human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers . SUMMARY BACKGROUND DATA A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results . METHODS Eligible patients with T1 - 2N0 - 1aM0 pancreatic head or T1 - 3N0 - 1aM0 periampullary cancer and histologically proven adenocarcinoma were r and omized after resection . RESULTS Between 1987 and 1995 , 218 patients were r and omized ( 108 patients in the observation group , 110 patients in the treatment group ) . Eleven patients were ineligible ( five in the observation group and six in the treatment group ) . Baseline characteristics were comparable between the two groups . One hundred fourteen patients ( 55 % ) had pancreatic cancer ( 54 in the observation group and 60 in the treatment group ) . In the treatment arm , 21 patients ( 20 % ) received no treatment because of postoperative complications or patient refusal . In the treatment group , only minor toxicity was observed . The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group ( log-rank , p = 0.208 ) . The 2-year survival estimates were 41 % and 51 % , respectively . The results when stratifying for tumor location showed a 2-year survival rate of 26 % in the observation group and 34 % in the treatment group ( log-rank , p = 0.099 ) in pancreatic head cancer ; in periampullary cancer , the 2-year survival rate was 63 % in the observation group and 67 % in the treatment group ( log-rank , p = 0.737 ) . No reduction of locoregional recurrence rates was apparent in the groups . CONCLUSIONS Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated . However , the benefit in this study was small ; routine use of adjuvant chemoradiotherapy is not warranted as st and ard treatment in cancer of the head of the pancreas or periampullary region Background We report the results of a multi-institutional phase II trial that used preoperative full-dose gemcitabine and radiotherapy for patients with potentially resectable pancreatic carcinoma . Methods Patients were treated before surgery with three cycles of full-dose gemcitabine ( 1000 mg/m2 intravenously ) , with radiation during the second cycle ( 36 Gy in daily 2.4-Gy fractions ) . Patients underwent surgery 4 to 6 weeks after the last gemcitabine infusion . Results There were 10 men and 10 women , with a median age of 58 years ( range , 50–80 years ) . Nineteen patients ( 95 % ) completed therapy without interruption , and one experienced grade 3 gastrointestinal toxicity . The mean weight loss after therapy was 4.0 % . Of 20 patients taken to surgery , 17 ( 85 % ) underwent resections ( 16 pancreaticoduodenectomies and 1 distal pancreatectomy ) . The complication rate was 24 % , with an average length of stay of 13.5 days . There were no operative deaths . Pathologic analysis revealed clear margins in 16 ( 94 % ) of 17 and uninvolved lymph nodes in 11 ( 65 % ) of 17 specimens . One specimen contained no residual tumor , and three specimens revealed only microscopic foci of residual disease . With a median follow-up of 18 months , 7 ( 41 % ) of the 17 patients with resected disease are alive with no recurrence , 3 ( 18 % ) are alive with distant metastases , and 7 ( 41 % ) have died . Conclusions Preoperative gemcitabine/radiotherapy is well tolerated and safe when delivered in a multi-institutional setting . This protocol had a high rate of subsequent resection , with acceptable morbidity . The high rate of negative margins and uninvolved nodes suggests a significant tumor response . Preliminary survival data are encouraging . This regimen should be considered in future neoadjuvant trials for pancreatic cancer Background Preoperative chemotherapy ( PCHT ) has recently been proposed also in patients with resectable pancreatic adenocarcinoma . Few data are currently available on the impact of PCHT on short-term postoperative outcome after pancreatic resection . The objective of this study is to assess the impact of PCHT on pancreatic structure and short-term outcome after surgical resection . Methods Fifty consecutive patients successfully underwent resection after PCHT .  Each patient was matched with two control patients with pancreatic adenocarcinoma selected from our prospect i ve electronic data base . Match criteria were age ( ±3 years ) , gender , American Society of Anesthesiologist score , type of resection , pancreatic duct diameter ( ±1 mm ) , and tumor size ( ±5 mm ) . Primary endpoint was morbidity rate . Secondary endpoints were pancreatic parenchymal structure , mortality rate , and length of hospital stay ( LOS ) . Results Both degree of fibrosis and fatty infiltration of the pancreas were similar in the two groups . Overall morbidity rate was 48.0 % in the PCHT group vs. 54.0 % in the control group ( p = 0.37 ) . Pancreatic fistula rate was 18.0 % in the PCHT group vs. 25.0 % in the control group ( p = 0.41 ) . Mortality was 4.0 % in the PCHT group vs. 2.0 % in the control group ( p = 0.60 ) . Mean LOS ( days ) was 12.7 in the PCHT group vs. 12.4 in the control group ( p = 0.74 ) . There was no difference in resection margin status , while the rate of patients without nodal involvement was higher in the PCHT group ( 46.0 vs. 23.0 % , p = 0.004 ) . Conclusion PCHT did not induce significant structural changes in pancreatic parenchyma and did not adversely affect short-term outcome after surgery The efficacy of combined radiation and fluorouracil as adjuvant therapy for pancreatic cancer is suggested by a prospect i ve r and omized study conducted by the Gastrointestinal Tumor Study Group ( GITSG ) . Twenty-two patients r and omized to no adjuvant treatment and 21 to combined therapy were analyzed . Neither life-threatening toxic reaction nor death due to toxic effect was encountered . The study was terminated prematurely because of an unacceptably low rate of accrual combined with the observation of increasingly large survival differences between the study arms . Median survival for the treatment group ( 20 months ) was significantly longer than that observed for the control group ( 11 months ) . Four patients , three in the treated and one in the control group , have survived five years or longer following surgery . The extent of the tumor and initial performance status were significantly and independently related to survival 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 MATERIAL S 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(G12D ) status and high CXCR7 expression and circulating CEA , CA19 - 9 , and HGF levels were associated with poor survival Objective : To analyze the histopathological indicators significantly associated with surgical outcome and the pattern of recurrence in the setting of preoperative gemcitabine-based chemoradiation therapy ( CRT ) and subsequent pancreatectomy . Background : Clinicopathological assessment of the resected specimen is an indispensable tool for predicting patient prognosis and localizing high-risk sites for tumor relapse . This procedure is also essential for the establishment of efficient postoperative follow-up protocol s in the setting of a preoperative CRT strategy . Methods : In a prospect i ve phase II clinical trial at our hospital , 110 patients received preoperative CRT and subsequent resection . All 110 resected cases were included in this study . We employed disease-free survival ( DFS ) as a surgical outcome , and the pattern of recurrence was divided into 2 categories : ( 1 ) recurrence in the abdominal cavity ( RAC ) , defined as either a locoregional or a peritoneal recurrence ; or ( 2 ) distant recurrence ( DR ) , defined as cancer recurrence in a distant organ . Clinicopathological variables were analyzed in association with DFS , RAC , and DR . Results : Positive nodal involvement and perineural invasion were independent factors that were significantly associated with an unfavorable DFS ( P = 0.021 and P = 0.026 , respectively ) . The presence of perineural invasion was the single independent variable significantly associated with an increased risk of RAC ( P = 0.002 ) , whereas the status of nodal involvement was the single independent variable significantly associated with an increased risk of DR ( P = 0.013 ) . Conclusions : The status of nodal involvement and perineural invasion in resected specimens are significantly associated with DFS and clearly predict the pattern of recurrence in the setting of a preoperative gemcitabine-based CRT strategy . This study is registered at UMIN-CTR and carries the ID number UMIN000001804 CONTEXT Gemcitabine and 5-fluorouracil ( 5-FU ) sensitize tumor cells to radiation . Furthermore , 5-FU enhances the cytotoxic effect of gemcitabine . OBJECTIVE We report the efficacy and the toxicity of concurrent chemoradiation with gemcitabine and 5-FU in the treatment of patients with locally advanced , unresectable pancreatic cancer . PATIENTS Thirty-two patients ( 20 men , 12 women ; median age 69.9 years ) with histologically proven advanced pancreatic carcinoma were included in the study . INTERVENTIONS The patients received chemotherapy with gemcitabine 300 mg/m2 on days 1 , 15 , 29 and 5-FU as continuous infusion 350 mg/m2/day of radiation while concurrent radiation ( 45 - 50 Gy ) was given to the tumor and regional lymph nodes ( 1.8 - 2.0 Gy/fraction on 5 days/week ) . Subsequent to chemoradiotherapy , the treatment was continued with an additional two cycles of gemcitabine ( 1,000 mg/m2 ) and cisplatin ( 50 mg/m2 ) applied on days 1 and 15 of a four-week cycle . MAIN OUTCOME MEASURES Patient survival , time to progression , and toxicity of chemoradiation . Tumor responses ( complete resolution ; partial response ; stable disease , and progressive disease ) were also evaluated . RESULTS After the completion of chemoradiotherapy , 2 patients ( 6.3 % ) achieved complete resolution and 18 patients ( 56.3 % ) a partial response , for an overall response rate of 62.5 % . Twelve patients ( 37.5 % ) were considered resectable and 9 underwent laparotomy , 7 of whom had definitive pancreatic resection . Four patients had negative surgical margins . With a median follow-up of 49.7 months ( 95 % CI : 48.6 - 60.8 months ) after the completion of chemoradiation , distant metastasis occurred in 25 patients ( 78.1 % ) while local recurrence was seen only in 4 of 32 patients ( 12.5 % ) . Median time to progression was 9.2 months ( 95 % CI : 8.2 - 1 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers . SUMMARY BACKGROUND DATA A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results . METHODS Eligible patients with T1 - 2N0 - 1aM0 pancreatic head or T1 - 3N0 - 1aM0 periampullary cancer and histologically proven adenocarcinoma were r and omized after resection . RESULTS Between 1987 and 1995 , 218 patients were r and omized ( 108 patients in the observation group , 110 patients in the treatment group ) . Eleven patients were ineligible ( five in the observation group and six in the treatment group ) . Baseline characteristics were comparable between the two groups . One hundred fourteen patients ( 55 % ) had pancreatic cancer ( 54 in the observation group and 60 in the treatment group ) . In the treatment arm , 21 patients ( 20 % ) received no treatment because of postoperative complications or patient refusal . In the treatment group , only minor toxicity was observed . The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group ( log-rank , p = 0.208 ) . The 2-year survival estimates were 41 % and 51 % , respectively . The results when stratifying for tumor location showed a 2-year survival rate of 26 % in the observation group and 34 % in the treatment group ( log-rank , p = 0.099 ) in pancreatic head cancer ; in periampullary cancer , the 2-year survival rate was 63 % in the observation group and 67 % in the treatment group ( log-rank , p = 0.737 ) . No reduction of locoregional recurrence rates was apparent in the groups . CONCLUSIONS Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated . However , the benefit in this study was small ; routine use of adjuvant chemoradiotherapy is not warranted as st and ard treatment in cancer of the head of the pancreas or periampullary region Background We report the results of a multi-institutional phase II trial that used preoperative full-dose gemcitabine and radiotherapy for patients with potentially resectable pancreatic carcinoma . Methods Patients were treated before surgery with three cycles of full-dose gemcitabine ( 1000 mg/m2 intravenously ) , with radiation during the second cycle ( 36 Gy in daily 2.4-Gy fractions ) . Patients underwent surgery 4 to 6 weeks after the last gemcitabine infusion . Results There were 10 men and 10 women , with a median age of 58 years ( range , 50–80 years ) . Nineteen patients ( 95 % ) completed therapy without interruption , and one experienced grade 3 gastrointestinal toxicity . The mean weight loss after therapy was 4.0 % . Of 20 patients taken to surgery , 17 ( 85 % ) underwent resections ( 16 pancreaticoduodenectomies and 1 distal pancreatectomy ) . The complication rate was 24 % , with an average length of stay of 13.5 days . There were no operative deaths . Pathologic analysis revealed clear margins in 16 ( 94 % ) of 17 and uninvolved lymph nodes in 11 ( 65 % ) of 17 specimens . One specimen contained no residual tumor , and three specimens revealed only microscopic foci of residual disease . With a median follow-up of 18 months , 7 ( 41 % ) of the 17 patients with resected disease are alive with no recurrence , 3 ( 18 % ) are alive with distant metastases , and 7 ( 41 % ) have died . Conclusions Preoperative gemcitabine/radiotherapy is well tolerated and safe when delivered in a multi-institutional setting . This protocol had a high rate of subsequent resection , with acceptable morbidity . The high rate of negative margins and uninvolved nodes suggests a significant tumor response . Preliminary survival data are encouraging . This regimen should be considered in future neoadjuvant trials for pancreatic cancer Background Preoperative chemotherapy ( PCHT ) has recently been proposed also in patients with resectable pancreatic adenocarcinoma . Few data are currently available on the impact of PCHT on short-term postoperative outcome after pancreatic resection . The objective of this study is to assess the impact of PCHT on pancreatic structure and short-term outcome after surgical resection . Methods Fifty consecutive patients successfully underwent resection after PCHT .  Each patient was matched with two control patients with pancreatic adenocarcinoma selected from our prospect i ve electronic data base . Match criteria were age ( ±3 years ) , gender , American Society of Anesthesiologist score , type of resection , pancreatic duct diameter ( ±1 mm ) , and tumor size ( ±5 mm ) . Primary endpoint was morbidity rate . Secondary endpoints were pancreatic parenchymal structure , mortality rate , and length of hospital stay ( LOS ) . Results Both degree of fibrosis and fatty infiltration of the pancreas were similar in the two groups . Overall morbidity rate was 48.0 % in the PCHT group vs. 54.0 % in the control group ( p = 0.37 ) . Pancreatic fistula rate was 18.0 % in the PCHT group vs. 25.0 % in the control group ( p = 0.41 ) . Mortality was 4.0 % in the PCHT group vs. 2.0 % in the control group ( p = 0.60 ) . Mean LOS ( days ) was 12.7 in the PCHT group vs. 12.4 in the control group ( p = 0.74 ) . There was no difference in resection margin status , while the rate of patients without nodal involvement was higher in the PCHT group ( 46.0 vs. 23.0 % , p = 0.004 ) . Conclusion PCHT did not induce significant structural changes in pancreatic parenchyma and did not adversely affect short-term outcome after surgery The efficacy of combined radiation and fluorouracil as adjuvant therapy for pancreatic cancer is suggested by a prospect i ve r and omized study conducted by the Gastrointestinal Tumor Study Group ( GITSG ) . Twenty-two patients r and omized to no adjuvant treatment and 21 to combined therapy were analyzed . Neither life-threatening toxic reaction nor death due to toxic effect was encountered . The study was terminated prematurely because of an unacceptably low rate of accrual combined with the observation of increasingly large survival differences between the study arms . Median survival for the treatment group ( 20 months ) was significantly longer than that observed for the control group ( 11 months ) . Four patients , three in the treated and one in the control group , have survived five years or longer following surgery . The extent of the tumor and initial performance status were significantly and independently related to survival 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 MATERIAL S 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(G12D ) status and high CXCR7 expression and circulating CEA , CA19 - 9 , and HGF levels were associated with poor survival Objective : To analyze the histopathological indicators significantly associated with surgical outcome and the pattern of recurrence in the setting of preoperative gemcitabine-based chemoradiation therapy ( CRT ) and subsequent pancreatectomy . Background : Clinicopathological assessment of the resected specimen is an indispensable tool for predicting patient prognosis and localizing high-risk sites for tumor relapse . This procedure is also essential for the establishment of efficient postoperative follow-up protocol s in the setting of a preoperative CRT strategy . Methods : In a prospect i ve phase II clinical trial at our hospital , 110 patients received preoperative CRT and subsequent resection . All 110 resected cases were included in this study . We employed disease-free survival ( DFS ) as a surgical outcome , and the pattern of recurrence was divided into 2 categories : ( 1 ) recurrence in the abdominal cavity ( RAC ) , defined as either a locoregional or a peritoneal recurrence ; or ( 2 ) distant recurrence ( DR ) , defined as cancer recurrence in a distant organ . Clinicopathological variables were analyzed in association with DFS , RAC , and DR . Results : Positive nodal involvement and perineural invasion were independent factors that were significantly associated with an unfavorable DFS ( P = 0.021 and P = 0.026 , respectively ) . The presence of perineural invasion was the single independent variable significantly associated with an increased risk of RAC ( P = 0.002 ) , whereas the status of nodal involvement was the single independent variable significantly associated with an increased risk of DR ( P = 0.013 ) . Conclusions : The status of nodal involvement and perineural invasion in resected specimens are significantly associated with DFS and clearly predict the pattern of recurrence in the setting of a preoperative gemcitabine-based CRT strategy . This study is registered at UMIN-CTR and carries the ID number UMIN000001804 CONTEXT Gemcitabine and 5-fluorouracil ( 5-FU ) sensitize tumor cells to radiation . Furthermore , 5-FU enhances the cytotoxic effect of gemcitabine . OBJECTIVE We report the efficacy and the toxicity of concurrent chemoradiation with gemcitabine and 5-FU in the treatment of patients with locally advanced , unresectable pancreatic cancer . PATIENTS Thirty-two patients ( 20 men , 12 women ; median age 69.9 years ) with histologically proven advanced pancreatic carcinoma were included in the study . INTERVENTIONS The patients received chemotherapy with gemcitabine 300 mg/m2 on days 1 , 15 , 29 and 5-FU as continuous infusion 350 mg/m2/day of radiation while concurrent radiation ( 45 - 50 Gy ) was given to the tumor and regional lymph nodes ( 1.8 - 2.0 Gy/fraction on 5 days/week ) . Subsequent to chemoradiotherapy , the treatment was continued with an additional two cycles of gemcitabine ( 1,000 mg/m2 ) and cisplatin ( 50 mg/m2 ) applied on days 1 and 15 of a four-week cycle . MAIN OUTCOME MEASURES Patient survival , time to progression , and toxicity of chemoradiation . Tumor responses ( complete resolution ; partial response ; stable disease , and progressive disease ) were also evaluated . RESULTS After the completion of chemoradiotherapy , 2 patients ( 6.3 % ) achieved complete resolution and 18 patients ( 56.3 % ) a partial response , for an overall response rate of 62.5 % . Twelve patients ( 37.5 % ) were considered resectable and 9 underwent laparotomy , 7 of whom had definitive pancreatic resection . Four patients had negative surgical margins . With a median follow-up of 49.7 months ( 95 % CI : 48.6 - 60.8 months ) after the completion of chemoradiation , distant metastasis occurred in 25 patients ( 78.1 % ) while local recurrence was seen only in 4 of 32 patients ( 12.5 % ) . Median time to progression was 9.2 months ( 95 % CI : 8.2 - 1 
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