The Role of Neoadjuvant Therapy in Pancreatic Cancer: A Review

References

• Griffin JF , SmalleySR, JewellWet al. Patterns of failure after curative resection of pancreatic carcinoma. Cancer66(1), 56–61 (1990).
   PubMed Web of Science ®Google Scholar
• Sohn TA , YeoCJ, CameronJLet al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J. Gastrointest. Surg.4(6), 567–579 (2000).
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP , StockenDD, BassiCet al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA304(10), 1073–1081 (2010).
   PubMed Web of Science ®Google Scholar
• Conroy T , DesseigneF, YchouMet al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med.364(19), 1817–1825 (2011).
   PubMed Web of Science ®Google Scholar
• Poplin E , FengY, BerlinJet al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30 mininfusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J. Clin. Oncol.27(23), 3778–3785 (2009).
   PubMed Web of Science ®Google Scholar
• Evans DB , VaradhacharyGR, CraneCHet al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J. Clin. Oncol.26(21), 3496–3502 (2008).
   PubMed Web of Science ®Google Scholar
• Hoffman JP , LipsitzS, PisanskyT, WeeseJL, SolinL, BensonAB3rd. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J. Clin. Oncol.16(1), 317–323 (1998).
   PubMed Web of Science ®Google Scholar
• White RR , HurwitzHI, MorseMAet al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann. Surg. Oncol.8(10), 758–765 (2001).
   PubMed Web of Science ®Google Scholar
• Moutardier V , MagninV, TurriniOet al. Assessment of pathologic response after preoperative chemoradiotherapy and surgery in pancreatic adenocarcinoma. Int. J. Radiat. Oncol. Biol. Phys.60(2), 437–443 (2004).
   PubMed Web of Science ®Google Scholar
• Palmer DH , StockenDD, HewittHet al. A randomized Phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic cancer: gemcitabine alone versus gemcitabine combined with cisplatin. Ann. Surg. Oncol.14(7), 2088–2096 (2007).
   PubMed Web of Science ®Google Scholar
• Piperdi M , McDadeTP, ShimJKet al. A neoadjuvant strategy for pancreatic adenocarcinoma increases the likelihood of receiving all components of care: lessons from a single-institution database. HPB (Oxford)12(3), 204–210 (2009).
   Web of Science ®Google Scholar
• Spitz FR , AbbruzzeseJL, LeeJEet al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J. Clin. Oncol.15(3), 928–937 (1997).
   PubMed Web of Science ®Google Scholar
• Klinkenbijl JH , JeekelJ, SahmoudTet al. 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. Ann. Surg.230(6), 776–782; discussion 782–774 (1999).
   PubMed Web of Science ®Google Scholar
• Oettle H , PostS, NeuhausPet al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA297(3), 267–277 (2007).
   PubMed Web of Science ®Google Scholar
• Gillen S , SchusterT, Meyer Zum BuschenfeldeC, FriessH, KleeffJ. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med.7(4), e1000267 (2010).
   PubMed Web of Science ®Google Scholar
• Varadhachary GR , WolffRA, CraneCHet al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J. Clin. Oncol.26(21), 3487–3495 (2008).
   PubMed Web of Science ®Google Scholar
• Heinrich S , SchaferM, WeberAet al. Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: results of a prospective Phase II trial. Ann. Surg.248(6), 1014–1022 (2008).
   PubMed Web of Science ®Google Scholar
• Le Scodan R , MornexF, GirardNet al. Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Ann. Oncol.20(8), 1387–1396 (2009).
   PubMed Web of Science ®Google Scholar
• Ohigashi H , IshikawaO, EguchiHet al. Feasibility and efficacy of combination therapy with preoperative full-dose gemcitabine, concurrent three-dimensional conformal radiation, surgery, and postoperative liver perfusion chemotherapy for T3-pancreatic cancer. Ann. Surg.250(1), 88–95 (2009).
   PubMed Web of Science ®Google Scholar
• Laurence JM , TranPD, MorarjiK, EslickGD, LamVW, SandroussiC. A systematic review and meta-analysis of survival and surgical outcomes following neoadjuvant chemoradiotherapy for pancreatic cancer. J. Gastrointest. Surg.15(11), 2059–2069 (2011).
   PubMed Web of Science ®Google Scholar
• Hosein PJ , MacintyreJ, KawamuraCet al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer12, 199 (2012).
   PubMed Web of Science ®Google Scholar
• Satoi S , YanagimotoH, ToyokawaHet al. Long-term results of surgical resection after preoperative chemoradiation in patients with pancreatic cancer. Pancreas41(2), 333–335 (2012).
   PubMed Web of Science ®Google Scholar
• Andriulli A , FestaV, BotteriEet al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann. Surg. Oncol.19(5), 1644–1662 (2012).
   PubMed Web of Science ®Google Scholar
• Lee JL , KimSC, KimJHet al. Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Surgery152(5), 851–862 (2012).
   PubMed Web of Science ®Google Scholar
• Abbott DE , TzengCW, MerkowRPet al. The cost–effectiveness of neoadjuvant chemoradiation is superior to a surgery-first approach in the treatment of pancreatic head adenocarcinoma. Ann. Surg. Oncol.20(Suppl. 3), S500–S508 (2013).
   PubMedGoogle Scholar
• Katz MH , PistersPW, EvansDBet al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J. Am. Coll. Surg.206(5), 833–846; discussion 846–838 (2008).
   PubMed Web of Science ®Google Scholar
• Vauthey JN , DixonE. AHPBA/SSO/SSAT Consensus Conference on Resectable and Borderline Resectable Pancreatic Cancer: rationale and overview of the conference. Ann. Surg. Oncol.16(7), 1725–1726 (2009).
   PubMed Web of Science ®Google Scholar
• Katz MH , MarshR, HermanJMet al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann. Surg. Oncol.20(8), 2787–2795 (2013).
   PubMed Web of Science ®Google Scholar
• Clinical trial database: NCT01821612. https://clinicaltrials.gov/ct2/show/NCT01821612.
   Google Scholar
• National, Comprehensive, Cancer, Network. NCCN Guidelines. V 1. 2013 (PancreaticAdenocarcinoma). www.nccn.org/professionals/physician_gls/f_guidelines.asp#site.
   Google Scholar
• House MG , YeoCJ, CameronJLet al. Predicting resectability of periampullary cancer with three-dimensional computed tomography. J. Gastrointest. Surg.8(3), 280–288 (2004).
   PubMed Web of Science ®Google Scholar
• Tran Cao HS , BalachandranA, WangHet al. Radiographic tumor-vein interface as a predictor of intraoperative, pathologic, and oncologic outcomes in resectable and borderline resectable pancreatic cancer. J. Gastrointest. Surg.18(2), 269–278; discussion 278 (2014).
   PubMed Web of Science ®Google Scholar
• Gnerlich JL , LukaSR, DeshpandeADet al. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch. Surg.147(8), 753–760 (2012).
   PubMedGoogle Scholar
• Turrini O , ViretF, Moureau-ZabottoLet al. Neoadjuvant 5 fluorouracil-cisplatin chemoradiation effect on survival in patients with resectable pancreatic head adenocarcinoma: a ten-year single institution experience. Oncology76(6), 413–419 (2009).
   PubMed Web of Science ®Google Scholar
• Evans DB , RichTA, ByrdDRet al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch. Surg.127(11), 1335–1339 (1992).
   PubMed Web of Science ®Google Scholar
• Pisters PW , AbbruzzeseJL, JanjanNAet al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J. Clin. Oncol.16(12), 3843–3850 (1998).
   PubMed Web of Science ®Google Scholar
• Yeung RS , WeeseJL, HoffmanJPet al. Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A Phase II study. Cancer72(7), 2124–2133 (1993).
   PubMed Web of Science ®Google Scholar
• Magnin V , MoutardierV, GiovanniniMHet al. Neoadjuvant preoperative chemoradiation in patients with pancreatic cancer. Int. J. Radiat. Oncol. Biol. Phys.55(5), 1300–1304 (2003).
   PubMed Web of Science ®Google Scholar
• Moutardier V , GiovanniniM, LelongBet al. A Phase II single institutional experience with preoperative radiochemotherapy in pancreatic adenocarcinoma. Eur. J. Surg. Oncol.28(5), 531–539 (2002).
   PubMedGoogle Scholar
• Burris HA 3rd , MooreMJ, AndersenJet al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol.15(6), 2403–2413 (1997).
   PubMed Web of Science ®Google Scholar
• Lawrence TS , EisbruchA, ShewachDS. Gemcitabine-mediated radiosensitization. Semin. Oncol.24(2 Suppl. 7), S7-24–S7-28 (1997).
   Web of Science ®Google Scholar
• Talamonti MS , SmallWJr, MulcahyMFet al. A multi-institutional Phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann. Surg. Oncol.13(2), 150–158 (2006).
   PubMed Web of Science ®Google Scholar
• Pisters PW , WolffRA, JanjanNAet al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J. Clin. Oncol.20(10), 2537–2544 (2002).
   PubMed Web of Science ®Google Scholar
• Breslin TM , HessKR, HarbisonDBet al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann. Surg. Oncol.8(2), 123–132 (2001).
   PubMed Web of Science ®Google Scholar
• Greer SE , PipasJM, SuttonJEet al. Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma. J. Am. Coll. Surg.206(3), 451–457 (2008).
   PubMed Web of Science ®Google Scholar
• Papalezova KT , TylerDS, BlazerDG3rdet al. Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer? J. Surg. Oncol. 106(1), 111–118 (2012).
   PubMed Web of Science ®Google Scholar
• Artinyan A , AnayaDA, MckenzieS, EllenhornJD, KimJ. Neoadjuvant therapy is associated with improved survival in resectable pancreatic adenocarcinoma. Cancer117(10), 2044–2049 (2011).
   PubMed Web of Science ®Google Scholar
• Van Buren G 2nd , RamanathanRK, KrasinskasAMet al. Phase II study of induction fixed-dose rate gemcitabine and bevacizumab followed by 30 Gy radiotherapy as preoperative treatment for potentially resectable pancreatic adenocarcinoma. Ann. Surg. Oncol.20(12), 3787–3793 (2013).
   PubMed Web of Science ®Google Scholar
• Motoi F , UnnoM, TakahashiHet al. Influence of preoperative anti-cancer therapy on resectability and perioperative outcomes in patients with pancreatic cancer: project study by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J. Hepatobiliary Pancreat. Sci.21(2), 148–158 (2013).
   PubMed Web of Science ®Google Scholar
• Heinrich S , PestalozziBC, SchaferMet al. Prospective Phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head. J. Clin. Oncol.26(15), 2526–2531 (2008).
   PubMed Web of Science ®Google Scholar
• Tajima H , OhtaT, KitagawaHet al. Pilot study of neoadjuvant chemotherapy with gemcitabine and oral S-1 for resectable pancreatic cancer. Exp. Ther. Med.3(5), 787–792 (2012).
   PubMed Web of Science ®Google Scholar
• O’reilly EM , PerelshteynA, JarnaginWRet al. A single-arm, nonrandomized Phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann. Surg.260(1), 142–148 (2014).
   PubMed Web of Science ®Google Scholar
• Faris JE , BlaszkowskyLS, McdermottSet al. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist18(5), 543–548 (2013).
   PubMed Web of Science ®Google Scholar
• Turrini O , YchouM, Moureau-ZabottoLet al. Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: new neoadjuvant regimen was safe and provided an interesting pathologic response. Eur. J. Surg. Oncol.36(10), 987–992 (2010).
   PubMed Web of Science ®Google Scholar
• Sho M , AkahoriT, TanakaTet al. Pathological and clinical impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer. J. Hepatobiliary Pancreat. Sci.20(2), 197–205 (2013).
   PubMed Web of Science ®Google Scholar
• Kim EJ , Ben-JosefE, HermanJMet al. A multi-institutional Phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer119(15), 2692–2700 (2013).
   PubMed Web of Science ®Google Scholar
• Pipas JM , ZakiBI, McgowanMMet al. Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Ann. Oncol.23(11), 2820–2827 (2012).
   PubMed Web of Science ®Google Scholar
• Shinoto M , YamadaS, YasudaSet al. Phase 1 trial of preoperative, short-course carbon-ion radiotherapy for patients with resectable pancreatic cancer. Cancer119(1), 45–51 (2013).
   PubMed Web of Science ®Google Scholar
• Willett CG , LewandrowskiK, WarshawAL, EfirdJ, ComptonCC. Resection margins in carcinoma of the head of the pancreas. Implications for radiation therapy. Ann. Surg.217(2), 144–148 (1993).
   PubMed Web of Science ®Google Scholar
• Chandler NM , CaneteJJ, StuartKE, CalleryMP. Preoperative chemoradiation in resectable pancreatic cancer. J. Hepatobiliary Pancreat. Surg.10(1), 61–66 (2003).
   PubMedGoogle Scholar
• Evans DB . Preoperative chemoradiation for resectable and locally advanced adenocarcinoma of the pancreas. J. Gastrointest. Surg.5(1), 2–5 (2001).
   PubMed Web of Science ®Google Scholar
• Russo S , ChabotJ, SaifMW. Resectable pancreatic cancer: is surgery the best first step?JOP13(2), 151–154 (2012).
   PubMedGoogle Scholar
• Landry J , CatalanoPJ, StaleyCet al. 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. J. Surg. Oncol.101(7), 587–592 (2010).
   PubMed Web of Science ®Google Scholar
• Massucco P , CapussottiL, MagninoAet al. Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of perioperative outcome and survival. Ann. Surg. Oncol.13(9), 1201–1208 (2006).
   PubMed Web of Science ®Google Scholar
• Mehta VK , PoenJC, FordJMet al. Protracted venous infusion 5-fluorouracil with concomitant radiotherapy compared with bolus 5-fluorouracil for unresectable pancreatic cancer. Am. J. Clin. Oncol.24(2), 155–159 (2001).
   PubMed Web of Science ®Google Scholar
• Patel M , HoffeS, MalafaMet al. Neoadjuvant GTX chemotherapy and IMRT-based chemoradiation for borderline resectable pancreatic cancer. J. Surg. Oncol.104(2), 155–161 (2011).
   PubMed Web of Science ®Google Scholar
• Small W Jr , BerlinJ, FreedmanGMet al. Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter Phase II trial. J. Clin. Oncol.26(6), 942–947 (2008).
   PubMed Web of Science ®Google Scholar
• Stokes JB , NolanNJ, StelowEBet al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann. Surg. Oncol.18(3), 619–627 (2011).
   PubMed Web of Science ®Google Scholar
• Huguet F , AndreT, HammelPet al. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR Phase II and III studies. J. Clin. Oncol.25(3), 326–331 (2007).
   PubMed Web of Science ®Google Scholar
• Krishnan S , RanaV, JanjanNAet al. Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy. Cancer110(1), 47–55 (2007).
   PubMed Web of Science ®Google Scholar
• Leone F , GattiM, MassuccoPet al. Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience. Cancer119(2), 277–284 (2013).
   PubMed Web of Science ®Google Scholar
• Mukherjee S , HurtCN, BridgewaterJet al. Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, Phase 2 trial. Lancet Oncol.14(4), 317–326 (2013).
   PubMed Web of Science ®Google Scholar
• Polistina F , CostantinG, CasamassimaFet al. Unresectable locally advanced pancreatic cancer: a multimodal treatment using neoadjuvant chemoradiotherapy (gemcitabine plus stereotactic radiosurgery) and subsequent surgical exploration. Ann. Surg. Oncol.17(8), 2092–2101 (2010).
   PubMed Web of Science ®Google Scholar
• Sahora K , KuehrerI, EisenhutAet al. NeoGemOx: gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery149(3), 311–320 (2011).
   PubMed Web of Science ®Google Scholar
• Sahora K , KuehrerI, SchindlM, KoelblingerC, GoetzingerP, GnantM. NeoGemTax: gemcitabine and docetaxel as neoadjuvant treatment for locally advanced nonmetastasized pancreatic cancer. World J. Surg.35(7), 1580–1589 (2011).
   PubMed Web of Science ®Google Scholar
• Shinchi H , TakaoS, NomaHet al. Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer. Int. J. Radiat. Oncol. Biol. Phys.53(1), 146–150 (2002).
   PubMed Web of Science ®Google Scholar
• Tinkl D , GrabenbauerGG, GolcherHet al. Downstaging of pancreatic carcinoma after neoadjuvant chemoradiation. Strahlenther. Onkol.185(9), 557–566 (2009).
   PubMed Web of Science ®Google Scholar
• Katz MH , FlemingJB, BhosalePet al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer118(23), 5749–5756 (2012).
   PubMed Web of Science ®Google Scholar
• Barugola G , PartelliS, CrippaSet al. Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy. Am. J. Surg.203(2), 132–139 (2012).
   PubMed Web of Science ®Google Scholar
• Kang CM , ChungYE, ParkJYet al. Potential contribution of preoperative neoadjuvant concurrent chemoradiation therapy on margin-negative resection in borderline resectable pancreatic cancer. J. Gastrointest. Surg.16(3), 509–517 (2012).
   PubMed Web of Science ®Google Scholar
• Mcclaine RJ , LowyAM, SussmanJJ, SchmulewitzN, GrisellDL, AhmadSA. Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer. HPB (Oxford)12(1), 73–79 (2010).
   PubMed Web of Science ®Google Scholar
• Chuong MD , SpringettGM, FreilichJMet al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated. Int. J. Radiat. Oncol. Biol. Phys.86(3), 516–522 (2013).
   PubMed Web of Science ®Google Scholar
• Christians KK , TsaiS, MahmoudAet al. Neoadjuvant FOLFIRINOX for borderline resectable pancreas cancer: a new treatment paradigm? Oncologist 19(3), 266–274 (2014).
   PubMed Web of Science ®Google Scholar
• Hong TS , RyanDP, BlaszkowskyLSet al. Phase I study of preoperative short-course chemoradiation with proton beam therapy and capecitabine for resectable pancreatic ductal adenocarcinoma of the head. Int. J. Radiat. Oncol. Biol. Phys.79(1), 151–157 (2011).
   PubMed Web of Science ®Google Scholar
• Hong TS , RyanDP, BorgerDRet al. 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. Int. J. Radiat. Oncol. Biol. Phys.89(4), 830–838 (2014).
   PubMed Web of Science ®Google Scholar
• Wo JY , MamonHJ, FerroneCRet al. Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer. Radiother. Oncol.110(1), 160–164 (2014).
   PubMed Web of Science ®Google Scholar
• Clinical trials database: NCT02598349. https://clinicaltrials.gov/ct2/show/NCT02598349.
   Google Scholar
• Chang DT , SchellenbergD, ShenJet al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer115(3), 665–672 (2009).
   PubMed Web of Science ®Google Scholar
• Herman JM , ChangDT, GoodmanKAet al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer121(7), 1128–1137 (2915).
   PubMed Web of Science ®Google Scholar
• Herman JM , ChangDT, GoodmanKAet al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer121(7), 1128–1137 (2015).
   PubMed Web of Science ®Google Scholar
• Boone BA , SteveJ, KrasinskasAMet al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J. Surg. Oncol.108(4), 236–241 (2013).
   PubMed Web of Science ®Google Scholar
• Rosati L , HeJ, MoningiSet al. The role of neoadjuvant stereotactic body radiation therapy in pancreatic cancer. Presented at: American Radium Society 97th Annual Meeting. Kauai, Hawaii, 2–5 May 2015 ( Abstract S021).
   Google Scholar
• Clinical trials database: NCT01926197. https://clinicaltrials.gov/ct2/show/NCT01926197.
   Google Scholar
• Ferrone CR , MarchegianiG, HongTSet al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann. Surg.261(1), 12–17 (2015).
   PubMed Web of Science ®Google Scholar
• Nanda RH , El-RayesB, MaithelSK, LandryJ. Neoadjuvant modified FOLFIRINOX and chemoradiation therapy for locally advanced pancreatic cancer improves resectability. J. Surg. Oncol.111(8), 1028–1034 (2015).
   PubMed Web of Science ®Google Scholar
• Petrelli F , CoinuA, BorgonovoKet al. FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies. Pancreas44(4), 515–521 (2015).
   PubMed Web of Science ®Google Scholar
• White R , LeeC, AnscherMet al. Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann. Surg. Oncol.6(1), 38–45 (1999).
   PubMed Web of Science ®Google Scholar
• Kim HJ , CzischkeK, BrennanMF, ConlonKC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer?J. Gastrointest. Surg.6(5), 763–769 (2002).
   PubMed Web of Science ®Google Scholar
• Assifi MM , LuX, EiblG, ReberHA, LiG, HinesOJ. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of Phase II trials. Surgery150(3), 466–473 (2011).
   PubMed Web of Science ®Google Scholar
• Dudeja V , GreenoEW, WalkerSP, JensenEH. Neoadjuvant chemoradiotherapy for locally advanced pancreas cancer rarely leads to radiological evidence of tumour regression. HPB (Oxford)15(9), 661–667 (2012).
   PubMed Web of Science ®Google Scholar
• Dholakia AS , Hacker-PrietzA, WildATet al. Resection of borderline resectable pancreatic cancer after neoadjuvant chemoradiation does not depend on improved radiographic appearance of tumor-vessel relationships. J. Radiat. Oncol.2(4), 413–425 (2013).
   PubMedGoogle Scholar
• Cassinotto C , MouriesA, LafourcadeJPet al. Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy. Radiology273(1), 108–116 (2014).
   PubMed Web of Science ®Google Scholar
• Dholakia AS , ChaudhryM, LealJPet al. Baseline metabolic tumor volume and total lesion glycolysis are associated with survival outcomes in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy. Int. J. Radiat. Oncol. Biol. Phys.89(3), 539–546 (2014).
   PubMed Web of Science ®Google Scholar
• Tzeng CW , BalachandranA, AhmadMet al. Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB (Oxford)16(5), 430–438 (2013).
   PubMed Web of Science ®Google Scholar
• Tachezy M , GebauerF, PetersenCet al. Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter Phase III study (NCT01900327, DRKS00003893, ISRCTN82191749). BMC Cancer14, 411 (2014).
   PubMed Web of Science ®Google Scholar
• Clinical trials database: NCT01900327. https://clinicaltrials.gov/ct2/show/NCT01900327.
   Google Scholar
• Clinical trials database: NCT01372735. https://clinicaltrials.gov/ct2/show/NCT01372735.
   Google Scholar
• Clinical trials database: NCT01521702. https://clinicaltrials.gov/ct2/show/NCT01521702.
   Google Scholar
• Clinical trials database: NCT01294358. https://clinicaltrials.gov/ct2/show/NCT01470417.
   Google Scholar
• Clinical trials database: NCT01294358. https://clinicaltrials.gov/ct2/show/NCT01294358.
   Google Scholar
• Clinical trials database: NCT01065870. https://clinicaltrials.gov/ct2/show/NCT01065870.
   Google Scholar
• Clinical trials database: NCT00609336. https://clinicaltrials.gov/ct2/show/NCT00609336.
   Google Scholar
• Clinical trials database: NCT01677988. https://clinicaltrials.gov/ct2/show/NCT01677988.
   Google Scholar
• Clinical trials database: NCT00727441. https://clinicaltrials.gov/ct2/show/NCT00727441.
   Google Scholar