particular during multimodal therapy protocols. The objective of this proof of principle study was to evaluate whether the amount of circulating plasma DNA has the potential to serve as a marker for therapy monitoring during the treatment course of locally advanced rectal cancer patients. We especially focused on kinetics of circulating DNA to assess whether variances in kinetics have the potential to discriminate between therapy responders and nonresponders.

  10. 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

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    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.

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

    International Nuclear Information System (INIS)

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

  12. Prognostic factors for disease-free survival in patients with T-4 or N+ rectal cancer treated with preoperative chemoradiation therapy, surgery, and intraoperative irradiation

    International Nuclear Information System (INIS)

    Purpose: Fluoropyrimidine-radiosensitizing agents in conjunction with preoperative radiotherapy have proven to induce tumor and nodal downstaging effects, sphincter preservation promotion, and mid-term favorable survival rates. Intraoperative electron beam radiation therapy may improve pelvic control in patients with locally advanced rectal cancer stages. Potential predictive factors for response and disease-free survival, with intense local multidisciplinary approach, are analyzed. Methods and Materials: One hundred fifteen patients with rectal cancer were treated with oral 5-fluorouracil or Tegafur with preoperative radiotherapy, surgery, and intraoperative electron beam radiation therapy to identify potential pre- and on-treatment characteristics that might be of prognostic value for disease outcome. Univariate and multivariate analyses were performed. Results: Older patients and those treated with Tegafur were more likely to achieve a major histologic response, categorized as persistence of minimal residual microscopic disease foci in the surgical specimen ('mic' response). Factors unfavorably associated with disease-free survival in the multivariate model were male gender and persistence of macroscopic disease in the rectal wall ('mac' response). Accordingly, 3-year disease-free survival rates in the groups of patients with 0, 1, or 2 of these risk factors were 100%, 81%, and 53%, respectively (p mic residue) to preoperative chemoradiotherapy have an excellent 3-year disease-free survival. This information might be of interest for stratification of patients in the development of adjuvant treatment trials

  13. Impact of hemoglobin level and use of recombinant erythropoietin on efficacy of preoperative chemoradiation therapy for squamous cell carcinoma of the oral cavity and oropharynx

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    Purpose: We assessed the influence of hemoglobin level and r-HuEPO administration on response to chemoradiotherapy, locoregional tumor control, and overall survival in patients treated with neoadjuvant chemoradiotherapy and surgery for a squamous cell carcinoma of the oral cavity or oropharynx. Methods and Materials: The 191 study patients were treated with mitomycin C (15 mg/m2 day 1), 5-fluorouracil (750 mg/m2/day, days 1-5), and radiotherapy (50 Gy in 25 fractions weeks 1-5), followed by resection of the primary tumor bed and neck dissection at the General Hospital Vienna, Austria, between November 1989 and October 1998 for a T2-4, N0-3, M0 SCC of the oral cavity or oropharynx. Starting in May 1996, patients with a low hemoglobin (Hgb) before or during chemoradiotherapy received r-HuEPO 10,000 IU/kg s.c. 3-6 times/week until the week of surgery. Results: On multivariate analysis, Hgb level and use of r-HuEPO were independent prognostic factors for response to chemoradiotherapy and locoregional tumor control (p14.5 g/dL (p≥0.3). Conclusion: Low pretreatment Hgb is a negative prognostic factor for oral cavity and oropharyngeal SCCA patients, but was completely abrogated by r-HuEpo administration during neoadjuvant chemoradiotherapy. Randomized trials of radiation and/or chemotherapy with or without r-HuEPO for patients whose Hgb level is either low at the start of therapy or is anticipated to become low during therapy are indicated

  14. Preclinical studies of concomitant chemoradiation

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

  15. Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non–Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Purpose: Patients treated with chemoradiotherapy for locally advanced non–small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray’s proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control

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

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    Arpit Chhabra

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

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

  19. 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

  20. Anemia During Sequential Induction Chemotherapy and Chemoradiation for Head and Neck Cancer: The Impact of Blood Transfusion on Treatment Outcome

    International Nuclear Information System (INIS)

    Purpose: Sequential treatment (chemotherapy followed by concomitant chemoradiation; CCRT) is increasingly being used for radical treatment of squamous cell cancer of the head and neck (SCCHN), which results in increased myelosuppression. In this study, we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion on disease outcomes in these patients. Methods and Materials: Retrospective review of the records of patients with SCCHN treated with sequential CCRT formed the basis of this study. The incidence of anemia and statistics on blood transfusion were documented. For the purpose of outcome analyses, patients were divided into four categories by (1) transfusion status, (2) nadir Hb concentration, (3) number of transfusion episodes, and (4) number of units of blood transfused (NOUT). Data on 3-year locoregional control (LRC), relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were analyzed. Results: One hundred and sixty-nine patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p = 0.03), DSS (71% vs. 66%, p = 0.02), and OS (58% vs. 42% p = 0.005) were significantly better for patients who did not have a transfusion vs. those who did. The LRC, RFS, DSS, and OS were also significantly better for patients with nadir Hb level >12 vs. 4. Conclusion: Our study seems to suggest that blood transfusion during radical treatment for SCCHN might be detrimental. Further research should be undertaken into the complex interactions among tumor hypoxia, anemia, and the treatment of anemia before making treatment recommendations

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

    International Nuclear Information System (INIS)

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

  2. 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

  3. Effect of Radiation Therapy Techniques on Outcome in N3-positive IIIB Non-small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

    OpenAIRE

    Noh, Jae Myoung; KIM, JIN MAN; Ahn, Yong Chan; Pyo, Hongryull; Kim, BoKyong; Oh, Dongryul; Ju, Sang Gyu; Kim, Jin Sung; Shin, Jung Suk; Hong, Chae-Seon; Park, Hyojung; Lee, Eonju

    2015-01-01

    Purpose This study was conducted to evaluate clinical outcomes following definitive concurrent chemoradiotherapy (CCRT) for patients with N3-positive stage IIIB (N3-IIIB) non-small cell lung cancer (NSCLC), with a focus on radiation therapy (RT) techniques. Materials and Methods From May 2010 to November 2012, 77 patients with N3-IIIB NSCLC received definitive CCRT (median, 66 Gy). RT techniques were selected individually based on estimated lung toxicity, with 3-dimensional conformal RT (3D-C...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-01

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

  5. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    International Nuclear Information System (INIS)

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

  6. 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.

  7. Evolución del proceso terapéutico en un caso de psicoterapia focal planificada mediante el método del tema central de conflicto relacional (CCRT)

    OpenAIRE

    López del Hoyo, Yolanda

    2010-01-01

    [ES]El objetivo del estudio era demostrar que el método del Tema Central de Conflicto Relacional (CCRT) recoge adecuadamente los patrones generales de interacción y la evolución del proceso terapéutico en un caso singular de larga duración. Para ello se aplicó el método en el caso de María, paciente española de 22 años diagnosticada de trastorno histriónico de personalidad, tratada durante 269 sesiones con psicoterapia focal planificada utilizando el sistema de categorías tradi...

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  10. 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

    International Nuclear Information System (INIS)

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% (α = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg2/day), cisplatin (15 mg/mg2/day), and paclitaxel (200 mg/mg2/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg2/day) with cisplatin (15 mg/mg2/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was ≥T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%–82%).

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-01

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

  12. Modern induction chemotherapy before chemoradiation for bulky locally-advanced nonsmall cell lung cancer improves survival

    Directory of Open Access Journals (Sweden)

    Inaya Ahmed

    2016-01-01

    Conclusion: In patients with large tumors or bulky nodal NSCLC, carboplatin-based induction chemotherapy may be an important addition to definitive CCRT in the modern era. Our findings strongly support further investigation induction chemotherapy in this population.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  16. Standardized pathologic evaluation of the esophagus after neoadjuvant chemoradiation

    NARCIS (Netherlands)

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

    2012-01-01

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

  17. Prevalence of swallowing and speech problems in daily life after chemoradiation for head and neck cancer based on cut-off scores of the patient-reported outcome measures SWAL-QOL and SHI

    NARCIS (Netherlands)

    Rinkel, Rico N; Verdonck-de Leeuw, Irma M; Doornaert, Patricia; Buter, Jan; de Bree, Remco; Langendijk, Johannes A; Aaronson, Neil K; Leemans, C René

    2015-01-01

    The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is

  18. Prevalence of swallowing and speech problems in daily life after chemoradiation for head and neck cancer based on cut-off scores of the patient-reported outcome measures SWAL-QOL and SHI

    NARCIS (Netherlands)

    Rinkel, Rico N.; Verdonck-de Leeuw, Irma M.; Doornaert, Patricia; Buter, Jan; de Bree, Remco; Langendijk, Johannes A.; Aaronson, Neil K.; Leemans, C. Rene

    2016-01-01

    The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is

  19. Continuous Low-Dose Oral Chemotherapy in Recurrent and Persistent Carcinoma of Cervix Following Chemoradiation: A Comparative Study Between Prolonged Oral Cyclophosphamide and Oral Etoposide

    OpenAIRE

    Upasana Baruah; Debabrata Barmon; Munlima Hazarika; Pankaj Deka; Amal Chandra Kataki; Sushruta Shrivastava

    2014-01-01

    Aim: To compare the efficacy and toxicities of low-dose oral cyclophosphamide and oral etoposide in patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy. Materials and Methods: 30 patients with recurrent and persistent cervical cancer with gross pelvic disease were enrolled in this trial. The patients were randomly divided into two groups of 15 patients each with one group receiving low dose oral cyclophosphamide ...

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

    Science.gov (United States)

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

    2016-03-01

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

  2. 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.

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

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    Sushma Agrawal

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

  5. Drug Combinations in Preoperative Chemoradiation for Rectal Cancer.

    Science.gov (United States)

    Glynne-Jones, Rob; Carvalho, Carlos

    2016-07-01

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

  6. Analysis of adjuvant treatment with chemoradiation in gastric cancer

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

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

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    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

  9. Integration of filgrastim into chemoradiation for limited small cell lung cancer: a phase I study

    International Nuclear Information System (INIS)

    Purpose: Recent studies document the value of early combined modality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation. Methods and Materials: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) ± filgrastim (5 μg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim. Results: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1-3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete). Conclusions: Despite

  10. Impact of chemotherapy and definitive radiotherapy for laryngeal preservation. A comparative study of concurrent chemoradiotherapy and induction chemotherapy followed by radiation therapy

    International Nuclear Information System (INIS)

    During the past 23 years, from June 1989 to December 2012, our treatment paradigm for head and neck squamous cell carcinoma (HNSCC) had involved comprehensive use of chemotherapy and radiation therapy followed by surgery. Between 1989 and 2005, chemotherapy using fluorouracil and carboplatin had been administered via intravenous drip infusion as induction chemotherapy (ICT), and more recently between 2006 and 2012 as concurrent chemoradiotherapy (CCRT). In the present study, we examined the superiority of definitive CCRT (dCCRT) over the ICT followed by definitive radiotherapy (ICT-dRT) as to the impact on the treatment of HNSCC with the stage-categories of T2-T4a, retrospectively analyzing survival rates and laryngeal preservation rates at the 3-year point between the two groups. The number of patients assigned for this study was 76, all of whom were previously untreated, and of whom 51 suffered from laryngeal carcinoma and 25 from hypopharyngeal carcinoma: 21 with Stage II, 25 with Stage III, 23 with Stage IV A, 7 with Stage IV C. The three-year overall survival rate and cause-specific survival rate were 54.5%, 73.5% in the ICT-dRT group and 69.2%, 80.5% in the dCCRT group, respectively, both of which statistically had no difference. But the dCCRT was found to contribute to obtaining a higher rate of laryngeal preservation than that of the ICT-dRT in T2 and T3 but not in T4a. In conclusion, dCCRT showed more significant efficacy for organ preservation on T2 and T3 HNSCC than ICT-dRT. (author)

  11. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    International Nuclear Information System (INIS)

    Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC

  12. Preoperative Chemoradiation for Rectal Cancer Using Capecitabine and Celecoxib Correlated With Posttreatment Assessment of Thymidylate Synthase and Thymidine Phosphorylase Expression

    International Nuclear Information System (INIS)

    Purpose: Thymidylate synthase (TS) and thymidine phosphorylase (TP) expression have been shown to be predictors of response to therapy. The toxicity, efficacy, surgical morbidity, and immunohistochemical TS and TP expression were assessed in surgical resection specimens after preoperative chemoradiation. Methods and Materials: Twenty patients with clinical stage I to III rectal adenocarcinoma received preoperative chemoradiation and underwent surgical resection 6 weeks later. Results: Posttreatment tumor stages were T1 to T2 and N0 in 30% of patients; T3 to T4 and N0 in 30% of patients; and T1 to T3 and N1 to N2 in 15% of patients. Pathologic complete response (pCR) was evident in 25% and tumor regression occurred in a total of 80% of patients. Anal sphincter-sparing surgery was performed in 80% of cases. Acute and perioperative complications were minimal, with no grade 3/4 toxicity or treatment breaks. Pelvic control was obtained in 90% of patients. With a median follow-up of 65.5 months (range, 8-80 months), the 6-year actuarial survival rate was 75%. Local failure was significantly associated with nonresponse to therapy and with high TS and low TP expression (p = 0.008 and p = 0.04, respectively). Conclusions: The combination of capecitabine, celecoxib, and x-radiation therapy yields excellent response: a 25% pathologic pCR, no acute grade 3/4 toxicity, and minimal surgical morbidity. Nonresponders expressed significantly increased TS levels and decreased TP levels in posttreatment resection specimens compared to responders.

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

    International Nuclear Information System (INIS)

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

  14. 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.

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

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    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

  16. Quality of life and tumor control after short split-course chemoradiation for anal canal carcinoma

    International Nuclear Information System (INIS)

    To evaluate quality of life (QOL) and outcome of patients with anal carcinoma treated with short split-course chemoradiation (CRT). From 1991 to 2005, 58 patients with anal cancer were curatively treated with CRT. External beam radiotherapy (52 Gy/26 fractions) with elective groin irradiation (24 Gy) was applied in 2 series divided by a median gap of 12 days. Chemotherapy including fluorouracil and Mitomycin-C was delivered in two sequences. Long-term QOL was assessed using the site-specific EORTC QLQ-CR29 and the global QLQ-C30 questionnaires. Five-year local control, colostomy-free survival, and overall survival were 78%, 94% and 80%, respectively. The global QOL score according to the QLQ-C30 was good with 70 out of 100. The QLQ-CR29 questionnaire revealed that 77% of patients were mostly satisfied with their body image. Significant anal pain or fecal incontinence was infrequently reported. Skin toxicity grade 3 or 4 was present in 76% of patients and erectile dysfunction was reported in 100% of male patients. Short split-course CRT for anal carcinoma seems to be associated with good local control, survival and long-term global QOL. However, it is also associated with severe acute skin toxicity and sexual dysfunction. Implementation of modern techniques such as intensity-modulated radiation therapy (IMRT) might be considered to reduce toxicity

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

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

    2006-09-15

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

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

    International Nuclear Information System (INIS)

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

  19. Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

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

  20. 认知矫正治疗慢性精神分裂症患者认知功能缺陷的随机对照研究%Effects of cognitive remediation therapy and computerized cognitive remediation therapy on cognitive deficits in patients with schizophrenia: a randomized controlled study

    Institute of Scientific and Technical Information of China (English)

    谭淑平; 韩标; 张丽霞; 宋崇升; 李钦云; 刘永昌; 屈威; 艾霞; 李东; 李晓玲; 周东丰; 邹义壮; 王向群; 权文香; 李占江; 郭俊花; 王健; 杨甫德; 张广慧; 崔勇; 崔介峰; 陈楠; 范宏振

    2010-01-01

    Objective To explore the effects of cognitive remediation therapy (CRT) and computerized cognitive remediation therapy ( CCRT ) on cognitive deficits in patients with schizophrenia. Methods A total of 180 chronic inpatients with schizophrenia in stable clinical condition was randomized divided into three groups: CCRT, CRT and Work and Amusement Therapy (WAT). In addition to medication as usual, and under directions of therapists, patients in CCRT group received computerized cognitive remediation therapy (CCRT) which developed by this research team, CRT group received a Chinese version of manual cognitive remediation therapy derived from Neurocognitive Remediation Manual which revised by Til, Wykes, WAT group received operative musical therapy and dancing training. All of the three types of therapy lasted 3 months with 4 sessions per week, 45 minutes per session. A series of assessment were administrated pre-and post-treatment and 3-month follow up, including clinical symptoms using the PANSS scales and cognitive functions using a Chinese cognitive function test battery of schizophrenia and Wisconsin card sorting test ( WCST ). Results A total of 108 ones was recruited in CCRT group, 36 in CRT group, and 36 in WAT group. There were no significant difference among three groups in age ( 46.4 ±8.9,47.5 ±8. 1,45.8 ± 8.3) ,years of education(10. 0 ±2.5,10.4 ±2.7,10. 1 ±2.6),duration of disease (years) (22. 1 ±10. 2, 23.8 ± 10. 2, 20.9 ± 10.5) ,total score of PANSS (60. 4 ±12.5,61.3 ± 11.7, 62.8 ± 14. 1 ) or any index of cognitive measurement at baseline. After a three-month treatment, comparing with WAT group, significant improvements revealed in categories of WCST test (F=4. 16,P=0. 017),trail A (F=4.25,P = 0. 016), spatial span(F=5.40,P=0. 005),symbol coding ( F = 3.09, P = 0. 048 ) both in CCRT and CRT groups. A significant advantage ( P < 0. 05 ) appeared in spatial span in CCRT group comparing to CRT. However, CRT had an advantage in symbol coding than

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

    International Nuclear Information System (INIS)

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

  2. Outcome With Neck Dissection After Chemoradiation for N3 Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Purpose: To evaluate the role of neck dissection (ND) after chemoradiation therapy (CRT) for head and neck squamous cell carcinoma (HNSCC) with N3 disease. Methods and Materials: From March 1998 to September 2006, 70 patients with HNSCC and N3 neck disease were treated with concomitant CRT as primary therapy. Response to treatment was assessed using clinical examination and computed tomography 6 to 8 weeks posttreatment. Neck dissection was not routinely performed and considered for those with less than complete response. Of the patients, 26 (37.1%) achieved clinical complete response (cCR) after CRT. A total of 31 (44.3%) underwent ND after partial response (cPR-ND). Thirteen patients (29.5%) did not achieve cCR and did not undergo ND for the following reasons: incomplete response/progression at primary site, refusal/contraindication to surgery, metastatic progression, or death. These patients were excluded from the analysis. Outcomes were computed using Kaplan-Meier curves and were compared with log rank tests. Results: Comparing the cCR and cPR-ND groups at 2 years, the disease-free survival was respectively 62.7% and 84.9% (p = 0.048); overall survival was 63.0% and 79.4% (p = 0.26), regional relapse-free survival was 87.8% and 96.0% (p = 0.21); and distant disease-free survival was 67.1% and 92.6% (p = 0.059). In the cPR-ND group, 71.0% had no pathologic evidence of disease (PPV of 29.0%). Conclusions: Patients with N3 disease achieving regional cPR and primary cCR who underwent ND seemed to have better outcomes than patients achieving global cCR without ND. Clinical assessment with computed tomography is not adequate for evaluating response to treatment. Because of the inherent limitations of our study, further confirmatory studies are warranted.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

  5. 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.

  6. Impact of weight loss on survival after chemoradiation for locally advanced head and neck Cancer: secondary results of a randomized phase III trial (SAKK 10/94)

    International Nuclear Information System (INIS)

    To analyze the impact of weight loss before and during chemoradiation on survival outcomes in patients with locally advanced head and neck cancer. From 07/1994-07/2000 a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to either hyperfractionated radiation therapy alone or the same radiation therapy combined with two cycles of concomitant cisplatin. The primary endpoint was time to any treatment failure (TTF); secondary endpoints were locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS). Patient weight was measured 6 months before treatment, at treatment start and treatment end. The proportion of patients with >5% weight loss was 32% before, and 51% during treatment, and the proportion of patients with >10% weight loss was 12% before, and 17% during treatment. After a median follow-up of 9.5 years (range, 0.1 – 15.4 years) weight loss before treatment was associated with decreased TTF, LRRFS, DMFS, cancer specific survival and OS in a multivariable analysis. However, weight loss during treatment was not associated with survival outcomes. Weight loss before and during chemoradiation was commonly observed. Weight loss before but not during treatment was associated with worse survival

  7. miR-193a-3p regulation of chemoradiation resistance in oesophageal cancer cells via the PSEN1 gene.

    Science.gov (United States)

    Meng, Fang; Qian, Liting; Lv, Lei; Ding, Bojin; Zhou, Gieping; Cheng, Xu; Niu, Sanqiang; Liang, Yu

    2016-04-01

    Chemoradiation therapy is an important component of the curative treatment for oesophageal carcinomas. These therapeutic effects are prevented in patients according to radioresistance and multi-drug resistance, and the cause of such resistance remains unclear. In this study, we identified the role of miR-193a-3p in modulating the radioresistance and chemoresistance of oesophageal cancer cells. We found that KYSE150 and KYSE410 cells could be characterized as relatively radiation-sensitive and radiation-resistant cells, respectively. Similarly, KYSE150 and KYSE410 cells were found to be chemosensitive and chemoresistant, respectively. Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1. Thus, miR-193a-3p and PSEN1 might be potential biomarkers for chemoradiation resistant cancers. PMID:26743123

  8. Adjuvant Therapy of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Chakra P Chaulagain

    2011-07-01

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

  9. Prevalence of swallowing and speech problems in daily life after chemoradiation for head and neck cancer based on cut-off scores of the patient-reported outcome measures SWAL-QOL and SHI.

    Science.gov (United States)

    Rinkel, Rico N; Verdonck-de Leeuw, Irma M; Doornaert, Patricia; Buter, Jan; de Bree, Remco; Langendijk, Johannes A; Aaronson, Neil K; Leemans, C René

    2016-07-01

    The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is a cross-sectional study. Department of Otolaryngology/Head and Neck Surgery of a University Medical Center. Sixty patients, 6 months to 5 years after chemoradiation for head and neck squamous cell carcinoma. Swallowing Quality of Life Questionnaire (SWAL-QOL) and SHI, both validated in Dutch and provided with cut-off scores. Associations were tested between the outcome measures and independent variables (age, gender, tumor stage and site, and radiotherapy technique, time since treatment, comorbidity and food intake). Fifty-two patients returned the SWAL-QOL and 47 the SHI (response rate 87 and 78 %, respectively). Swallowing and speech problems were present in 79 and 55 %, respectively. Normal food intake was noticed in 45, 35 % had a soft diet and 20 % tube feeding. Patients with soft diet and tube feeding reported more swallowing problems compared to patients with normal oral intake. Tumor subsite was significantly associated with swallowing outcome (less problems in larynx/hypopharynx compared to oral/oropharynx). Radiation technique was significantly associated with psychosocial speech problems (less problems in patients treated with IMRT). Swallowing and (to a lesser extent) speech problems in daily life are frequently present after chemoradiation therapy for head and neck cancer. Future prospective studies will give more insight into the course of speech and swallowing problems after chemoradiation and into efficacy of new radiation techniques and swallowing and speech rehabilitation programs. PMID:26071622

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

    International Nuclear Information System (INIS)

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

  11. Adjuvant Therapy of Pancreatic Cancer

    OpenAIRE

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

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

  13. 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.

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

    International Nuclear Information System (INIS)

    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

  15. Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients – A triple blinded randomized controlled trial

    International Nuclear Information System (INIS)

    Background and purpose: Oral mucositis (OM) is most cumbersome acute side effect of concurrent chemoradiotherapy (CCRT) for head and neck cancer (HNC). OM associated pain affects oral functions and nutrition of the patient that may result in discontinuity of treatment. Several modalities have been tried to prevent and treat OM, but none proved completely successful until date. We used prophylactic low level laser therapy (LLLT) for the prevention and treatment of CCRT induced OM. Materials and methods: In this triple blinded study, 221 HNC patients scheduled to undergo CCRT (Cisplatin (1, 22, 43 day) + RT = 66 Grays (2 Gy/fraction), 33 fractions, 5 fractions/week, for 45 days) were block randomized into laser (n = 111) and placebo (n = 110) group. Laser group received LLLT (HeNe, λ = 632.8 nm, power-density = 24 mW, dosage = 3.0 J/point, total dosage/session = 36–40 J, spot-size = 1 cm2, 5 sessions/week) while placebo received sham treatment daily prior to radiation. OM (RTOG/EORTC Scale), oral pain (VAS), dysphagia (FIS), weight loss and CCRT break were assessed. Data were analyzed using frequencies and percentage, generalized estimating equations (GEE) and odds ratio. Results: There was significant reduction in incidence of severe OM (F = 16.64, df = 8876, p < 0.0001) and its associated pain (F = 25.06, df = 8876, p < 0.0001), dysphagia (F = 20.17, df = 8876, p < 0.0001) and opioid analgesics use (p < 0.0001) in laser than placebo group patients. Conclusions: LLLT decreased the incidence of CCRT induced severe OM and its associated pain, dysphagia and opioid analgesics use.

  16. Cervical necrosis after chemoradiation for cervical cancer: case series and literature review

    International Nuclear Information System (INIS)

    The aim of this study was to assess the management of cervical necrosis (CN) following radiotherapy (RT) and the impact of smoking status. This rare complication mimics a neoplastic recurrence, and causes concern among attending physicians. Between July 2008 and March 2013, 5 women on 285 with localized cervical cancer had a CN following RT. Patients were treated with concomitant chemoradiation. The medical records were reviewed to abstract demographic and clinical information until March 2013. 1.75% (95% confidence interval: 0.23 to 3.28%) developed CN. All patients were smokers with a mean of 19.5 pack-years (range: 7.5-45 pack-years). All patients were treated with weekly Cisplatin chemotherapy and external beam radiation to the pelvis, 45 Gy in 25 fractions. Four patients received an extra boost with a median dose of 7.2 Gy (range: 5.4-10 Gy). All patients had intracavitary brachytherapy (range: 27.9 to 30 Gy). Clinical presentation was similar for all the cases: vaginal discharge associated with pain. Mean time for time post-radiation therapy to necrosis was 9.3 months (range: 2.2-20.5 months). Standard workup was done to exclude cancer recurrence: biopsies and radiologic imaging. Conservative treatment was performed with excellent results. Resolution of the necrosis was complete after a few months (range: 1 to 4 months). Median follow-up until March 2013 was 19 months. All the patients were alive with no clinical evidence of disease. This study, the largest to date, shows that conservative management of CN after RT is effective, and should be attempted. This complication is more common in smokers, and counseling intervention should result in fewer complications of CN

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

    International Nuclear Information System (INIS)

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

  18. Role of radiation therapy in gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Lisa Hazard; John O'Connor; Courtney Scaife

    2006-01-01

    Outcomes in patients with gastric cancer in the United States remain disappointing, with a five-year overall survival rate of approximately 23%. Given high rates of local-regional control following surgery, a strong rationale exists for the use of adjuvant radiation therapy.Randomized trials have shown superior local control with adjuvant radiotherapy and improved overall survival with adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who have undergone D2 lymph node dissection by an experienced surgeon is not known, and the benefit of adjuvant radiation therapy in addition to adjuvant chemotherapy continues to be defined.In unresectable disease, chemoradiation allows long-term survival in a small number of patients and provides effective palliation. Most trials show a benefit to combined modality therapy compared to chemotherapy or radiation therapy alone.The use of pre-operative, intra-operative, 3D conformal, and intensity modulated radiation therapy in gastric cancer is promising but requires further study.The current article reviews the role of radiation therapy in the treatment of resectable and unresectable gastric carcinoma, focusing on current recommendations in the United States.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Gregory MM Videtic

    2003-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Pramana, J.

    2014-01-01

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

  4. Relationship Between Low Hemoglobin Levels and Outcomes After Treatment With Radiation or Chemoradiation in Patients With Cervical Cancer: Has the Impact of Anemia Been Overstated?

    International Nuclear Information System (INIS)

    Purpose: Previous reports have suggested that anemia increases rates of recurrence after radiation therapy for cervical cancer. However, these studies may not have fully corrected for confounding risk factors. Using a well-characterized cohort of cervical cancer patients, we examined the association between anemia and outcomes before and after the introduction of chemoradiation as standard of care. Methods and Materials: We reviewed the records of 2454 patients who underwent definitive radiation therapy from 1980 through 2011. Minimum hemoglobin level (Hgbmin) was recorded for 2359 patients (96%). Endpoints included freedom from central recurrence (FFCR), freedom from distant metastasis (FFDM), and disease-specific survival (DSS). Results: For the entire cohort, hemoglobin concentrations of 9, 10, and 12 g/dL before and during radiation were all significantly associated with FFCR, FFDM, and DSS (all P<.001) on univariate analysis. However, on multivariate analysis, only Hgbmin less than 10 g/dL during RT (RT-Hgb<10) remained significant, and it was correlated with lower DSS (P=.02, hazard ratio [HR] = 1.28) and FFDM (P=.03, HR = 1.33) but not with FFCR. In a subset analysis of patients receiving chemoradiation (n=678), RT-Hgb<10 was associated only with DSS (P=.008, HR = 1.49), not with FFCR or FFDM. In this subgroup, despite an association between RT-Hgb<10 and DSS, the use of transfusion was not correlated with benefit. Conclusions: No evidence was found supporting anemia as an independent predictor of central recurrence in patients treated with definitive radiation therapy with or without chemotherapy. Less emphasis on correcting anemia in cervical cancer patients may be warranted

  5. Relationship Between Low Hemoglobin Levels and Outcomes After Treatment With Radiation or Chemoradiation in Patients With Cervical Cancer: Has the Impact of Anemia Been Overstated?

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, Andrew J.; Allen, Pamela K.; Klopp, Ann H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Meyer, Larissa A. [Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eifel, Patricia J., E-mail: peifel@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-01-01

    Purpose: Previous reports have suggested that anemia increases rates of recurrence after radiation therapy for cervical cancer. However, these studies may not have fully corrected for confounding risk factors. Using a well-characterized cohort of cervical cancer patients, we examined the association between anemia and outcomes before and after the introduction of chemoradiation as standard of care. Methods and Materials: We reviewed the records of 2454 patients who underwent definitive radiation therapy from 1980 through 2011. Minimum hemoglobin level (Hgb{sub min}) was recorded for 2359 patients (96%). Endpoints included freedom from central recurrence (FFCR), freedom from distant metastasis (FFDM), and disease-specific survival (DSS). Results: For the entire cohort, hemoglobin concentrations of 9, 10, and 12 g/dL before and during radiation were all significantly associated with FFCR, FFDM, and DSS (all P<.001) on univariate analysis. However, on multivariate analysis, only Hgb{sub min} less than 10 g/dL during RT (RT-Hgb{sub <10}) remained significant, and it was correlated with lower DSS (P=.02, hazard ratio [HR] = 1.28) and FFDM (P=.03, HR = 1.33) but not with FFCR. In a subset analysis of patients receiving chemoradiation (n=678), RT-Hgb{sub <10} was associated only with DSS (P=.008, HR = 1.49), not with FFCR or FFDM. In this subgroup, despite an association between RT-Hgb{sub <10} and DSS, the use of transfusion was not correlated with benefit. Conclusions: No evidence was found supporting anemia as an independent predictor of central recurrence in patients treated with definitive radiation therapy with or without chemotherapy. Less emphasis on correcting anemia in cervical cancer patients may be warranted.

  6. Correlation of F-18 FDG PET with morphometric tumor response after neoadjuvant chemoradiation in locally advanced (stage III) non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Aim: To determine the role of 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) positron emission tomography (PET) in morphometric tumor response after neoadjuvant chemoradiation, findings in 32 patients were analyzed prospectively in an ongoing multicenter trial (LUCAS-MD, Germany). Material and Methods: Inclusion criteria was histologically confirmed NSCLC stage IIIA/IIIB. For staging all patients received a PET scan in addition to a spiral CT and/or MRI before therapy. Neoadjuvant treatment consisted of 2-3 cycles of chemotherapy with paclitaxel (225 mg/m2) and carboplatin (AUC 6), each d1 q22 and a block of chemoradiation (45Gy, 1.5Gy b.i.d., concomitant with paclitaxel (50 mg/m2) and carboplatin (AUC = 2), each d1, d8, d15) followed by surgery. All patients received a second PET after completion of neoadjuvant therapy prior to surgery. Whole-body PET (ECAT Exact 47) studies (attenuation corrected, iteratively reconstructed) were obtained 60 min. after injection of 6 MBq/kg body weight F-18 FDG. For semi-quantitative analysis, the tumor standardized uptake values (SUV), the tumor to background SUV ratio (T/B ratio), the metabolic tumor diameter (MTD) and the metabolic tumor index (MTI = SUV x MTD) were assessed in all primary tumors and in metastatic lymph nodes. Additionally, image fusion of PET with CT data was applied (using a HERMES Computer, Nuclear Diagnostics, Sweden). Results: So far, all patients (7/32) with complete metabolic response in lymph node metastases detected by PET, had no vital tumor cells (morphometric regression grade III). In primary tumors showing complete metabolic response, the regression grade was IIB (less than 10% vital tumor cells) or III. Conclusion: Morphometric tumor response after neoadjuvant therapy correlates strongly with metabolic remission by FDG-PET. PET precedes the tumor response as measured by CT after neoadjuvant treatment and may predict the long term therapeutic outcome in stage III NSCLC

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

    Energy Technology Data Exchange (ETDEWEB)

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

    International Nuclear Information System (INIS)

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

  9. 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

  10. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    International Nuclear Information System (INIS)

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

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

    International Nuclear Information System (INIS)

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

  12. Small Bowel Dose Parameters Predicting Grade ≥3 Acute Toxicity in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation: An Independent Validation Study Comparing Peritoneal Space Versus Small Bowel Loop Contouring Techniques

    International Nuclear Information System (INIS)

    Purpose: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. Methods and Materials: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Results: Grade ≥3 small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. Conclusion: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity

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

    International Nuclear Information System (INIS)

    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.

  14. In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, Joseph W., E-mail: jwshelt@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waxweiler, Timothy V.; Landry, Jerome; Gao, Huiying; Xu, Yanbo; Wang, Lanfang [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); El-Rayes, Bassel [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Shu, Hui-Kuo G. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2013-07-01

    Purpose: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. Methods and Materials: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assays were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm{sup 3}. Results: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. Conclusion: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens.

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

    Directory of Open Access Journals (Sweden)

    Prasad Eswaran

    2013-01-01

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

  16. In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Purpose: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. Methods and Materials: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assays were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm3. Results: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. Conclusion: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens

  17. Pathological stage after neoadjuvant chemoradiation and esophagectomy superiorly predicts survival in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Background and purpose: To assess the usefulness of pathological stage according to the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC–AJCC) as a prognostic tool in patients undergoing neoadjuvant chemoradiation followed by esophagectomy (trimodality therapy, TMT) for locally advanced esophageal squamous cell carcinoma. Material and methods: One hundred twenty-five eligible patients completing TMT were enrolled for analysis. The clinical (cTNM7) and pathological (ypTNM7) stage groups of their tumors were prospectively classified, and re-grouped by the 6th edition (ypTNM6). Survival was analyzed using the Kaplan–Meier method. The Cox proportional hazard model and the Akaike information criterion (AIC) were used to compare the performance of staging systems. Results: With a median follow-up of 24.6 months, 54 patients (43.2%) died. Forty patients (32%) achieved pathological complete remission (pCR). The median survival was 31.8 months. On multivariate analysis, ypTNM7 (but not pCR or pN) was the only independent factor affecting overall survival (p < 0.001). The ypTNM7 was superior to cTNM7 or ypTNM6 in predicting both overall and recurrence-free survival after TMT based on AIC values and Cox proportional hazard model analysis. Conclusions: In patients with locally advanced esophageal squamous cell carcinoma undergoing TMT, ypTNM7 is the best predictor of survival

  18. Expression of phosphoenolpyruvate carboxykinase linked to chemoradiation susceptibility of human colon cancer cells

    International Nuclear Information System (INIS)

    Resistance to 5-fluorouracil (5-FU) in patients with colorectal cancer prevents effective treatment and leads to unnecessary and burdensome chemotherapy. Therefore, prediction of 5-FU resistance is imperative. To identify the proteins linked to 5-FU resistance, two-dimensional gel electrophoresis-based proteomics was performed using the human colon cancer cell line SNU-C4R with induced 5-FU resistance. Proteins showing altered expression in SNU-C4R were identified by matrix-associated laser desorption/ionization–time-of-flight analysis, and their roles in susceptibility to 5-FU or radiation were evaluated in various cell lines by transfection of specific siRNA or creation of overexpression constructs. Changes in cellular signaling and expression of mitochondrial apoptotic factors were investigated by Western Blot analysis. A mitochondrial membrane potential probe (JC-1 dye) and a flow cytometry system were employed to determine the mitochondrial membrane potential. Finally, protein levels were determined by Western Blot analysis in tissues from 122 patients with rectal cancer to clarify whether each identified protein is a useful predictor of a chemoradiation response. We identified mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK) as a candidate predictor of 5-FU resistance. PEPCK was downregulated in SNU-C4R compared with its parent cell line SNU-C4. Overexpression of mPEPCK did not significantly alter the susceptibility to either 5-FU or radiation. Suppression of mPEPCK led to a decrease in both the cellular level of phosphoenolpyruvate and the susceptibility to 5-FU and radiation. Furthermore, the cellular levels of phosphoenolpyruvate (an end product of PEPCK and a substrate of pyruvate kinase), phosphorylated AKT, and phosphorylated 4EBP1 were decreased significantly secondary to the mPEPCK suppression in SNU-C4. However, mPEPCK siRNA transfection induced changes in neither the mitochondrial membrane potential nor the expression levels of

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

    International Nuclear Information System (INIS)

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

  20. Continuous low-dose oral chemotherapy in recurrent and persistent carcinoma of cervix following chemoradiation: A comparative study between prolonged oral cyclophosphamide and oral etoposide

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    Upasana Baruah

    2014-01-01

    Full Text Available Aim: To compare the efficacy and toxicities of low-dose oral cyclophosphamide and oral etoposide in patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy. Materials and Methods: 30 patients with recurrent and persistent cervical cancer with gross pelvic disease were enrolled in this trial. The patients were randomly divided into two groups of 15 patients each with one group receiving low dose oral cyclophosphamide (100 mg/day and the other group receiving low-dose oral etoposide (50 mg/day. Results were statistically analysed by IBM SPSS Statistics 19. Results: Oral etoposide was not well tolerated with grade 2 neutropenia occurring in 33.3% and grade 3 neutropenia in 6.6% and thrombocytopenia occurring in 13.3%. Oral cyclophosphamide group on the other hand was better tolerated with none of the patients having thrombocytopenia and 6.6% patients having grade 2 neutropenia. There were two complete response (15.38% and one partial response at the end of study (7.6% in the cyclophosphamide group whereas there was no complete response and two partial response (16.6% in the oral etoposide group. Conclusion: Long-term, low-dose oral etoposide was found to be less tolerated without any significant effect with patients with persistent and recurrent cervical cancer with gross pelvic disease following full course of chemoradiation therapy in contrast to oral cyclophosphamide which was found to be effective and well-tolerated by the patients.

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

    International Nuclear Information System (INIS)

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

  2. Brachytherapy versus radical hysterectomy after external beam chemoradiation: a non-randomized matched comparison in IB2-IIB cervical cancer patients

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    Flores Vladimir

    2009-02-01

    Full Text Available Abstract Background A current paradigm in the treatment of cervical cancer with radiation therapy is that intracavitary brachytherapy is an essential component of radical treatment. This is a matched retrospective comparison of the results of treatment in patients treated with external beam chemoradiation (EBRT-CT and radical hysterectomy versus those treated with identical chemoradiation followed by brachytherapy. Methods In this non-randomized comparison EBRT-CT protocol was the same in both groups of 40 patients. In the standard treated patients, EBRT-CT was followed by one or two intracavitary Cesium (low-dose rate applications within 2 weeks of finishing external radiation to reach a point A dose of at least 85 Gy. In the surgically treated patients, radical hysterectomy with bilateral pelvic lymph node dissection and para-aortic lymph node sampling were performed within 7 weeks after EBRT-CT. Response, toxicity and survival were evaluated. Results A total of 80 patients were analyzed. The patients receiving EBRT-CT and surgery were matched with the standard treated cases. There were no differences in the clinicopathological characteristics between groups or in the delivery of EBRT-CT. The pattern of acute and late toxicity differed. Standard treated patients had more chronic proctitis while the surgically treated had acute complications of surgery and hydronephrosis. At a maximum follow-up of 60 months, median follow-up 26 (2–31 and 22 (3–27 months for the surgery and standard therapy respectively, eight patients per group have recurred and died. The progression free and overall survival are the same in both groups. Conclusion The results of this study suggest that radical hysterectomy can be used after EBRT-CT without compromising survival in FIGO stage IB2-IIB cervical cancer patients in settings were brachytherapy is not available. A randomized study is needed to uncover the value of surgery after EBRT-CT.

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

    OpenAIRE

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

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Aghili M

    2010-10-01

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

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

    International Nuclear Information System (INIS)

    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.)

  9. Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation

    International Nuclear Information System (INIS)

    The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer. From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed. With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0–1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2–3 group with no statistical significance (P = 0.873). An elevated baseline NLR is a valuable and easily available prognostic factor for OS in

  10. Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.

    Science.gov (United States)

    Gómez Del Pulgar, Teresa; Cebrián, Arancha; Fernández-Aceñero, Maria Jesús; Borrero-Palacios, Aurea; Del Puerto-Nevado, Laura; Martínez-Useros, Javier; Marín-Arango, Juan Pablo; Caramés, Cristina; Vega-Bravo, Ricardo; Rodríguez-Remírez, María; Cruz-Ramos, Marlid; Manzarbeitia, Félix; García-Foncillas, Jesús

    2016-09-01

    Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio- and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre-treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease-free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence. PMID:27171907

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

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    Reynolds John

    2007-08-01

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

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

    International Nuclear Information System (INIS)

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

  13. State of the art of radiation therapy for esophageal cancer

    International Nuclear Information System (INIS)

    Radiation therapy has a critical role in the treatment of esophageal cancer. To improve the treatment outcome of radiotherapy, not only strengthening the treatment intensity but also decreasing the long term toxicity is needed. To reduce the long term cardiopulmonary toxicity of chemoradiation, JCOG is now running a clinical trial which combines three dimensional conformal radiation therapy (3D-CRT) and mild irradiation dose. New techniques of radiation therapy, such as intensity modulated radiation therapy (IMRT) or particle therapy are also promising in both treatment intensity and decreased toxicity. (author)

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

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

    2013-06-01

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

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

    International Nuclear Information System (INIS)

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

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

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

    2014-03-15

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

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

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  20. 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.

  1. Value of gadofosveset-enhanced MRI and multiplanar reformatting for selecting good responders after chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Our primary objective was to evaluate diagnostic performance of gadofosveset T1-weighted magnetic resonance imaging (T1W MRI) for discriminating between ypT0-2 and ypT3-4 tumours after chemoradiation therapy (CRT) for rectal cancer compared with T2W MRI for a general and expert reader. Second objectives included assessing the value of multiplanar reformatting (MPR) and interobserver agreement. A general and expert reader evaluated 49 patients for likelihood of ypT0-2 tumour after CRT on T2W, gadofosveset T1W MRI, and gadofosveset T1W MRI + T2W MRI. The general reader scored with and without MPR. Confidence level scores were used to construct receiver-operating characteristic (ROC) curves. Area under the curve (AUC) values and diagnostic parameters were calculated and compared. Gadofosveset T1W MRI + T2W MRI showed slightly superior sensitivity than T2W MRI for the general but not the expert reader. Specificity was higher for the expert on gadofosveset T1W MRI only compared with T2W MRI only (100 % vs. 82 %). MPR did not increase diagnostic performance. Interobserver agreement was highest for the combination of gadofosveset-enhanced T1W imaging plus T2W MRI. The sole use or addition of gadofosveset-enhanced T1W MRI to T2W MRI did not increase significantly diagnostic performance for assessing ypT0-2 tumours. Adding gadofosveset-enhanced T1W MRI slightly increased sensitivity for the general reader and specificity for the expert reader, but this increase was not significant for more accurate clinical decision making. MPR did not improve diagnostic performance. (orig.)

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

    International Nuclear Information System (INIS)

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

  3. Two-year results of a prospective preventive swallowing rehabilitation trial in patients treated with chemoradiation for advanced head and neck cancer

    NARCIS (Netherlands)

    L. van der Molen; M. van Rossum; C.R.N. Rasch; L.E. Smeele; F.J.M. Hilgers

    2013-01-01

    The objective of the study was the assessment of the results of a prospective clinical trial with two preventive swallowing rehabilitation programs on the long-term side effects of chemoradiotherapy (CCRT) in advanced head and neck cancer patients. The study cohort consisted of 29 patients, randomiz

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

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    Biswamit Bhattacharya

    2014-01-01

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

  5. Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

    International Nuclear Information System (INIS)

    Purpose: This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Methods and Materials: Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m2, days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m2/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). Results: pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Conclusions: Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging

  6. Chemoradiation With Concomitant Boosts Followed by Radical Surgery in Locally Advanced Cervical Cancer: Long-term Results of the ROMA-2 Prospective Phase 2 Study

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    Ferrandina, Gabriella, E-mail: gabriella.ferrandina@libero.it [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Gambacorta, Antonietta [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Gallotta, Valerio [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Smaniotto, Daniela [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Fagotti, Anna [Gynecologic Surgery, University of Perugia, Terni (Italy); Tagliaferri, Luca [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Foti, Elvira; Fanfani, Francesco [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Autorino, Rosa [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy); Scambia, Giovanni [Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome (Italy); Valentini, Vincenzo [Division of Radiotherapy, Catholic University of the Sacred Heart, Rome (Italy)

    2014-11-15

    Purpose: This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. Methods and Materials: Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m{sup 2}, days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m{sup 2}/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; β error = 0.1). Results: pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. Conclusions: Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  11. 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.

  12. Usefulness of tirapazamine as a combined agent in chemoradiation and thermo-chemoradiation therapy at mild temperatures. Reference to the effect on intratumor quiescent cells

    International Nuclear Information System (INIS)

    C3H/He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received one of six different DNA-damaging agents with or without mild temperature hyperthermia (40 deg C, 30 min, MTH). These agents were adriamycin (ADM), mitomycin C (MMC), cyclophosphamide (CPA), bleomycin (BLM), cisplatin (CDDP), and tirapazamine (TPZ). After the drug treatment, the tumor-bearing mice were irradiated with a series of doses of γ-rays. Immediately after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumor cells was determined from the tumors that had not been pretreated with BrdU. MTH significantly increased the MN frequency of total cells in tumors irradiated with γ-rays combined with CPA, BLM, CDDP or TPZ, and that of Q cells in tumors irradiated with γ-rays combined with BLM or TPZ. The sensitivity difference in the MN frequency between total and Q tumor cells was significantly decreased by the combination with TPZ. TPZ combined with radiotherapy and TPZ combined with thermo-radiotherapy at mild temperatures appear to be promising modalities for sensitizing tumor cells in vivo, including Q tumor cells. (author)

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

    International Nuclear Information System (INIS)

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

  14. Neoadjuvant chemoradiation for resectable and borderline pancreatic cancer: a review

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    Pancreatic adenocarcinoma (PC) is arguably the most fatal of malignancies. Given the 37,000 cases diagnosed annually in the United States, it represents 2% of all cancer cases but 6% of all cancer deaths. It represents the fourth leading cause of cancer death, behind lung, colorectal, and breast cancer, despite the fact that each of these cancers has at least fourfold the incidence of PC. Two thirds of patients present with locally advanced or metastatic disease at presentation. For those patients who undergo surgery, 5-year survival ranges from 15%-20%. Cure is rare, including in patients with resected cancer in whom disease recurs in 80% of patients within 2 years of diagnosis. Improved pre-operative imaging, combined with neoadjuvant therapy, holds many potential advantages over traditional surgical approaches towards pancreatic cancer. Improvements in computerized tomography (CT) optimized for pancreas imaging and the use of EUS allow for more accurate staging. This, in turn leads to better prediction of positive margins and the presence of lymphadenopathy. We present evidence that positive margins at surgery result in worsened survival. The neoadjuvant approach also allows for earlier treatment of microscopic metastatic disease, which would otherwise remain unchecked until recovery from surgery. Furthermore, chemotherapy and radiation may be more effective in the setting of an uninterrupted vasculature. Finally, delaying surgery helps select those patients whose tumor biology is less aggressive, possibly resulting in better survival in those patients going to the operating room.(author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-07-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

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

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

    International Nuclear Information System (INIS)

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

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

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  3. Botanical Therapy in Treating Mucositis in Patients With Head and Neck Cancer Who Have Undergone Chemoradiation Therapy

    Science.gov (United States)

    2013-05-14

    Mucositis; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

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

    International Nuclear Information System (INIS)

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

  5. Cytokines levels, Severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer - a prospective pilot study

    International Nuclear Information System (INIS)

    The purpose of this pilot study was to detect a correlation between serum cytokine levels and severity of mucositis, necessitating installation of a percutaneous endoscopic gastrostomy tube (PEG) in head and neck (H&N) cancer patients receiving combined chemo-radiation therapy. Fifteen patients with H&N epithelial cancer were recruited to this study. All patients received radiotherapy to the H&N region, with doses ranging from 50-70 Gy. Chemotherapy with cisplatin, carboplatin, 5-fluorouracil and taxanes was given to high-risk patients, using standard chemotherapy protocols. Patients were evaluated for mucositis according to WHO common toxicity criteria, and blood samples were drawn for inflammatory (IL-1, IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokine levels before and during treatment. A positive correlation was found between IL-6 serum levels and severity of mucositis and dysphagia; specifically, high IL-6 levels at week 2 were correlated with a need for PEG tube installation. A seemingly contradictory correlation was found between low IL-8 serum levels and a need for a PEG tube. These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study

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

    International Nuclear Information System (INIS)

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

  7. 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

    International Nuclear Information System (INIS)

    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.

  8. 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

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    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.

  9. 17-Week Delay Surgery after Chemoradiation in Rectal Cancer with Complete Pathological Response

    Directory of Open Access Journals (Sweden)

    Marisa D. Santos

    2015-01-01

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

  10. [Radiation therapy of pancreatic cancer].

    Science.gov (United States)

    Huguet, F; Mornex, F; Orthuon, A

    2016-09-01

    Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended. PMID:27523418

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

    International Nuclear Information System (INIS)

    To proof feasibility of hydrogel application in patients with advanced cervical cancer undergoing chemo-radiation in order to reduce rectal toxicity from external beam radiation as well as brachytherapy. Under transrectal sonographic guidance five patients with proven cervical cancer underwent hydro gel (20 cc) instillation into the tip of rectovaginal septum adherent to posterior part of the visible cervical tumor. Five days after this procedure all patients underwent T2 weighted transversal and sagittal MRI for brachytherapy planning. MRI protocol included T2 weighted fast spin echo (FSE) imaging in sagittal, coronal and para-axial orientation using an 1.5 Tesla MRI. Separation of anterior rectal wall and cervix was documented. Hydrogel application was uneventful in all patients and no toxicity was reported. Separation ranged from 7 to 26 mm in width (median 10 mm). The length of the separation varied between 18 and 38 mm (median 32 mm). In all patients displacement was seen in the posterior vaginal fornix, and/or at the deepest part of uterine cervix depending on the extension of the cul-de-sac in correlation to the posterior wall of the uterus. In patients with bulky tumor and/or deep (vaginal) extend of peritoneal cavity tumour was seen mainly cranial from the rectovaginal space and therefore above the hydrogeI application. Only in the extra-peritoneal (lower) part of the cervix a good separation could be achieved between the rectum and cervix. Hydrgel instillation in patients with cervial cancer undergoing chemoradiation is safe and feasible. Because of the loose tissue of the cul-de-sac and its intra- and extraperitoneal part, hydrogel instillation of 20 cc did not result in a sufficient separation of the cervix from anterior wall

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer

    International Nuclear Information System (INIS)

    Background and purpose: Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation. Patients and methods: One hundred and twenty-five consecutive patients with newly diagnosed inoperable stage III and IV head and neck cancer were enrolled for intra-arterial chemoradiation. There were 28 women (22%) and 97 men (78%) and the mean age was 55 years (range 30-80). One hundred and nine patients had stage IV disease (87%), 16 patients (13%) had stage III disease. Statistical analyses were performed to identify an association between factors and acute/late toxicity. Results: There were eight treatment-related deaths (6%). Severe acute toxicity (grade 3-4), mainly mucositis and dysphagia as categorized by the RTOG toxicity criteria, was recorded in 51% of the patients. Leucopenia (grade 3-4) occurred in 39% and aspiration pneumonia in 20% of patients. Tracheotomy was necessary in 15 (12%) patients. Neurological complications during treatment occurred in 3 (2%) patients. Severe late toxicity occurred in 34% of the patients. The most important of these were pneumonia (14%), osteoradionecrosis (9%) and swallowing problems with permanent percutaneous gastrostomy (20%). Statistical analysis did show a significant association between site and severe acute mucositis (p = 0.007), site and osteoradionecrosis (p = 0.014) and age and xerostomia (p = 0.004). Conclusions: Chemoradiation is frequently associated with serious toxicity. Oral cavity tumours and older age are related to acute mucositis/osteoradionecrosis and xerostomia, respectively

  14. Non-small cell lung cancer: current status of chemoradiation for locally advanced disease and an update on susceptibility and prevention

    International Nuclear Information System (INIS)

    Locally advanced, inoperable non-small cell lung cancer (NSCLC) afflicts 40,000 patients yearly. The traditional treatment has been radiation therapy (RT) alone with 5 year survival rates averaging around 5%. Recent reports of randomized clinical trials using combined radiochemotherapy suggest significant improvement in survival compared to RT alone. These trials are difficult to evaluate because of differences in dose, timing and sequencing of both the chemotherapy (CT) and the RT. Dr. Byhardt will give an overview of the significant chemoradiation trials, especially with respect to the factors associated with reduction of local failure and distant metastasis. Dr. Tishler will review the biologic rationale of these regimens and make some prognostications about the potential role of new chemotherapy agents, new developments in RT dose-time-fractionation, and new RT technology in future radiochemotherapy trials. While progress continues to be made using the more traditional cancer treatment modalities, investigations in NSCLC epidemiology and prevention are providing new insights regarding susceptibility, etiology, failure risk stratification, and potential avenues of therapeutic intervention. Dr. Spitz will discuss NSCLC as a paradigm of an environmentally induced disease in which host susceptibility may be determined by genetically determined modulation of environmental exposures. A mutagen sensitivity assay can determine individuals at high risk for developing NSCLC if exposed to carcinogens such as those in cigarette smoke. This susceptibility may have prognostic implications that could influence choice of therapy. Highly susceptible individuals can also be selected for special counseling, smoking cessation, with consideration given to chemoprevention. Dr. Gritz will review major work done in this area

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

    International Nuclear Information System (INIS)

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

  16. 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.)

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

    International Nuclear Information System (INIS)

    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.)

  18. Acute toxicity of chemoradiation for rectal cancer; Akuttoxizitaet der simultanen Radiochemotherapie des Rektumkarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, C. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Fietkau, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Keilholz, L. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Grabenbauer, G.G. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik; Kessler, H. [Erlangen-Nuernberg Univ., Erlangen (Germany). Chirurgische Klinik; Martus, P. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizinische Statistik und Dokumentation; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Strahlentherapeutische Klinik

    1997-08-01

    Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41,4 to 56 Gy) {+-} 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m{sup 2}/d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. Results: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p = 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p = 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0,04; grade 2 to 3-nausea/emesis: 21% vs 8% in men, p = 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p = 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. (orig./AJ) [Deutsch] Von 1987 bis 1995 wurde bei 120 Patienten mit Rektumkarzinom (73 Primaertumoren, 47 Rezidivtumoren) eine simultane Radiochemotherapie durchgefuehrt. 56 Patienten wurden praeoperativ, 64 Patienten postoperativ behandelt. Die Bestrahlung erfolgte ueber eine Vier-Felder-Technik mit 6- bis 10-MV-Photonen. Die Einzeldosis betrug 1,8 Gy im Referenzpunkt (Isozentrum, ICRU 50

  19. Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

    International Nuclear Information System (INIS)

    Purpose: While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials: From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ2 or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis. Results: The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions: The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation

  20. Predictors of Postoperative Complications After Trimodality Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jingya [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Myles, Bevan; Palmer, Matthew [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hofstetter, Wayne L.; Swisher, Stephen G. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H., E-mail: SHLin@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-08-01

    Purpose: While trimodality therapy for esophageal cancer has improved patient outcomes, surgical complication rates remain high. The goal of this study was to identify modifiable factors associated with postoperative complications after neoadjuvant chemoradiation. Methods and Materials: From 1998 to 2011, 444 patients were treated at our institution with surgical resection after chemoradiation. Postoperative (pulmonary, gastrointestinal [GI], cardiac, wound healing) complications were recorded up to 30 days postoperatively. Kruskal-Wallis tests and χ{sup 2} or Fisher exact tests were used to assess associations between continuous and categorical variables. Multivariate logistic regression tested the association between perioperative complications and patient or treatment factors that were significant on univariate analysis. Results: The most frequent postoperative complications after trimodality therapy were pulmonary (25%) and GI (23%). Lung capacity and the type of radiation modality used were independent predictors of pulmonary and GI complications. After adjusting for confounding factors, pulmonary and GI complications were increased in patients treated with 3-dimensional conformal radiation therapy (3D-CRT) versus intensity modulated radiation therapy (IMRT; odds ratio [OR], 2.018; 95% confidence interval [CI], 1.104-3.688; OR, 1.704; 95% CI, 1.03-2.82, respectively) and for patients treated with 3D-CRT versus proton beam therapy (PBT; OR, 3.154; 95% CI, 1.365-7.289; OR, 1.55; 95% CI, 0.78-3.08, respectively). Mean lung radiation dose (MLD) was strongly associated with pulmonary complications, and the differences in toxicities seen for the radiation modalities could be fully accounted for by the MLD delivered by each of the modalities. Conclusions: The radiation modality used can be a strong mitigating factor of postoperative complications after neoadjuvant chemoradiation.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    OpenAIRE

    Chakra P Chaulagain; Muhammad Wasif Saif; Janice Rothschild

    2013-01-01

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

  3. Tumor Regression Grades: Can They Influence Rectal Cancer Therapy Decision Tree?

    OpenAIRE

    Marisa D. Santos; Cristina Silva; Anabela Rocha; Eduarda Matos; Carlos Nogueira; Carlos Lopes

    2013-01-01

    Background. Evaluating impact of tumor regression grade in prognosis of patients with locally advanced rectal cancer (LARC). Materials and Methods. We identified from our colorectal cancer database 168 patients with LARC who received neoadjuvant therapy followed by complete mesorectum excision surgery between 2003 and 2011: 157 received 5-FU-based chemoradiation (CRT) and 11 short course RT. We excluded 29 patients, the remaining 139 were reassessed for disease recurrence and survival; the sl...

  4. 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

  5. Two cases of superficial esophageal cancer after chemoradiation treatment for lung cancer

    International Nuclear Information System (INIS)

    We report two cases of superficial esophageal cancer after chemoradiation treatment (CRT) for lung cancer. A 74-year-old man had a type 0-IIc cancer of the upper thoracic esophagus 12 years after CRT, including 45-Gy irradiation, for left lung small cell cancer. Transthoracic esophagectomy was performed, and pathological examination revealed that the tumor was squamous cell carcinoma invading the submucosal layer (SM3) without nodal metastasis. He has had no recurrence of esophageal cancer for more than 3.5 years since the operation. A 61-year-old man had a type 0-IIc cancer of the upper thoracic esophagus 20 years after CRT, including 60-Gy irradiation, for left lung small cell cancer. Transthoracic esophagectomy was performed, and pathological examination revealed that the tumor was squamous cell carcinoma invading the submucosal layer (SM2) without nodal metastasis. He has had no recurrence of esophageal cancer for more than 2 years. A possible causal relationship between the previous CRT and the two esophageal cancers was suspected. The treatment strategy for patients after CRT should be carefully decided based on the patient's general status. In surgery, scarring and blood circulation disorders of the organs in the irradiated field should be taken into consideration. (author)

  6. Optimal Timing for Assessment of Tumor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer: Do All Patients Benefit From Waiting Longer Than 6 Weeks?

    International Nuclear Information System (INIS)

    Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([18FDG]PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied ( (ClinicalTrials.org) identifier (NCT00254683)). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks from CRT completion). Clinical assessment was at 12 weeks. Maximal standard uptake value (SUVmax) of the primary tumor was measured and recorded at each PET/CT study after 1 h (early) and 3 h (late) from 18FDG injection. Patients with an increase in early SUVmax between 6 and 12 weeks were considered “bad” responders and the others as “good” responders. Results: Ninety-one patients were included; 46 patients (51%) were “bad” responders, whereas 45 (49%) patients were “good” responders. “Bad” responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; P=.001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; P=.008) and exhibited greater final tumor dimension (4.3 cm vs. 3.3 cm; P=.03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CT was a significant predictor of “good” response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients.

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

    International Nuclear Information System (INIS)

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

  8. 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.)

  9. {sup 18}F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data

    Energy Technology Data Exchange (ETDEWEB)

    Siva, Shankar; Hicks, Rodney J.; Callahan, Jason [Peter MacCallum Cancer Centre, Division of Radiation Oncology and Cancer Imaging, East Melbourne, Victoria (Australia); University of Melbourne, Sir Peter MacCallum Department of Oncology, Parkville (Australia); Deb, Siddhartha [Peter MacCallum Cancer Centre, Department of Pathology, East Melbourne (Australia); Young, Richard J. [Peter MacCallum Cancer Centre, Molecular Therapeutics and Biomarkers Laboratory, East Melbourne (Australia); Bressel, Mathias [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, East Melbourne (Australia); Mileshkin, Linda [Peter MacCallum Cancer Centre, Department of Cancer Medicine, East Melbourne (Australia); Rischin, Danny [University of Melbourne, Sir Peter MacCallum Department of Oncology, Parkville (Australia); Peter MacCallum Cancer Centre, Department of Cancer Medicine, East Melbourne (Australia); Bernshaw, David; Narayan, Kailash [Peter MacCallum Cancer Centre, Division of Radiation Oncology and Cancer Imaging, East Melbourne, Victoria (Australia)

    2015-11-15

    To report 5-year outcomes of a prospective registry study investigating posttherapy FDG PET/CT in women with locally advanced cervical cancer. A secondary analysis assessing the prognostic significance of HPV infection was performed. Patients underwent definitive chemoradiation followed by a single FDG PET/CT scan for response assessment. A complete metabolic response (CMR) was defined as no evidence of FDG-avid disease. Patients were dichotomized according to HPV infection status into a 'higher-risk' group and a 'lower-risk' group, with the higher-risk group comprising those with alpha-7 strain HPV (subtypes 18, 39 and 45) and those who were HPV-negative and the lower-risk group comprising those with alpha-9 strain HPV (subtypes 16, 31, 33, 52 and 58) and those with mixed strains. Survival outcomes, patterns of failure and salvage therapy outcomes were investigated for their association with metabolic response and HPV status. In 105 patients the median prospective follow-up was 5.2 years. The 5-year cancer-specific, overall and progression-free survival rates in patients with a CMR were 97 %, 93 % and 86 %, respectively. In patients without a CMR, the corresponding 5-year survival rates were 36 %, 22 % and 0 % respectively (p < 0.01). PET response was associated with patterns of failure (p < 0.01), with the 5-year freedom from local, nodal and distant failure in patients with a CMR being 94 %, 90 % and 94 %, respectively. Of 16 patients who underwent salvage therapy, 12 had disease detected on the surveillance PET scan, and 8 achieved a post-salvage CMR of whom all were alive at a median of 4.9 years. DNA adequate for HPV analysis was extracted in 68 patients. The likelihood of a PET metabolic response was not influenced by HPV infection status, with 71 % and 75 % of higher-risk and lower-risk patients, respectively, achieving CMR (p = 0.83). Higher-risk patients had a poorer OS (HR 2.6, range 1.0 - 6.6, p = 0.05) in univariable analysis but

  10. 18F-FDG PET/CT following chemoradiation of uterine cervix cancer provides powerful prognostic stratification independent of HPV status: a prospective cohort of 105 women with mature survival data

    International Nuclear Information System (INIS)

    To report 5-year outcomes of a prospective registry study investigating posttherapy FDG PET/CT in women with locally advanced cervical cancer. A secondary analysis assessing the prognostic significance of HPV infection was performed. Patients underwent definitive chemoradiation followed by a single FDG PET/CT scan for response assessment. A complete metabolic response (CMR) was defined as no evidence of FDG-avid disease. Patients were dichotomized according to HPV infection status into a 'higher-risk' group and a 'lower-risk' group, with the higher-risk group comprising those with alpha-7 strain HPV (subtypes 18, 39 and 45) and those who were HPV-negative and the lower-risk group comprising those with alpha-9 strain HPV (subtypes 16, 31, 33, 52 and 58) and those with mixed strains. Survival outcomes, patterns of failure and salvage therapy outcomes were investigated for their association with metabolic response and HPV status. In 105 patients the median prospective follow-up was 5.2 years. The 5-year cancer-specific, overall and progression-free survival rates in patients with a CMR were 97 %, 93 % and 86 %, respectively. In patients without a CMR, the corresponding 5-year survival rates were 36 %, 22 % and 0 % respectively (p < 0.01). PET response was associated with patterns of failure (p < 0.01), with the 5-year freedom from local, nodal and distant failure in patients with a CMR being 94 %, 90 % and 94 %, respectively. Of 16 patients who underwent salvage therapy, 12 had disease detected on the surveillance PET scan, and 8 achieved a post-salvage CMR of whom all were alive at a median of 4.9 years. DNA adequate for HPV analysis was extracted in 68 patients. The likelihood of a PET metabolic response was not influenced by HPV infection status, with 71 % and 75 % of higher-risk and lower-risk patients, respectively, achieving CMR (p = 0.83). Higher-risk patients had a poorer OS (HR 2.6, range 1.0 - 6.6, p = 0.05) in univariable analysis but

  11. Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis

    International Nuclear Information System (INIS)

    It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes. From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation. Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15). Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients. (orig.)

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

    International Nuclear Information System (INIS)

    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.)

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  15. A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

    OpenAIRE

    McCormack, M; Kadalayil, L; Hackshaw, A; Hall-Craggs, M A; Symonds, R P; Warwick, V; Simonds, H.; Fernando, I.; Hammond, M.; James, L.; Feeney, A.; Ledermann, J. A.

    2013-01-01

    Background: We investigated the feasibility of dose-dense neoadjuvant chemotherapy (NACT) with paclitaxel and carboplatin before radical chemoradiation (CRT) and assessed the response rate to such a regimen. Methods: CxII is a single-arm phase II trial of 46 patients, with locally advanced cervical cancer (stage Ib2-IVa). Patients received dose-dense carboplatin (AUC2) and paclitaxel (80 mg m−2) weekly for six cycles followed by CRT (40 mg m−2 of weekly cisplatin, 50.4 G...

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

    Energy Technology Data Exchange (ETDEWEB)

    Trog, D.; Bank, P.; Wendt, T.G. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Radiation Oncology; Koscielny, S.; Beleites, E. [Friedrich-Schiller Univ., Jena (Germany). Dept. of Ear Nose Throat Diseases

    1999-09-01

    Background: In patients with loco-regionally advanced head and neck cancer conventionally fractionated radiotherapy alone results in poor loco-regional control and survival rates. Treatment intensification by simultaneous administration of cytotoxic drugs produces higher acute morbidity. Therefore chemical radioprotection of normal tissues may be of clinical benefit. Patients and Methods: In a pilot study patients with advanced nonresectable head neck cancer treated with conventionally fractionated radical radiotherapy (60 to 66 Gy total doses) and concomitantly given 5-fluorouracil as protracted venous infusion, 250 mg/sqm/24 h over the entire treatment period were given amifostine 300 mg absolutely before each fraction. Acute treatment related mobidity was scored according to CTC classification and loco-regional control and survival rates were estimated. Comparison was made with a historical control group of identical chemoradiation but without amifostine application. Results: Chemoradiation induced oral mucositis was delayed and showed significant lower degrees at all 10 Gy increments (p<0.05) except 60 Gy and over (p>0.05). No significant toxicity was recorded with respect to blood pressure, serum calcium, potassium, hematologic parameters, emesis, nausea or body weight loss. Progression free survival and overall survival probability at 2 years were not statistically different in both cohorts. Conclusion: Amifostine given before each fraction of radiotherapy over 6 weeks has no cumulative toxicity, was well tolerated and may reduce treatment induced oral mucositis. No tumor protective effect was observed. (orig.) [German] Hintergrund: Bei Patienten mit lokoregionaer fortgeschrittenen Karzinomen im Kopf-Hals-Bereich fuehrt die alleinige konventionell fraktionierte Radiotherapie zu unuenstigen lokoregionaeren Tumorkontrollraten und Ueberlebensraten. Die Therapieintensivierung durch simultane Radiochemotherapie fuehrt zu gesteigerter Akutmorbiditaet. Die chemische

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

    International Nuclear Information System (INIS)

    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.

  18. 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.

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

    International Nuclear Information System (INIS)

    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). 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. 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. 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

  20. 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.

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

    International Nuclear Information System (INIS)

    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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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 clinically relevant changes in the dose distribution of radiotherapy. Methods: A prospective study was conducted in patients who were treated with nCRT consisting of carboplatin and paclitaxel concomitant with radiotherapy (41.4 Gy/1.8 Gy per fraction). Physical parameters, cardiac volume on CT and Cone beam CT, cardiac blood markers and cardiac ultrasound were obtained. Results: In 23 patients a significant decrease of 55.3 ml in heart volume was detected (95% CI 36.7–73.8 ml, p < 0.001). There was a decrease in both systolic (mean decrease 18 mmHg, 95% CI 11–26 mmHg, p < 0.001) and diastolic blood pressure (mean decrease 8 mmHg, 95% CI 2–14 mmHg, p = 0.008) and an increase in heart rate with 6 beats/min (95% CI 1–11 beats/min, p = 0.021). Except for Troponin T, no change in other cardiac markers and echocardiography parameters were observed. The change in heart volume did not result in a clinically relevant change in radiation dose distribution. Conclusion: Heart volume was significantly reduced, but was not accompanied by overt cardiac dysfunction. All observed changes in hemodynamic parameters are consistent with volume depletion. Adaptation of the treatment plan during the course of radiotherapy is not advocated

  4. 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.

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

    International Nuclear Information System (INIS)

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

  6. Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma

    OpenAIRE

    Fields, R. C.; Strong, V E; Gönen, M.; Goodman, K A; Rizk, N P; Kelsen, D P; Ilson, D H; Tang, L. H.; Brennan, M.F.; Coit, D G; Shah, M.A.

    2011-01-01

    Background: To characterise recurrence patterns and survival following pathologic complete response (pCR) in patients who received preoperative therapy for localised gastric or gastrooesophageal junction (GEJ) adenocarcinoma. Methods: A retrospective review of a prospective database identified patients with pCR after preoperative chemotherapy for gastric or preoperative chemoradiation for GEJ (Siewert II/III) adenocarcinoma. Recurrence patterns, overall survival, recurrence-free survival, and...

  7. Aspekte der Therapie des Zervixkarzinoms in Deutschland 2012

    OpenAIRE

    Rauer, Andreas

    2016-01-01

    Introduction: Platinum-based primary or ad¬juvant chemoradiation (RCTX) is the treatment of choice for patients with cervical cancer. How¬ever, despite national guidelines and inter¬national recommendations, many aspects in diagnosis, therapy, and follow-up of pa¬tients with cervical cancer are not based on valid data. Method: To evaluate the current patterns of care for patients with cervical cancer in Ger¬many, a questionnaire with 25 items was sent to 281 radiooncologic departments and...

  8. The Effect of Biofeedback Therapy on Anorectal Function After the Reversal of Temporary Stoma When Administered During the Temporary Stoma Period in Rectal Cancer Patients With Sphincter-Saving Surgery

    OpenAIRE

    Kye, Bong-Hyeon; Kim, Hyung-Jin; Kim, Gun; Yoo, Ri Na; Cho, Hyeon-Min

    2016-01-01

    Abstract We evaluated the effect of biofeedback therapy (BFT) on anorectal function after stoma closure when administered during the interval of temporary stoma after sphincter-preserving surgery for rectal cancer. Impaired anorectal function is common after lower anterior resections, though no specific treatment options are currently available to prevent this adverse outcome. Fifty-six patients who underwent neoadjuvant chemoradiation therapy after sphincter-preserving surgery with temporary...

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

    International Nuclear Information System (INIS)

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

  10. Clinical outcome and dosimetric parameters of chemo-radiation including MRI guided adaptive brachytherapy with tandem-ovoid applicators for cervical cancer patients: A single institution experience.

    NARCIS (Netherlands)

    Nomden, C.N.; Leeuw, A.A. de; Roesink, J.M.; Tersteeg, R.J.; Moerland, M.A.; Witteveen, P.O.; Schreuder, H.W.B.; Dorst, E.B. van; Jurgenliemk-Schulz, I.M.

    2013-01-01

    PURPOSE: To evaluate dosimetric parameters and clinical outcome for cervical cancer patients treated with chemo-radiation and MR-image guided adaptive brachytherapy (MR-IGABT) using tandem-ovoid applicators for intracavitary or combined intracavitary/interstitial approaches. METHOD: This retrospecti

  11. Glutathione S-Transferase Gene Polymorphisms and Treatment Outcome in Cervical Cancer Patients under Concomitant Chemoradiation.

    Directory of Open Access Journals (Sweden)

    Mohammad Abbas

    Full Text Available Cisplatin based concomitant chemoradiation (CRT is the standard treatment for locally advanced cervical cancer (CC. Glutathione S-transferase (GST, a phase II antioxidant enzyme is induced by oxidative stress generated by drugs and reactive oxidants. The present study was undertaken to evaluate the association of GSTM1, T1 and P1 polymorphisms with the outcome of CRT treatment in CC patients.A total of 227 cervical cancer patients with stages IIB-IIIB treated with the same chemoradiotherapy regimen were enrolled and genotyped for GSTM1, T1 and P1 gene polymorphisms by multiplex polymerase chain reaction (mPCR and PCR-restriction fragment length polymorphism (PCR-RFLP. Overall survival was evaluated using Kaplan-Meier survival function and Cox proportional hazards model. All data were analyzed using SPSS (version 21.0.Stratified analysis showed that GSTM1 null (M1- genotype was associated with a significantly better survival among patients with stage IIB cervical cancer (log-rank P = 0.004 than cases with stage IIIA/IIIB. Death and recurrence were significantly higher in patients with GSTM1 present genotype (M1+ (P = 0.037 and P = 0.003 respectively and those with M1- showed reduced hazard of death with an adjusted hazard ratio 'HR' of 0.47 (95% CI, 0.269-0.802, P = 0.006. Women with M1- genotype as well as in combination with GSTT1 null (T1-, GSTP1 (AG+GG and GSTT1 null/GSTP1 (AG+GG showed better survival and also reduced risk of death (HR = 0.31, P = 0.016; HR = 0.45, P = 0.013; HR = 0.31, P = 0.02 respectively.To the best of our knowledge, this is the first study to correlate the association of GSTM1, T1 and P1 gene polymorphisms with treatment outcome of CRT treated CC patients. Our results suggested that individuals with GSTM1 null genotype and in combination with GSTT1 null and GSTP1 (AG+GG had a survival advantage. Such genetic studies may provide prognostic information in CRT treated CC patients.

  12. Pancreatic cancer-Neoadjuvant therapy%胰腺癌:新辅助治疗

    Institute of Scientific and Technical Information of China (English)

    R. Krempien; M. W. Munter; W. Harms; J. Debus

    2007-01-01

    In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. Surgical therapy currently offers the only potential monomodal cure for pancreatic adenocarcinoma. However only 10%-20% of patients present with tumors that are amenable to resection,and even after resection of localized cancers, long term survival is rare. The addition of chemoradiation therapy significantly increases median survival. To achieve long-term success in treating this disease it is therefore increasingly important to identify effective neoadjuvant/adjuvant multimodality therapies. Preoperative chemoradiation for potentially resectable pancreatic cancer has the following advantages:(1) neoadjuvant treatment would eliminate the delay of adjuvant treatment due to postoperative complications; (2) neoadjuvant treatment could avoid unnecessary surgery for patients with metastatic disease evident on restaging after neoadjuvant therapy; (3) downstaging after neoadjuvant therapy may increase the likelihood for negative surgical margins; and (4) neoadjuvant treatment could prevent peritoneal tumor cell implantation and dissemination caused during surgery. This review systematically summarizes the current status, controversies, and prospects of neoadjuvant treatment of pancreatic cancer.

  13. Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

    International Nuclear Information System (INIS)

    Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m2 of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m2 of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal

  14. Twenty-year results of treatment of patients with stage i-IIA Hodgkin's lymphoma using radiation therapy with accelerated dose fractionation

    International Nuclear Information System (INIS)

    The findings of investigation of 20-year survival of 234 patients with stage IA-IIA Hodgkin's lymphoma (HL) are analyzed. In case of a favorable prognosis according to EORTC criteria total relapse-free survival was 90 and 76% respectively at 10-year and 79 and 73% at 20 year terms of observation. The use of chemoradiation therapy at unfavorable prognosis eliminated the difference in the survival of the patients from different prognostic groups.

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

    Institute of Scientific and Technical Information of China (English)

    Asma Sultana; John Neoptolemos; Paula Ghaneh

    2007-01-01

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

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

    International Nuclear Information System (INIS)

    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.)

  17. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience

    International Nuclear Information System (INIS)

    Purpose: To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer. Materials and Methods: Preoperative chemoradiotherapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed. Results: The pathological tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4N1 in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor downstaging occurred in 72 (62%) cases. Only 3% of cases had pathologic evidence of progressive disease. Pretreatment tumor size (1 T-stage level was accomplished in 45% of those downstaged. Overall, a sphincter-saving (SP) procedure was possible in 59% of patients and an abdominoperineal resection (APR) was required in 41% of cases. Factors predictive of SP included downstaging (p 40 years (p 6 cm from the anal verge, SP was performed in 14 of the 15 (93%) patients with a CR and 32 of 33 (97%) of patients with residual disease (p < 0.00004). Conclusions: Significant tumor downstaging results from preoperative chemoradiation allowing sphincter sparing surgery in over 40% of patients whose tumors were located < 6 cm from the anal verge and who otherwise would have required colostomy

  18. Molecular targeted treatment and radiation therapy for rectal cancer

    International Nuclear Information System (INIS)

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  19. Molecular targeted treatment and radiation therapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marquardt, Friederike; Roedel, Franz; Capalbo, Gianni; Weiss, Christian; Roedel, Claus [Dept. of Radiation Therapy, Univ. of Frankfurt/Main (Germany)

    2009-06-15

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  20. Chemoradiation May Help Some Patients with Bladder Cancer Avoid Radical Surgery

    Science.gov (United States)

    Researchers in the United Kingdom have found that adding chemotherapy to radiation therapy as a treatment for bladder cancer may reduce the risk of a recurrence more than radiation alone, without causing a substantial increase in side effects.

  1. STOMATOLOGIC ASPECTS IN THERAPY OF LOCALLY DISTRIBUTED CANCER OF ORAL CAVITY MUCUS

    Directory of Open Access Journals (Sweden)

    G. G. Matyakin

    2013-01-01

    Full Text Available Aim of the investigation: to improve prophylaxis of dental complications during the therapy in the patients with locally distributed cancer of oral cavity mucus.Materials. Results of sanation of oral cavity in 305 patients with cancer of oral and pharyngeal area are analyzed.Results. The best results are noted in the patients given surgical sanation before chemo-radial therapy. The most number of complications is observed when teeth were extracted after chemical therapy in the period of radial therapy at summary focal dose above 20 Gy as well as in the late periods after radial therapy.Conclusion. A complex of preventive measures with using haemostatic sponge with canamycin in such patients decreases the number of complications and the terms of healing of alveoli of extracted teeth.

  2. 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.

  3. Sequential chemoradiation in locally advanced head and neck cancer after induction chemotherapy: an induction chemotherapy schedule more suited to a limited resource setting

    OpenAIRE

    Gangopadhyay, Aparna; Nath, Partha; Biswas, Jaydip

    2015-01-01

    Background In our experience, induction docetaxel, platinum, and fluorouracil (TPF) chemotherapy and sequential chemoradiation in locally advanced head and neck cancer lowers compliance owing to their considerable toxicity. Most of our head and neck cancer patients have locally advanced disease at presentation. Physicians frequently prefer paclitaxel–cisplatin induction chemotherapy instead, because of better patient tolerance. Materials and methods A total of 207 locally advanced head and ne...

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

    International Nuclear Information System (INIS)

    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

  5. Effect of neoadjuvant chemoradiation and postoperative radiotherapy on expression of heat shock protein 70 (HSP70) in head and neck vessels

    International Nuclear Information System (INIS)

    Preoperative radiotherapy and chemotherapy in patients with head and neck cancer result in changes to the vessels that are used to construct microsurgical anastomoses. The aim of the study was to investigate quantitative changes and HSP70 expression of irradiated neck recipient vessels and transplant vessels used for microsurgical anastomoses. Of 20 patients included in this study five patients received neoadjuvant chemoradiation, another five received conventional radiotherapy and 10 patients where treated without previous radiotherapy. During surgical procedure, vessel specimens where obtained by the surgeon. Immunhistochemical staining of HSP70 was performed and quantitative measurement and evaluation of HSP70 was carried out. Conventional radiation and neoadjuvant chemoradiation revealed in a thickening of the intima layer of recipient vessels. A increased expression of HSP70 could be detected in the media layer of the recipient veins as well as in the transplant veins of patients treated with neoadjuvant chemoradiation. Radiation and chemoradiation decreased the HSP70 expression of the intima layer in recipient arteries. Conventional radiation led to a decrease of HSP70 expression in the media layer of recipient arteries. Our results showed that anticancer drugs can lead to a thickening of the intima layer of transplant and recipient veins and also increase the HSP70 expression in the media layer of the recipient vessels. In contrast, conventional radiation decreased the HSP70 expression in the intima layer of arteries and the media layer of recipient arteries and veins. Comparing these results with wall thickness, it was concluded, that high levels of HSP70 may prevent the intima layer of arteries and the media layer of vein from thickening

  6. Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, F.A. [Hospital General Universitario Gregorio Maranon, Department of Oncology, Madrid (Spain); Complutense University, School of Medicine, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria, Madrid (Spain); Sole, C.V. [Hospital General Universitario Gregorio Maranon, Department of Oncology, Madrid (Spain); Complutense University, School of Medicine, Madrid (Spain); Instituto de Radiomedicina, Service of Radiation Oncology, Santiago (Chile); Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria, Madrid (Spain); Serrano, J. [Complutense University, School of Medicine, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Service of Radiation Oncology, Madrid (Spain); Valle, E. del; Rodriguez, M. [Hospital General Universitario Gregorio Maranon, Service of General Surgery I, Madrid (Spain); Munoz-Calero, A.; Garcia-Sabrido, J.L. [Complutense University, School of Medicine, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Service of General Surgery I, Madrid (Spain); Garcia-Alfonso, P. [Complutense University, School of Medicine, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Service of Medical Oncology, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria, Madrid (Spain); Peligros, I. [Hospital General Universitario Gregorio Maranon, Department of Pahology, Madrid (Spain); Alvarez, E. [Complutense University, School of Medicine, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Department of Pahology, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria, Madrid (Spain)

    2014-02-15

    It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes. From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation. Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15). Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients. (orig.) [German] Es wurde bereits berichtet, dass eine kurze FOLFOX-4-Induktion das gesamte pathologische Ansprechen bei Patienten mit lokal fortgeschrittenem Rektumkarzinom (LARC), die praeoperativ mittels Strahlenchemotherapie (CRT) behandelt wurden, signifikant verbessert. In einer groesseren und aktualisierten Patientengruppe analysierten wir die FOLFOX-4-Wirksamkeit hinsichtlich Sphinktererhalt und Langzeitergebnissen. Von Januar 1995 bis Dezember 2010 wurden 335 LARC-Patienten praeoperativ mit einer

  7. 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

  8. Cisplatin-based chemotherapy: the only alternative in chemoradiation of head and neck cancer? Experience of the Institute of Oncology, Ljubljana, Slovenia

    International Nuclear Information System (INIS)

    Background: Concomitant chemoradiation is a widely used therapeutic concept in intensified locoregional treatment of high risk head and neck cancer patients. In this context, cisplatin monotherapy or in combination with other chemotherapeutics is recognized as the most effective drug to be added to radiotherapy. Aim: The aim of this review is to present the rationale for combining radiotherapy with cisplatin in the treatment of head and neck cancer and to summarize the experience of the Institute of Oncology Ljubljana, Slovenia, gained through two prospective randomized trials on chemoradiation with mitomycin C and bleomycin in operable as well as inoperable head and neck cancer patients. Furthermore, recent developments in technology and biological drug modeling are discussed, which are considered to have a potential to add significantly to the locoregional effectiveness of radiotherapy. Materials/Methods: References were retrieved using the online data base of the National Library of Medicine (PubMed: http://www.ncbi.nlm.nih.gov/PubMed). Terms used included: head and neck carcinoma, squamous cell carcinoma, concomitant chemoradiotherapy, cisplatin, mitomycin C, bleomycin. The results of studies using cisplatin- based chemoradiation regimens in the treatment of patients with inoperable tumors and on postoperative stetting were compared with the results of the studies, conducted at the Institute of Oncology and ENT Department at the Clinical Center Ljubljana, Slovenia. Results; When comparing mitomycin C-bleomycin chemotherapy with other comparable series on exclusively inoperable oropharyngeal cancer, but with cisplatin (or carboplatin) and 5-fluorouracil chemotherapy, and to standard dose cisplatin regimen used in postoperative setting, the effectiveness of our unconventional drug combination appeared to be at least equivalent to the well established platinum based chemotherapy standard. Conclusions: At the moment, concomitant chemoradiation with cisplatin

  9. New and emerging combination therapies for esophageal cancer

    International Nuclear Information System (INIS)

    Esophageal cancer comprises two different histological forms – squamous cell carcinoma (SCC) and adenocarcinoma (AC). While the incidence of AC has increased steeply in Western countries during the last few years, the incidence of SCC is fairly stable. Both forms differ in pathogenesis and response to chemotherapy and radiation therapy. Plenty of studies have evaluated new chemotherapy combination regimens in the neoadjuvant, adjuvant, and palliative setting. In addition, new radiation and chemoradiation protocols have been investigated. Finally, molecular-targeted therapy has been included in several new randomized prospective trials. Therefore, this review presents new data on this topic and critically discusses promising approaches towards a more effective treatment in a disease with a grim prognosis

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

    OpenAIRE

    Soumik Ghosh; Rakesh Kapoor; Rajesh Gupta; Divya Khosla; Rakesh Kochhar; Oinam, Arun S.; Reena Sharma; Sharma, Suresh C.

    2012-01-01

    Aims: To evaluate the feasibility whether intensity-modulated radiotherapy (IMRT) can be used to reduce doses to normal thoracic structures than three-dimensional conformal radiotherapy (3DCRT) in treating esophageal cancer and to compare normal tissue complication probability (NTCP) for lung between two treatment plans. Materials and Methods: A prospective study was carried out from 2009 to 2011, in which 15 inoperable patients of esophageal cancer who were suitable for radical chemoradiatio...

  11. Sustained Complete Response after Maintenance Therapy with Topotecan and Erlotinib for Recurrent Cervical Cancer with Distant Metastases

    Directory of Open Access Journals (Sweden)

    Donato Callegaro-Filho

    2014-01-01

    Full Text Available Introduction: Recurrent cervical cancer is associated with a poor prognosis. Most treatment responses are partial and of short duration. The development of new therapies is vital to improve treatment for recurrent disease. Epidermal growth factor receptor (EGFR inhibitors may have a role in this setting. Case Description: A 53-year-old woman with stage IB2 squamous cell carcinoma of the cervix was initially treated with chemoradiation. Six months after completing treatment, she developed a recurrence in the common iliac and para-aortic lymph nodes above the previous radiation field and was treated with additional radiation therapy. Two years later, she developed recurrent disease in the left supraclavicular lymph nodes and was treated with chemoradiation followed by 3 cycles of adjuvant cisplatin and topotecan. She had a complete response and was placed on maintenance therapy with topotecan and erlotinib, which was well tolerated and produced minimal side effects. After 20 months of maintenance therapy, it was discontinued given the long interval without evidence of disease. The patient is currently without evidence of disease 5 years after completing the topotecan-erlotinib treatment. Conclusion: We noted a sustained response in a patient with recurrent metastatic cervical cancer treated with radiotherapy, cisplatin, and topotecan followed by maintenance therapy with topotecan and erlotinib. Further evaluation of the role of EGFR inhibitors in this setting should be considered given their favorable toxicity profile and biological relevance.

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

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    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.

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  15. Epidermal growth factor receptor as a prognostic factor in locally advanced rectal-cancer patients treated with preoperative chemoradiation

    International Nuclear Information System (INIS)

    Purpose: We investigated the prognostic value of epidermal growth factor receptor (EGFR) expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer treated with preoperative chemoradiation. Methods and Materials: Pretreatment biopsy specimens from 92 patients with locally advanced rectal cancer were examined for EGFR expression by immunohistochemistry. EGFR expression was assessed by immunoreactive score (IRS). The prognostic value of EGFR expression was evaluated according to the level of EGFR expression. Results: Epidermal growth factor receptor expression was positive in 65 patients (71%). EGFR expression levels were low (IRS 0 to 5) in 83 patients (90%) and high (IRS 6 to 7) in 9 patients (10%). A high level of EGFR expression was statistically significant for shorter overall survival (p = 0.013), disease-free survival (p = 0.002), and distant metastasis-free survival (p = 0.003), as compared with a low level of expression in univariate analysis. Grouping based on positive or negative EGFR expression did not represent prognostic significance for survival. In multivariate analysis, high EGFR expression was an independent prognostic factor for decreased disease-free survival (relative risk 2.4, p = 0.041) and distant metastasis-free survival (relative risk 2.6, p = 0.04). Conclusions: Our results suggest that high level of EGFR expression in a pretreatment biopsy specimen may be a significant adverse prognostic factor for disease-free survival and distant metastasis-free survival

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

    International Nuclear Information System (INIS)

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

  17. 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.

  18. Human pancreatic cancer-associated stellate cells remain activated after in vivo chemoradiation

    Directory of Open Access Journals (Sweden)

    Marina Carla Cabrera

    2014-05-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is characterized by an extensive fibrotic reaction or desmoplasia and complex involvement of the surrounding tumor microenvironment. Pancreatic stellate cells are a key mediator of the pancreatic matrix and they promote progression and invasion of pancreatic cancer by increasing cell proliferation and offering protection against therapeutic interventions. Our study utilizes human tumor-derived pancreatic stellate cells (HTPSCs isolated from fine needle aspirates of pancreatic cancer tissue from patients with locally advanced, unresectable pancreatic adenocarcinoma before and after treatment with full dose gemcitabine plus concurrent hypo-fractionated stereotactic radiosurgery. We show that HTPSCs survive in vivo chemotherapy and radiotherapy treatment and display a more activated phenotype post therapy. These data support the idea that stellate cells play an essential role in supporting and promoting pancreatic cancer and further research is needed to develop novel treatments targeting the pancreatic tumor microenvironment.

  19. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy

  20. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Du, Zhongli [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Wencheng [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Xiao, Zefen, E-mail: xiaozefen@sina.com [Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Tan, Wen, E-mail: tanwen@cicams.ac.cn [State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Department of Etiology and Carcinogenesis (Beijing Key Laboratory for Carcinogenesis and Cancer Prevention), Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  1. Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

    International Nuclear Information System (INIS)

    Purpose: To assess how neoadjuvant chemoradiation regimens modulate the immune system state in tumor-draining lymph nodes (TDLN), in the setting of advanced cervical cancer. Methods and Materials: Tumor-draining lymph nodes of patients undergoing chemotherapy only (nonirradiated, NI-TDLN) and chemoradiation with lower-dose (39.6 Gy, LD-TDLN) and higher-dose radiation (50 Gy, HD-TDLN) were analyzed by multicolor flow cytometry. Results: Enlarging our previous data, LD-TDLN showed features overall indicative of an enhanced antitumor response as compared with NI-TDLN, namely a significant Th1 and Tc1 polarization and a lower amount of the potent CD4+Foxp3+CD25high regulatory T cell (Treg) subset identified by neuropilin-1 expression. Conversely, compared with NI-TDLN, HD-TDLN showed features overall indicative of an impaired antitumor response, namely a significantly inverted CD4/CD8 cell ratio, a higher Nrp1+Treg frequency, and a higher frequency of CCR4+Treg, a Treg subset facilitated in migrating out from TDLN to suppress the immune response against distant cancer cells. Moreover, the Th1 and Tc1 polarization induced by LD radiation was lost, and there was an unfavorable tolerogenic/immunogenic dendritic cell ratio compared with LD-TDLN. Conclusions: Even minor differences in radiation dose in neoadjuvant regimens for locally advanced cervical cancer are crucial for determining the balance between a tolerogenic and an efficacious antitumor immune response in TDLN. Because most of the anticancer immune response takes place in TDLN, the present findings also emphasize the importance of chemoradiation protocols in the context of immunotherapeutic trials.

  2. Current status of radiation therapy. Evidence-based medicine (EBM) of radiation therapy. Current management of patients with esophageal cancer

    International Nuclear Information System (INIS)

    The best management for small mucosal esophageal cancer is generally endoscopic mucosal resection. However, for submucosal cancer and extensive mucosal caner, either radical surgery or radiation seems to be an equally efficacious option. Radiation therapy concurrent with chemotherapy is more effective than radiation therapy alone for patients with unresectable esophageal cancer. The key drugs are cisplatin and 5-fluorouracil. However, for patients with poor performance status or for aged patients, radiation therapy alone is still a choice of treatment. Surgery has generally been indicated for patients with resectable esophageal cancer. However, outcomes of concurrent chemoradiation therapy may be comparable with those of surgery. Therefore, a prospective randomized study should be performed to determine the best management for patients with resectable esophageal cancer. The usefulness of intra-cavitary irradiation for esophageal cancer has not been clarified. A prospective randomized trial with a large number of patients is necessary to determine the effectiveness of intra-cavitary irradiation. The best management for patients with loco-regionally recurrent esophageal cancer after surgery has not been determined. Intensive therapy should be considered if the site of recurrence is limited and the time interval from surgery to recurrence is long. Chemotherapy is essential in the management of patients with small cell esophageal cancer. However, the best local therapy has not been determined. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

  5. Current therapy of hilar cholangiocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Stephanie HiuYan Lau; WanYee Lau

    2012-01-01

    BACKGROUND: Hilar cholangiocarcinoma (HC) is an adeno-carcinoma of the extrahepatic biliary tree arising from the main left or right hepatic ducts or their confluence. This tumor is still considered to be difficult to treat or to cure. DATA SOURCES: We reviewed the medical literature on HC. Relevant and updated information on this tumor was analyzed in a concise and easy-to-read manner. The article is not intended to be a systematic review, but an extensive search was conducted on PubMed and MEDLINE using the keywords "hilar cholangiocarcinoma" and "Klatskin tumor" until July 2011. RESULTS: The selection and the timing of management options for patients with HC are determined by the degree of certainty of the diagnosis, the general condition of the patients, the underlying liver function and the stage of the disease. Current treatment of HC can be divided into curative and palliative treatment. For the curative treatment, local excision should only be used on small tumors which are confined to the bile duct wall and Bismuth I papillary carcinoma. Partial hepatectomy should be combined with caudate lobe resection and porta-hepatis lymph node dissection. The results of these major resections can be improved with portal vein embolization, and staging laparoscopy and laparoscopic ultrasound. The role of preoperative biliary drainage is controversial. Autotransplantation for HC gave disappointing results while the Mayo Protocol of chemoradiation for selecting patients with unresectable HC for orthotopic liver transplantation has been widely accepted. Palliative treatment included bypass surgery, endoscopic or percutaneous stenting, photodynamic therapy, intraluminal brachytherapy, and external radiation and systemic therapy. CONCLUSIONS: Adequate surgery with R0 resection should be the main goal of treatment. For patients with unresectable HC, treatment aims to improve the quality and quantity of their survival.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers.

    Science.gov (United States)

    Minniti, Giuseppe; Arcella, Antonella; Scaringi, Claudia; Lanzetta, Gaetano; Di Stefano, Domenica; Scarpino, Stefania; Pace, Andrea; Giangaspero, Felice; Osti, Mattia Falchetto; Enrici, Riccardo Maurizi

    2014-01-01

    Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA. PMID:24162810

  8. The potential of proton beam therapy in paediatric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bjoerk-Eriksson, Thomas [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Oncology; Glimelius, Bengt [Karolinska Inst., Stockholm (Sweden). Dept. of Oncology and Pathology; Akademiska sjukhuset, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology

    2005-12-01

    A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. It is estimated that in paediatric cancers, proton beams are of potential importance in 80-100 children annually in Sweden. About 20 of the patients have medulloblastoma. The main purpose is to reduce late sequelae, but these are also increased chances to avoid myelosupression during e.g. concomitant chemo-radiation and to further intensify the chemotherapy.

  9. Childhood Trauma and Adult Interpersonal Functioning: A Study Using the Core Conflictual Relationship Theme Method (CCRT)

    Science.gov (United States)

    Drapeau, M.; Perry, J.C.

    2004-01-01

    Objective: This study aimed to examine the long-term correlates of childhood trauma in regard to interpersonal functioning in adulthood. Method: One hundred and nineteen (N=119) subjects from the Austen Riggs Follow-along Study were included in the study. The Traumatic Antecedent Interview scoring method was used to assess 10 types of childhood…

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

    International Nuclear Information System (INIS)

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

  11. Combined chemoradiation and interstitial IR-192 implant for T3 and T4 anal cancer

    International Nuclear Information System (INIS)

    Introduction: We have previously shown that 30 Gy + 5-FU + Mitomycin-C (MMC) combined modality therapy (CM) will control T1 and T2 anal cancers with no late morbidity. However control of T3 and T4 cancers was poor, with an overall local control rate (LCR) of 38%. We now report our experience with the addition of an interstitial Ir-192 implant (SPI) for persistent disease (PD) or T3 or T4 tumors. Methods: All patients received 30 Gy EBRT + infusional 5-FU (1000 mg/m2) + 1 dose of MMC (10 mg/m2). The radiation field encompassed the inguinal nodes and pelvis from mid SI joint to 1 cm below the anus. This was followed by a single plane circular implant (SPI) using a proprietary template which can be loaded with up to 8 needles. Median dose was 28.48 Gy (range 20 to 31.6 Gy), delivered at a median rate of 0.43 Gy/Hr (range 0.28 to 0.50 Gy/Hr). All patients were followed-up at regular intervals including sigmoidoscopy. Results: Of 2 male and 10 female patients treated with CM + implant, 10 were stage T3, 1 was stageT4 and 1 was stage T1; 1 was N1, 11 were N0, 1 was grade 1, 5 were grade 2 and 6 were grade 3. Average tumor size was 6 cm (range 2 to 9 cm). The median interval from EBRT to SPI was 6 weeks (range 4 to 12 weeks). The median decrease in tumor size after CM, but before SPI, was 34% (range 0% to 88%). With a follow-up of 2 to 38 months the LCR is 67% ((8(12))). Four patients had PD and 3 subsequently underwent salvage surgery, 2 of whom died of disease. Overall survival is 75% ((9(12))). Conclusions: Although follow-up time is still relatively short, the addition of SPI to our standard CM protocol appears to markedly improve the LCR for this group of anal cancers

  12. 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:

  13. The Impact of Tumor Expression of Erythropoietin Receptors and Erythropoietin on Clinical Outcome of Esophageal Cancer Patients Treated With Chemoradiation

    International Nuclear Information System (INIS)

    Background: To investigate the impact of tumor erythropoietin receptors (Epo-R) and erythropoietin (Epo) expression in 64 patients with Stage III esophageal cancer receiving or not receiving erythropoietin during chemoradiation. Materials and Methods: The impact of tumor Epo-R expression, Epo expression, and 10 additional factors (age, Karnofsky-Performance-Score [KPS], tumor length, T and N stage, histology and grading, hemoglobin during radiotherapy, erythropoietin administration, surgery) on overall survival (OS) and locoregional control (LC) was evaluated. Results: Improved OS was associated with low (≤20%) Epo expression (p = 0.049), KPS >80 (p 0.008), T3 stage (p = 0.010), hemoglobin ≥12 g/dL (p < 0.001), and surgery (p = 0.010). Erythropoietin receptor expression showed a trend (p = 0.09). Locoregional control was associated with T stage (p = 0.005) and hemoglobin (p < 0.001), almost with erythropoietin administration (p = 0.06). On multivariate analyses, OS was associated with KPS (p = 0.045) and hemoglobin (p = 0.032), LC with hemoglobin (p < 0.001). Patients having low expression of both Epo-R and Epo had better OS (p = 0.003) and LC (p = 0.043) than others. Two-year OS was nonsignificantly better (p = 0.25) in patients with low Epo-R expression receiving erythropoietin (50%) than in those with higher Epo-R expression receiving erythropoietin (21%), low Epo-R expression/no erythropoietin administration (29%), or higher Epo-R expression/no erythropoietin administration (18%). Two-year LC rates were, respectively, 65%, 31%, 26%, and 29% (p = 0.20). Results for Epo expression were similar. Conclusions: Higher Epo-R expression or Epo expression seemed to be associated with poorer outcomes. Patients with low expression levels receiving erythropoietin seemed to do better than patients with higher expression levels or not receiving erythropoietin. The data need to be confirmed in a larger series of patients

  14. Proton Therapy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Proton Therapy Proton therapy delivers radiation to tumor tissue ... feel during and after the procedure? What is proton therapy and how is it used? Protons are ...

  15. Should helical tomotherapy replace brachytherapy for cervical cancer? Case report

    International Nuclear Information System (INIS)

    Stereotactic body radiation therapy (SBRT) administered via a helical tomotherapy (HT) system is an effective modality for treating lung cancer and metastatic liver tumors. Whether SBRT delivered via HT is a feasible alternative to brachytherapy in treatment of locally advanced cervical cancer in patients with unusual anatomic configurations of the uterus has never been studied. A 46-year-old woman presented with an 8-month history of abnormal vaginal bleeding. Biopsy revealed squamous cell carcinoma of the cervix. Magnetic resonance imaging (MRI) showed a cervical tumor with direct invasion of the right parametrium, bilateral hydronephrosis, and multiple uterine myomas. International Federation of Gynecology and Obstetrics (FIGO) stage IIIB cervical cancer was diagnosed. Concurrent chemoradiation therapy (CCRT) followed by SBRT delivered via HT was administered instead of brachytherapy because of the presence of multiple uterine myomas with bleeding tendency. Total abdominal hysterectomy was performed after 6 weeks of treatment because of the presence of multiple uterine myomas. Neither pelvic MRI nor results of histopathologic examination at X-month follow-up showed evidence of tumor recurrence. Only grade 1 nausea and vomiting during treatment were noted. Lower gastrointestinal bleeding was noted at 14-month follow-up. No fistula formation and no evidence of haematological, gastrointestinal or genitourinary toxicities were noted on the most recent follow-up. CCRT followed by SBRT appears to be an effective and safe modality for treatment of cervical cancer. Larger-scale studies are warranted

  16. Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation

    OpenAIRE

    Batchelor, Tracy T.; Gerstner, Elizabeth R.; Emblem, Kyrre E; Dan G Duda; Kalpathy-Cramer, Jayashree; Snuderl, Matija; Ancukiewicz, Marek; Polaskova, Pavlina; Pinho, Marco C.; Jennings, Dominique; Plotkin, Scott R.; Chi, Andrew S.; Eichler, April F.; Dietrich, Jorg; Hochberg, Fred H.

    2013-01-01

    This study demonstrates that antiangiogenic therapy increases tumor blood perfusion in a subset of newly diagnosed glioblastoma patients, and that it is these patients who survive longer when this expensive and potentially toxic therapy is combined with standard radiation and chemotherapy. This study provides fresh insights into the selection of glioblastoma patients most likely to benefit from antiangiogenic treatments.

  17. Hypofractionated stereotactic radiation therapy for recurrent glioblastoma: single institutional experience

    International Nuclear Information System (INIS)

    Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Tumor control and survival have improved with the use of radiotherapy (RT) plus concomitant and adjuvant chemotherapy, but the prognosis remain poor. In most cases the recurrence occurs within 7–9 months after primary treatment. Currently, many approaches are available for the salvage treatment of patients with recurrent GBM, including resection, re-irradiation or systemic agents, but no standard of care exists. We analysed a cohort of patients with recurrent GBM treated with frame-less hypofractionated stereotactic radiation therapy with a total dose of 25 Gy in 5 fractions. Of 91 consecutive patients with newly diagnosed GBM treated between 2007 and 2012 with conventional adjuvant chemo-radiation therapy, 15 underwent salvage RT at recurrence. The median time interval between primary RT and salvage RT was 10.8 months (range, 6–54 months). Overall, patients undergoing salvage RT showed a longer survival, with a median survival of 33 vs. 9.9 months (p= 0.00149). Median overall survival (OS) from salvage RT was 9.5 months. No patients demonstrated clinically significant acute morbidity, and all patients were able to complete the prescribed radiation therapy without interruption. Our results suggest that hypofractionated stereotactic radiation therapy is effective and safe in recurrent GBM. However, until prospective randomized trials will confirm these results, the decision for salvage treatment should remain individual and based on a multidisciplinary evaluation of each patient

  18. Trimodality Therapy for an Advanced Thymic Carcinoma With Both Aorta and Vena Cava Invasion.

    Science.gov (United States)

    Momozane, Tohru; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Okumura, Meinoshin

    2016-08-01

    A case of locally advanced thymic carcinoma that was successfully resected with the great vessels after chemoradiation therapy is reported. A 57-year-old man with Masaoka stage III thymic carcinoma received two cycles of cisplatin/docetaxel and 60 Gy irradiation. The response was stable disease with 19% size reduction, and a radical resection with the ascending aorta and superior vena cava with the patient under circulatory arrest with the use of cardiopulmonary bypass was performed. The postoperative course was uneventful, and the patient has been free of disease for 28 months. Trimodality therapy with use of a cardiovascular surgical procedure might be a valuable option in locally advanced thymic carcinoma. PMID:27449450

  19. Hypopharyngeal Dose Is Associated With Severe Late Toxicity in Locally Advanced Head-and-Neck Cancer: An RTOG Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Machtay, Mitchell, E-mail: mitchell.machtay@uhhospitals.org [University Hospitals Seidman Cancer Center and Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Moughan, Jennifer [Radiation Therapy Oncology Group Headquarters and Statistical Center, Philadelphia, Pennsylvania (United States); Farach, Andrew [Thomas Jefferson University, Philadelphia, Pennsylvania (United States); University of Texas Health Science Center/Baylor College of Medicine, Houston, Texas (United States); Martin-O' Meara, Elizabeth [Radiation Therapy Oncology Group Headquarters and Statistical Center, Philadelphia, Pennsylvania (United States); Galvin, James [Radiation Therapy Oncology Group Headquarters and Statistical Center, Philadelphia, Pennsylvania (United States); Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Garden, Adam S.; Weber, Randal S. [MD Anderson Cancer Center, Houston, Texas (United States); Cooper, Jay S. [Maimonides Medical Center, New York, New York (United States); Forastiere, Arlene [Johns Hopkins University Medical Center, Baltimore, Maryland (United States); Ang, K. Kian [MD Anderson Cancer Center, Houston, Texas (United States)

    2012-11-15

    Purpose: Concurrent chemoradiation therapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases local tumor control but at the expense of increased toxicity. We recently showed that several clinical/pretreatment factors were associated with the occurrence of severe late toxicity. This study evaluated the potential relationship between radiation dose delivered to the pharyngeal wall and toxicity. Methods and Materials: This was an analysis of long-term survivors from 3 previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG trials 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3-4 pharyngeal/laryngeal toxicity and/or requirement for a feeding tube {>=}2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Radiation dosimetry (2-dimensional) analysis was performed centrally at RTOG headquarters to estimate doses to 4 regions of interest along the pharyngeal wall (superior oropharynx, inferior oropharynx, superior hypopharynx, and inferior hypopharynx). Case-control analysis was performed with a multivariate logistic regression model that included pretreatment and treatment potential factors. Results: A total of 154 patients were evaluable for this analysis, 71 cases (patients with severe late toxicities) and 83 controls; thus, 46% of evaluable patients had a severe late toxicity. On multivariate analysis, significant variables correlated with the development of severe late toxicity, including older age (odds ratio, 1.062 per year; P=.0021) and radiation dose received by the inferior hypopharynx (odds ratio, 1.023 per Gy; P=.016). The subgroup of patients receiving {<=}60 Gy to the inferior hypopharynx had a 40% rate of severe late toxicity compared with 56% for patients receiving >60 Gy. Oropharyngeal dose was not associated with this outcome. Conclusions: Severe late toxicity following CCRT is

  20. 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

  1. 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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    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

  4. Metformin use and improved response to therapy in rectal cancer

    International Nuclear Information System (INIS)

    Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision (TME). Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy. In this study, we examined the effect of metformin use on pathologic complete response (pCR) rates and outcomes in rectal cancer. The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was 50.4 Gy (range 19.8–63). Nearly, all patients were treated with concurrent 5-fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%). Patients were categorized as nondiabetic (422), diabetic not taking metformin (40), or diabetic taking metformin (20). No significant differences between groups were found in clinical tumor classification, nodal classification, tumor distance from the anal verge or circumferential extent, pretreatment carcinoembryonic antigen level, or pathologic differentiation. pCR rates were 16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for diabetics taking metformin, with metformin users having significantly higher pCR rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P = 0.007). Metformin use was significantly associated with pCR rate on univariate (P = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking metformin had significantly increased disease-free (P = 0.013) and overall survival (P = 0.008) compared with other diabetic patients. Metformin use is associated with significantly higher pCR rates as well as improved survival. These promising data warrant further prospective study

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

    OpenAIRE

    Prasad Eswaran; Kumaravelu S Azmi

    2013-01-01

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

  6. Robotic versus laparoscopic surgery for mid or low rectal cancer in male patients after neoadjuvant chemoradiation therapy: comparison of short-term outcomes.

    Science.gov (United States)

    Serin, Kursat Rahmi; Gultekin, Fatma Ayca; Batman, Burçin; Ay, Serden; Kapran, Yersu; Saglam, Sezer; Asoglu, Oktar

    2015-09-01

    The aim of our study was to compare short-term outcomes of robotic and laparoscopic sphincter-saving total mesorectal excision (TME) in male patients with mid-low rectal cancer (RC) after neadjuvant chemoradiotherapy (NCRT). The study was conducted as a retrospective review of a prospectively maintained database, and we analyzed 14 robotic and 65 laparoscopic sphincter saving TME (R-TME and L-TME, respectively) performed by one surgeon between 2005 and 2013. Patient characteristics, perioperative recovery, postoperative complications and and pathology results were compared between the two groups. The patient characteristics did not differ significantly between the two groups. Median operating time was longer in the R-TME than in the L-TME group (182 min versus 140 min). Only two conversions occurred in the L-TME group. No difference was found between groups regarding perioperative recovery and postoperative complication rates. The median number of harvested lymph nodes was higher in the RTME than in the L-TME group (32 versus 23, p = 0.008). The median circumferential margin (CRM) was 10 mm in the R-TME group, 6.5 mm in the L-TME group (p = 0.047. The median distal resection margin (DRM) was 27.5 mm in the R-TME, 15 mm in the L-TME group (p = 0.014). Macroscopic grading of the specimen in the R-TME group was complete in all patients. In the L-TME group, grading was complete in 52 (80%) and incomplete in 13 (20%) cases (p = 0.109). R-TME is a safe and feasible procedure that facilitates performing of TME in male patients with mid-low RC after NCRT. PMID:26531198

  7. Locally advanced rectal cancer: diffusion-weighted MR tumour volumetry and the apparent diffusion coefficient for evaluating complete remission after preoperative chemoradiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Hong Il [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Hallym University Medical Center, Hallym University Sacred Heart Hospital, Department of Radiology, Anyang-si, Gyeonggi-do (Korea, Republic of); Kim, Ah Young; Park, Seong Ho; Ha, Hyun Kwon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Yu, Chang Sik [University of Ulsan College of Medicine, Asan Medical Center, Department of Colon and Rectal Surgery, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate DW MR tumour volumetry and post-CRT ADC in rectal cancer as predicting factors of CR using high b values to eliminate perfusion effects. One hundred rectal cancer patients who underwent 1.5-T rectal MR and DW imaging using three b factors (0, 150, and 1,000 s/mm{sup 2}) were enrolled. The tumour volumes of T2-weighted MR and DW images and pre- and post-CRT ADC{sub 150-1000} were measured. The diagnostic accuracy of post-CRT ADC, T2-weighted MR, and DW tumour volumetry was compared using ROC analysis. DW MR tumour volumetry was superior to T2-weighted MR volumetry comparing the CR and non-CR groups (P < 0.001). Post-CRT ADC showed a significant difference between the CR and non-CR groups (P = 0.001). The accuracy of DW tumour volumetry (A{sub z} = 0.910) was superior to that of T2-weighed MR tumour volumetry (A{sub z} = 0.792) and post-CRT ADC (A{sub z} = 0.705) in determining CR (P = 0.015). Using a cutoff value for the tumour volume reduction rate of more than 86.8 % on DW MR images, the sensitivity and specificity for predicting CR were 91.4 % and 80 %, respectively. DW MR tumour volumetry after CRT showed significant superiority in predicting CR compared with T2-weighted MR images and post-CRT ADC. (orig.)

  8. Post-chemoradiation intraoperative electron-beam radiation therapy boost in resected locally advanced rectal cancer: Long-term results focused on topographic pattern of locoregional relapse

    International Nuclear Information System (INIS)

    Background: Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT. Methods: A total of 335 patients with LARC [⩾cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed. Results: Median follow-up was 72.6 months (range, 4–205). In multivariate analysis distal margin distance ⩽10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1–2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC. Conclusions: Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment

  9. Prevention of radiation esophagitis by polaprezinc (zinc L-carnosine) in patients with non-small cell lung cancer who received chemoradiotherapy

    OpenAIRE

    Yanase, Komei; Funaguchi, Norihiko; Iihara, Hirotoshi; Yamada, Maya; Kaito, Daizo; Endo, Junki; Ito, Fumitaka; Ohno, Yasushi; Tanaka, Hidekazu; Itoh, Yoshinori; Minatoguchi, Shinya

    2015-01-01

    Background: Concurrent chemoradiotherapy (CCRT) plays an important role in multimodality therapy for non-small cell lung cancer. However, esophagitis often develops as a complication of CCRT, causing treatment delays and reducing the patient’s quality of life. We examined the efficacy of polaprezinc (PZ), zinc L-carnosine used for the therapy of gastric ulcer, against the onset of esophagitis caused by CCRT for lung cancer. Patients and Methods: Patients who concurrently underwent chemotherap...

  10. Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

    International Nuclear Information System (INIS)

    To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer. Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m2 intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully. HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted

  11. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

    Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

  12. Radiation Therapy

    Science.gov (United States)

    ... therapy. At this time, you will have a physical exam , talk about your medical history , and maybe have imaging tests . Your doctor or nurse will discuss external beam radiation therapy, its benefits and side effects, and ways you can care ...

  13. Therapy Services.

    Science.gov (United States)

    Austin Independent School District, TX.

    Reviewed are the goals and activities of the therapy services in the Austin Early Childhood Special Education Program. Specific sections detail activities for speech therapy (such as diagnostic assessment, habilitation, consultation, and reporting procedures), occupational therapy (including identification and assessment, and services to children,…

  14. Response to Therapy and Outcomes in Oropharyngeal Cancer Are Associated With Biomarkers Including Human Papillomavirus, Epidermal Growth Factor Receptor, Gender, and Smoking

    International Nuclear Information System (INIS)

    Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile

  15. 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

  16. 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.

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

    International Nuclear Information System (INIS)

    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

  18. Proton therapy

    International Nuclear Information System (INIS)

    Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)

  19. EGFR expression and survival in patients given cetuximab and chemoradiation for stage III non-small cell lung cancer: A secondary analysis of RTOG 0324

    International Nuclear Information System (INIS)

    Purpose: We investigated whether expression of epidermal growth factor receptor (EGFR) was associated with survival and disease control in this secondary analysis of a phase II trial of cetuximab + chemoradiation for stage III non-small cell lung cancer. Methods: Patients received cetuximab weekly before and during radiation (63 Gy/35 fractions/7 weeks) with weekly carboplatin + paclitaxel. We analyzed EGFR expression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in pretreatment biopsy specimens and compared findings with overall and progression-free survival (OS, PFS) and time to progression (TTP). Results: Specimens for IHC and FISH were collected from 51 and 45 of 87 evaluable patients. Pretreatment characteristics did not differ for patients with (n = 51) or without (n = 36) EGFR IHC data, or with (n = 45) or without (n = 42) FISH data. However, patients without IHC data had worse OS (HR = 1.63, P = 0.05), worse PFS (HR = 1.88, P = 0.008), and worse TTP [HR = 1.99, P = 0.01] than those with IHC data. EGFR protein expression was not related to pretreatment characteristics or OS; FISH-positive disease was associated with better performance status but not with OS, PFS, or TTP. Conclusions: Surprisingly, outcomes differed not by EGFR expression but by the availability of samples for analysis, underscoring the importance of obtaining biopsy samples in such trials

  20. 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.

  1. 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

    International Nuclear Information System (INIS)

    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/m2. 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.

  2. Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

    International Nuclear Information System (INIS)

    Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques

  3. Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

    Energy Technology Data Exchange (ETDEWEB)

    Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham [Andrew Love Cancer Centre, Geelong Hospital, Geelong, Victoria (Australia)

    2013-12-15

    Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques.

  4. Gene therapy.

    OpenAIRE

    Mota Biosca, Anna

    1992-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases.

  5. Phase II trial of first-line chemoradiotherapy with intensity-modulated radiation therapy followed by chemotherapy for synchronous unresectable distant metastases rectal adenocarcinoma

    International Nuclear Information System (INIS)

    Based on the hypothesis that first-line chemoradiation followed by chemotherapy was superior for primary tumor and non-inferior for distant lesions compared to chemotherapy alone in synchronous unresectable distant metastases rectal adenocarcinoma, this study was designed to assess the efficacy and safety of this strategy. Thirty two eligible patients received intensity modulated radiation therapy (45 Gy to the pelvis and a concomitant 10 Gy boost to the gross tumor), along with concurrent weekly capecitabine and oxaliplatin. Patients underwent radical surgery if all lesions were visually evaluated as resectable and received chemotherapy for a total of 6 months, whether pre- or post-operatively (definitive therapy group). The remaining patients received 6 months of consolidation chemotherapy followed by maintenance chemotherapy (non-definitive therapy group). The toxicities were acceptable, with radiation-induced dermatitis around the anal verge being the most common (18.8%). Fourteen patients underwent surgical resection of the rectal tumor, with 5 (35.7%) experiencing a pathological complete response. Nine out of 14 received definitive treatment, defined as R0 resections of all visible tumors. At a median follow-up of 12 months (range, 4–23 months), 2 cases were evaluated as local failure, and the median overall survival (OS) and progression free survival (PFS) for all 32 patients were 17.5 and 12 months, respectively. OS differed significantly in the definitive and non-definitive therapy groups (p=0.045), and PFS tended to differ (p=0.274). It was demonstrated that the strategy of first-line chemoradiation followed by chemotherapy was effective and tolerable, especially for local control. OS and PFS were superior in patients who did than did not undergo curative therapy

  6. Câncer ano-reto-cólico: aspectos atuais III - câncer de reto - terapêutica neoadjuvante Anal canal and colorectal cancer: current features III - rectal cancer - neodajuvant chemoradiation

    Directory of Open Access Journals (Sweden)

    Júlio César M Santos Jr

    2008-03-01

    abdominoperineal resection was done for cancer of middle or distal rectum. However, rectal cancer has prominent tendency to recur locally which is often catastrophic - it is a very symptomatic and debilitating disease. On rectal cancer, this is the major threats for patients afflicted, in such a way that the prevention of local recurrence is one of the main goals of rectal cancer surgery. This has been possible with advances that it was brought because of surgical techniques improvement by total mesorectal excision (TME, because of wide variety of oncological drugs, because of role of endoscopic ultrasound and magnetic resonance imaging in the evaluation of rectal cancer, and the acquired knowledge on preoperative chemoradiation as a neoadjuvant therapy.

  7. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    Energy Technology Data Exchange (ETDEWEB)

    Westover, Kenneth D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gerber, David E. [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Iyengar, Puneeth; Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Hughes, Randy; Schiller, Joan; Dowell, Jonathan [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wardak, Zabi [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sher, David [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Christie, Alana; Xie, Xian-Jin [Department of Clinical Science, Southwestern Medical Center, Dallas, Texas (United States); Corona, Irma [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sharma, Akanksha [School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wadsworth, Margaret E. [Radiation Oncology of Mississippi, Jackson, Mississippi (United States); Timmerman, Robert, E-mail: Robert.Timmerman@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

  8. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    International Nuclear Information System (INIS)

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follo