Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Survival after combined modality therapy for pancreatic cancer. Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations. Phase II study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations. Unresectable Locally Advanced Pancreatic Cancer: A Multimodal Treatment Using Neoadjuvant Chemoradiotherapy (Gemcitabine Plus Stereotactic Radiosurgery) and Subsequent Surgical Exploration Guidelines for Perioperative Care for Pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS®) Society Recommendations Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. Role of neoadjuvant concurrent chemoradiation in locally advanced unresectable pancreatic cancer: a feasibility study at tertiary care centre. Phase II trial of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer Evaluating the Impact of a Single-Day Multidisciplinary Clinic on the Management of Pancreatic Cancer Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Regional versus systemic chemotherapy for advanced pancreatic cancer: a randomized study. Quality of life after adjuvant intra‐arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer Regional Targeting Chemoimmunotherapy in Patients Undergoing Pancreatic Resection in an Advanced Stage of Their Disease: A Prospective Randomized Study Combined intraoperative radiation and perioperative chemotherapy for unresectable cancers of the pancreas. Locally Advanced Pancreatic Head Cancer: Margin-Positive Resection or Bypass?
PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer . METHODS American Society of Clinical Oncology convened an Expert Panel of medical oncology , radiation oncology , surgical oncology , gastroenterology , palliative care , and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015 . Outcomes included overall survival , disease-free survival , progression-free survival , and adverse events . RESULTS Twenty-six r and omized controlled trials met the systematic review criteria . RECOMMENDATIONS A multiphase computed tomography scan of the chest , abdomen , and pelvis should be performed . Baseline performance status and comorbidity profile should be evaluated . The goals of care , patient preferences , psychological status , support systems , and symptoms should guide decisions for treatments . A palliative care referral should occur at first visit . Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile . There is no clear evidence to support one regimen over another . The gemcitabine-based combinations and treatments recommended in the metastatic setting ( eg , fluorouracil , leucovorin , irinotecan , and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel ) have not been evaluated in r and omized controlled trials involving locally advanced , unresectable pancreatic cancer . If there is local disease progression after induction chemotherapy , without metastasis , then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile . If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities , radiation therapy may be offered as an alternative . Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline . Follow-up visits every 3 to 4 months are recommended . Additional information is available at www.asco.org/ guidelines /LAPC and www.asco.org/ guidelines /MetPC and www.asco.org/ guidelines wiki Twenty consecutive patients with unresectable , locally advanced pancreatic cancer were treated with split courses of radiotherapy ( RT ) and simultaneous multidrug chemotherapy consisting of 5 fluorouracil , continuous infusion , streptozotocin , and cisplatin . A separate , retrospective study identified a group of 28 contemporary patients with less advanced pancreatic cancers , all of which were successfully resected . The survival rate of the two groups were similar over the first 2 years , although it initially favored the unresectable group . This pattern of survival among patients treated with combined modality therapy provides a basis for new studies . At the two clinical extremes , these include treatment of unresectable tumors previously considered ineligible for this treatment and initial treatment before resection of stage I tumors 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 PURPOSE S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer . The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer . METHODS AND MATERIAL S Patients with histopathologically proven , unresectable , locally advanced pancreatic cancer were eligible .  Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks . S-1 was administered orally twice a day at a dose of 80 mg/m(2)/day from day 1 to 14 and 22 to 35 . Two weeks after the completion of chemoradiotherapy , maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression . RESULTS Thirty-four patients were enrolled in this study . The most common Grade 3 toxicities during chemoradiotherapy were anorexia ( 24 % ) and nausea ( 12 % ) . The overall response rate was 41 % ( 95 % confidence interval , 25%-58 % ) and overall disease control rate ( partial response plus stable disease ) was 97 % . More than 50 % decrease in serum CA 19 - 9 was seen in 27 of 29 evaluable patients ( 93 % ) . The median progression-free survival was 8.7 months . The median overall survival and 1-year survival rate were 16.8 months and 70.6 % , respectively . CONCLUSIONS Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer . This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion BACKGROUND & AIMS Protocol s for enhanced recovery provide comprehensive and evidence -based guidelines for best perioperative care . Protocol implementation may reduce complication rates and enhance functional recovery and , as a result of this , also reduce length-of-stay in hospital . There is no comprehensive framework available for pancreaticoduodenectomy . METHODS An international working group constructed within the Enhanced Recovery After Surgery ( ERAS ® ) Society constructed a comprehensive and evidence -based framework for best perioperative care for pancreaticoduodenectomy patients . Data were retrieved from st and ard data bases and personal archives . Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group . The quality of evidence was rated " high " , " moderate " , " low " or " very low " . Recommendations were grade d as " strong " or " weak " . RESULTS Comprehensive guidelines are presented . Available evidence is summarised and recommendations given for 27 care items . The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations . CONCLUSIONS The present evidence -based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy . A unified protocol allows for comparison between centres and across national borders . It facilitates multi-institutional prospect i ve cohort registries and adequately powered r and omised trials 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 Background Protocol s for enhanced recovery provide comprehensive and evidence -based guidelines for best perioperative care . Protocol implementation may reduce complication rates and enhance functional recovery and , as a result of this , also reduce length-of-stay in hospital . There is no comprehensive framework available for pancreaticoduodenectomy . Methods An international working group constructed within the Enhanced Recovery After Surgery ( ERAS ® ) Society constructed a comprehensive and evidence -based framework for best perioperative care for pancreaticoduodenectomy patients . Data were retrieved from st and ard data bases and personal archives . Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group . The quality of evidence was rated “ high ” , “ moderate ” , “ low ” or “ very low ” . Recommendations were grade d as “ strong ” or “ weak ” . Results Comprehensive guidelines are presented . Available evidence is summarised and recommendations given for 27 care items . The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations . Conclusions The present evidence -based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy . A unified protocol allows for comparison between centres and across national borders . It facilitates multi-institutional prospect i ve cohort registries and adequately powered r and omised trials R and omized trials of the Gastrointestinal Tumor Study Group have previously demonstrated enhanced survival of patients with locally unresectable pancreatic cancer treated with  5-fluorouracil in combination with radiation therapy compared with that of patients treated with radiation therapy alone  . The present study compared the survival of patients treated with  multidrug chemotherapy [ streptozocin , mitomycin , and 5-fluorouracil ( SMF ) ] versus radiation combined with 5-fluorouracil followed by the same three-drug SMF combination . In 43 patients r and omly allocated between these two arms , an improved median survival for the combined-modality therapy ( 42 weeks ) compared with chemotherapy alone ( 32 weeks ) was demonstrated . Overall survival following this combined-modality treatment program ( 41 % at 1 year ) was significantly superior to that following SMF chemotherapy alone ( 19 % at 1 year ) , by a two-tailed log rank test ( P less than .02 ) . Serial studies of the Gastrointestinal Tumor Study Group with patients with locally unresectable pancreatic adenocarcinoma have shown that combined-modality therapy is superior to either optimal radiotherapy or chemotherapy alone 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 S-1 has a favorable effect in unresectable pancreatic cancer and a potential radiosensitizer . In addition , daily oral administration of S-1 is more convenient than continuous infusion of 5-fluorouracil . This study was design ed to evaluate the efficacy and safety of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer . Methods Eligibility criteria were histologically proven pancreatic adenocarcinoma , locally advanced disease , and no previous treatment .  S-1 was administered orally at a dose of 40 mg/m2 twice daily from day 1 to 14 and from day 22 to 35 , and concurrent radiotherapy ( a total dose of 50.4 Gy ) was delivered in 28 fractions . One month after treatment completion , tumor response was evaluated by computed tomography ( CT ) . Results A total of 25 patients were evaluable for efficacy and toxicity on the basis of the intention-to-treat analysis . The response rate and disease control rate were 24.0 and 68.0 % , respectively . There was no treatment-related death or grade 4 toxicity . The most common grade 3 hematologic and non-hematologic toxicities were thrombocytopenia ( 4.0 % ) and anorexia ( 20 % ) , respectively . All toxicities were tolerable and transient . The median time-to-progression and median overall survival were 6.5 months ( 95 % confidence interval , 4.1–9.0 months ) and 12.9 months ( 95 % confidence interval , 6.7–19.0 months ) , respectively , and the 1-year survival rate was estimated to be 43 % . Conclusions S-1 and concurrent radiotherapy shows favorable efficacy for disease control against locally advanced pancreatic cancer and was well tolerated with no severe toxicities Purpose To evaluate the impact of a multidisciplinary clinic on the clinical care recommendations of patients with pancreatic cancer compared with the recommendations the patients received prior to review by the multidisciplinary tumor board . Methods The records of 203 consecutive patients referred to the Johns Hopkins pancreatic multidisciplinary clinic were prospect ively collected from November 2006 to October 2007 .  Cross-sectional imaging , pathology , and medical history were evaluated by a panel of medical/radiation oncologists , surgical oncologists , pathologists , diagnostic radiologists , and geneticists . Alterations in treatment recommendations between the outside institution and the multidisciplinary clinic were recorded and compared . Results On presentation , the outside computed tomography ( CT ) report described locally advanced/unresectable disease ( 34.9 % ) , metastatic disease ( 17.7 % ) , and locally advanced disease with metastasis ( 1.1 % ) . On review of su bmi tted imaging and imaging performed at Hopkins , 38 out of 203 ( 18.7 % ) patients had a change in the status of their clinical stage . Review of the histological slides by dedicated pancreatic pathologists result ed in changes in the interpretation for 7 of 203 patients ( 3.4 % ) . Overall , 48 out of 203 ( 23.6 % ) patients had a change in their recommended management based on clinical review of their case by the multidisciplinary tumor board . Enrollment into the National Familial Pancreas Tumor Registry increased from 52 out of 106 ( 49.2 % ) patients in 2005 to 158 out of 203 ( 77.8 % ) with initiation of the multidisciplinary clinic . Conclusion The single-day pancreatic multidisciplinary clinic provided a comprehensive and coordinated evaluation of patients that led to changes in therapeutic recommendations in close to one-quarter of patients PURPOSE To determine the feasibility and toxicity of delivering stereotactic radiosurgery to patients with locally advanced pancreatic cancer . METHODS AND MATERIAL S Patients with Eastern Cooperative Oncology Group performance status < or=2 and locally advanced pancreatic cancer were enrolled on this Phase I dose escalation study . Patients received a single fraction of radiosurgery consisting of either 15 Gy , 20 Gy , or 25 Gy to the primary tumor . Acute gastrointestinal toxicity was scored according to the Radiation Therapy Oncology Group criteria . Response to treatment was determined by serial high-resolution computed tomography scanning . RESULTS Fifteen patients were treated at 3 dose levels ( 3 patients received 15 Gy , 5 patients received 20 Gy , and 7 patients received 25 Gy ) . At these doses , no Grade 3 or higher acute gastrointestinal toxicity was observed . This trial was stopped before any dose-limiting toxicity was reached , because the clinical objective of local control was achieved in all 6 evaluable patients treated at 25 Gy . CONCLUSIONS It is feasible to deliver stereotactic radiosurgery to patients with locally advanced pancreatic cancer . The recommended dose to achieve local control without significant acute gastrointestinal toxicity is 25 Gy BACKGROUND / AIMS In an attempt to improve treatment protocol s for advanced pancreatic cancer , the value of regional chemotherapy compared with systemic chemotherapy was investigated in this r and omized study . METHODOLOGY Fourteen patients with advanced non-resectable pancreatic adenocarcinoma were r and omized receiving either systemic chemotherapy with mitomycin , mitoxanthrone and cisplatin ( 5pts . ) or celiac axis infusion regional chemotherapy with SpherexR microembolization . In the systemic group one patient was stage III , four patients were stage IV , in the intraarterial group two patients were specified stage III and seven were stage IV . RESULTS In the systemic group one stable disease and four progressive diseases were noted , in the regional group two stable diseases and seven partial responses were noted . Median survival was 11 weeks in the systemically treated patients versus 33 weeks in the patients treated with intraarterial infusion ( p=0.001 ) . One patient became resectable ( R0 ) . CONCLUSIONS Performance status improved during regional chemotherapy whilst it steadily decreased in the patients treated systemically . The study was terminated at that point Adjuvant therapies for pancreatic and periampullary cancer reportedly achieve only a marginal survival benefit . In this r and omized controlled trial , 120 patients with resected pancreatic or periampullary cancer received either adjuvant celiac axis infusion chemotherapy combined with radiotherapy ( CAI/RT ) or no adjuvant treatment . The objective of the study was to compare the quality of life ( QoL ) in patients who received CAI/RT after pancreatoduodenectomy with the QoL in patients who did not receive adjuvant treatment Purpose To evaluate in a prospect i ve r and omized study the long-term results of adjuvant locoregional chemoimmunotherapy in a number of patients with stage III pancreatic duct cancer who underwent pancreatic resection between November 1993 and October 2000 . Methods One hundred twenty-eight patients were divided into three groups . Group A ( n = 40 ) patients had surgical resection alone . Group B ( n = 45 ) patients had , using a side arterial branch of the jejunal artery , an arterial catheter advanced under fluoroscopic control into the superior mesenteric artery . Group B patients also received adjuvant chemotherapy . Group C ( n = 43 ) patients had the same kind of arterial catheter and received as an adjuvant treatment locoregional chemoimmunotherapy . During the initial surgical exploration , all patients underwent pancreatic resection . Pancreatic resection involved a st and ard technique of extended duodenopancreatectomy with regional lymphadenectomy and was carried out in all patients by the first author . At the end of intervention , all patients were r and omly assigned to the above-mentioned groups . R and omization was based mainly on histologic evidence of the stage of the disease . Results The 2- and 5-year survival rates were 29 % and 0 % for group A , 52 % and 10 % for group B , and 65 % and 18 % for group C. The respective percentages for disease-free survival were 20 % and 0 % for group A , 35 % and 7 % for group B , and 58 % and 11 % for group C. Since statistical differences among groups were observed from the second and third years , the study was interrupted early for ethical reasons . Conclusions When applied regionally , combined chemoimmunotherapy is simple , safe , and effective . This type of therapy offers substantial advantages in terms of prolonging overall survival and improving disease-free survival compared to surgical resection alone or to surgical resection and adjuvant regional chemotherapy PURPOSE To evaluate the effectiveness of combined intraoperative radiation therapy ( IORT ) and perioperative chemotherapy in the management of unresectable pancreatic cancer . MATERIAL S AND METHODS Forty-nine patients with localized unresectable adenocarcinoma of the pancreas were treated in a multimodality program of initial IORT and perioperative chemotherapy ( fluorouracil [5-FU]/leucovorin ) followed by combined external-beam radiation ( 40 to 55 Gy ) and continued chemotherapy . Patients were evaluated for toxicity , pattern of failure , and survival . The follow-up times of these patients range from a minimum of 12 months to a maximum of 62 months , with a median of 28 months . RESULTS The incidence of perioperative mortality was 0 % . Early postsurgical morbidity ( grade 3/4 ) was observed in seven of 49 patients ( 14 % ) and late treatment-related morbidity ( grade 3/4 ) in eight of 43 patients ( 19 % ) alive beyond 6 months . Morbidity was primarily gastrointestinal ( GI ) , with no hematologic toxicities observed . The median survival time in the total group of patients is 16 months , with a 2-year survival rate of 22 % and a 4-year survival rate of 7 % . Freedom from local progression of disease was achieved in 71 % of patients . CONCLUSION The patients who undergo IORT with electrons and treated with perioperative chemotherapy ( 5-FU leucovorin ) followed by additional external-beam radiation and chemotherapy appear to have improved survival , with few early or late complications . Dose escalation of external-beam radiation and chemotherapy may further improve local control of disease and survival of patients Pancreatic cancer is a highly aggressive disease with poor survival . The only effective therapy offering long-term survival is complete surgical resection . In the setting of nonmetastatic disease , locally advanced tumors constitute a technical challenge to the surgeon and may result in margin-positive resection margins . Few studies have evaluated the implication s of the latter in depth . The aim of this study was to compare the margin-positive situation to palliative bypass procedures and margin-negative resections in terms of perioperative and long-term outcome . By retrospective analysis of prospect ively maintained data from 360 patients operated for pancreatic cancer at our institution , we provide evidence that margin-positive resection still yields a significant survival benefit over palliative bypass procedures . At the same time , perioperative severe morbidity and mortality are not significantly increased . Our observations suggest that pancreatic cancer should be resected whenever technically feasible , including , cases of locally advanced disease
Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile .
There is no clear evidence to support one regimen over another .
PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer .