***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 
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    Input: Pancreatic carcinoma is a leading cause of cancer-related mortality . Approximately 30 % of pancreatic cancer patients present with locally advanced , unresectable nonmetastatic disease . For these patients , two therapeutic options exist : systemic chemotherapy or chemoradiotherapy . Within this context , the optimal technique for pancreatic irradiation is not clearly defined . A search to identify relevant studies was undertaken using the Medline data base . All Phase III r and omized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included , as were some noncontrolled Phase II and retrospective studies . An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines . Each member of the working group independently evaluated five endpoints : total dose , target volume definition , radiotherapy planning technique , dose constraints to organs at risk , and quality assurance . Based on this analysis of the literature , we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction . We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly , posteriorly , and laterally , and 2 to 3 cm craniocaudally to generate the planning target volume . The craniocaudal margins can be reduced with the use of respiratory gating . Organs at risk are liver , kidneys , spinal cord , stomach , and small bowel .  Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials . Radiotherapy quality assurance is m and atory in clinical trials . These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy . Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity concepts Background : To evaluate the efficacy and tolerability of the urokinase plasminogen activator ( uPA ) inhibitor upamostat in combination with gemcitabine in locally advanced pancreatic adenocarcinoma ( LAPC ) . Methods : Within a prospect i ve multicenter study , LAPC patients were r and omly assigned to receive 1000 mg m−2 of gemcitabine IV weekly either alone ( arm A ) or in combination with 200 mg ( arm B ) or 400 mg ( arm C ) oral upamostat daily . Efficacy endpoints of this proof-of-concept study included response rate , time to first metastasis , progression-free and overall survival ( OS ) . Results : Of the 95 enroled patients , 85 were evaluable for response and 93 for safety . Median OS was 12.5 months ( 95 % CI 8.2–18.2 ) in arm C , 9.7 months ( 95 % CI 8.4–17.1 ) in arm B and 9.9 months ( 95 % CI 7.4–12.1 ) in arm A ; corresponding 1-year survival rates were 50.6 % , 40.7 % and 33.9 % , respectively . More patients achieved a partial remission ( confirmed responses by RECIST ) with upamostat combination therapy ( arm C : 12.9 % ; arm B : 7.1 % ; arm A : 3.8 % ) . Overall , only 12 patients progressed by developing detectable distant metastasis ( arm A : 4 , arm B : 6 , arm C : 2 ) . The most common adverse events considered to be related to upamostat  were asthenia , fever and nausea . Conclusion : In this proof-of-concept study targeting the uPA system in LAPC , the addition of upamostat to gemcitabine was tolerated well ; similar survival results were observed for the three treatment arms Purpose 5-FU-based concurrent chemoradiotherapy ( CRT ) has been the mainstay of treatment for locally advanced pancreatic cancer ( LAPC ) for the past decades , but the prognosis remains dismal . Methods Patients with pathologically confirmed LAPC of the pancreas , an ECOG PS of 0–2 and no prior chemo- or radiotherapy were eligible . The treatment consisted of induction ( IND ) chemotherapy with a fixed dose rate gemcitabine 1,000 mg/m² on days 1 and 8 and CDDP 60 mg/m² on day 1 every 3 weeks for 3 cycles . Subsequently , the patients without progression received CRT of 55.8 Gy/31 fractions with capecitabine 650 mg/m² twice daily . Gemcitabine was given for 3 cycles after CRT . The primary endpoint was time to progression . Results Thirty-seven patients with LAPC were enrolled . Median age was 55 years , there were 20 males and 17 females , and ECOG PS was 0 in 6 and 1 in 31 . Three patients ( 9.7 % ) achieved partial responses after IND chemotherapy . Twenty-five patients received CRT with a mean radiation dose of 54.0 Gy , with one additional patient achieving a partial response . The median time to progression was 7.2 months ( 95 % CI , 4.4–10 ) , and the median overall survival was 16.8 months ( 95 % CI , 12.9–20.7 ) . The grade 3/4 toxicities included neutropenia ( 29 % /6.5 % ) , thrombocytopenia ( 3.2 % /0 % ) and anemia ( 9.7 % /0 % ) during the IND phase and grade 3 neutropenia and diarrhea occurring in one and two patients during CRT phase . Conclusions IND chemotherapy with gemcitabine and cisplatin followed by CRT with capecitabine and maintenance gemcitabine was well tolerated and exhibited promising efficacy for the treatment of LAPC PURPOSE To evaluate , in a phase 2 study , the safety and efficacy of induction gemcitabine , oxaliplatin , and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer ( BRPC or LAPC , respectively ) . METHODS AND MATERIAL S Patients received gemcitabine and oxaliplatin chemotherapy repeated every 14 days for 6 cycles , combined with weekly cetuximab . Patients were then restaged ; " downstaged " patients with resectable disease underwent attempted resection . Remaining patients were treated with chemoradiation consisting of intensity modulated radiation therapy ( 54 Gy ) and concurrent capecitabine ;  patients with borderline resectable disease or better at restaging underwent attempted resection . RESULTS A total of 39 patients were enrolled , of whom 37 were evaluable . Protocol treatment was generally well tolerated . Median follow-up for all patients was 11.9 months . Overall , 29.7 % of patients underwent R0 surgical resection ( 69.2 % of patients with BRPC ; 8.3 % of patients with LAPC ) . Overall 6-month progression-free survival ( PFS ) was 62 % , and median PFS was 10.4 months . Median overall survival ( OS ) was 11.8 months . In patients with LAPC , median OS was 9.3 months ; in patients with BRPC , median OS was 24.1 months . In the group of patients who underwent R0 resection ( all of which were R0 resections ) , median survival had not yet been reached at the time of analysis . CONCLUSIONS This regimen was well tolerated in patients with BRPC or LAPC , and almost one-third of patients underwent R0 resection . Although OS for the entire cohort was comparable to that in historical controls , PFS and OS in patients with BRPC and /or who underwent R0 resection was markedly improved Summary Background In the UK , chemotherapy is the st and ard treatment for inoperable , locally advanced , non-metastatic pancreatic cancer .  Chemoradiotherapy is also an acceptable treatment option , for which gemcitabine , fluorouracil , or capecitabine can be used as concurrent chemotherapy agents . We aim ed to assess the activity , safety , and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer . Methods In this open-label , r and omised , two-arm , phase 2 trial , patients aged 18 years or older with histologically proven , locally advanced pancreatic cancer ( with a tumour diameter of 7 cm or less ) were recruited from 28 UK centres between Dec 24 , 2009 and Oct 25 , 2011 . After 12 weeks of induction gemcitabine and capecitabine chemotherapy ( three cycles of gemcitabine [ 1000 mg/m2 on days 1 , 8 , 15 of a 28-day cycle ] and capecitabine [ 830 mg/m2 twice daily on days 1–21 of a 28-day cycle ] ) , patients with stable or responding disease , tumour diameter of 6 cm or less , and WHO performance status 0–1 were r and omly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine ( 300 mg/m2 once per week ) or capecitabine ( 830 mg/m2 twice daily , Monday to Friday only ) , both in combination with radiation ( 50·4 Gy in 28 fractions ) . R and omisation ( 1:1 ) was done via a central computerised system and used stratified minimisation . The primary endpoint was 9-month progression-free survival , analysed by intention to treat including only those patients with valid CT assessment s. This trial is registered with IS RCT N , number 96169987 . Findings 114 patients were registered and 74 were r and omly allocated ( 38 to the gemcitabine group and 36 to the capecitabine group ) . After 9 months , 22 of 35 assessable patients ( 62·9 % , 80 % CI 50·6–73·9 ) in the capecitabine group and 18 of 35 assessable patients ( 51·4 % , 39·4–63·4 ) in the gemcitabine group had not progressed . Median overall survival was 15·2 months ( 95 % CI 13·9–19·2 ) in the capecitabine group and 13·4 months ( 95 % CI 11·0–15·7 ) in the gemcitabine group ( adjusted hazard ratio [ HR ] 0·39 , 95 % CI 0·18–0·81 ; p=0·012 ) . 12-month overall survival was 79·2 % ( 95 % CI 61·1–89·5 ) in the capecitabine group and 64·2 ( 95 % CI 46·4–77·5 ) in the gemcitabine group . Median progression-free survival was 12·0 months ( 95 % CI 10·2–14·6 ) in the capecitabine group and 10·4 months ( 95 % CI 8·9–12·5 ) in the gemcitabine group ( adjusted HR 0·60 , 95 % CI 0·32–1·12 ; p=0·11 ) . Eight patients in the capecitabine group had an objective response at 26 weeks , as did seven in the gemcitabine group . More patients in the gemcitabine group than in the capecitabine group had grade 3–4 haematological toxic effects ( seven [ 18 % ] vs none , p=0·008 ) and non-haematological toxic effects ( ten [ 26 % ] vs four [ 12 % ] , p=0·12 ) during chemoradiation treatment ; the most frequent events were leucopenia , neutropenia , and fatigue . Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy . Of the 34 patients in the capecitabine group who received chemoradiotherapy , 25 ( 74 % ) received the full protocol dose of radiotherapy , compared with 26 ( 68 % ) of 38 patients in the gemcitabine group . Quality -of-life scores were not significantly different between the treatment groups . Interpretation Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer . However , these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small . Funding Cancer Research UK The objective of the present study was to define the role of chemotherapy , in the form of the EP regimen , consisting of epirubicin ( E ) and cisplatin ( P ) in addition to irradiation in combination with 5-fluorouracil ( 5-FU ) for treatment of pancreatic cancer . 53 eligible patients with histologically or cytologically proven locally advanced pancreatic cancer were treated with three cycles of E 60 mg/m2 ( if this dose was well tolerated then the dose of E was increased by 10 mg/m2 in the next cycle ; 80 mg/m2 was the maximum dose for the following cycles ) and P 100 mg/m2 once every 3 weeks , followed after 4 weeks by a split course of irradiation of 40 Gy with 5-FU 500 mg/m2 on each of the first 3 days of each 20 Gy treatment segment . This was followed by another three cycles of EP in patients who achieved stable disease ( SD ) or a 
    Output:
    
Conclusion The survival benefit of ICT+CCRT over chemotherapy alone in treating LAPC was noted when ICT lasted for at least 3 months .
Fluorouracil-based CCRT , and maintenance chemotherapy were associated with improved clinical outcomes