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 optimum approach to neoadjuvant therapy for patients with borderline resectable pancreatic cancer is undefined . Herein we report the outcomes of an extended neoadjuvant chemotherapy regimen in patients presenting with borderline resectable adenocarcinoma of the pancreatic head . Methods Patients identified as having borderline resectable pancreatic head cancer by American Hepato-Pancreato-Biliary Association/Society of Surgical Oncology consensus criteria from 2008 to 2012 were tracked in a prospect ively maintained registry . Included patients were initiated on a 24-week course of neoadjuvant chemotherapy .  Medically fit patients who completed neoadjuvant treatment without radiographic progression were offered resection with curative intent . Clinicopathologic variables and surgical outcomes were collected retrospectively and analyzed . Results Sixty-four patients with borderline resectable pancreatic cancer started neoadjuvant therapy . Thirty-nine ( 61 % ) met resection criteria and underwent operative exploration with curative intent , and 31 ( 48 % ) were resected . Of the resected patients , 18 ( 58 % ) had positive lymph nodes , 15 ( 48 % ) required en-bloc venous resection , 27 ( 87 % ) had a R0 resection , and 3 ( 10 % ) had a complete pathologic response . There were no postoperative deaths at 90 days , 16 % of patients had a severe complication , and the 30-day readmission rate was 10 % . The median overall survival of all 64 patients was 23.6 months , whereas that of unresectable patients was 15.4 months . Twenty-five of the resected patients ( 81 % ) are still alive at a median follow-up of 21.6 months . Conclusions Extended neoadjuvant chemotherapy is well tolerated by patients with borderline resectable pancreatic head adenocarcinoma , selects a subset of patients for curative surgery with low perioperative morbidity , and is associated with favorable survival Background Surgical resection is the only curative strategy for pancreatic ductal adenocarcinoma ( PDAC ) , but recurrence rates are high even after purported curative resection . First-line treatment with gemcitabine and S-1 ( GS ) is associated with promising antitumor activity with a high response rate . The aim of this study was to assess the feasibility and efficacy of GS in the neoadjuvant setting . Methods In a multi-institutional single-arm phase 2 study , neoadjuvant chemotherapy ( NAC ) with gemcitabine and S-1 , repeated every 21 days , was administered for two cycles ( NAC-GS ) to patients with resectable and borderline PDAC . The primary end point was the 2-year survival rate . Secondary end points were feasibility , resection rate , pathological effect , recurrence-free survival , and tumor marker status . Results Of 36 patients enrolled , 35 were eligible for this clinical trial conducted between 2008 and 2010 . The most common toxicity was neutropenia in response to 90 % of the relative dose intensity . Responses to NAC included radiological tumor shrinkage ( 69 % ) and decreases in CA19 - 9 levels ( 89 % ) . R0 resection was performed for 87 % in resection , and the morbidity rate ( 40 % ) was acceptable . The 2-year survival rate of the total cohort was 45.7 % . Patients who underwent resection without metastases after NAC-GS ( n = 27 ) had an increased median overall survival ( 34.7 months ) compared with those who did not undergo resection ( P = 0.0017 ) . Conclusions NAC-GS was well tolerated and safe when used in a multi-institutional setting . The R0 resection rate and the 2-year survival rate analysis are encouraging for patients with resectable and borderline PDAC BACKGROUND Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma ( PDAC ) but no st and ard of care exists . Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging pre clinical activity in PDAC . We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy ( IMRT ) as neoadjuvant therapy in patients with localized or locally advanced PDAC . EXPERIMENTAL DESIGN Treatment consisted of cetuximab load at 400 mg/m(2 ) followed by cetuximab 250 mg/m(2 ) weekly and gemcitabine 50 mg/m(2 ) twice-weekly given concurrently with IMRT to 54 Gy . Following therapy , patients were considered for resection . RESULTS Thirty-seven patients were enrolled with 33 assessable for response . Ten patients ( 30 % ) manifested partial response and 20 ( 61 % ) manifested stable disease by RECIST . Twenty-five patients ( 76 % ) underwent resection , including 18/23 previously borderline and 3/6 previously unresectable tumors . Twenty-three ( 92 % ) of these had negative surgical margins . Pathology revealed that 24 % of resected tumors had grade III/IV tumor kill , including two pathological complete responses ( 8 % ) . Median survival was 24.3 months in resected patients . Outcome did not vary by epidermal growth factor receptor status . CONCLUSIONS Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC . Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival . Pathological complete responses can occur . This combination warrants further investigation 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 Background Survival after surgery for pancreas cancer remains low . This improves with adjuvant chemotherapy , but up to 30 % patients do not receive the prescribed treatment . Neoadjuvant therapy may increase the proportion of patients who receive all treatment components , may downstage disease before surgery , and may provide early treatment of micrometastases . This r and omized phase 2 study compares gemcitabine-based chemotherapy regimens to identify the most promising regimen for future study . Methods Fifty patients with potentially resectable pancreas lesions were enrolled onto the study . Twenty-four patients were r and omized to gemcitabine ( 1000 mg/m2 ) every 7 days for 43 days ; 26 patients were r and omized to gemcitabine ( 1000 mg/m2 ) and cisplatin ( 25 mg/m2 ) , 7 to the original schedule ( omitting day 22 ) and 19 to a revised schedule due to neutropenia ( omitting days 15 and 36 ) . The primary outcome measure was resection rate . Results Patients who were allocated to gemcitabine received a median of 85 % of the planned dose . Patients who were allocated to combination treatment received a median of 88 % and 92 % of the planned gemcitabine and cisplatin doses , respectively . There were 10 episodes of grade III/IV hematological toxicity in each group . Twenty-seven patients ( 54 % ) underwent pancreatic resection , 9 ( 38 % ) in the gemcitabine arm and 18 ( 70 % ) in the combination arm , with no increase in surgical complications . To date , 34 patients ( 68 % ) have died . Twelve-month survival for the gemcitabine and combination groups was 42 % and 62 % . Conclusions Chemotherapy can be safely administered before pancreatic surgery . Combination therapy with gemcitabine and cisplatin is associated with a high resection rate and an encouraging survival rate , suggesting that further study is warranted PURPOSE To test the safety of neoadjuvant chemotherapy for resectable pancreatic cancer . PATIENTS AND METHODS Patients with cytologically proven resectable adenocarcinoma of the pancreatic head were eligible for this prospect i ve phase II trial . After confirmation of resectability by contrast-enhanced computed tomography ( ceCT ) , positron emission tomography/CT , laparoscopy , and endoscopic ultrasound , patients received four biweekly cycles of gemcitabine 1,000 mg/m(2 ) and cisplatin 50 mg/m(2 ) . Thereafter , staging was repeated and patients underwent surgery .  Quality of life ( QoL ) and prealbumin serum levels were determined pre- and postchemotherapy . Follow-up included  
    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 optimum approach to neoadjuvant therapy for patients with borderline resectable pancreatic cancer is undefined . Herein we report the outcomes of an extended neoadjuvant chemotherapy regimen in patients presenting with borderline resectable adenocarcinoma of the pancreatic head . Methods Patients identified as having borderline resectable pancreatic head cancer by American Hepato-Pancreato-Biliary Association/Society of Surgical Oncology consensus criteria from 2008 to 2012 were tracked in a prospect ively maintained registry . Included patients were initiated on a 24-week course of neoadjuvant chemotherapy .  Medically fit patients who completed neoadjuvant treatment without radiographic progression were offered resection with curative intent . Clinicopathologic variables and surgical outcomes were collected retrospectively and analyzed . Results Sixty-four patients with borderline resectable pancreatic cancer started neoadjuvant therapy . Thirty-nine ( 61 % ) met resection criteria and underwent operative exploration with curative intent , and 31 ( 48 % ) were resected . Of the resected patients , 18 ( 58 % ) had positive lymph nodes , 15 ( 48 % ) required en-bloc venous resection , 27 ( 87 % ) had a R0 resection , and 3 ( 10 % ) had a complete pathologic response . There were no postoperative deaths at 90 days , 16 % of patients had a severe complication , and the 30-day readmission rate was 10 % . The median overall survival of all 64 patients was 23.6 months , whereas that of unresectable patients was 15.4 months . Twenty-five of the resected patients ( 81 % ) are still alive at a median follow-up of 21.6 months . Conclusions Extended neoadjuvant chemotherapy is well tolerated by patients with borderline resectable pancreatic head adenocarcinoma , selects a subset of patients for curative surgery with low perioperative morbidity , and is associated with favorable survival Background Surgical resection is the only curative strategy for pancreatic ductal adenocarcinoma ( PDAC ) , but recurrence rates are high even after purported curative resection . First-line treatment with gemcitabine and S-1 ( GS ) is associated with promising antitumor activity with a high response rate . The aim of this study was to assess the feasibility and efficacy of GS in the neoadjuvant setting . Methods In a multi-institutional single-arm phase 2 study , neoadjuvant chemotherapy ( NAC ) with gemcitabine and S-1 , repeated every 21 days , was administered for two cycles ( NAC-GS ) to patients with resectable and borderline PDAC . The primary end point was the 2-year survival rate . Secondary end points were feasibility , resection rate , pathological effect , recurrence-free survival , and tumor marker status . Results Of 36 patients enrolled , 35 were eligible for this clinical trial conducted between 2008 and 2010 . The most common toxicity was neutropenia in response to 90 % of the relative dose intensity . Responses to NAC included radiological tumor shrinkage ( 69 % ) and decreases in CA19 - 9 levels ( 89 % ) . R0 resection was performed for 87 % in resection , and the morbidity rate ( 40 % ) was acceptable . The 2-year survival rate of the total cohort was 45.7 % . Patients who underwent resection without metastases after NAC-GS ( n = 27 ) had an increased median overall survival ( 34.7 months ) compared with those who did not undergo resection ( P = 0.0017 ) . Conclusions NAC-GS was well tolerated and safe when used in a multi-institutional setting . The R0 resection rate and the 2-year survival rate analysis are encouraging for patients with resectable and borderline PDAC BACKGROUND Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma ( PDAC ) but no st and ard of care exists . Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging pre clinical activity in PDAC . We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy ( IMRT ) as neoadjuvant therapy in patients with localized or locally advanced PDAC . EXPERIMENTAL DESIGN Treatment consisted of cetuximab load at 400 mg/m(2 ) followed by cetuximab 250 mg/m(2 ) weekly and gemcitabine 50 mg/m(2 ) twice-weekly given concurrently with IMRT to 54 Gy . Following therapy , patients were considered for resection . RESULTS Thirty-seven patients were enrolled with 33 assessable for response . Ten patients ( 30 % ) manifested partial response and 20 ( 61 % ) manifested stable disease by RECIST . Twenty-five patients ( 76 % ) underwent resection , including 18/23 previously borderline and 3/6 previously unresectable tumors . Twenty-three ( 92 % ) of these had negative surgical margins . Pathology revealed that 24 % of resected tumors had grade III/IV tumor kill , including two pathological complete responses ( 8 % ) . Median survival was 24.3 months in resected patients . Outcome did not vary by epidermal growth factor receptor status . CONCLUSIONS Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC . Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival . Pathological complete responses can occur . This combination warrants further investigation 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 Background Survival after surgery for pancreas cancer remains low . This improves with adjuvant chemotherapy , but up to 30 % patients do not receive the prescribed treatment . Neoadjuvant therapy may increase the proportion of patients who receive all treatment components , may downstage disease before surgery , and may provide early treatment of micrometastases . This r and omized phase 2 study compares gemcitabine-based chemotherapy regimens to identify the most promising regimen for future study . Methods Fifty patients with potentially resectable pancreas lesions were enrolled onto the study . Twenty-four patients were r and omized to gemcitabine ( 1000 mg/m2 ) every 7 days for 43 days ; 26 patients were r and omized to gemcitabine ( 1000 mg/m2 ) and cisplatin ( 25 mg/m2 ) , 7 to the original schedule ( omitting day 22 ) and 19 to a revised schedule due to neutropenia ( omitting days 15 and 36 ) . The primary outcome measure was resection rate . Results Patients who were allocated to gemcitabine received a median of 85 % of the planned dose . Patients who were allocated to combination treatment received a median of 88 % and 92 % of the planned gemcitabine and cisplatin doses , respectively . There were 10 episodes of grade III/IV hematological toxicity in each group . Twenty-seven patients ( 54 % ) underwent pancreatic resection , 9 ( 38 % ) in the gemcitabine arm and 18 ( 70 % ) in the combination arm , with no increase in surgical complications . To date , 34 patients ( 68 % ) have died . Twelve-month survival for the gemcitabine and combination groups was 42 % and 62 % . Conclusions Chemotherapy can be safely administered before pancreatic surgery . Combination therapy with gemcitabine and cisplatin is associated with a high resection rate and an encouraging survival rate , suggesting that further study is warranted PURPOSE To test the safety of neoadjuvant chemotherapy for resectable pancreatic cancer . PATIENTS AND METHODS Patients with cytologically proven resectable adenocarcinoma of the pancreatic head were eligible for this prospect i ve phase II trial . After confirmation of resectability by contrast-enhanced computed tomography ( ceCT ) , positron emission tomography/CT , laparoscopy , and endoscopic ultrasound , patients received four biweekly cycles of gemcitabine 1,000 mg/m(2 ) and cisplatin 50 mg/m(2 ) . Thereafter , staging was repeated and patients underwent surgery .  Quality of life ( QoL ) and prealbumin serum levels were determined pre- and postchemotherapy . Follow-up included  
    Output:
    