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: Background . The optimal care for patients with unresectable , non-metastatic pancreatic adenocarcinoma ( PAC ) is debated . We treated 17 consecutive cases with preoperative radiochemotherapy ( RCT ) as a means for downstaging their tumours and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period . Methods . The patients had biopsy proven , unresectable , non-metastatic PAC which engaged ≥50 % of the circumference of a patent mesenteric/portal vein for a distance ≥2 cm and /or < 50 % of the circumference of a central artery for < 2 cm . The preop therapy included two courses of Xelox ( oxaliplatin 130 mg/m2 d1 ; capecitabine 2 000 mg/m2 d1–14 q 3 w ) followed by 3-D conformal radiotherapy ( 50.4 Gy ; 1.8 Gy fractions ) with reduced Xelox ( d1 - 5 q 1 w X 6 ) . Results . No incident of RCT -related CTC Grade 3–4 haematologic and six cases of non-haematologic side-effects were diagnosed . Sixteen patients completed the RCT and were rescanned with CT and reevaluated for surgery 4 weeks post- RCT . Five cases were diagnosed with new metastases to the liver . Eleven patients were accepted for surgery whereof eight underwent a curative R0-resection . The median overall survival for the latter group was 29 months , which compared favourably with our control group of patients undergoing direct curative surgery for primarily resectable PAC ( median OS : 16 months ; RO-rate : 75 % ) . Perioperative morbidity was similar in the two cohorts but the duration of surgery was longer ( 576 vs. 477 min ) and the op blood loss was greater ( 3288 vs. 1460 ml ) in the RCT -cohort ( p < 0.05 ) . The 30-day mortality was zero in both groups . Conclusion . Preoperative RCT in patients with locally advanced PAC result ed in a high rate of curative resections and promising median survival in our treatment series . This trimodality approach merits further exploration in new studies , which are currently underway at our Department CONTEXT Among patients with locally advanced metastatic pancreatic adenocarcinoma , gemcitabine has been shown to improve outcomes compared with fluorouracil . OBJECTIVE To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation ( chemotherapy plus radiation ) improves survival for patients with resected pancreatic adenocarcinoma . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18 , 2006 , at 164 US and Canadian institutions . INTERVENTION Chemotherapy with either fluorouracil ( continuous infusion of 250 mg/m2 per day ; n = 230 ) or gemcitabine ( 30-minute infusion of 1000 mg/m2 once per week ; n = 221 ) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy . Chemoradiation with a continuous infusion of fluorouracil ( 250 mg/m2 per day ) was the same for all patients ( 50.4 Gy ) . MAIN OUTCOME MEASURES Survival for all patients and survival for patients with pancreatic head tumors  were the primary end points . Secondary end points included toxicity . RESULTS A total of 451 patients were r and omized , eligible , and analyzable . Patients with pancreatic head tumors ( n = 388 ) had a median survival of 20.5 months and a 3-year survival of 31 % in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22 % in the fluorouracil group ( hazard ratio , 0.82 [ 95 % confidence interval , 0.65 - 1.03 ] ; P = .09 ) . The treatment effect was strengthened on multivariate analysis ( hazard ratio , 0.80 [ 95 % confidence interval , 0.63 - 1.00 ] ; P = .05 ) . Grade 4 hematologic toxicity was 1 % in the fluorouracil group and 14 % in the gemcitabine group ( P < .001 ) without a difference in febrile neutropenia or infection . There were no differences in the ability to complete chemotherapy or radiation therapy ( > 85 % ) . CONCLUSIONS The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer , although this improvement was not statistically significant . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00003216 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 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 examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy ( PD ) for pancreatic adenocarcinoma ( PC ) in patients undergoing resection at Johns Hopkins Hospital ( JHH ; Baltimore , MD ) . PATIENTS AND METHODS Between August 30 , 1993 , and February 28 , 2005 , a total of 908 patients underwent PD for PC at JHH . A prospect i ve data base was review ed to determine which patients received fluorouracil ( FU ) -based CRT .  Excluded patients had metastatic disease , died 60 or fewer days after PD , received preoperative therapy , an experimental vaccine , adjuvant chemotherapy or radiation alone . The final cohort includes 616 patients . RESULTS The median follow-up was 17.8 months ( interquartile range , 9.7 to 33.5 months ) . Overall median survival was 17.9 months ( 95 % CI , 16.3 to 19.5 months ) . Groups were similar with respect to tumor size , nodal status , and margin status , but the CRT group was younger ( P < .001 ) , and less likely to present with a severe comorbid disease ( P = .001 ) . Patients with carcinomas larger than 3 cm ( P = .001 ) , grade 3 and 4 ( P < .001 ) , margin-positive resection ( P = .001 ) , and complications after surgery ( P = .017 ) had poor long-term survival . Patients receiving CRT experienced an improved median ( 21.2 v 14.4 months ; P < .001 ) , 2-year ( 43.9 % v 31.9 % ) , and 5-year ( 20.1 % v 15.4 % ) survival compared with no CRT . After controlling for high-risk features , CRT was still associated with improved survival ( relative risk = 0.74 ; 95 % CI , 0.62 to 0.89 ) . CONCLUSION These data suggest that adjuvant concurrent FU-based CRT significantly improves survival after PD for PC when compared with patients not receiving CRT . These data support the use of combined adjuvant CRT for PC Background : This multicentre r and omised phase III trial was design ed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer . Methods : Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy . Patients were r and omly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group . Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m−2 over 30 min on days 1 , 8 and 15 , every 4 weeks for 3 cycles . Results : Between April 2002 and March 2005 , 119 patients were enrolled in this study . Among them , 118 were eligible and analysable ( 58 in the gemcitabine group and 60 in the surgery-only group ) . Both groups were well balanced in terms of baseline characteristics . Although heamatological toxicity was frequently observed in the gemcitabine group , most toxicities were transient , and grade 3 or 4 non-heamatological toxicity was rare . Patients in the gemcitabine group showed significantly longer disease-free survival ( DFS ) than those in the surgery-only group ( median DFS , 11.4versus 5.0 months ; hazard ratio=0.60 ( 95 % confidence interval ( CI ) : 0.40–0.89 ) ; P=0.01 ) , although overall survival did not differ significantly between the gemcitabine and surgery-only groups ( median overall survival , 22.3 versus 18.4 months ; hazard ratio=0.77 ( 95 % CI : 0.51–1.14 ) ; P=0.19 ) . Conclusion : The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer PURPOSE Adjuvant chemotherapy prolongs survival in patients with pancreatic cancer , but its benefit is limited . Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study . PATIENTS AND METHODS Between 2004 and 2007 , 132 R0/R1 resected patients received either fluorouracil ( FU ) , cisplatin , and interferon alfa-2b ( IFN α-2b ) plus radiotherapy followed by two cycles of FU ( arm A , n=64 ) or six cycles of FU monotherapy ( arm B , n=68 ) . One hundred ten patients ( arm A , n=53 ; arm B , n=57 ) received at least one dose of the study medication , and these patients composed the per- protocol ( PP ) population . Biomarkers were analyzed longitudinally for their predictive value . RESULTS Median survival for all r and omly assigned patients was 26.5 months ( 95 % CI , 21.6 to 39.5 months ) in arm A and 28.5 months ( 95 % CI , 20.4 to 38.6 months ) in arm B 
    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: Background . The optimal care for patients with unresectable , non-metastatic pancreatic adenocarcinoma ( PAC ) is debated . We treated 17 consecutive cases with preoperative radiochemotherapy ( RCT ) as a means for downstaging their tumours and compared outcome with 35 patients undergoing direct surgery for primarily resectable PAC during the same time period . Methods . The patients had biopsy proven , unresectable , non-metastatic PAC which engaged ≥50 % of the circumference of a patent mesenteric/portal vein for a distance ≥2 cm and /or < 50 % of the circumference of a central artery for < 2 cm . The preop therapy included two courses of Xelox ( oxaliplatin 130 mg/m2 d1 ; capecitabine 2 000 mg/m2 d1–14 q 3 w ) followed by 3-D conformal radiotherapy ( 50.4 Gy ; 1.8 Gy fractions ) with reduced Xelox ( d1 - 5 q 1 w X 6 ) . Results . No incident of RCT -related CTC Grade 3–4 haematologic and six cases of non-haematologic side-effects were diagnosed . Sixteen patients completed the RCT and were rescanned with CT and reevaluated for surgery 4 weeks post- RCT . Five cases were diagnosed with new metastases to the liver . Eleven patients were accepted for surgery whereof eight underwent a curative R0-resection . The median overall survival for the latter group was 29 months , which compared favourably with our control group of patients undergoing direct curative surgery for primarily resectable PAC ( median OS : 16 months ; RO-rate : 75 % ) . Perioperative morbidity was similar in the two cohorts but the duration of surgery was longer ( 576 vs. 477 min ) and the op blood loss was greater ( 3288 vs. 1460 ml ) in the RCT -cohort ( p < 0.05 ) . The 30-day mortality was zero in both groups . Conclusion . Preoperative RCT in patients with locally advanced PAC result ed in a high rate of curative resections and promising median survival in our treatment series . This trimodality approach merits further exploration in new studies , which are currently underway at our Department CONTEXT Among patients with locally advanced metastatic pancreatic adenocarcinoma , gemcitabine has been shown to improve outcomes compared with fluorouracil . OBJECTIVE To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation ( chemotherapy plus radiation ) improves survival for patients with resected pancreatic adenocarcinoma . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18 , 2006 , at 164 US and Canadian institutions . INTERVENTION Chemotherapy with either fluorouracil ( continuous infusion of 250 mg/m2 per day ; n = 230 ) or gemcitabine ( 30-minute infusion of 1000 mg/m2 once per week ; n = 221 ) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy . Chemoradiation with a continuous infusion of fluorouracil ( 250 mg/m2 per day ) was the same for all patients ( 50.4 Gy ) . MAIN OUTCOME MEASURES Survival for all patients and survival for patients with pancreatic head tumors  were the primary end points . Secondary end points included toxicity . RESULTS A total of 451 patients were r and omized , eligible , and analyzable . Patients with pancreatic head tumors ( n = 388 ) had a median survival of 20.5 months and a 3-year survival of 31 % in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22 % in the fluorouracil group ( hazard ratio , 0.82 [ 95 % confidence interval , 0.65 - 1.03 ] ; P = .09 ) . The treatment effect was strengthened on multivariate analysis ( hazard ratio , 0.80 [ 95 % confidence interval , 0.63 - 1.00 ] ; P = .05 ) . Grade 4 hematologic toxicity was 1 % in the fluorouracil group and 14 % in the gemcitabine group ( P < .001 ) without a difference in febrile neutropenia or infection . There were no differences in the ability to complete chemotherapy or radiation therapy ( > 85 % ) . CONCLUSIONS The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer , although this improvement was not statistically significant . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00003216 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 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 examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy ( PD ) for pancreatic adenocarcinoma ( PC ) in patients undergoing resection at Johns Hopkins Hospital ( JHH ; Baltimore , MD ) . PATIENTS AND METHODS Between August 30 , 1993 , and February 28 , 2005 , a total of 908 patients underwent PD for PC at JHH . A prospect i ve data base was review ed to determine which patients received fluorouracil ( FU ) -based CRT .  Excluded patients had metastatic disease , died 60 or fewer days after PD , received preoperative therapy , an experimental vaccine , adjuvant chemotherapy or radiation alone . The final cohort includes 616 patients . RESULTS The median follow-up was 17.8 months ( interquartile range , 9.7 to 33.5 months ) . Overall median survival was 17.9 months ( 95 % CI , 16.3 to 19.5 months ) . Groups were similar with respect to tumor size , nodal status , and margin status , but the CRT group was younger ( P < .001 ) , and less likely to present with a severe comorbid disease ( P = .001 ) . Patients with carcinomas larger than 3 cm ( P = .001 ) , grade 3 and 4 ( P < .001 ) , margin-positive resection ( P = .001 ) , and complications after surgery ( P = .017 ) had poor long-term survival . Patients receiving CRT experienced an improved median ( 21.2 v 14.4 months ; P < .001 ) , 2-year ( 43.9 % v 31.9 % ) , and 5-year ( 20.1 % v 15.4 % ) survival compared with no CRT . After controlling for high-risk features , CRT was still associated with improved survival ( relative risk = 0.74 ; 95 % CI , 0.62 to 0.89 ) . CONCLUSION These data suggest that adjuvant concurrent FU-based CRT significantly improves survival after PD for PC when compared with patients not receiving CRT . These data support the use of combined adjuvant CRT for PC Background : This multicentre r and omised phase III trial was design ed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer . Methods : Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy . Patients were r and omly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group . Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m−2 over 30 min on days 1 , 8 and 15 , every 4 weeks for 3 cycles . Results : Between April 2002 and March 2005 , 119 patients were enrolled in this study . Among them , 118 were eligible and analysable ( 58 in the gemcitabine group and 60 in the surgery-only group ) . Both groups were well balanced in terms of baseline characteristics . Although heamatological toxicity was frequently observed in the gemcitabine group , most toxicities were transient , and grade 3 or 4 non-heamatological toxicity was rare . Patients in the gemcitabine group showed significantly longer disease-free survival ( DFS ) than those in the surgery-only group ( median DFS , 11.4versus 5.0 months ; hazard ratio=0.60 ( 95 % confidence interval ( CI ) : 0.40–0.89 ) ; P=0.01 ) , although overall survival did not differ significantly between the gemcitabine and surgery-only groups ( median overall survival , 22.3 versus 18.4 months ; hazard ratio=0.77 ( 95 % CI : 0.51–1.14 ) ; P=0.19 ) . Conclusion : The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer PURPOSE Adjuvant chemotherapy prolongs survival in patients with pancreatic cancer , but its benefit is limited . Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study . PATIENTS AND METHODS Between 2004 and 2007 , 132 R0/R1 resected patients received either fluorouracil ( FU ) , cisplatin , and interferon alfa-2b ( IFN α-2b ) plus radiotherapy followed by two cycles of FU ( arm A , n=64 ) or six cycles of FU monotherapy ( arm B , n=68 ) . One hundred ten patients ( arm A , n=53 ; arm B , n=57 ) received at least one dose of the study medication , and these patients composed the per- protocol ( PP ) population . Biomarkers were analyzed longitudinally for their predictive value . RESULTS Median survival for all r and omly assigned patients was 26.5 months ( 95 % CI , 21.6 to 39.5 months ) in arm A and 28.5 months ( 95 % CI , 20.4 to 38.6 months ) in arm B 
    Output:
    