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The Effect of Neoadjuvant Chemoradiotherapy in Converting Unresectable and Locally Advanced Pancreatic Adenocarcinoma to Resectable Status: A Systematic Review and Meta-analysis

Articles in Press

Document Type : Review Article(s)

Authors

1 Department of Internal Medicine, School of Medicine, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran

2 School of Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Department of Public Health, Torbat Jam Faculty of Medical Sciences, Torbat Jam, Iran

4 Department of General Surgery, School of Medicine, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran

5 Department of Medical Library and Information Sciences, Educational Development Center, Iran University of Medical Sciences, Tehran, Iran

10.30476/mejc.2026.106444.2266

Abstract

Background: Neoadjuvant chemoradiotherapy (NCRT) is increasingly used in locally advanced unresectable pancreatic adenocarcinoma. In the present study, we systematically evaluated the effects of NCRT on downstaging, resectability, and survival.
Method: A systematic review and meta-analysis of 70 full-text studies published before December 2023 (PubMed, Scopus, and Web of Science) was conducted. Data were extracted independently. Random-effects models were applied with substantial heterogeneity (Cochran’s Q, I²). Subgroup analyses and publication-bias assessments (Egger’s test, funnel plots, trim-and-fill) were conducted (P < 0.05).
Results: The pooled conversion rate from unresectable to resectable disease was 30.6% (95% confidence interval (CI): 28.2–32.2%). Conversion was higher with chemoradiotherapy than with chemotherapy alone (32.5% vs. 22.9%). Tumors in the pancreatic body showed a higher conversion rate than tumors in mixed locations (37.0% vs 29.7%). Overall tumor size reduction was 23% (95% CI: 15–30%), greater with chemoradiotherapy than chemotherapy (25% vs 16.7%). Mean overall survival after neoadjuvant therapy was 17.96 months (95% CI: 16.40–19.52), with no clear difference between regimens. Disease-free survival was 12.97 months (95% CI: 11.22–14.72). The pooled R0 resection rate was 41.7% (95% CI: 33.2–50.2%).
Conclusion: The results of the study indicate that NCRT improves conversion to resection and tumor shrinkage versus chemotherapy alone, particularly for pancreatic body tumors, but does not demonstrate a consistent survival advantage.

Highlights

Bahareh Shateri Amiri (google scholar)

Vahid Rahmanian (google scholar)

 

Keywords

Main Subjects

Please cite this article as: Shateri Amiri B, Mansouri S, Farsinejad N, Rahmanian V, Khosravi Mashizi M, Soleimanpour S. The Effect of Neoadjuvant Chemoradiotherapy in Converting Unresectable and Locally Advanced Pancreatic Adenocarcinoma to Resectable Status: A Systematic Review and Meta-analysis. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.106444.2266.

References
  1. Gueiderikh A, Tarabay A, Abdelouahab M, Smolenschi C, Tanguy ML, Valery M, et al. Pancreatic adenocarcinoma third line systemic treatments: a retrospective cohort study. BMC Cancer. 2024;24(1):272. doi: 10.1186/s12885-024-12016-z. PMID: 38408958; PMCID: PMC10898186.
  2. Orth M, Metzger P, Gerum S, Mayerle J, Schneider G, Belka C, et al. Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches. Radiat Oncol. 2019;14(1):141. doi: 10.1186/s13014-019-1345-6. PMID: 31395068; PMCID: PMC6688256.
  3. Balaban EP, Mangu PB, Yee NS. Locally advanced unresectable pancreatic cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary. J Oncol Pract. 2017;13(4):265-9. doi: 10.1200/JOP.2016.017376. PMID: 28399382.
  4. Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267. doi: 10.1371/journal.pmed.1000267. PMID: 20422030; PMCID: PMC2857873.
  5. Heinrich S, Lang H. Neoadjuvant therapy of pancreatic cancer: Definitions and benefits. Int J Mol Sci. 2017;18(8):1622. doi: 10.3390/ijms18081622. PMID: 28933761; PMCID: PMC5578014.
  6. Hank T, Strobel O. Conversion surgery for advanced pancreatic cancer. J Clin Med. 2019;8(11):1945. doi: 10.3390/jcm8111945. PMID: 31718103; PMCID: PMC6912686.
  7. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Systematic reviews of prevalence and incidence. In: Aromataris E, Munn Z, editors. Joanna Briggs Institute Reviewer’s Manual. The Joanna Briggs Institute; 2017.
  8. van Veldhuisen E, Vogel JA, Klompmaker S, Busch OR, van Laarhoven HWM, et al. Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy. HPB (Oxford). 2018;20(7):605-11. doi: 10.1016/j.hpb.2018.01.001. PMID: 29475787.
  9. Wada K, Sano K, Amano H, Miura F, Toyota N, Ito H, et al Biweekly gemcitabine plus S-1 for locally advanced and metastatic pancreatic cancer: a preliminary feasibility study. J Hepatobiliary Pancreat Sci. 2015;22(9):692-8. doi: 10.1002/jhbp.274. PMID: 26136371.
  10. White R, Lee C, Anscher M, Gottfried M, Wolff R, Keogan M, et al. Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann Surg Oncol. 1999;6(1):38-45. doi: 10.1007/s10434-999-0038-z. PMID: 10030414.
  11. Wilkowski R, Thoma M, Schauer R, Wagner A, Heinemann V. Effect of chemoradiotherapy with gemcitabine and cisplatin on locoregional control in patients with primary inoperable pancreatic cancer. World J Surg. 2004;28(10):1011-8. doi: 10.1007/s00268-004-7338-z. PMID: 15573257.
  12. Wilkowski R, Thoma M, Bruns C, Wagner A, Heinemann V. Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP. 2006;7(4):349-60. PMID: 16832132.
  13. Woo SM, Kim MK, Joo J, Yoon KA, Park B, Park SJ, et al. Induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost-intensity modulated radiotherapy with concurrent gemcitabine for locally advanced unresectable pancreatic cancer: Results from a feasibility study. Cancer Res Treat. 2017;49(4):1022-32. doi: 10.4143/crt.2016.495. PMID: 28111423; PMCID: PMC5654154.
  14. Yamada S, Fujii T, Yokoyama Y, Kawashima H, Maeda O, Suzuki K, et al. Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer. Cancer Chemother Pharmacol. 2018;81(5):815-21. doi: 10.1007/s00280-018-3554-3. PMID: 29502139.
  15. Reni M, Cereda S, Balzano G, Passoni P, Rognone A, Zerbi A, et al. Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2009;64(6):1253-9. doi: 10.1007/s00280-009-0995-8. PMID: 19381632.
  16. Turrini O, Viret F, Moureau-Zabotto L, Guiramand J, Moutardier V, Lelong B, et al. Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma. Eur J Surg Oncol. 2009;35(12):1306-11. doi: 10.1016/j.ejso.2009.06.005. PMID: 19576722.
  17. Gillmore R, Laurence V, Raouf S, Tobias J, Blackman G, Meyer T, et al. Chemoradiotherapy with or without induction chemotherapy for locally advanced pancreatic cancer: a UK multi-institutional experience. Clin Oncol (R Coll Radiol). 2010;22(7):564-9. doi: 10.1016/j.clon.2010.05.007. PMID: 20605709.
  18. Mattiucci GC, Morganti AG, Valentini V, Ippolito E, Alfieri S, Antinori A, et al. External beam radiotherapy plus 24-hour continuous infusion of gemcitabine in unresectable pancreatic carcinoma: long-term results of a phase II study. Int J Radiat Oncol Biol Phys. 2010;76(3):831-8. doi: 10.1016/j.ijrobp.2009.02.013. PMID: 19427747.
  19. Polistina F, Costantin G, Casamassima F, Francescon P, Guglielmi R, Panizzoni G, et al. Unresectable locally advanced pancreatic cancer: a multimodal treatment using neoadjuvant chemoradiotherapy (gemcitabine plus stereotactic radiosurgery) and subsequent surgical exploration. Ann Surg Oncol. 2010;17(8):2092-101. doi: 10.1245/s10434-010-1019-y. PMID: 20224860.
  20. Cardenes HR, Moore AM, Johnson CS, Yu M, Helft P, Chiorean EG, et al. A phase II study of gemcitabine in combination with radiation therapy in patients with localized, unresectable, pancreatic cancer: a Hoosier Oncology Group study. Am J Clin Oncol. 2011;34(5):460-5. doi: 10.1097/COC.0b013e3181e9c103. PMID: 20881474.
  21. Sahora K, Kuehrer I, Eisenhut A, Akan B, Koellblinger C, Goetzinger P, et al. NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer. Surgery. 2011;149(3):311-20. doi: 10.1016/j.surg.2010.07.048. PMID: 20817204.
  22. Naumann P, Ottensmeier F, Farnia B, Ben-Josef E, Liermann J, Maier-Hein KH, et al. Radiographic response of vessel involvement and resectability after neoadjuvant chemoradiation in patients with locally advanced pancreatic cancer. Am J Clin Oncol. 2020;43(11):776-83. doi: 10.1097/COC.0000000000000746. PMID: 32815856.
  23. Philip PA, Lacy J, Portales F, Sobrero A, Pazo-Cid R, Manzano Mozo JL, et al. Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study. Lancet Gastroenterol Hepatol. 2020;5(3):285-94. doi: 10.1016/S2468-1253(19)30327-9. PMID: 31953079.
  24. Weniger M, Moir J, Damm M, Maggino L, Kordes M, Rosendahl J, et al; RESPECT-study group. Neoadjuvant therapy in elderly patients receiving FOLFIRINOX or gemcitabine/nab-paclitaxel for borderline resectable or locally advanced pancreatic cancer is feasible and lead to a similar oncological outcome compared to non-aged patients - Results of the RESPECT-Study. Surg Oncol. 2020;35:285-97. doi: 10.1016/j.suronc.2020.08.031. PMID: 32949968.
  25. Weniger M, Moir J, Damm M, Maggino L, Kordes M, Rosendahl J, et al; RESPECT-study group. Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer. Pancreatology. 2020;20(6):1131-8. doi: 10.1016/j.pan.2020.06.012. PMID: 32739267.
  26. Yoo C, Hwang I, Song TJ, Lee SS, Jeong JH, Park DH, et al. FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma. Ther Adv Med Oncol. 2020;12:1758835920953294. doi: 10.1177/1758835920953294. PMID: 32983266; PMCID: PMC7498966.
  27. Arscott WT, Nead KT, Bear A, Venigalla S, Shabason J, Lukens JN, et al. Concurrent nab-paclitaxel and radiotherapy: Novel radiosensitization for borderline resectable or unresectable pancreatic cancer. Am J Clin Oncol. 2021;44(9):469-74. doi: 10.1097/COC.0000000000000854. PMID: 34310350; PMCID: PMC8404955.
  28. Auclin E, Marthey L, Abdallah R, Mas L, Francois E, Saint A, et al. Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort. Br J Cancer. 2021;124(12):1941-8. doi: 10.1038/s41416-021-01341-w. PMID: 33772154; PMCID: PMC8185101.
  29. Fietkau R, Grützmann R, Wittel UA, Croner RS, Jacobasch L, Neumann UP, et al. R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007± trial. Strahlenther Onkol. 2021;197(1):8-18. doi: 10.1007/s00066-020-01680-2. PMID: 32914237; PMCID: PMC7801312.
  30. Fukahori M, Miwa K, Murotani K, Naito Y, Ushijima T, Sakaue T, et al. A phase II study of gemcitabine plus nab-paclitaxel as first-line therapy for locally advanced pancreatic cancer. Medicine (Baltimore). 2021;100(20):e26052. doi: 10.1097/MD.0000000000026052. PMID: 34011119; PMCID: PMC8137062.
  31. Hayuka K, Okuyama H, Murakami A, Okita Y, Nishiuchi T, Okano K, et al. Gemcitabine plus nab-paclitaxel as second-line chemotherapy following FOLFIRINOX in patients with unresectable pancreatic cancer: A single-institution, retrospective analysis. Chemotherapy. 2021;66(3):58-64. doi: 10.1159/000517244. PMID: 34284397.
  32. Kunzmann V, Siveke JT, Algül H, Goekkurt E, Siegler G, Martens U, et al; German Pancreatic Cancer Working Group (AIO-PAK) and NEOLAP investigators. Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2021;6(2):128-38. doi: 10.1016/S2468-1253(20)30330-7. PMID: 33338442.
  33. Takada R, Ikezawa K, Daiku K, Maeda S, Abe Y, Urabe M, et al. The survival benefit of chemoradiotherapy following induction chemotherapy with gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer. Cancers (Basel). 2021;13(18):4733. doi: 10.3390/cancers13184733. PMID: 34572960; PMCID: PMC8470784.
  34. Walma MS, Brada LJ, Patuleia SIS, Blomjous JG, Bollen TL, Bosscha K, et al. Treatment strategies and clinical outcomes in consecutive patients with locally advanced pancreatic cancer: A multicenter prospective cohort. Eur J Surg Oncol. 2021;47(3 Pt B):699-707. doi: 10.1016/j.ejso.2020.11.137. PMID: 33280952.
  35. Botta GP, Huynh TR, Spierling-Bagsic SR, Agelidis A, Schaffer R, Lin R, et al. Neoadjuvant chemotherapy and radiotherapy outcomes in borderline-resectable and locally-advanced pancreatic cancer patients. Cancer Med. 2023;12(7):7713-23. doi: 10.1002/cam4.5523. PMID: 36478411; PMCID: PMC10134275.
  36. Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199. doi: 10.1186/1471-2407-12-199. PMID: 22642850; PMCID: PMC3404979.
  37. Jessup JM, Steele G, Mayer RJ, Posner M, Busse P, Cady B, et al. Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg. 1993;128(5):559-64. doi: 10.1001/archsurg.1993.01420170093014. PMID: 8098206.
  38. Kamachi H, Tsuruga Y, Orimo T, Wakayama K, Shimada S, Nagatsu A, et al. R0 resection for locally advanced pancreatic cancer with low-dose gemcitabine with wide irradiation area as neoadjuvant chemoradiotherapy. In Vivo. 2018;32(5):1183-91. doi: 10.21873/invivo.11362. PMID: 30150442; PMCID: PMC6199618.
  39. Karachaliou GS, Lazarou V, Giannis D, Astras G, Moris D, Petrou A. Initial experience with neoadjuvant FOLFIRINOX as first line therapy for locally advanced pancreatic cancer. J BUON. 2020;25(5):2525-7. PMID: 33277879.
  40. Ke QH, Zhou SQ, Yang JY, Du W, Liang G, Lei Y, et al. S-1 plus gemcitabine chemotherapy followed by concurrent radiotherapy and maintenance therapy with S-1 for unresectable pancreatic cancer. World J Gastroenterol. 2014;20(38):13987-92. doi: 10.3748/wjg.v20.i38.13987. PMID: 25320537; PMCID: PMC4194583.
  41. Dempsey N, Maldonado JC, Loaiza-Bonilla A, Velez M, Carcas L, Dammrich D, et al. Full dose neoadjuvant FOLFIRINOX is associated with prolonged survival in patients with locally advanced pancreatic adenocarcinoma. Pancreatology. 2015;15(6):667-73. doi: 10.1016/j.pan.2015.08.010. PMID: 26412296.
  42. Kim EJ, Ben‐Josef E, Herman JM, Bekaii‐Saab T, Dawson LA, Griffith KA, et al. A multi-institutional phase 2 study of neoadjuvant gemcitabine and oxaliplatin with radiation therapy in patients with pancreatic cancer. Cancer. 2013;119(15):2692-700. doi: 10.1002/cncr.28117. PMID: 23720019; PMCID: PMC4174603.
  43. Kim HJ, Czischke K, Brennan MF, Conlon KC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg. 2002;6(5):763-9. doi: 10.1016/s1091-255x(02)00017-3. PMID: 12399067.
  44. Kondo N, Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakagawa N, et al. A phase 1 study of gemcitabine/nab-paclitaxel/S-1 (GAS) combination neoadjuvant chemotherapy for patients with locally advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2017;79(4):775-81. doi: 10.1007/s00280-017-3274-0. PMID: 28293715.
  45. Lee J, Lee JC, Gromski MA, Kim HW, Kim J, Kim J, et al. Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: A single center experience. Medicine (Baltimore). 2018;97(50):e13592. doi: 10.1097/MD.0000000000013592. PMID: 30558029; PMCID: PMC6320053.
  46. Lee JL, Kim SC, Kim JH, Lee SS, Kim TW, Park DH, et al. Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Surgery. 2012;152(5):851-62. doi: 10.1016/j.surg.2012.03.010. PMID: 22682078.
  47. Leone F, Gatti M, Massucco P, Colombi F, Sperti E, Campanella D, et 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. Cancer. 2013;119(2):277-84. doi: 10.1002/cncr.27736. PMID: 22778019.
  48. Murphy JE, Wo JY, Ryan DP, Clark JW, Jiang W, Yeap BY, et al. Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: A phase 2 clinical trial. JAMA Oncol. 2019;5(7):1020-7. doi: 10.1001/jamaoncol.2019.0892. PMID: 31145418; PMCID: PMC6547247.
  49. Osti MF, Costa AM, Bianciardi F, De Nicolò M, Donato V, Silecchia G, et al. Concomitant radiotherapy with protracted 5-fluorouracil infusion in locally advanced carcinoma of the pancreas: a phase II study. Tumori. 2001;87(6):398-401. doi: 10.1177/030089160108700609. PMID: 11989594.
  50. Passardi A, Scarpi E, Neri E, Parisi E, Ghigi G, Ercolani G, et al. Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for unresectable locally advanced pancreatic cancer: A phase II study. Cancers (Basel). 2019;11(5):663. doi: 10.3390/cancers11050663. Erratum in: Cancers (Basel). 2020;12(1):E178. doi: 10.3390/cancers12010178. PMID: 31086093; PMCID: PMC6562444.
  51. Peterson SL, Husnain M, Pollack T, Pimentel A, Loaiza-Bonilla A, Westendorf-Overley C, et al. Neoadjuvant nab-paclitaxel and gemcitabine in borderline resectable or locally advanced unresectable pancreatic adenocarcinoma in patients who are ineligible for FOLFIRINOX. Anticancer Res. 2018;38(7):4035-9. doi: 10.21873/anticanres.12692. PMID: 29970528; PMCID: PMC9375526.
  52. Pipas JM, Mitchell SE, Barth RJ, Vera-Gimon R, Rathmann J, Meyer LP, et al. Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys. 2001;50(5):1317-22. doi: 10.1016/s0360-3016(01)01580-2. PMID: 11483344.
  53. Pipas JM, Zaki BI, McGowan MM, Tsapakos MJ, Ripple GH, Suriawinata AA, et al. Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma. Ann Oncol. 2012;23(11):2820-7. doi: 10.1093/annonc/mds109. PMID: 22571859; PMCID: PMC3577039.
  54. Pouypoudat C, Buscail E, Cossin S, Cassinotto C, Terrebonne E, Blanc JF, et al. FOLFIRINOX-based neoadjuvant chemoradiotherapy for borderline and locally advanced pancreatic cancer: A pilot study from a tertiary centre. Dig Liver Dis. 2019;51(7):1043-9. doi: 10.1016/j.dld.2019.03.004. PMID: 31000479.
  55. Safran H, Cioffi W, Iannitti D, Mega A, Akerman P. Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma. Front Biosci. 1998;3:E204-6. doi: 10.2741/a378. PMID: 9792903.
  56. Saif MW, Black G, Roy S, Bell D, Russo S, Eloubeidi MA, et al. Phase II study of capecitabine with concomitant radiotherapy for patients with locally advanced pancreatic cancer: up-regulation of thymidine phosphorylase. Cancer J. 2007;13(4):247-56. doi: 10.1097/PPO.0b013e31813c12b8. PMID: 17762760.
  57. Shabason JE, Chen J, Apisarnthanarax S, Damjanov N, Giantonio B, Loaiza-Bonilla A, et al. A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer. Cancer Chemother Pharmacol. 2018;81(3):609-14. doi: 10.1007/s00280-018-3519-6. PMID: 29362902.
  58. Sherman WH, Chu K, Chabot J, Allendorf J, Schrope BA, Hecht E, et al. Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma. Cancer. 2015;121(5):673-80. doi: 10.1002/cncr.29112. PMID: 25492104.
  59. Small Jr W, Berlin J, Freedman GM, Lawrence T, Talamonti MS, Mulcahy MF, et al. Full-dose gemcitabine with concurrent radiation therapy in patients with nonmetastatic pancreatic cancer: a multicenter phase II trial. J Clin Oncol. 2008;26(6):942-7. doi: 10.1200/JCO.2007.13.9014. PMID: 18281668.
  60. Suker M, Nuyttens JJ, Eskens FALM, Haberkorn BCM, Coene P-PLO, van der Harst E, et al. Efficacy and feasibility of stereotactic radiotherapy after folfirinox in patients with locally advanced pancreatic cancer (LAPC-1 trial). EClinicalMedicine. 2019;17:100200. doi: 10.1016/j.eclinm.2019.10.013. PMID: 31891135; PMCID: PMC6933188.
  61. Smeenk HG, de Castro SMM, Jeekel JJ, Kazemier G, Busch ORC, Incrocci L, et al. Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil: a first step to neoadjuvant treatment? Dig Surg. 2005;22(3):191-7. doi: 10.1159/000087973. PMID: 16137997.
  62. Tsujimoto A, Sudo K, Nakamura K, Kita E, Hara R, Takayama W, et al. Gemcitabine plus nab-paclitaxel for locally advanced or borderline resectable pancreatic cancer. Sci Rep. 2019;9(1):16187. doi: 10.1038/s41598-019-52486-x. PMID: 31700023; PMCID: PMC6838159.
  63. Fiore M, Ramella S, Valeri S, Caputo D, Floreno B, Trecca P, et al. Phase II study of induction chemotherapy followed by chemoradiotherapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer. Sci Rep. 2017;7:45845. doi: 10.1038/srep45845. PMID: 28378800; PMCID: PMC5381116.
  64. Fiore M, Trodella L, Valeri S, Borzomati D, Floreno B, Ippolito E, et al. Prospective study of cetuximab and gemcitabine in combination with radiation therapy: feasibility and efficacy in locally advanced pancreatic head cancer. Radiat Oncol. 2015;10:255. doi: 10.1186/s13014-015-0564-8. PMID: 26670587; PMCID: PMC4681028.
  65. Gemenetzis G, Groot VP, Blair AB, Laheru DA, Zheng L, Narang AK, et al. Survival in locally advanced pancreatic cancer after neoadjuvant therapy and surgical resection. Ann Surg. 2019;270(2):340-7. doi: 10.1097/SLA.0000000000002753. PMID: 29596120; PMCID: PMC6985003.
  66. Habermehl D, Kessel K, Welzel T, Hof H, Abdollahi A, Bergmann F, et al. Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer. Radiat Oncol. 2012;7:28. doi: 10.1186/1748-717X-7-28. PMID: 22385572; PMCID: PMC3338091.
  67. Hosein PJ, Macintyre J, Kawamura C, Maldonado JC, Ernani V, Loaiza-Bonilla A, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199. doi: 10.1186/1471-2407-12-199. PMID: 22642850; PMCID: PMC3404979.
  68. Hackert T, Sachsenmaier M, Hinz U, Schneider L, Michalski CW, Springfeld C, et al. Locally advanced pancreatic cancer: Neoadjuvant therapy with Folfirinox results in resectability in 60% of the patients. Ann Surg. 2016;264(3):457-63. doi: 10.1097/SLA.0000000000001850. PMID: 27355262.
  69. Aristu J, Cañón R, Pardo F, Martínez-Monge R, Martin-Algarra S, Manuel Ordoñez J, et al. Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer. Am J Clin Oncol. 2003;26(1):30-6. doi: 10.1097/00000421-200302000-00007. PMID: 12576921.
  70. Badiyan SN, Olsen JR, Lee AY, Yano M, Menias CO, Khwaja S, et al. Induction chemotherapy followed by concurrent full-dose gemcitabine and intensity-modulated radiation therapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Am J Clin Oncol. 2016;39(1):1-7. doi: 10.1097/COC.0000000000000003. PMID: 2613236
  71. Bjerregaard JK, Mortensen MB, Jensen HA, Fristrup C, Svolgaard B, Schønnemann KR, et al. Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer. Radiother Oncol. 2009;92(2):226-30. doi: 10.1016/j.radonc.2009.04.010. PMID: 19435643.
  72. Brunner TB, Grabenbauer GG, Klein P, Baum U, Papadopoulos T, Bautz W, et al. Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2003;55(1):144-53. doi: 10.1016/s0360-3016(02)03818-x. PMID: 12504047.
  73. Brunner TB, Grabenbauer GG, Klein P, Baum U, Papadopoulos T, Bautz W, et al. Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2003;55(1):144-53. doi: 10.1016/s0360-3016(02)03818-x. PMID: 12504047.
  74. Cetin V, Piperdi B, Bathini V, Walsh WV, Yunus S, Tseng JF, et al. Phase II trial of cetuximab, gemcitabine, 5-fluorouracil, and radiation therapy in locally advanced nonmetastatic pancreatic adenocarcinoma. Gastrointest Cancer Res. 2013;6(4 Suppl 1):S2-9. PMID: 24312684; PMCID: PMC3849911.
  75. Chadha AS, Skinner HD, Gunther JR, Munsell MF, Das P, Minsky BD, et al. Phase I trial of consolidative radiotherapy with concurrent bevacizumab, erlotinib and capecitabine for unresectable pancreatic cancer. PLoS One. 2016;11(6):e0156910. doi: 10.1371/journal.pone.0156910. PMID: 27336466; PMCID: PMC4919049.
  76. Chao YJ, Sy ED, Hsu HP, Shan YS. Predictors for resectability and survival in locally advanced pancreatic cancer after gemcitabine-based neoadjuvant therapy. BMC Surg. 2014;14:72. doi: 10.1186/1471-2482-14-72. PMID: 25258022; PMCID: PMC4182443.
  77. Chen-Zhao X, Hernando O, López M, Sánchez E, Montero A, García-Aranda M, et al. A prospective observational study of the clinical and pathological impact of stereotactic body radiotherapy (SBRT) as a neoadjuvant strategy of chemoradiation in pancreatic cancer. Clin Transl Oncol. 2020;22(9):1499-505. doi: 10.1007/s12094-020-02287-w. PMID: 31974820.
  78. Epelbaum R, Rosenblatt E, Nasrallah S, Faraggi D, Gaitini D, Mizrahi S, et al. Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer. J Surg Oncol. 2002;81(3):138-43. doi: 10.1002/jso.10159. PMID: 12407726.
  79. Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, et al. FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist. 2013;18(5):543-8. doi: 10.1634/theoncologist.2012-0435. PMID: 23657686; PMCID: PMC3662845.
  80. Roselló S, Pizzo C, Huerta M, Muñoz E, Aliaga R, Vera A, et al. Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre. ESMO Open. 2020;5(6):e000929. doi: 10.1136/esmoopen-2020-000929. PMID: 33229503; PMCID: PMC7684818.
  81. Botta GP, Huynh TR, Spierling-Bagsic SR, Agelidis A, Schaffer R, Lin R, et al. Neoadjuvant chemotherapy and radiotherapy outcomes in borderline-resectable and locally-advanced pancreatic cancer patients. Cancer Med. 2023;12(7):7713-23. doi: 10.1002/cam4.5523. PMID: 36478411; PMCID: PMC10134275.
  82. Ninomiya R, Abe S, Chiyoda T, Kogure R, Kimura A, Komagome M, et al. Predicting conversion surgery in patients with locally advanced pancreatic cancer after modified FOLFIRINOX treatment. Asian J Surg. 2023;46(9):3542-8. doi: 10.1016/j.asjsur.2023.03.162. PMID: 37087347.
  83. Napolitano F, Formisano L, Giardino A, Girelli R, Servetto A, Santaniello A, et al. Neoadjuvant treatment in locally advanced pancreatic cancer (LAPC) patients with FOLFIRINOX or gemcitabine nabpaclitaxel: A single-center experience and a literature review. Cancers (Basel). 2019;11(7):981. doi: 10.3390/cancers11070981. PMID: 31337045; PMCID: PMC6678351.
  84. Fietkau R, Grützmann R, Wittel UA, Croner RS, Jacobasch L, Neumann UP, et al. R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007 ± trial. Strahlenther Onkol. 2021;197(1):8-18. doi: 10.1007/s00066-020-01680-2. PMID: 32914237; PMCID: PMC7801312.
  85. Zakem SJ, Mueller AC, Meguid C, Torphy RJ, Holt DE, Schefter T, et al. Impact of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) on R0 resection rate for borderline resectable and locally advanced pancreatic cancer. HPB (Oxford). 2021;23(7):1072-83. doi: 10.1016/j.hpb.2020.11.004. PMID: 33277184.
  86. Versteijne E, Vogel JA, Besselink MG, Busch ORC, Wilmink JW, Daams JG, et al. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg. 2018;105(8):946-58. doi: 10.1002/bjs.10870. PMID: 29708592; PMCID: PMC6033157.
Middle East Journal of Cancer

Articles in Press, Accepted Manuscript
Available Online from 01 July 2026
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