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 : This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC . Summary Background Data : Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer ( BRPC ) , no high-level evidence exists to support the role of such treatment . Methods : This phase 2/3 multicenter r and omized controlled trial was design ed to enroll 110 patients with BRPC who were r and omly assigned to gemcitabine-based neoadjuvant chemoradiation treatment ( 54 Gray external beam radiation ) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea . The primary endpoint was the 2-year survival rate ( 2-YSR ) . Interim analysis was planned at the time of 50 % case enrollment . Results : After excluding the patients who withdrew consent ( n = 8) from the 58 enrolled patients , 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups . The overall 2-YSR was 34.0 % with a median survival of 16 months . In the intention-to-treat analysis , the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [ 40.7 % , 21 months vs 26.1 % , 12 months , hazard ratio 1.495 ( 95 % confidence interval 0.66–3.36 ) , P = 0.028 ] . R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery ( n = 14 , 51.8 % vs n = 6 , 26.1 % , P = 0.004 ) . The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy . Conclusion : This is the first prospect i ve r and omized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC . Compared to upfront surgery , neoadjuvant chemoradiation provides oncological benefits in patients with BRPC Background In nonr and omized 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 r and omized phase II trial . Radiological staging defining resectability was basic information prior to r and omization in contrast to adjuvant therapy trials resting on pathological staging . Patients and methods Patients with resectable adenocarcinoma of the pancreatic head were r and omized 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 ) . Results 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 ) . Conclusion This worldwide first r and omized 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 . IS RCT N78805636 ; NCT00335543.ZusammenfassungHintergrundMehrere nichtr and omisierte Studien zeigten , dass eine neoadjuvante Therapie das Überleben bei Patienten mit Pankreaskarzinom verlängert . Beim lokal fortgeschrittenen Rektumkarzinom gehört die neoadjuvante Radiochemotherapie bereits zum Therapiest and ard . Analog wurde der Stellenwert einer Radiochemotherapie beim Pankreaskarzinom in einer r and omisierten Phase-II-Studie untersucht . Das prätherapeutische radiologische Staging war Grundlage dieser Studie i m Gegensatz zu adjuvanten Therapiestudien , die auf pathohistologischem Staging basieren . Patienten und Method enPatienten mit resektablem Pankreaskopfkarzinom wurden r and omisiert in primäre Operation ( Arm A ) versus neoadjuvante Radiochemotherapie gefolgt von einer Operation ( Arm B ) . Beide Gruppen erhielten eine adjuvante Chemotherapie . Es waren 254 Patienten erforderlich , um eine Verbesserung des medianen Gesamtüberlebens von 4,33 Monaten zu erfassen . ErgebnisseDie Studie wurde wegen zögerlicher Rekrutierung nach Einschluss von 73 Patienten beendet . Insgesamt konnten 66 Patienten ausgewertet werden . Die ihnen zugeordnete Radiochemotherapie erhielten 29 von 33 Patienten . Alle Patienten bekamen die vollständige Bestrahlungstherapie . Wegen der Toxizität wurde bei 3 Patienten die Chemotherapie reduziert . Eine Pankreastumorresektion erhielten 23 vs. 19 Patienten ( A vs. B ) . Die R0-Resektionsrate betrug 48 % ( A ) und 52 % ( B , P = 0,81 ) . Bei 30 % ( A ) versus 39 % ( B , P = 0,44 ) der resezierten Patienten waren keine Lymphknotenmetastasen vorh and en . Die postoperativen Komplikationen waren in beiden Gruppen vergleichbar . Das mediane Gesamtüberleben betrug 14,4 vs. 17,4 Monate ( A vs. B ; „ Intention-to-treat“-Analyse ; P = 0,96 ) . Nach Pankreastumorresektion stieg das Gesamtüberleben auf 18,9 vs. 25,0 Monate ( A vs. B ; P = 0,79).SchlussfolgerungDiese weltweit erste r and omisierte Studie zur neoadjuvanten Radiochemotherapie beim Pankreaskopfkarzinom war in Bezug auf Toxizität sowie perioperative Morbidität und Mortalität gut durchführbar . Die Ergebnisse sind jedoch nicht signifikant , da diese r and omisierte Studie vorzeitig wegen mangelnder Rekrutierung beendet werden musste . IS RCT N78805636 ; NCT00335543 PURPOSE We conducted a phase II trial to assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy ( PD ) for stage I/II pancreatic adenocarcinoma . PATIENTS AND METHODS Eligible patients with pancreatic head/uncinate process adenocarcinoma and radiographically defined potentially resectable disease received chemoradiation with 7 weekly intravenous ( IV ) infusions of gemcitabine ( 400 mg/m(2 ) IV over 30 minutes ) plus radiation therapy ( 30 Gy in 10 fractions over 2 weeks ) . Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and , in the absence of disease progression , were taken to surgery . RESULTS The study enrolled 86 patients . At the time of restaging , disease progression or a decline in performance status precluded 13 patients from surgery . Seventy-three ( 85 % ) of 86 patients were taken to surgery , extrapancreatic disease was found in nine , and 64 ( 74 % ) of 86 underwent a successful PD . Median overall survival ( 86 patients ) was 22.7 months with a 27 % 5-year survival . Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients ( P < .001 ) . The 5-year survival for those who did and did not undergo PD was 36 % and 0 % , respectively . CONCLUSION Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets : patients likely to benefit from PD ( n = 64 ) and those in whom surgery would be unlikely to provide clinical benefit ( n = 22 ) . Furthermore , the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer AIM To explore whether preoperative chemoradiation therapy improves survival of patients with pancreatic cancer undergoing resectional surgery .  METHODS Forty-seven patients with a malignant pancreatic tumor localized in the head or uncinate process of the pancreas underwent radical pancreatico-duodenectomy .  Twenty-two received chemoradiation therapy ( gemcitabine and radiation dose 50.4 Gy ) before surgery ( CRR ) and 25 patients underwent surgery only ( RO ) . The study was non-r and omised . Patients were identified from a prospect i ve data base . RESULTS The median survival time was 30.2 mo in the CRR group and 35.9 mo in the RO group . No statistically significant differences were found in subclasses according to lymph node involvement , TNM stages , tumor size , or perineural invasion . The one , three and five year survival rates were 81 % , 33 % and 33 % , respectively , in the CRR group and 72 % , 47 % and 23 % , respectively , in the RO group . In ductal adenocarcinoma , the median survival time was 27 mo in the CRR group and 20 mo in the RO group . No statistically significant differences were found in the above subclasses . The one , three and five year survival rates were 79 % , 21 % and 21 % , respectively , in the CRR group and 64 % , 50 % and 14 % , respectively , in the RO group . The overall hospital mortality rate was 2 % . The morbidity rate was 45 % in the CRR group and 32 % ( NS ) in the RO group . CONCLUSION Major multicenter r and omized studies are needed to conclusively assess the impact of neoadjuvant treatment in the management of pancreatic cancer Resection of localized pancreatic head ductal adenocarcinoma ( LPHDA ) has a limited impact on survival . Mechanisms of improvement provided by preoperative chemoradiation therapy ( CRT ) remain under debate . This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT . Among 87 patients with LPHDA , 17 had a pancreaticoduodenectomy alone ( group I ) . Thirtynine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy ( group II ) . Thirty-one with initially unresectable cancers were similarly treated by CRT ( group III ) . Patients in groups II and III were restaged after completion of CRT . In patients with resectable disease , resection was planned . Patients in groups I and II were statistically comparable in terms of age , sex , and pretherapeutic stage . Median survival and 2-year overall survival in group I were 13.7 months and 31 % , respectively . In group II , 23 patients ( 59 % ) had a pancreaticoduodenectomy ( group IIa ) and 16 patients ( 41 % ) did not have resection ( group IIb ) . Median survival and 2-year overall survival were as follows : group IIa , 26.6 months and 51 % ; and group IIb , 6.1 months and 0 % , respectively . In group IIa , pathologic examination revealed eight major responses ( 35 % ) including two sterilized specimens , and none of the patients had locoregional recurrence . In group III , none of the patients had resection , and median survival was 8 months with one 2-year survivor . Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy . However , a high histologic response rate and excellent local control can also be achieved IMPORTANCE The prognosis for patients with pancreatic cancer is poor , even after resection with curative intent . Gemcitabine-based chemotherapy is st and ard treatment for advanced pancreatic cancer , but its effect on survival in the adjuvant setting has not been demonstrated . OBJECTIVE To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival . DESIGN , SETTING , AND PATIENTS CONKO-001 ( Charité Onkologie 001 ) , a multicenter , open-label , phase 3 r and omized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection . Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria . Follow-up ended in September 2012 . INTER 
    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 : This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC . Summary Background Data : Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer ( BRPC ) , no high-level evidence exists to support the role of such treatment . Methods : This phase 2/3 multicenter r and omized controlled trial was design ed to enroll 110 patients with BRPC who were r and omly assigned to gemcitabine-based neoadjuvant chemoradiation treatment ( 54 Gray external beam radiation ) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea . The primary endpoint was the 2-year survival rate ( 2-YSR ) . Interim analysis was planned at the time of 50 % case enrollment . Results : After excluding the patients who withdrew consent ( n = 8) from the 58 enrolled patients , 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups . The overall 2-YSR was 34.0 % with a median survival of 16 months . In the intention-to-treat analysis , the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [ 40.7 % , 21 months vs 26.1 % , 12 months , hazard ratio 1.495 ( 95 % confidence interval 0.66–3.36 ) , P = 0.028 ] . R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery ( n = 14 , 51.8 % vs n = 6 , 26.1 % , P = 0.004 ) . The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy . Conclusion : This is the first prospect i ve r and omized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC . Compared to upfront surgery , neoadjuvant chemoradiation provides oncological benefits in patients with BRPC Background In nonr and omized 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 r and omized phase II trial . Radiological staging defining resectability was basic information prior to r and omization in contrast to adjuvant therapy trials resting on pathological staging . Patients and methods Patients with resectable adenocarcinoma of the pancreatic head were r and omized 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 ) . Results 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 ) . Conclusion This worldwide first r and omized 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 . IS RCT N78805636 ; NCT00335543.ZusammenfassungHintergrundMehrere nichtr and omisierte Studien zeigten , dass eine neoadjuvante Therapie das Überleben bei Patienten mit Pankreaskarzinom verlängert . Beim lokal fortgeschrittenen Rektumkarzinom gehört die neoadjuvante Radiochemotherapie bereits zum Therapiest and ard . Analog wurde der Stellenwert einer Radiochemotherapie beim Pankreaskarzinom in einer r and omisierten Phase-II-Studie untersucht . Das prätherapeutische radiologische Staging war Grundlage dieser Studie i m Gegensatz zu adjuvanten Therapiestudien , die auf pathohistologischem Staging basieren . Patienten und Method enPatienten mit resektablem Pankreaskopfkarzinom wurden r and omisiert in primäre Operation ( Arm A ) versus neoadjuvante Radiochemotherapie gefolgt von einer Operation ( Arm B ) . Beide Gruppen erhielten eine adjuvante Chemotherapie . Es waren 254 Patienten erforderlich , um eine Verbesserung des medianen Gesamtüberlebens von 4,33 Monaten zu erfassen . ErgebnisseDie Studie wurde wegen zögerlicher Rekrutierung nach Einschluss von 73 Patienten beendet . Insgesamt konnten 66 Patienten ausgewertet werden . Die ihnen zugeordnete Radiochemotherapie erhielten 29 von 33 Patienten . Alle Patienten bekamen die vollständige Bestrahlungstherapie . Wegen der Toxizität wurde bei 3 Patienten die Chemotherapie reduziert . Eine Pankreastumorresektion erhielten 23 vs. 19 Patienten ( A vs. B ) . Die R0-Resektionsrate betrug 48 % ( A ) und 52 % ( B , P = 0,81 ) . Bei 30 % ( A ) versus 39 % ( B , P = 0,44 ) der resezierten Patienten waren keine Lymphknotenmetastasen vorh and en . Die postoperativen Komplikationen waren in beiden Gruppen vergleichbar . Das mediane Gesamtüberleben betrug 14,4 vs. 17,4 Monate ( A vs. B ; „ Intention-to-treat“-Analyse ; P = 0,96 ) . Nach Pankreastumorresektion stieg das Gesamtüberleben auf 18,9 vs. 25,0 Monate ( A vs. B ; P = 0,79).SchlussfolgerungDiese weltweit erste r and omisierte Studie zur neoadjuvanten Radiochemotherapie beim Pankreaskopfkarzinom war in Bezug auf Toxizität sowie perioperative Morbidität und Mortalität gut durchführbar . Die Ergebnisse sind jedoch nicht signifikant , da diese r and omisierte Studie vorzeitig wegen mangelnder Rekrutierung beendet werden musste . IS RCT N78805636 ; NCT00335543 PURPOSE We conducted a phase II trial to assess the outcomes of patients who received preoperative gemcitabine-based chemoradiation and pancreaticoduodenectomy ( PD ) for stage I/II pancreatic adenocarcinoma . PATIENTS AND METHODS Eligible patients with pancreatic head/uncinate process adenocarcinoma and radiographically defined potentially resectable disease received chemoradiation with 7 weekly intravenous ( IV ) infusions of gemcitabine ( 400 mg/m(2 ) IV over 30 minutes ) plus radiation therapy ( 30 Gy in 10 fractions over 2 weeks ) . Patients underwent restaging 4 to 6 weeks after completion of chemoradiation and , in the absence of disease progression , were taken to surgery . RESULTS The study enrolled 86 patients . At the time of restaging , disease progression or a decline in performance status precluded 13 patients from surgery . Seventy-three ( 85 % ) of 86 patients were taken to surgery , extrapancreatic disease was found in nine , and 64 ( 74 % ) of 86 underwent a successful PD . Median overall survival ( 86 patients ) was 22.7 months with a 27 % 5-year survival . Median survival was 34 months for the 64 patients who underwent PD and 7 months for the 22 unresected patients ( P < .001 ) . The 5-year survival for those who did and did not undergo PD was 36 % and 0 % , respectively . CONCLUSION Preoperative gemcitabine-based chemoradiation followed by restaging and evaluation for surgery separated the study population into two different subsets : patients likely to benefit from PD ( n = 64 ) and those in whom surgery would be unlikely to provide clinical benefit ( n = 22 ) . Furthermore , the encouraging overall survival observed in this large trial supports the continued investigation of gemcitabine-based preoperative therapy in resectable pancreatic cancer AIM To explore whether preoperative chemoradiation therapy improves survival of patients with pancreatic cancer undergoing resectional surgery .  METHODS Forty-seven patients with a malignant pancreatic tumor localized in the head or uncinate process of the pancreas underwent radical pancreatico-duodenectomy .  Twenty-two received chemoradiation therapy ( gemcitabine and radiation dose 50.4 Gy ) before surgery ( CRR ) and 25 patients underwent surgery only ( RO ) . The study was non-r and omised . Patients were identified from a prospect i ve data base . RESULTS The median survival time was 30.2 mo in the CRR group and 35.9 mo in the RO group . No statistically significant differences were found in subclasses according to lymph node involvement , TNM stages , tumor size , or perineural invasion . The one , three and five year survival rates were 81 % , 33 % and 33 % , respectively , in the CRR group and 72 % , 47 % and 23 % , respectively , in the RO group . In ductal adenocarcinoma , the median survival time was 27 mo in the CRR group and 20 mo in the RO group . No statistically significant differences were found in the above subclasses . The one , three and five year survival rates were 79 % , 21 % and 21 % , respectively , in the CRR group and 64 % , 50 % and 14 % , respectively , in the RO group . The overall hospital mortality rate was 2 % . The morbidity rate was 45 % in the CRR group and 32 % ( NS ) in the RO group . CONCLUSION Major multicenter r and omized studies are needed to conclusively assess the impact of neoadjuvant treatment in the management of pancreatic cancer Resection of localized pancreatic head ductal adenocarcinoma ( LPHDA ) has a limited impact on survival . Mechanisms of improvement provided by preoperative chemoradiation therapy ( CRT ) remain under debate . This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT . Among 87 patients with LPHDA , 17 had a pancreaticoduodenectomy alone ( group I ) . Thirtynine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy ( group II ) . Thirty-one with initially unresectable cancers were similarly treated by CRT ( group III ) . Patients in groups II and III were restaged after completion of CRT . In patients with resectable disease , resection was planned . Patients in groups I and II were statistically comparable in terms of age , sex , and pretherapeutic stage . Median survival and 2-year overall survival in group I were 13.7 months and 31 % , respectively . In group II , 23 patients ( 59 % ) had a pancreaticoduodenectomy ( group IIa ) and 16 patients ( 41 % ) did not have resection ( group IIb ) . Median survival and 2-year overall survival were as follows : group IIa , 26.6 months and 51 % ; and group IIb , 6.1 months and 0 % , respectively . In group IIa , pathologic examination revealed eight major responses ( 35 % ) including two sterilized specimens , and none of the patients had locoregional recurrence . In group III , none of the patients had resection , and median survival was 8 months with one 2-year survivor . Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy . However , a high histologic response rate and excellent local control can also be achieved IMPORTANCE The prognosis for patients with pancreatic cancer is poor , even after resection with curative intent . Gemcitabine-based chemotherapy is st and ard treatment for advanced pancreatic cancer , but its effect on survival in the adjuvant setting has not been demonstrated . OBJECTIVE To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival . DESIGN , SETTING , AND PATIENTS CONKO-001 ( Charité Onkologie 001 ) , a multicenter , open-label , phase 3 r and omized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection . Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria . Follow-up ended in September 2012 . INTER 
    Output:
    