Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. A Multi-Institutional Phase II Trial of Preoperative Full-Dose Gemcitabine and Concurrent Radiation for Patients With Potentially Resectable Pancreatic Carcinoma Preoperative Chemotherapy Does Not Adversely Affect Pancreatic Structure and Short-Term Outcome after Pancreatectomy Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Perineural Invasion and Lymph Node Involvement as Indicators of Surgical Outcome and Pattern of Recurrence in the Setting of Preoperative Gemcitabine-Based Chemoradiation Therapy for Resectable Pancreatic Cancer Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. Extended Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer Demonstrates Promising Postoperative Outcomes and Survival A phase I trial of combination therapy using gemcitabine and S-1 concurrent with full-dose radiation for resectable pancreatic cancer Neoadjuvant Chemotherapy with Gemcitabine and S-1 for Resectable and Borderline Pancreatic Ductal Adenocarcinoma: Results from a Prospective Multi-institutional Phase 2 Trial Phase 1 trial of preoperative, short‐course carbon‐ion radiotherapy for patients with resectable pancreatic cancer Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy. Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study. Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. Unresectable Locally Advanced Pancreatic Cancer: A Multimodal Treatment Using Neoadjuvant Chemoradiotherapy (Gemcitabine Plus Stereotactic Radiosurgery) and Subsequent Surgical Exploration Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. Neoadjuvant interferon-based chemoradiation for borderline resectable and locally advanced pancreas cancer: a Phase II pilot study. Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Efficacy of Neoadjuvant Versus Adjuvant Therapy for Resectable Pancreatic Adenocarcinoma: A Decision Analysis Docetaxel/Gemcitabine Followed by Gemcitabine and External Beam Radiotherapy in Patients With Pancreatic Adenocarcinoma A phase II trial of two durations of Bevacizumab added to neoadjuvant gemcitabine for borderline and locally advanced pancreatic cancer. Preoperative Chemoradiation and Intra-Operative Radiotherapy for Pancreatic Carcinoma A Randomized Phase 2 Trial of Neoadjuvant Chemotherapy in Resectable Pancreatic Cancer: Gemcitabine Alone Versus Gemcitabine Combined with Cisplatin Chemoradiotherapy in the Treatment of Regional Pancreatic Carcinoma: A Phase II Study Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head. Phase I/II Trial of Induction Chemotherapy Followed by Concurrent Chemoradiotherapy and Surgery for Locoregionally Advanced Pancreatic Cancer Phase I-II trial of twice-weekly gemcitabine and concomitant irradiation in patients undergoing pancreaticoduodenectomy with extended lymphadenectomy for locally advanced pancreatic cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. Preoperative staging and assessment of resectability of pancreatic cancer. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma A Single-Arm, Nonrandomized Phase II Trial of Neoadjuvant Gemcitabine and Oxaliplatin in Patients With Resectable Pancreas Adenocarcinoma Using 18F-Fluorodeoxyglucose Positron Emission Tomography to Monitor Clinical Outcomes in Patients Treated With Neoadjuvant Chemo-Radiotherapy for Locally Advanced Pancreatic Cancer Phase I Study of Nab-Paclitaxel plus Gemcitabine as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer. Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. A Pilot Study of Diffusion-Weighted MRI in Patients Undergoing Neoadjuvant Chemoradiation for Pancreatic Cancer Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. Role of neoadjuvant concurrent chemoradiation in locally advanced unresectable pancreatic cancer: a feasibility study at tertiary care centre. Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: New neoadjuvant regimen was safe and provided an interesting pathologic response.
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 Background We report the results of a multi-institutional phase II trial that used preoperative full-dose gemcitabine and radiotherapy for patients with potentially resectable pancreatic carcinoma . Methods Patients were treated before surgery with three cycles of full-dose gemcitabine ( 1000 mg/m2 intravenously ) , with radiation during the second cycle ( 36 Gy in daily 2.4-Gy fractions ) . Patients underwent surgery 4 to 6 weeks after the last gemcitabine infusion . Results There were 10 men and 10 women , with a median age of 58 years ( range , 50–80 years ) . Nineteen patients ( 95 % ) completed therapy without interruption , and one experienced grade 3 gastrointestinal toxicity . The mean weight loss after therapy was 4.0 % . Of 20 patients taken to surgery , 17 ( 85 % ) underwent resections ( 16 pancreaticoduodenectomies and 1 distal pancreatectomy ) . The complication rate was 24 % , with an average length of stay of 13.5 days . There were no operative deaths . Pathologic analysis revealed clear margins in 16 ( 94 % ) of 17 and uninvolved lymph nodes in 11 ( 65 % ) of 17 specimens . One specimen contained no residual tumor , and three specimens revealed only microscopic foci of residual disease . With a median follow-up of 18 months , 7 ( 41 % ) of the 17 patients with resected disease are alive with no recurrence , 3 ( 18 % ) are alive with distant metastases , and 7 ( 41 % ) have died . Conclusions Preoperative gemcitabine/radiotherapy is well tolerated and safe when delivered in a multi-institutional setting . This protocol had a high rate of subsequent resection , with acceptable morbidity . The high rate of negative margins and uninvolved nodes suggests a significant tumor response . Preliminary survival data are encouraging . This regimen should be considered in future neoadjuvant trials for pancreatic cancer Background Preoperative chemotherapy ( PCHT ) has recently been proposed also in patients with resectable pancreatic adenocarcinoma . Few data are currently available on the impact of PCHT on short-term postoperative outcome after pancreatic resection . The objective of this study is to assess the impact of PCHT on pancreatic structure and short-term outcome after surgical resection . Methods Fifty consecutive patients successfully underwent resection after PCHT .  Each patient was matched with two control patients with pancreatic adenocarcinoma selected from our prospect i ve electronic data base . Match criteria were age ( ±3 years ) , gender , American Society of Anesthesiologist score , type of resection , pancreatic duct diameter ( ±1 mm ) , and tumor size ( ±5 mm ) . Primary endpoint was morbidity rate . Secondary endpoints were pancreatic parenchymal structure , mortality rate , and length of hospital stay ( LOS ) . Results Both degree of fibrosis and fatty infiltration of the pancreas were similar in the two groups . Overall morbidity rate was 48.0 % in the PCHT group vs. 54.0 % in the control group ( p = 0.37 ) . Pancreatic fistula rate was 18.0 % in the PCHT group vs. 25.0 % in the control group ( p = 0.41 ) . Mortality was 4.0 % in the PCHT group vs. 2.0 % in the control group ( p = 0.60 ) . Mean LOS ( days ) was 12.7 in the PCHT group vs. 12.4 in the control group ( p = 0.74 ) . There was no difference in resection margin status , while the rate of patients without nodal involvement was higher in the PCHT group ( 46.0 vs. 23.0 % , p = 0.004 ) . Conclusion PCHT did not induce significant structural changes in pancreatic parenchyma and did not adversely affect short-term outcome after surgery 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 evaluate the safety , efficacy and biomarkers of short-course proton beam radiation and capecitabine , followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma ( PDAC ) patients . METHODS AND MATERIAL S Patients with radiographically resectable , biopsy-proven PDAC were treated with neoadjuvant short-course ( 2-week ) proton-based radiation with capecitabine , followed by surgery and adjuvant gemcitabine . The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of < 20 % . Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood . RESULTS The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled , of whom 35 patients were treated in the phase 2 portion . There were no grade 4 or 5 toxicities , and only 2 of 35 patients ( 4.1 % ) experienced a grade 3 toxicity event ( chest wall pain grade 1 , colitis grade 1 ) . Of 48 patients eligible for analysis , 37 underwent pancreaticoduodenectomy . Thirty of 37 ( 81 % ) had positive nodes . Locoregional failure occurred in 6 of 37 resected patients ( 16.2 % ) , and distant recurrence occurred in 35 of 48 patients ( 72.9 % ) . With median follow-up of 38 months , the median progression-free survival for the entire group was 10 months , and overall survival was 17 months . Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12 , stromal CXCR7 expression , and circulating biomarkers CEA , CA19 - 9 , and HGF ( all , P<.05 ) . CONCLUSIONS This study met the primary endpoint by showing a rate of 4.1 % grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation . Treatment was associated with favorable local control . In exploratory analyses , KRAS(G12D ) status and high CXCR7 expression and circulating CEA , CA19 - 9 , and HGF levels were associated with poor survival Objective : To analyze the histopathological indicators significantly associated with surgical outcome and the pattern of recurrence in the setting of preoperative gemcitabine-based chemoradiation therapy ( CRT ) and subsequent pancreatectomy . Background : Clinicopathological assessment of the resected specimen is an indispensable tool for predicting patient prognosis and localizing high-risk sites for tumor relapse . This procedure is also essential for the establishment of efficient postoperative follow-up protocol s in the setting of a preoperative CRT strategy . Methods : In a prospect i ve phase II clinical trial at our hospital , 110 patients received preoperative CRT and subsequent resection . All 110 resected cases were included in this study . We employed disease-free survival ( DFS ) as a surgical outcome , and the pattern of recurrence was divided into 2 categories : ( 1 ) recurrence in the abdominal cavity ( RAC ) , defined as either a locoregional or a peritoneal recurrence ; or ( 2 ) distant recurrence ( DR ) , defined as cancer recurrence in a distant organ . Clinicopathological variables were analyzed in association with DFS , RAC , and DR . Results : Positive nodal involvement and perineural invasion were independent factors that were significantly associated with an unfavorable DFS ( P = 0.021 and P = 0.026 , respectively ) . The presence of perineural invasion was the single independent variable significantly associated with an increased risk of RAC ( P = 0.002 ) , whereas the status of nodal involvement was the single independent variable significantly associated with an increased risk of DR ( P = 0.013 ) . Conclusions : The status of nodal involvement and perineural invasion in resected specimens are significantly associated with DFS and clearly predict the pattern of recurrence in the setting of a preoperative gemcitabine-based CRT strategy . This study is registered at UMIN-CTR and carries the ID number UMIN000001804 CONTEXT Gemcitabine and 5-fluorouracil ( 5-FU ) sensitize tumor cells to radiation . Furthermore , 5-FU enhances the cytotoxic effect of gemcitabine . OBJECTIVE We report the efficacy and the toxicity of concurrent chemoradiation with gemcitabine and 5-FU in the treatment of patients with locally advanced , unresectable pancreatic cancer . PATIENTS Thirty-two patients ( 20 men , 12 women ; median age 69.9 years ) with histologically proven advanced pancreatic carcinoma were included in the study . INTERVENTIONS The patients received chemotherapy with gemcitabine 300 mg/m2 on days 1 , 15 , 29 and 5-FU as continuous infusion 350 mg/m2/day of radiation while concurrent radiation ( 45 - 50 Gy ) was given to the tumor and regional lymph nodes ( 1.8 - 2.0 Gy/fraction on 5 days/week ) . Subsequent to chemoradiotherapy , the treatment was continued with an additional two cycles of gemcitabine ( 1,000 mg/m2 ) and cisplatin ( 50 mg/m2 ) applied on days 1 and 15 of a four-week cycle . MAIN OUTCOME MEASURES Patient survival , time to progression , and toxicity of chemoradiation . Tumor responses ( complete resolution ; partial response ; stable disease , and progressive disease ) were also evaluated . RESULTS After the completion of chemoradiotherapy , 2 patients ( 6.3 % ) achieved complete resolution and 18 patients ( 56.3 % ) a partial response , for an overall response rate of 62.5 % . Twelve patients ( 37.5 % ) were considered resectable and 9 underwent laparotomy , 7 of whom had definitive pancreatic resection . Four patients had negative surgical margins . With a median follow-up of 49.7 months ( 95 % CI : 48.6 - 60.8 months ) after the completion of chemoradiation , distant metastasis occurred in 25 patients ( 78.1 % ) while local recurrence was seen only in 4 of 32 patients ( 12.5 % ) . Median time to progression was 9.2 months ( 95 % CI : 8.2 - 10.2 months ) . Median survival amounted to 13.6 months ( 95 % CI : 12.7 - 14.6 months ) for all patients while it was prolonged to 16.4 months ( 95 % CI : 13.4 - 19.4 months ) for those undergoing secondary resection . In addition , performance status proved to be another prognostic factor for overall survival . The main toxicity of chemoradiation included grade 3 - 4 leukopenia in 18 patients ( 56.3 % ) and thrombocytopenia in 8 patients ( 25.0 % ) . Episodes of cholangitis were observed in 7 patients ( 21.9 % ) . CONCLUSION Gemcitabine and 5-FU can safely be combined with external beam radiation . This preoperative treatment approach is highly effective and appears to improve survival in patients with good performance status and in those who are eligible for a secondary resection 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 Purpose Use of the fourth-generation oral fluoropyrimidine S-1 together with gemcitabine has shown striking anticancer effects . In this single-arm phase I trial of preoperative combination therapy using gemcitabine and S-1 concurrently with radiotherapy , we verified the safety and feasibility and determined the maximum-tolerated dose of each drug in patients with resectable pancreatic cancer . Methods A st and ard 3 + 3 dose escalation scheme was used . Patients with cytologically or histologically proven resectable pancreatic ductal adenocarcinoma were administered 30-min intravenous gemcitabine infusions on days 1 , 8 , 22 , and 29 and S-1 orally on days 1–5 , 8–12 , 22–26 , and 29–33 . A total radiation dose of 50.4 Gy ( 1.8 Gy/day , 5 times per week , 28 fractions ) was concurrently delivered . Surgical exploration was scheduled 4–7 weeks after the final radiation fraction . Results Twenty-one patients were enrolled . No treatment-related deaths occurred during this study . Recommended doses were determined to be 80 mg/m2 of S-1 daily and 1,000 mg/m2 of  gemcitabine . CA19 - 9 was reduced to < 50 % of baseline values in 12 ( 75 % ) of 16 measurable patients . Nineteen of 21 enrolled patients successfully underwent surgical resection . Conclusions Preoperative chemoradiotherapy consisting of gemcitabine and S-1 concurrent with full-dose radiation is feasible and well tolerated 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 The authors evaluated the tolerance and efficacy of carbon‐ion radiotherapy ( CIRT ) as a short‐course , preoperative treatment and determined the recommended dose needed to reduce the risk of postoperative local recurrence without excess injury to normal tissue PURPOSE To prospect ively evaluate the utility of computed tomography ( CT ) for determination of tumor response and prediction of resectability after neoadjuvant combined chemotherapy and radiation therapy ( CRT ) in patients with nonmetastatic locally advanced pancreatic cancer . MATERIAL S AND METHODS This study received institutional review board approval , and all participants provided written informed consent . Consecutive patients with cephalic locally advanced pancreatic cancer who underwent surgical exploration and /or resection following neoadjuvant CRT were prospect ively enrolled from June 2009 to May 2013 . Two radiologists independently analyzed the baseline and post-CRT CT scans for the size , attenuation , and circumferential vascular contacts of the tumor . Associations between the postoperative histologic grade of the tumor response ( pTNM ) and the clinical , biologic , and CT criteria were assessed by using Spearman correlation coefficients . CT criteria related to the presence of complete ( ie , R0 ) resection were assessed by using logistic regression . RESULTS Forty-seven patients were included , 33 with an R0 resection and 14 with positive margins ( ie , R1 ) or no resection . Variables demonstrating a significant correlation with the histologic tumor classification of tumor response were post-CRT carbohydrate antigen 19 - 9 level ( r = 0.46 ) , post-CRT largest tumor axis ( r = 0.44 ) , post-CRT sum of the largest and smallest tumor axes ( r = 0.46 ) , change in the largest axis ( r = -0.31 ) , change in the sum of the largest and smallest axes ( r = -0.39 ) , change in superior mesenteric vein ( SMV ) and /or portal vein ( hereafter , SMV/portal vein ) contact ( r = -0.38 ) , and post-CRT superior mesenteric artery contact ( r = 0.34 ) . Partial regression of tumor contact with the SMV/portal vein was associated in all cases with R0 resection ( 10 of 10 patients , positive predictive value = 100 % ) , and partial regression of tumor contact with any peripancreatic vascular axis was associated with R0 resection in 91 % of cases ( 20 of 22 patients , positive predictive value = 91 % ) . Persistence of SMV/portal vein stenosis after CRT was not predictive of R1 resection . CONCLUSION Partial regression of tumor-vessel contact indicates suitability for surgical exploration , irrespective of the degree of decrease in tumor size or the degree of residual vascular involvement PURPOSE To determine the safety , efficacy , and tolerability of biweekly gemcitabine with concurrent radiotherapy ( RT ) for resected and locally advanced ( LA ) pancreatic cancer . METHODS AND MATERIAL S Eligible patients had either LA or resected pancreatic cancer . Between March 1999 and July 2001 , 63 patients ( 31 with LA and 32 with resected disease ) were treated . Of the 63 patients , 28 were enrolled in a Phase I study of increasing radiation doses ( 35 Gy [ n = 7 ] , 43.75 Gy [ n = 11 ] , and 52.5 Gy [ n = 10 ] given within 4 , 5 , or 6 weeks , respectively , in 1.75-Gy fractions ) concurrently with 40 mg/m(2 ) gemcitabine biweekly . Subsequently , 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m(2 ) within 7 or 8 weeks to concurrent biweekly gemcitabine ( 40 mg/m(2 ) ) and 52.5 Gy RT within 6 weeks . RESULTS In the LA population , the best response observed was a complete response in 1 , partial response in 3 , stable disease in 10 , and progressive disease in 17 . In the phase II trial , gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone ( n = 5 ) or by patient request ( n = 3 ) . On intent-to-treat analysis , the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1 % . In the resected population , the median progression-free survival was 8.3 months , the median survival was 18.4 months , and the 2- and 5-year survival rate was 36 % and 19.4 % , respectively . The treatment was well tolerated ; the median gemcitabine dose intensity was 96 % of the planned dose in the neoadjuvant and concurrent portions of the Phase II study . No treatment-related deaths occurred . CONCLUSION Biweekly gemcitabine ( 40 mg/m(2 ) ) concurrently with RT ( 52.5 Gy in 30 fractions of 1.75 Gy ) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer 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 CONTEXT The role of adjuvant therapy in resectable pancreatic cancer is still uncertain , and no recommended st and ard exists . OBJECTIVE To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more . DESIGN , SETTING , AND PATIENTS Open , multicenter , r and omized controlled phase 3 trial with stratification for resection , tumor , and node status . Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria . A total of 368 patients with gross complete ( R0 or R1 ) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups . INTERVENTION Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1 , 8 , and 15 every 4 weeks ( n = 179 ) , or observation ( [ control ] n = 175 ) . MAIN OUTCOME MEASURES Primary end point was disease-free survival , and secondary end points were overall survival , toxicity , and quality of life . Survival analysis was based on all eligible patients ( intention-to-treat ) . RESULTS More than 80 % of patients had R0 resection . The median number of chemotherapy cycles in the gemcitabine group was 6 ( range , 0 - 6 ) . Grade 3 or 4 toxicities rarely occurred with no difference in quality of life ( by Spitzer index ) between groups . During median follow-up of 53 months , 133 patients ( 74 % ) in the gemcitabine group and 161 patients ( 92 % ) in the control group developed recurrent disease . Median disease-free survival was 13.4 months in the gemcitabine group ( 95 % confidence interval , 11.4 - 15.3 ) and 6.9 months in the control group ( 95 % confidence interval , 6.1 - 7.8 ; P<.001 , log-rank ) . Estimated disease-free survival at 3 and 5 years was 23.5 % and 16.5 % in the gemcitabine group , and 7.5 % and 5.5 % in the control group , respectively . Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection . There was no difference in overall survival between the gemcitabine group ( median , 22.1 months ; 95 % confidence interval , 18.4 - 25.8 ; estimated survival , 34 % at 3 years and 22.5 % at 5 years ) and the control group ( median , 20.2 months ; 95 % confidence interval , 17 - 23.4 ; estimated survival , 20.5 % at 3 years and 11.5 % at 5 years ; P = .06 , log-rank ) . CONCLUSIONS Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone . These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N34802808 Background Pancreatic cancer accounts for approximately 3 % of cancer deaths in Europe . Locally advanced pancreatic cancer ( LAPC ) involves vascular structures , and resectability is low , with a median survival time of 6 to 11 months . We conducted a prospect i ve , nonr and omized study of patients with LAPC to assess the effect of stereotactic body radiotherapy ( SBRT ) on local response , pain control , and quality of life ( QOL ) . Methods Twenty-three patients with histologically confirmed LAPC underwent SBRT . Radiotherapy ( 30 Gy ) was delivered in three fractions , and treatment toxicity was assessed according to the Common Terminology Criteria for Adverse Events ( CTCAE v. 3.0 ) . All patients received also gemcitabine chemotherapy and were followed up until death . Local control was assessed according to Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria , pain control was assessed with a visual analog scale , and QOL was assessed with the SF-36 instrument ( Italian v. 1.6 ) . Results No grade 2 or higher acute or late toxicity was observed . The overall local response ratio was 82.6 % ( 14 partial response , 2 complete response , 3 stable disease ) . SBRT showed a good short-term efficacy in controlling both pain and QOL . Median survival was 10.6 months , with a median follow-up of 9 months . The LAPC became resectable in 8 % of the patients . Median time to progression of disease was 7.3 months . Six patients developed early metastatic disease . Conclusions The SBRT method is a promising treatment for LAPC . Local control rates , even compared to historical data from conventional radiotherapy , can be achieved with minimal toxicity . Resectability can also be achieved 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 OBJECTIVES Neoadjuvant chemoradiotherapy ( CRT ) is a viable treatment strategy for patients with pancreatic cancer . This study was conducted to evaluate the Virginia Mason Protocol ( 5-fluorouracil , cisplatin , interferon-α and radiation ) given in the neoadjuvant setting for the treatment of locally advanced pancreatic cancer . METHODS A Phase II pilot study evaluating interferon-based neoadjuvant CRT in patients with locally advanced pancreatic cancer was performed . RESULTS A total of 23 patients were enrolled . The mean age of the patients was 58.6 years . Of the 23 patients , seven ( 30.4 % ) completed all treatments . In the remaining 16 ( 69.6 % ) patients , treatment was interrupted as a result of toxicity . The most commonly reported effects of toxicity were leucopoenia/cytopoenia ( n = 19 , 82.6 % ) and gastrointestinal effects ( n = 19 , 82.6 % ) . Surgical resection was successful in seven ( 30.4 % ) patients . Margins were negative in six ( 85.7 % ) of these seven patients . Positive lymph nodes were identified in three ( 42.9 % ) of seven patients . Overall survival was 11.5 months . Surgery provided improved survival ( 22.6 months ) compared with CRT alone ( 8.8 months ) . Disease-free survival in resected patients was 17.2 months . CONCLUSIONS Interferon-based neoadjuvant CRT may allow for resection of locally advanced pancreatic cancer , but with significant toxicity . In the absence of surgical resection , survival remains dismal BACKGROUND We explored the feasibility and the histologic assessment of treatment effect of preoperative chemoradiation in patients presenting with resectable pancreatic adenocarcinoma . PATIENTS AND METHODS Treatment consisted of concurrent radiotherapy ( 50 Gy within 5 weeks ) and chemotherapy with 5-fluorouracil ( 300 mg/m(2)/day , 5 days/week , weeks 1 - 5 ) and cisplatin ( 20 mg/m(2)/day , days 1 - 5 and 29 - 33 ) , followed by surgical resection of the pancreatic tumor in patients without progression . RESULTS In all , 41 patients were enrolled ; 38 ( 93 % ) received > or=47 Gy ; 30 patients ( 73 % ) received > or=75 % of the prescribed doses of chemotherapy . Among 40 assessable patients , 27 ( 67.5 % ; 95 % confidence interval 50.9 % to 81.4 % ) were successfully treated ( entire dose of radiation , > or=75 % of the chemotherapy dose , no grade 4 non-hematologic toxicity ) . In all , 26 patients ( 63 % ) underwent surgical resection with curative intent and 21 ( 80.7 % ) had R0 resection . A total of 13 of 26 specimens ( 50 % ) presented a major pathologic response ( > or=80 % of severely degenerative cancer cells ) , with one complete pathologic response . Operative mortality was 2.8 % . The local recurrence and 2-year survival rates were 4 % and 32 % , respectively , for the 26 operated patients . CONCLUSIONS This proposed preoperative scheme is feasible , does not prevent successful surgery , and provides antitumoral effect associated with major histopathological response in 50 % of patients and a high R0 resection rate Abstract Background Neoadjuvant therapy-based protocol s for potentially resectable pancreatic adenocarcinoma ( PAC ) have not been directly compared with adjuvant protocol s in large prospect i ve r and omized trials . This study aim ed to compare the efficacy of neoadjuvant versus adjuvant therapy-based management by using a formal decision analytic model . Methods A decision analytic model was created with a Markov process to compare neoadjuvant and adjuvant chemo- and /or chemoradiation therapy-based strategies for simulated cohorts of patients with potentially resectable PAC . Base-case probabilities were derived from the published data of 21 prospect i ve phases 2 and 3 trials ( 3708 patients ) between 1997 and 2014 . The primary outcome measures determined in an intent-to-treat fashion were overall and quality -adjusted survival rates . One- and two-way sensitivity analyses were performed to assess the effects of model uncertainty on outcomes . Results The median overall survival and 2-year survival rates for the patients in the st and ard adjuvant therapy arm of the study were 20 months and 42.2 % versus 22 months and 46.8 % for those in the neoadjuvant strategy arm . Quality -adjusted survival was 18.4 and 19.8 months , respectively . Sensitivity analysis demonstrated that when recurrence-free survival after completion of neoadjuvant therapy and resection is less than 13.9 months or when the rate for progression of disease precluding resection during neoadjuvant therapy is greater than 44 % , the neoadjuvant strategy is no longer the favored option . Conclusions The decision analytic model suggests that neoadjuvant therapy-based management improves the outcomes for patients with potentially resectable pancreatic cancer . However , the benefits in terms of overall and quality -adjusted survival are modest Background Pancreatic cancer remains highly lethal . Previous attempts with neoadjuvant therapy in this disease have been inconclusive , but a potential for benefit exists . We conducted a phase II trial of dose-intense docetaxel and gemcitabine followed by twice-weekly gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma . Methods Patients with stage I to III disease were eligible .  Docetaxel 65 mg/m2 intravenously over 1 hour and gemcitabine 4000 mg/m2 given intravenously over 30 minutes were given on days 1 , 15 , and 29 . On day 43 , radiotherapy was begun at 50.4 Gy with gemcitabine 50 mg/m2 intravenously over 30 minutes twice weekly for 12 doses . After treatment , patients were considered for resection . Results Twenty-four assessable patients were recruited onto the trial . All but one patient completed a full 12 weeks of therapy . Grade 3 and 4 hematological and nonhematological toxicities were common but manageable , and neutropenic fever did not occur . No patient had local tumor progression . Twelve patients ( 50 % ) responded by Response Evaluation Criteria in Solid Tumors Group ( RECIST ) criteria , including one radiographic complete response . Seventeen patients underwent resection after therapy . Margin-negative resections were performed in 13 patients , including 9 patients whose disease was borderline or unresectable before treatment . A treatment effect was seen in all resection specimens . There have been no local recurrences of tumor , and several patients remain alive without evidence of disease . Conclusions Docetaxel/gemcitabine followed by gemcitabine/radiotherapy is active in the treatment of pancreatic adenocarcinoma , with manageable toxicity . Tumor downstaging occurs in some patients to allow complete resection . Further investigation of this regimen is warranted BACKGROUND We report the results of a phase II trial of adding the anti-ascular endothelial growth factor ( VEGF ) bevacizumab to gemcitabine neoadjuvant chemotherapy for patients with borderline and unresectable non-metastatic pancreatic cancer . PATIENTS AND METHODS Patients were assigned to one of the two treatment arms . Both groups received 1,000 mg/m(2 ) gemcitabine on days 1 , 8 , and 15 of a 4-week cycle for a total of four cycles . Group 1 received 5 mg/kg bevacizumab for six weeks ( three doses ) , every second week , starting at week 6 of gemcitabine therapy . Group 2 received 5 mg/kg bevacizumab for 12 weeks ( six doses ) , every second week , starting at week 1 of gemcitabine therapy . The objective of the present study was to assess the rate of complete radical resection and overall survival . RESULTS A total of 30 patients were enrolled : 19 patients had unresectable and 11 patients had borderline-resectable pancreatic cancer . Eleven patients ( 37 % ) underwent resection . The median overall survival of patients who underwent tumor resection was 13 months ( 95 % confidence interval=11 - 15 months ) . CONCLUSION In general , adding bevacizumab to neoadjuvant gemcitabine does not improve outcomes for patients with locally advanced pancreatic cancer . However , in individual cases , surgery is consequently possible and prolonged survival may be observed Aims and background In recent years , preoperative chemoradiation has received growing interest for the treatment of locally advanced pancreatic cancer . In an attempt to improve resectability and disease control , we used preoperative radiation therapy and concomitant 5-fluorouracil in a combined modality therapy protocol . The aim of the study was to evaluate definitive results in terms of toxicity , response and clinical outcome . Material and methods Twenty-eight patients with unresectable ( cT4,19 patients ) or resectable ( cT3 , 9 patients ) nonmetastatic pancreatic tumors received radiotherapy ( 39.6 Gy ) plus 5-fluorouracil ( continuous infusion , days 1 - 4 at 1000 mg/m2/day ) . After 4 weeks , patients were evaluated for surgical resection . In 9 resected patients , electron-beam intra-operative radiotherapy ( 10 Gy ) was given before reconstruction . Thereafter , in resected patients , adjuvant chemotherapy was prescribed . Results During chemoradiation , 1 patient ( 3.6 % ) developed grade 3 acute gastrointestinal toxicity and 2 patients ( 7.1 % ) developed grade 3 hematological toxicity . Three of 19 patients with unresectable tumors had tumor downstaging ( 15.8 % ) . Two patients showed partial response ( response rate , 7.1 % ; 95 % CI , 0.2 - 25.3 ) and 4 patients ( 14.3 % ) had minimal tumor response . Four patients ( 14.3 % ) showed progressive disease after chemoradiation . One postoperative death was recorded . The median survival time was 11.3 months ( 20.5 and 9.0 months in resected and unresected patients , respectively ) . Only one local failure was recorded in 8 patients resected with negative margins . Conclusions Although the response rate is still low , our preliminary results suggest that preoperative 5-fluorouracil chemoradiation is well tolerated and may result in tumor downstaging . Delivery of intra-operative radiotherapy seems to be associated with a low rate of local recurrences 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 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 BACKGROUND This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma ( BRPC ) that would have worldwide acceptability . METHODS An international panel of pancreatic surgeons from well-established , high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer . RESULTS The International Study Group of Pancreatic Surgery ( ISGPS ) supports the National Comprehensive Cancer Network criteria for the definition of BRPC . Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis ; in addition , a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS . Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings . Formal arterial resections are not recommended ; however , in exceptional circumstances , individual therapeutic approaches may be evaluated under experimental protocol s. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection ( tumor within 1 mm from the margin ) used by the British Royal College of Pathologists . St and ard preoperative diagnostics for BRPC may include : ( 1 ) serum levels of CA19 - 9 , because CA19 - 9 levels predict survival in large retrospective series ; and also ( 2 ) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response . Various regimens of neoadjuvant therapy are recommended only in the setting of prospect i ve trials at high-volume centers . CONCLUSION Current evidence justifies portomesenteric venous resection in patients with BRPC . Basic definitions were identified , that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup . A consensus for each topic is given 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 3-month CA 19 - 9 measurements and ceCT after 6 , 12 , 18 , and 24 months . Histologic tumor response was assessed by two scoring systems . RESULTS Twenty-eight patients entered this study .  Adverse effects were mainly gastrointestinal and hematologic , most often mild , and never of grade 4 . Twenty-six patients ( 93 % ) had resectable cancer on restaging examinations , and the R0 resection rate was 80 % . Histologic tumor response and cytopathic effects were documented in 54 % and 83 % of patients , respectively . On intention-to-treat analysis , disease-free and overall survival were 9.2 months ( 95 % CI , 5.6 to 12.9 months ) and 26.5 months ( 95 % CI , 11.4 to 41.5 months ) and 9 months ( 95 % CI , 6.99 to 10.1 months ) and 19.1 months ( 95 % CI , 15 to 23.1 months ) for ductal adenocarcinoma , respectively . QoL improved in two items and was unchanged in all other items . Moreover , prealbumin serum levels significantly improved during chemotherapy ( P = .008 ) . CONCLUSION Neoadjuvant chemotherapy with gemcitabine and cisplatin is well tolerated and does not impair resectability of pancreatic cancer . Furthermore , it improves the QoL and the nutritional status of affected patients with favorable overall and disease-free survival Background We used a novel combination of induction chemotherapy with gemcitabine ( GEM ) and cisplatin ( CDDP ) , followed by concurrent chemoradiotherapy ( CCRT ) with the same agents in patients with locoregionally advanced pancreatic cancer . Surgery or additional chemotherapy followed on the basis of response . Methods Patients with borderline resectable or locally advanced pancreatic cancer received induction weekly with GEM ( 1000 mg/m2 ) or CDDP ( 30 g/m2 ) . Patients without progression of disease then underwent surgery or CCRT , including four cohorts of escalating GEM/CDDP doses combined with full-dose radiotherapy . After CCRT , patients deemed resectable underwent surgery ; patients with disease that remained unresectable and that did not progress received additional GEM/CDDP for 2 months . Results A mean 76 % of intended GEM dose and 75 % of CDDP dose was delivered during induction ( n = 26 ) . There were three incidences of grade 4 toxicity ( fever or neutropenia ) . After induction , five patients progressed and one patient underwent resection . Eighteen patients received CCRT , and three patients underwent resection . After CCRT , disease of 10 patients progressed , and in 5 patients , it remained unresectable without progression , and the patient received additional GEM/CDDP .  Dose-limiting toxicity was at dose level IV ( thrombocytopenia ) . Median overall and disease-specific survival was 13 months . Conclusion GEM/CDDP induction chemotherapy followed by CCRT is well tolerated and rendered the disease of 4 of 26 patients resectable in this study . The recommended phase II dose for GEM and CDDP in combination with full-dose radiotherapy ( 5040 cGy ) is 300 mg/m2 and 10 mg/m2 weekly for 5 weeks . Median survival in this group was 13 months . This neoadjuvant combined modality approach is both feasible and active ; further studies are warranted PURPOSE Define the maximum tolerated dose ( MTD ) , tolerability , and efficacy of gemcitabine given concomitantly with radiotherapy in patients with locally advanced pancreatic cancer . METHODS AND MATERIAL S Patients were required to have locally advanced T1-T3 resectable pancreatic cancer .  Gemcitabine , given twice weekly before irradiation as a 30-min infusion , was tested at 3 dose levels : 20 , 50 , and 100 mg/m(2 ) . The radiation dose was 50.4 Gy ( ICRU ) in 28 fractions . The targeted irradiation volume included the tumor , edema , and a 1-cm margin . RESULTS Twenty-eight of 34 patients was eligible for analysis of the treatment . The median age was 67 years ( range 38 - 82 ) . Six patients had T1 , 9 had T2 , and 19 had T3 diseases ( AJCC ) .  Dose-limiting toxicities were Grade 4 , fatigue and nausea ; Grade 3 , thrombocytopenia , diarrhea , and infection . The MTD established was at the 50-mg/m(2 ) gemcitabine dose . A total of 21 of 28 patients underwent surgery : 18 had pancreaticoduodenectomy , 2 had total pancreatectomy , and 1 for palliative surgery . At the time of analysis , 13 of 28 ( 46 % ) were disease-free . The estimated median survival was 25 months and overall survival rate at 2 years ( Kaplan-Meier ) was 55 % . CONCLUSION Gemcitabine 50 mg/m(2 ) given twice weekly with concomitant irradiation induces acceptable and manageable toxicity and might prolong survival BACKGROUND The effect of adjuvant treatment on survival in pancreatic cancer is unclear . We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and up date the interim results . METHODS In a multicenter trial using a two-by-two factorial design , we r and omly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone ( 20 Gy over a two-week period plus fluorouracil ) , 75 patients to chemotherapy alone ( fluorouracil ) , 72 patients to both chemoradiotherapy and chemotherapy , and 69 patients to observation .  RESULTS The analysis was based on 237 deaths among the 289 patients ( 82 percent ) and a median follow-up of 47 months ( interquartile range , 33 to 62 ) . The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy ( P=0.05 ) . The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy ( P=0.009 ) . The benefit of chemotherapy persisted after adjustment for major prognostic factors . CONCLUSIONS Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer , whereas adjuvant chemoradiotherapy has a deleterious effect on survival To study the accuracy of preoperative staging techniques for assessing resectability of pancreatic and ampullary adenocarcinoma , we entered 88 consecutive c and i date s into a prospect i ve study of contrast-enhanced computed tomography , magnetic resonance imaging , angiography , and laparoscopy .  Resectability was proved in 16 ( 29 % ) of 55 patients for the head of the pancreas , 1 ( 6 % ) of 17 for the body and tail of the pancreas , and 14 ( 88 % ) of 16 for the ampulla . The combined findings of computed tomography and angiography showed that more than 87 % of pancreatic head tumors were unresectable because of vascular encasement , but neither modality sufficed alone . Small liver and peritoneal metastases were found in 15 ( 27 % ) of 55 cancers of the head of the pancreas , 11 ( 65 % ) of 17 cancers of the body and tail of the pancreas , and 1 ( 6 % ) of 16 cancers of the ampulla ; computed tomography missed all but 2 of these instances of metastasis , but laparoscopy with biopsy identified 22 ( 96 % ) of 23 instances . Magnetic resonance imaging findings did not differ significantly from computed tomography and conferred no added benefit . Ninety percent of unresectable tumors were identified . Seventy-eight percent of pancreatic head cancers were resectable when all test results were negative vs 5 % ( 2/37 ) when any test result was positive . This study demonstrates that accurate and efficient triage is possible for patients with cancer of the pancreas and ampulla PURPOSE We conducted a phase II trial of preoperative gemcitabine and cisplatin chemotherapy in addition to chemoradiation ( Gem-Cis-XRT ) and pancreaticoduodenectomy ( PD ) for patients with stage I/II pancreatic adenocarcinoma . PATIENTS AND METHODS Chemotherapy consisted of gemcitabine ( 750 mg/m(2 ) ) and cisplatin ( 30 mg/m(2 ) ) given every 2 weeks for four doses . Chemoradiation consisted of four weekly infusions of gemcitabine ( 400 mg/m(2 ) ) combined with radiation therapy ( 30 Gy in 10 fractions administered over 2 weeks ) delivered 5 days per week . 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 90 patients ; 79 patients ( 88 % ) completed chemo-chemoradiation . Sixty-two ( 78 % ) of 79 patients were taken to surgery and 52 ( 66 % ) of 79 underwent PD . The median overall survival of all 90 patients was 17.4 months . Median survival for the 79 patients who completed chemo-chemoradiation was 18.7 months , with a median survival of 31 months for the 52 patients who underwent PD and 10.5 months for the 27 patients who did not undergo surgical resection of their primary tumor ( P < .001 ) . CONCLUSION Preoperative Gem-Cis-XRT did not improve survival beyond that achieved with preoperative gemcitabine-based chemoradiation ( Gem-XRT ) alone . The longer preoperative interval required more durable biliary decompression ( metal stents ) but was not associated with local tumor progression . The gemcitabine-based chemoradiation platform is a reasonable foundation on which to build future phase II multimodality trials for stage I/II pancreatic cancer incorporating emerging systemic therapies This prospect i ve study was undertaken to assess toxicity , resectability , and survival in pancreatic adenocarcinoma patients presenting with locally advanced , unresectable disease treated with neoadjuvant gemcitabine , docetaxel , and capecitabine ( GTX ) and gemcitabine and capecitabine (GX)/radiation therapy ( RT ) Background : The role for neoadjuvant systemic therapy in resectable pancreas adenocarcinoma remains undefined . Objective : We evaluated the efficacy of gemcitabine and oxaliplatin administered as preoperative therapy in patients with resectable pancreas adenocarcinoma . Methods : Eligible patients were screened using  computed tomography – pancreas angiography , laparoscopy , endoscopic ultrasonography , and fine-needle aspiration cytology to identify 38 patients who received 4 cycles of neoadjuvant gemcitabine 1000 mg/m2 intravenously over 100 minutes and oxaliplatin 80 mg/m2 intravenously over 2 hours , every 2 weeks . Patients whose tumors remained resectable at restaging proceeded to operation and subsequently received 5 cycles of adjuvant gemcitabine ( 1000 mg/m2 intravenously over 30 minutes days 1 , 8 , and 15 every 4 weeks ) . The primary endpoint was 18-month overall survival and secondary endpoints included radiological , tumor marker and pathological response to neoadjuvant therapy , time to recurrence , patterns of failure , and feasibility of obtaining preoperative core biopsies . Results : Thirty-five of 38 patients ( 92 % ) completed neoadjuvant therapy . Twenty-seven patients underwent tumor resection ( resectability rate 71 % ) , of which 26 initiated adjuvant therapy for a total of 23 patients ( 60.5 % ) who completed all planned therapy . The 18-month survival was 63 % ( 24 patients alive ) . The median overall survival for all 38 patients was 27.2 months ( 95 % confidence interval : 17–NA ) and the median disease-specific survival was 30.6 months ( 95 % confidence interval : 19–NA ) . Conclusions : This study met its endpoint and provided a signal suggesting that exploration of neoadjuvant systemic therapy is worthy of further investigation in resectable pancreas adenocarcinoma . Improved patient selection and more active systemic regimens are key . Clinical trials identification : NCT00536874 Background : Pancreatic cancer ranks as the fourth leading cause of cancer death in the United States with 5-year survival ranging from 1 % to 5 % . Positron emission tomography ( PET ) is a metabolic imaging system that is widely used for the initial staging of cancer and detecting residual disease after treatment . There are limited data , however , on the use of this molecular imaging technique to assess early tumor response after treatment in pancreatic cancer . Methods : The objective of the study was to explore the relationship of early treatment response using the 18F-fluorodeoxyglucose ( FDG ) PET with surgical outcome and overall survival in patients with locally advanced pancreatic cancer .  FDG-PET measurements of maximum st and ardized uptake value and kinetic parameters were compared with the clinical outcome . Results : Twenty patients were enrolled in the study evaluating neoadjuvant induction chemotherapy followed by concurrent chemoradiotherapy ( chemo-RT ) for locally advanced pancreatic cancer . All 20 patients had pre study PET scans and a total of fifty PET scans were performed . Among patients who were PET responders ( ≥50 % decrease in st and ardized uptake value after cycle 1 ) , 100 % ( 2/2 ) had complete surgical resection . Only 6 % ( 1/16 ) had surgical resection in the PET nonresponders ( < 50 % decrease ) . Two patients did not have the second PET scan because of clinical progression or treatment toxicity . Mean survival was 23.2 months for PET responders and 11.3 months for nonresponders ( P = 0.234 ) . Similar differences in survival were also noted when response was measured using Patlak analysis . Conclusions : FDG-PET can aid in monitoring the clinical outcome of patients with locally advanced pancreatic cancer treated with neoadjuvant chemo-RT . FDG-PET may be used to aid patients who could have complete surgical resection as well as prognosticate patients ' survival BACKGROUND / AIM The aim of this study was to investigate the safety and feasibility of neoadjuvant nab-paclitaxel plus gemcitabine therapy for patients with borderline resectable pancreatic carcinoma ( BRPC ) . PATIENTS AND METHODS The study was a prospect i ve single-center phase I trial for patients with BRPC . The primary endpoint was the toxicity , and secondary endpoints were the resection rate , the R0 resection rate and quality of life ( QOL ) regarding the peripheral sensory neuropathy ( PSN ) . This trial was registered on the UMIN Clinical Trials Registry ( UMIN000018382 ) and on Clinical Trials.gov ( NCT02506803 ) . RESULTS The overall rate of any grade and grade 3 - 4 events ( CTCAE ver . 4.0 criteria ) were 100 % and 90 % . The majority of these adverse events represented expected neutropenia . The resection and R0 resection rates were 80 % and 70 % , respectively . CONCLUSION We found that neoadjuvant nab-paclitaxel plus gemcitabine therapy was safe and feasible without stringent selection of patients with BRPC BACKGROUND To determine the safety and efficacy of neoadjuvant gemcitabine/capecitabine followed by surgery for the treatment of locally advanced pancreatic adenocarcinoma ( LAPC ) . METHODS Patients with histologically confirmed LAPC were given 3 - 6 cycles of fixed-dose rate gemcitabine/capecitabine every 3 weeks . At the end of chemotherapy , patients were restaged and underwent surgery if the disease was not classified as unresectable . Our institutional criteria were used to classify respectability , which was recategorized on the basis of National Comprehensive Cancer Network ( NCCN ) criteria retroactively . The primary end point was rate of microscopic curative resection . RESULTS Forty-three eligible patients ( 18 with borderline resectable disease and 25 with unresectable disease on the basis of NCCN criteria ) were enrolled . The radiologic response rate was 18.6 % . Grade three or worse adverse events were mainly h and -foot syndrome ( 11 % ) , and there were no grade four adverse events . Surgery was performed in 17 patients ( 39.5 % ) ; pathologic curative resection ( R0 ) was achieved in 14 patients ( 32.5 % ) among total 43 patients , and 82.3 % ( 14/17 ) among the 17 resected patients . With 43-month follow-up , the median overall was 16.6 months with a median progression-free survival of 10.0 months . Median overall survival was 23.1 months in patients who underwent surgery and 13.2 months in patients who could not complete the surgery ( P = .017 ) . CONCLUSION A subset of patients with borderline or unresectable pancreatic cancer could be performed curative tumor resection after neoadjuvant chemotherapy . Some patients might be benefit on survival from neoadjuvant chemotherapy after surgical resection PURPOSE : In the current study we examined the ability of diffusion MRI ( dMRI ) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation . METHODS : We performed a prospect i ve pilot study of dMRI in patients with resectable pancreatic cancer . Patients underwent dMRI prior to neoadjuvant chemoradiation . Surgical specimens were grade d according to the percent tumor cell destruction . Apparent diffusion coefficient ( ADC ) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values . The primary objective of the study was to correlate ADC parameters with pathologic and CT response . RESULTS : Ten of the 12 patients enrolled on the study completed chemoradiation  and had surgery . Three were found to be unresectable at the time of surgery and no specimen was obtained . Out of the 7 patients who underwent pancreaticoduodenectomy  , 3 had a grade III histopathologic response ( > 90 % tumor cell destruction ) , 2 had a grade IIB response ( 51 % to 90 % tumor cell destruction ) , 1 had a grade IIA response ( 11 % to 50 % tumor cell destruction ) , and 1 had a grade I response ( > 90 % viable tumor ) . Median survival for patients with a grade III response , grade I-II response , and unresectable disease were 25.6 , 18.7 , and 6.1 months , respectively . There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 ( P = .001 ) . Mean pre-treatment ADC was 161 × 10− 5 mm2/s ( n = 3 ) in responding patients ( > 90 % tumor cell destruction ) compared to 125 × 10− 5 mm2/s ( n = 4 ) in non-responding patients ( > 10 % viable tumor ) . CT imaging showed no significant change in tumor size in responders or non-responders . CONCLUSIONS : dMRI may be useful to predict response to chemoradiation in pancreatic cancer . In our study , tumors with a low ADC mean value at baseline responded poorly to st and ard chemoradiation and would be c and i date s for intensified therapy The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells . From quite early in the history of radiation therapy , it was apparent that there were striking differences in effects in the panoply of normal tissues . Although there was early appreciation of some late effects in normal tissues , often not predicted by acute reactions , only in recent years has there been full documentation of the slow and progressive increase in severity of late damage . Pathophysiological mechanisms of acute and late radiation effects are better understood today ( 2 ) , but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae . The work of Stone ( 3 ) is a classic example of unanticipated late effects , which result ed from irradiation with ‘ fast neutrons .  Acute reactions were moderate and tolerable , but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades . The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in  fast neutron therapy  and  Radiation Therapy Oncology Group ( RTOG ) staff . In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG . Recognizing the results of Stone , this committee , led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy . Investigators from the European Organization for Research and Treatment of Cancer ( EORTC ) , led by William Duncan of the Western General Hospital of Edinburgh , wished to have common toxicity criteria in anticipation of joint studies . RTOG Protocol 7929 , an international registry of patients treated with heavy particles , was started in 1980 . At the annual meetings of the international participants in particle studies , there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity , but no publications document these efforts . The first prospect i ve trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001 , a study of fast neutron therapy for malignant tumors arising in salivary gl and s. Although the RTOG began to use these criteria in reporting  toxicity  in patients enrolled in all studies from 198 1 ( beginning with RTOG Protocol 8 115 ) , the criteria only became a published part of protocol s in 1983 . At that time , statistical methods began to be used , which presented time-adjusted estimates of late effects , the rationale for which was described by Cox ( 1 ) . It is now considered st and ard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival . The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria . The National Cancer Institute promulgated st and ard toxicity criteria in 1990 , but late effects were not considered . An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the St and ard for Breast Conservation Treatment . The current RTOG Acute  Radiation Morbidity Scoring Criteria are presented in Table 1 . The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2 . In both tables , 0 means an absence of radiation effects and 5 means the effects led to death . The PURPOSE A r and omized phase II trial ( E1200 ) was design ed to assess toxicities and surgical resection rates in two neoadjuvant gemcitabine-based chemoradiation regimens in patients with borderline resectable pancreatic cancer . The trial was terminated early due to poor accrual . PATIENTS AND METHODS Patients with borderline resectable adenocarcinomas of the pancreas were enrolled . Arm A patients ( n = 10 ) received gemcitabine 500 mg/m(2 ) IV weekly for 6 weeks , with radiation to 50.4 Gy followed by surgical resection . Arm B patients ( n = 11 ) received preoperative gemcitabine 175 mg/m(2 ) on days 1 , 5 , 29 , and 33 , cisplatin 20 mg/m(2 ) on days 1 - 5 and 29 - 32 , 5-FU 600 mg/m(2 ) on days 1 - 5 and 29 - 32 , followed by radiation with continuous infusion 5-FU 225 mg/m(2 ) for 6 weeks . All patients received adjuvant gemcitabine 1,000 mg/m(2 ) weekly x 3 for five cycles . RESULTS Three patients in arm A , and two patients in arm B were resected . Hematologic toxicity was comparable between the two arms except more patients in arm B developed grade 3 or 4 thrombocytopenia than those in arm A. Arm B had fewer grade 1 - 2 GI toxicities although more patients ( 45 % ) experienced grade 3 - 4 GI toxicity . CONCLUSIONS This phase II trial showed that both regimens were tolerable , and resectability and survival were comparable to previous studies BACKGROUND Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance . There is a strong rationale for a neoadjuvant approach , since a relevant percentage of pancreatic cancer patients present with non-metastatic but locally advanced disease . The objective of the present study was to assess the effect of neoadjuvant chemoradiation therapy ( NACRT ) on tumor response , down staging and resection , toxicity and any survival advantage . MATERIAL S AND METHODS A prospect i ve pilot study was carried out from January 2009 to June 2011 in which 15 patients of locally advanced unresectable pancreatic cancer were included . All patients were treated with NACRT protocol with oral Capecitabine and 3D conformal radiotherapy ( 3DCRT ) of 30 Gy in 10 fractions . The patients were restaged 3 to 4 weeks after the completion of NACRT and explored for resection . RESULTS Out of 15 patients , fourteen were evaluable . Four patients underwent surgery , 5 had partial response but remained unresectable , 2 patients had stable disease and 3 had progressive disease . Most of the toxicities were slight and were in grade 1 to 2 . None of the patients developed grade 3 or 4 gastrointestinal or hematological toxicity . The median survival was 15 months for resected patients and 8.6 months for unresected patients , respectively . The 2 year actuarial overall survival was 34.6 % . CONCLUSION All patients with locally unresectable pancreatic cancer should be offered chemoradiation therapy , in hopes of down staging the tumor for possible resection and achieving higher survival PURPOSE To assess the safety and efficacy of a new neoadjuvant chemoradiation ( CRT ) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body . PATIENTS AND METHODS 34 patients with histologically-confirmed resectable pancreatic adenocarcinoma were included in this prospect i ve two-center phase II study . Radiotherapy was delivered at the dose of 45 Gy in 25 fractions of 1.8 Gy per fractions , 5 days/week , over 5 weeks . Docetaxel was administered as a 1-h intravenous ( IV ) infusion repeated every week during 5 weeks . The dose was 30 mg/m(2)/week . All patients were restaged after completion of CRT . RESULTS Tumor progression was documented in 11 patients ( 32 % ) , stable disease was documented in 20 patients ( 59 % ) , and partial remission was documented in 3 patients ( 9 % ) . 23 patients still with local disease at restaging underwent explorative laparotomy . Of this , 17 patients ( 50 % ) had a curative pancreaticoduodenectomy with lymphadenectomy . Morbidity and mortality rates were 29 % and 0 % , respectively . Three patients ( 17 % ) had complete histological responses and 5 patients had minimal residual disease . All resected patients ( n = 17 ) underwent R0 resection . The median and five-year survival times for the resected patients were 32 months and 41 % , respectively . Among the resected patients , ten ( 59 % ) died as a result of recurrent pancreatic cancer without local tumor bed recurrence . CONCLUSIONS Neoadjuvant docetaxel-based chemoradiation is well-tolerated . Resected patients had a prolonged survival time . Further studies are needed to confirm our findings and determine the role of such a neoadjuvant approach
Abstract There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer ( PC ) .
However , study results have varied significantly .
In this study , a systematic review and meta‐ analysis of prospect i ve studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC .