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 Recent studies suggest that neoadjuvant chemoradiation can downstage locally advanced pancreatic tumors . There is limited evaluable data to support this approach . We review our experience with preoperative chemoradiation for surgically staged , locally advanced pancreatic cancer to determine whether patients are downstaged with multimodal therapy allowing for curative resection . A prospect ively collected data base from Memorial Sloan-Kettering Cancer Center was review ed . Patients admitted between January 1993 and March 1999 with locally advanced pancreatic adenocarcinoma were identified ( N = 163 ) .  Chemoradiation was administered to 87 ( 53.3 % ) of 163 , and regimens varied from st and ard 5-fluorouracil/gemcitabine-based therapies to experimental protocol s. Only three patients ( 3/87 ; 3.4 % ) had a sufficient clinical response on restaging to warrant reexploration . Of these , two thirds were unresectable on subsequent laparoscopy because of extensive vascular involvement or metastatic disease . Only one patient underwent a potentially curative resection , with a survival of 18 months despite negative margins and no nodal involvement . The overall median survival for all patients with locally advanced disease treated with  chemoradiation  was 11 months ( 6.5 months without multimodal therapy ; P = 0.004 ) . Although hemora-diation is associated with improved overall survival in locally advanced disease , it rarely leads to surgical “ downstaging ” allowing for potentially curative pancreatic resections . Novel multimodality approaches are required Two groups of patients with adenocarcinoma of the pancreas treated with either preoperative chemoradiation ( preop CTRT ) or postoperative chemoradiation ( postop CTRT )  were retrospectively analyzed for various treatment-related parameters . Between November 1986 and October 1996 , a total of 70 patients with pancreatic adenocarcinoma were enrolled into preop CTRT protocol s at our institution . Twenty-five patients with adenocarcinoma of the head of the pancreas underwent pancreaticoduodenectomy with curative intent .  After the closure of the preop CTRT protocol s , we had the opportunity to perform 23 pancreatic resections without preop CTRT . After surgery , these patients were advised to undergo CTRT . These two groups of patients were therefore selected consecutively , dependent only on the time of referral and no other bias . These two cohorts of patients are compared for various intraoperative parameters , length of hospital stay , pathologic findings , time to recurrence , and survival .  Mean age was 65 and 66 years in the preop and postop CTRT groups , respectively . Sex distribution was almost equal . Treatment breaks result ing in greater than 1 week delay in the radiotherapy occurred in 2 ( 8 % ) of 25 patients in the preop CTRT group ( myelotoxicity in 1 case and biliary sepsis in 1 case ) , whereas no treatment breaks > 1 week occurred in those receiving postop CTRT . Eleven patients in preop CTRT had grade 3 or 4 toxicity , whereas none was noted in those with postop CTRT . There was one postoperative death in the preop CTRT group and none in the postop CTRT group . Mean time to the start of CTRT was 45 days ( range , 20 - 66 days ) after pancreaticoduodenectomy . Delay of > 60 days to the onset of CTRT occurred in 2 ( 22 % ) patients and was attributable to patient delays in time to recover from surgery or patient noncompliance . Furthermore , 5 of 23 patients ( 22 % ) in the postop CTRT group did not receive treatment for various reasons . Average estimated operative blood loss was 1933 mL ( median 1550 ) and 1060 mL ( median 1000 ) for preop and postop CTRT groups , respectively . Mean length of operation was 488 minutes ( median 480 ) and 486 minutes ( median 480 ) . Median length of postoperative stay was 22 and 20 days ( ranges , 9 - 144 and 10 - 38 ) . Pathological findings in the resected specimens showed significantly fewer involved nodes in the preop CTRT group ( 28 vs 87 % ; P = 0.0006 ) , whereas similar numbers of nodes/patient were counted in each group ( 14 vs 22 , P = 0.11 ) . More negative resection margins were observed in the preop CTRT group ( 28 vs 56 % ; P = not significant ) . A significantly greater amount of fibrosis replacing the tumor was observed in the preop CTRT group ( 70 vs 40 % ; P = 0.0001 ) . There were no significant survival differences observed ( median 20 months vs 25 months ; P = 0.48 ) , in follow-up that ranged from 4 to 76 months ( median 44 months for surviving patients ) for the preop group and 4 to 40 months ( median 16 months for surviving patients ) for those with postop CTRT . Local failure either alone or as a component of distant failure occurred in 16 per cent ( 4 of 25 patients ) with preop CTRT and 16.6 per cent ( 3 of 18 ) with postop CTRT . Analysis of differences between those treated with preoperative and postoperative CTRT demonstrates similarity in toxicity and effects . However , 22 per cent of patients intended for postoperative therapy did not receive treatment Twenty consecutive patients with unresectable , locally advanced pancreatic cancer were treated with split courses of radiotherapy ( RT ) and simultaneous multidrug chemotherapy consisting of 5 fluorouracil , continuous infusion , streptozotocin , and cisplatin . A separate , retrospective study identified a group of 28 contemporary patients with less advanced pancreatic cancers , all of which were successfully resected . The survival rate of the two groups were similar over the first 2 years , although it initially favored the unresectable group . This pattern of survival among patients treated with combined modality therapy provides a basis for new studies . At the two clinical extremes , these include treatment of unresectable tumors previously considered ineligible for this treatment and initial treatment before resection of stage I tumors 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 In locally advanced pancreatic cancer , the utilization of chemotherapy and radiotherapy is increasing , although in view of the reported long-term results of several contemporary trials , further improvements are certainly needed . Encouraging results using the combination of cisplatin , cytarabine , caffeine , and continuous infusion ( CI ) 5-fluorouracil ( 5-FU ) ( PACE ) for the treatment of advanced pancreatic carcinoma prompted a phase II study using PACE followed by external beam radiotherapy with CI of 5-FU ( PACE-RT ) for localized disease . Forty-one patients were treated with PACE-RT as adjuvant therapy after surgical resection ( 21 patients ) , or as primary therapy for locally advanced , unresectable disease ( 20 patients ) , with reevaluation for resection after completion of treatment . PACE consisted of cisplatin 100 mg/m2 IV on day 1 , cytarabine 2 g/m2 IV every 12 hours × 2 doses , and caffeine 400 mg/m2 subcutaneously after each cytarabine dose ; and days 3 to 21 , 5-FU 250 mg/m2/d given by CI . Cycles were repeated every 28 days . After 2 cycles of PACE , radiation therapy was given concurrently with 5-FU at 200 mg/m2/d . In the adjuvant setting , the tumor bed and the draining lymph node basin received 50.4 Gy and 45 Gy , respectively . In the neoadjuvant setting , the primary and regional lymph nodes were to receive 39.6 Gy followed by a neutron boost of 8 NGy to the gross tumor volume . Photon therapy was delivered at 1.8 Gy per fraction and neutron therapy at 0.8 NGy per fraction , 5 days a week . All patients were evaluable for toxicity and survival . The most common toxicity was myelosuppression , with grade III to IV neutropenia occurring in 59 % of the patients . The median survival times in the locally advanced and adjuvant patients were 13.4 and 18.1 months , with 1-year survival rates of 52 % and 65 % , respectively . Nine of 20 patients receiving PACE-RT for unresectable carcinoma had sufficient tumor regression to meet clinical criteria for exploration ; three were resected with curative intent . The survival of these three patients undergoing resection after neo-adjuvant therapy was 22.4 , 24.3 and 40 months . The treatment program was active , but only moderately well tolerated . Modification of this regimen with newer , less toxic drugs may provide better results and reduced toxicity AIMS To evaluate a single centre 's experience with pancreatic carcinoma focused on preoperative chemoradiation therapy ( CRT ) for treatment of locally advanced pancreatic carcinoma . The aim of the present analysis was to evaluate the median overall survival time ( OS ) after preoperative CRT and to compare it with OS after primary resection of pancreatic carcinoma . In conclusion a new treatment strategy was developed using multimodality treatment for pancreatic carcinoma deemed to be resectable by CT-scan . PATIENTS AND METHODS Between 1995 and 2003 , 302 patients with ductal adenocarcinoma of the pancreatic head and body were recorded prospect ively and OS was analysed with regard to therapy . RESULT 
    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 Recent studies suggest that neoadjuvant chemoradiation can downstage locally advanced pancreatic tumors . There is limited evaluable data to support this approach . We review our experience with preoperative chemoradiation for surgically staged , locally advanced pancreatic cancer to determine whether patients are downstaged with multimodal therapy allowing for curative resection . A prospect ively collected data base from Memorial Sloan-Kettering Cancer Center was review ed . Patients admitted between January 1993 and March 1999 with locally advanced pancreatic adenocarcinoma were identified ( N = 163 ) .  Chemoradiation was administered to 87 ( 53.3 % ) of 163 , and regimens varied from st and ard 5-fluorouracil/gemcitabine-based therapies to experimental protocol s. Only three patients ( 3/87 ; 3.4 % ) had a sufficient clinical response on restaging to warrant reexploration . Of these , two thirds were unresectable on subsequent laparoscopy because of extensive vascular involvement or metastatic disease . Only one patient underwent a potentially curative resection , with a survival of 18 months despite negative margins and no nodal involvement . The overall median survival for all patients with locally advanced disease treated with  chemoradiation  was 11 months ( 6.5 months without multimodal therapy ; P = 0.004 ) . Although hemora-diation is associated with improved overall survival in locally advanced disease , it rarely leads to surgical “ downstaging ” allowing for potentially curative pancreatic resections . Novel multimodality approaches are required Two groups of patients with adenocarcinoma of the pancreas treated with either preoperative chemoradiation ( preop CTRT ) or postoperative chemoradiation ( postop CTRT )  were retrospectively analyzed for various treatment-related parameters . Between November 1986 and October 1996 , a total of 70 patients with pancreatic adenocarcinoma were enrolled into preop CTRT protocol s at our institution . Twenty-five patients with adenocarcinoma of the head of the pancreas underwent pancreaticoduodenectomy with curative intent .  After the closure of the preop CTRT protocol s , we had the opportunity to perform 23 pancreatic resections without preop CTRT . After surgery , these patients were advised to undergo CTRT . These two groups of patients were therefore selected consecutively , dependent only on the time of referral and no other bias . These two cohorts of patients are compared for various intraoperative parameters , length of hospital stay , pathologic findings , time to recurrence , and survival .  Mean age was 65 and 66 years in the preop and postop CTRT groups , respectively . Sex distribution was almost equal . Treatment breaks result ing in greater than 1 week delay in the radiotherapy occurred in 2 ( 8 % ) of 25 patients in the preop CTRT group ( myelotoxicity in 1 case and biliary sepsis in 1 case ) , whereas no treatment breaks > 1 week occurred in those receiving postop CTRT . Eleven patients in preop CTRT had grade 3 or 4 toxicity , whereas none was noted in those with postop CTRT . There was one postoperative death in the preop CTRT group and none in the postop CTRT group . Mean time to the start of CTRT was 45 days ( range , 20 - 66 days ) after pancreaticoduodenectomy . Delay of > 60 days to the onset of CTRT occurred in 2 ( 22 % ) patients and was attributable to patient delays in time to recover from surgery or patient noncompliance . Furthermore , 5 of 23 patients ( 22 % ) in the postop CTRT group did not receive treatment for various reasons . Average estimated operative blood loss was 1933 mL ( median 1550 ) and 1060 mL ( median 1000 ) for preop and postop CTRT groups , respectively . Mean length of operation was 488 minutes ( median 480 ) and 486 minutes ( median 480 ) . Median length of postoperative stay was 22 and 20 days ( ranges , 9 - 144 and 10 - 38 ) . Pathological findings in the resected specimens showed significantly fewer involved nodes in the preop CTRT group ( 28 vs 87 % ; P = 0.0006 ) , whereas similar numbers of nodes/patient were counted in each group ( 14 vs 22 , P = 0.11 ) . More negative resection margins were observed in the preop CTRT group ( 28 vs 56 % ; P = not significant ) . A significantly greater amount of fibrosis replacing the tumor was observed in the preop CTRT group ( 70 vs 40 % ; P = 0.0001 ) . There were no significant survival differences observed ( median 20 months vs 25 months ; P = 0.48 ) , in follow-up that ranged from 4 to 76 months ( median 44 months for surviving patients ) for the preop group and 4 to 40 months ( median 16 months for surviving patients ) for those with postop CTRT . Local failure either alone or as a component of distant failure occurred in 16 per cent ( 4 of 25 patients ) with preop CTRT and 16.6 per cent ( 3 of 18 ) with postop CTRT . Analysis of differences between those treated with preoperative and postoperative CTRT demonstrates similarity in toxicity and effects . However , 22 per cent of patients intended for postoperative therapy did not receive treatment Twenty consecutive patients with unresectable , locally advanced pancreatic cancer were treated with split courses of radiotherapy ( RT ) and simultaneous multidrug chemotherapy consisting of 5 fluorouracil , continuous infusion , streptozotocin , and cisplatin . A separate , retrospective study identified a group of 28 contemporary patients with less advanced pancreatic cancers , all of which were successfully resected . The survival rate of the two groups were similar over the first 2 years , although it initially favored the unresectable group . This pattern of survival among patients treated with combined modality therapy provides a basis for new studies . At the two clinical extremes , these include treatment of unresectable tumors previously considered ineligible for this treatment and initial treatment before resection of stage I tumors 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 In locally advanced pancreatic cancer , the utilization of chemotherapy and radiotherapy is increasing , although in view of the reported long-term results of several contemporary trials , further improvements are certainly needed . Encouraging results using the combination of cisplatin , cytarabine , caffeine , and continuous infusion ( CI ) 5-fluorouracil ( 5-FU ) ( PACE ) for the treatment of advanced pancreatic carcinoma prompted a phase II study using PACE followed by external beam radiotherapy with CI of 5-FU ( PACE-RT ) for localized disease . Forty-one patients were treated with PACE-RT as adjuvant therapy after surgical resection ( 21 patients ) , or as primary therapy for locally advanced , unresectable disease ( 20 patients ) , with reevaluation for resection after completion of treatment . PACE consisted of cisplatin 100 mg/m2 IV on day 1 , cytarabine 2 g/m2 IV every 12 hours × 2 doses , and caffeine 400 mg/m2 subcutaneously after each cytarabine dose ; and days 3 to 21 , 5-FU 250 mg/m2/d given by CI . Cycles were repeated every 28 days . After 2 cycles of PACE , radiation therapy was given concurrently with 5-FU at 200 mg/m2/d . In the adjuvant setting , the tumor bed and the draining lymph node basin received 50.4 Gy and 45 Gy , respectively . In the neoadjuvant setting , the primary and regional lymph nodes were to receive 39.6 Gy followed by a neutron boost of 8 NGy to the gross tumor volume . Photon therapy was delivered at 1.8 Gy per fraction and neutron therapy at 0.8 NGy per fraction , 5 days a week . All patients were evaluable for toxicity and survival . The most common toxicity was myelosuppression , with grade III to IV neutropenia occurring in 59 % of the patients . The median survival times in the locally advanced and adjuvant patients were 13.4 and 18.1 months , with 1-year survival rates of 52 % and 65 % , respectively . Nine of 20 patients receiving PACE-RT for unresectable carcinoma had sufficient tumor regression to meet clinical criteria for exploration ; three were resected with curative intent . The survival of these three patients undergoing resection after neo-adjuvant therapy was 22.4 , 24.3 and 40 months . The treatment program was active , but only moderately well tolerated . Modification of this regimen with newer , less toxic drugs may provide better results and reduced toxicity AIMS To evaluate a single centre 's experience with pancreatic carcinoma focused on preoperative chemoradiation therapy ( CRT ) for treatment of locally advanced pancreatic carcinoma . The aim of the present analysis was to evaluate the median overall survival time ( OS ) after preoperative CRT and to compare it with OS after primary resection of pancreatic carcinoma . In conclusion a new treatment strategy was developed using multimodality treatment for pancreatic carcinoma deemed to be resectable by CT-scan . PATIENTS AND METHODS Between 1995 and 2003 , 302 patients with ductal adenocarcinoma of the pancreatic head and body were recorded prospect ively and OS was analysed with regard to therapy . RESULT 
    Output:
    