30,220
Views
28
CrossRef citations to date
0
Altmetric
Review Article

Pancreatic Cancer: A Review of Current Treatment and Novel Therapies

, , &
Article: 2129884 | Received 09 Jul 2022, Accepted 21 Sep 2022, Published online: 03 Oct 2022

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA A Cancer J Clin. 2019;69(1):1–11. doi:10.3322/caac.21551.
  • Howlander N, Noone A, Krapcho M, et al. SEER cancer statistics review, 1975-2017. Bethesda, MD: National Cancer Institute; 2019; Based on November 2019 SEER data submission, posted to the SEER web site April 2020. https://seer.cancer.gov/csr/1975_2017/. Accessed April 1, 2022.
  • National Cancer Institute. Surveillance, Epidemiology and End Results Program. 2020. https://seer.cancer.gov/explorer/application.html?site=40&data_type=1&graph_type=4&compareBy=sex&chk_sex_1=1&race=1&age_range=1&advopt_precision=1. Accessed December 8, 2020.
  • Millikan KW, Deziel DJ, Silverstein JC, et al. Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas. Am Surg. 1999;65(7):618–623.
  • Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas - 616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4(6):567–579. doi:10.1016/S1091-255X(00)80105-5.
  • Raut CP, Tseng JF, Sun CC, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246(1):52–60. doi:10.1097/01.sla.0000259391.84304.2b.
  • Katz MHG, Marsh R, Herman JM, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013;20(8):2787–2795. doi:10.1245/s10434-013-2886-9.
  • National Comprehensive Cancer Network. Pancreatic Adenocarcinoma, Version 1.2020. www2.tri-kobe/nccn/guideline/pancreas/english/pancreatic.pdf. Published 2019. Accessed May 8 2020.
  • Schnelldorfer T, Sarr MG. Alessandro codivilla and the first pancreatoduodenectomy. Arch Surg. 2009;144(12):1179–1184. doi:10.1001/archsurg.2009.219.
  • Whipple AO, Parsons WB, Mullins CR. Treatment of carcinoma of the ampulla of vater. Ann Surg. 1935;102(4):763–779. doi:10.1097/00000658-193510000-00023.
  • Fernández-del Castillo C, Morales-Oyarvide V, McGrath D, et al. Evolution of the whipple procedure at the Massachusetts general hospital. Surgery. 2012;152(3 Suppl 1):S56–S63. doi:10.1016/j.surg.2012.05.022.
  • Gallitano A, Fransen H, Martin RG. Carcinoma of the pancreas. Results of treatment. Cancer. 1968;22(5):939–944. doi:10.1002/1097-0142(196811)22:5 < 939::aid-cncr2820220507 > 3.0.co;2-e.
  • Winter JM, Cameron JL, Campbell KA, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg. 2006;10(9):1199–1211. doi:10.1016/j.gassur.2006.08.018.
  • Wright GP, Koehler TJ, Davis AT, Chung MH. The drowning whipple: perioperative fluid balance and outcomes following pancreaticoduodenectomy. J Surg Oncol. 2014;110(4):407–411. doi:10.1002/jso.23662.
  • Hata T, Motoi F, Ishida M, et al. Effect of hospital volume on surgical outcomes after pancreaticoduodenectomy: a systematic review and meta-analysis. Ann Surg. 2016;263(4):664–672. doi:10.1097/SLA.0000000000001437.
  • Macedo FIB, Jayanthi P, Mowzoon M, Yakoub D, Dudeja V, Merchant N. The Impact of surgeon volume on outcomes after pancreaticoduodenectomy: a meta-analysis. J Gastrointest Surg. 2017;21(10):1723–1731. doi:10.1007/s11605-017-3498-7.
  • Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138(1):8–13. doi:10.1016/j.surg.2005.05.001.
  • Eisenberg JD, Rosato EL, Lavu H, Yeo CJ, Winter JM. Delayed gastric emptying after pancreaticoduodenectomy: an analysis of risk factors and cost. J Gastrointest Surg. 2015;19(9):1572–1580. doi:10.1007/s11605-015-2865-5.
  • Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007;142(5):761–768. doi:10.1016/j.surg.2007.05.005.
  • Hanna MM, Gadde R, Allen CJ, et al. Delayed gastric emptying after pancreaticoduodenectomy. J Surg Res. 2016;202(2):380–388. doi:10.1016/j.jss.2015.12.053.
  • Sánchez-Velázquez P, Muller X, Malleo G, et al. Benchmarks in pancreatic surgery: a novel tool for unbiased outcome comparisons. Ann Surg. 2019;270(2):211–218. https://journals.lww.com/annalsofsurgery/Fulltext/2019/08000/Benchmarks_in_Pancreatic_Surgery__A_Novel_Tool_for.4.aspx.
  • Dindo D, Demartines N, Clavien PA. Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–213. doi:10.1097/01.sla.0000133083.54934.ae.
  • Strobel O, Lorenz P, Hinz U, et al. Actual five-year survival after upfront resection for pancreatic ductal adenocarcinoma: who beats the odds? Ann Surg. 2020;275(5):962–971. https://journals.lww.com/annalsofsurgery/Fulltext/9000/Actual_Five_year_Survival_After_Upfront_Resection.94393.aspx.
  • Müller SA, Hartel M, Mehrabi A, et al. Vascular resection in pancreatic cancer surgery: survival determinants. J Gastrointest Surg. 2009;13(4):784–792. doi:10.1007/s11605-008-0791-5.
  • Macedo FI, Ryon E, Maithel SK, et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270(3):400–413. doi:10.1097/SLA.0000000000003468.
  • Katz MHG, Wang H, Fleming JB, et al. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009;16(4):836–847. doi:10.1245/s10434-008-0295-2.
  • Kolbeinsson H, Hoppe A, Bayat A, et al. Recurrence patterns and postrecurrence survival after curative intent resection for pancreatic ductal adenocarcinoma. Surgery. 2021;169(3):649–654. doi:10.1016/j.surg.2020.06.042.
  • Groot VP, Rezaee N, Wu W, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2018;267(5):936–945. doi:10.1097/SLA.0000000000002234.
  • Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21(2):195–200. doi:10.1007/s002689900215.
  • Kim RY, Christians KK, Aldakkak M, et al. Total neoadjuvant therapy for operable pancreatic cancer. Ann Surg Oncol. 2021;28(4):2246–2256. doi:10.1245/s10434-020-09149-3.
  • Van Tienhoven G, Versteijne E, Suker M, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial. JCO. 2018;36(18_suppl):LBA4002–LBA4002. doi:10.1200/JCO.2018.36.18_suppl.LBA4002.
  • Janssen QP, van Dam JL, Bonsing BA, et al. Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled t. BMC Cancer. 2021;21(1):300. doi:10.1186/s12885-021-08031-z.
  • Miyasaka Y, Ohtsuka T, Kimura R, et al. Neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel for borderline resectable pancreatic cancer potentially improves survival and facilitates surgery. Ann Surg Oncol. 2019;26(5):1528–1534. doi:10.1245/s10434-019-07309-8.
  • Gagner M, Pomp A. Laparoscopic pylorus-preserving pancreatoduodenectomy. Surg Endosc. 1994;8(5):408–410. doi:10.1007/BF00642443.
  • Gagner M, Palermo M. Laparoscopic Whipple procedure: review of the literature. J Hepatobiliary Pancreat Surg. 2009;16(6):726–730. doi:10.1007/s00534-009-0142-2.
  • Croome KP, Farnell MB, Que FG, et al. Pancreaticoduodenectomy with major vascular resection: a comparison of laparoscopic versus open approaches. J Gastrointest Surg. 2015;19(1):189–194; discussion 194. doi:10.1007/s11605-014-2644-8.
  • Kendrick ML, Sclabas GM. Major venous resection during total laparoscopic pancreaticoduodenectomy. HPB (Oxford). 2011;13(7):454–458. doi:10.1111/j.1477-2574.2011.00323.x.
  • Poves I, Burdío F, Morató O, et al. Comparison of perioperative outcomes between laparoscopic and open approach for pancreatoduodenectomy: the PADULAP randomized controlled trial. Ann Surg. 2018;268(5):731–739. doi:10.1097/SLA.0000000000002893.
  • Jiang Y-L, Zhang R-C, Zhou Y-C. Comparison of overall survival and perioperative outcomes of laparoscopic pancreaticoduodenectomy and open pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. BMC Cancer. 2019;19(1):781. doi:10.1186/s12885-019-6001-x.
  • Yin Z, Jian Z, Hou B, Jin H. Surgical and oncological outcomes of laparoscopic versus open pancreaticoduodenectomy in patients with pancreatic duct adenocarcinoma. Pancreas. 2019;48(7):861–867. doi:10.1097/MPA.0000000000001363.
  • Song KB, Kim SC, Hwang DW, et al. Matched case-control analysis comparing laparoscopic and open pylorus-preserving pancreaticoduodenectomy in patients with periampullary tumors. Ann Surg. 2015;262(1):146–155. doi:10.1097/SLA.0000000000001079.
  • Croome KP, Farnell MB, Que FG, et al. Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches? Ann Surg. 2014;260(4):633–640. doi:10.1097/SLA.0000000000000937.
  • Stauffer JA, Coppola A, Villacreses D, et al. Laparoscopic versus open pancreaticoduodenectomy for pancreatic adenocarcinoma: long-term results at a single institution. Surg Endosc. 2017;31(5):2233–2241. doi:10.1007/s00464-016-5222-1.
  • Zureikat AH, Postlewait LM, Liu Y, et al. A multi-institutional comparison of perioperative outcomes of robotic and open pancreaticoduodenectomy. Ann Surg. 2016;264(4):640–649. doi: https://journals.lww.com/annalsofsurgery/Fulltext/2016/10000/A_Multi_institutional_Comparison_of_Perioperative.12.aspx.
  • Adam MA, Choudhury K, Dinan MA, et al. Minimally invasive versus open pancreaticoduodenectomy for cancer: practice patterns and short-term outcomes among 7061 patients. Ann Surg. 2015;262(2):372–377. doi:10.1097/SLA.0000000000001055.
  • Nussbaum DP, Adam MA, Youngwirth LM, et al. Minimally invasive pancreaticoduodenectomy does not improve use or time to initiation of adjuvant chemotherapy for patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2016;23(3):1026–1033. doi:10.1245/s10434-015-4937-x.
  • Bold RJ, Charnsangavej C, Cleary KR, et al. Major vascular resection as part of pancreaticoduodenectomy for cancer: radiologic, intraoperative, and pathologic analysis. J Gastrointest Surg. 1999;3(3):233–243. doi:10.1016/S1091-255X(99)80065-1.
  • Ravikumar R, Sabin C, Abu Hilal M, et al. Portal vein resection in borderline resectable pancreatic cancer: a United Kingdom multicenter study. J Am Coll Surg. 2014;218(3):401–411. doi:10.1016/j.jamcollsurg.2013.11.017.
  • Chua TC, Saxena A. Extended pancreaticoduodenectomy with vascular resection for pancreatic cancer: a systematic review. J Gastrointest Surg. 2010;14(9):1442–1452. doi:10.1007/s11605-009-1129-7.
  • Okada K, Kawai M, Tani M, et al. Surgical strategy for patients with pancreatic body/tail carcinoma: Who should undergo distal pancreatectomy with en-bloc celiac axis resection? Surgery. 2013;153(3):365–372. doi:10.1016/j.surg.2012.07.036.
  • Rubinsky B, Onik G, Mikus P. Irreversible electroporation: a new ablation modality–clinical implications. Technol Cancer Res Treat. 2007;6(1):37–48. doi:10.1177/153303460700600106.
  • Martin RCG, 2nd, McFarland K, Ellis S, Velanovich V. Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. J Am Coll Surg. 2012;215(3):361–369. doi:10.1016/j.jamcollsurg.2012.05.021.
  • Maor E, Ivorra A, Leor J, Rubinsky B. The effect of irreversible electroporation on blood vessels. Technol Cancer Res Treat. 2007;6(4):307–312. doi:10.1177/153303460700600407.
  • Ansari D, Kristoffersson S, Andersson R, Bergenfeldt M. The role of irreversible electroporation (IRE) for locally advanced pancreatic cancer: a systematic review of safety and efficacy. Scand J Gastroenterol. 2017;52(11):1165–1171. doi:10.1080/00365521.2017.1346705.
  • Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825. doi:10.1056/NEJMoa1011923.
  • Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–1703. doi:10.1056/NEJMoa1304369.
  • Raphael MJ, Raskin W, Habbous S, et al. The association of drug-funding reimbursement with survival outcomes and use of new systemic therapies among patients with advanced pancreatic cancer. JAMA Netw Open. 2021;4(11):e2133388–e2133388. doi:10.1001/jamanetworkopen.2021.33388.
  • Wang-Gillam A, Li C-P, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet (London, England. 2016;387(10018):545–557. doi:10.1016/S0140-6736(15)00986-1.
  • Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381(4):317–327. doi:10.1056/NEJMoa1903387.
  • Carrato A, Vieitez JM, Benavides M, et al. Phase I/II trial of sequential treatment of nab-paclitaxel in combination with gemcitabine followed by modified FOLFOX chemotherapy in patients with untreated metastatic exocrine pancreatic cancer: Phase I results. Eur J Cancer. 2020;139:51–58. doi:10.1016/j.ejca.2020.07.035.
  • Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–1024. doi:10.1016/S0140-6736(16)32409-6.
  • Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395–2406. doi:10.1056/NEJMoa1809775.
  • Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20. doi:10.1056/NEJMoa055531.
  • Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–1740. doi:10.1056/NEJMoa040694.
  • Yamada S, Fujii T, Sugimoto H, et al. Aggressive surgery for borderline resectable pancreatic cancer: evaluation of National Comprehensive Cancer Network guidelines. Pancreas. 2013;42(6):1004–1010. doi:10.1097/MPA.0b013e31827b2d7c.
  • Okada K-I, Hirono S, Kawai M, et al. Phase I study of nab-paclitaxel plus gemcitabine as neoadjuvant therapy for borderline resectable pancreatic cancer. Anticancer Res. 2017;37(2):853–858. doi:10.21873/anticanres.11389.
  • Reni M, Zanon S, Balzano G, et al. A randomised phase 2 trial of nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in locally advanced or borderline resectable pancreatic adenocarcinoma. Eur J Cancer. 2018;102:95–102. doi:10.1016/j.ejca.2018.07.007.
  • Murphy JE, Wo JY, Ryan DP, et al. Total neoadjuvant therapy with FOLFIRINOX followed by individualized chemoradiotherapy for borderline resectable pancreatic adenocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2018;4(7):963–969. doi:10.1001/jamaoncol.2018.0329.
  • Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–17. doi:10.1097/SLA.0000000000000867.
  • Katz MHG, Shi Q, Ahmad SA, et al. Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer: alliance for clinical trials in oncology trial A021101. JAMA Surg. 2016;151(8):e161137. doi:10.1001/jamasurg.2016.1137.
  • Barbour AP, Samra JS, Haghighi KS, et al. The AGITG GAP study: a phase ii study of perioperative gemcitabine and nab-paclitaxel for resectable pancreas cancer. Ann Surg Oncol. 2020;27(7):2506–2515. doi:10.1245/s10434-020-08205-2.
  • OʼReilly EM, Perelshteyn A, Jarnagin WR, et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma. Ann Surg. 2014;260(1):142–148. doi:10.1097/SLA.0000000000000251.
  • Ielpo B, Duran H, Diaz E, et al. Preoperative treatment with gemcitabine plus nab-paclitaxel is a safe and effective chemotherapy for pancreatic adenocarcinoma. Eur J Surg Oncol. 2016;42(9):1394–1400. doi:10.1016/j.ejso.2016.01.006.
  • MacKenzie S, Zeh H, McCahill LE, PCRT, et al. A pilot phase II multicenter study of nab-paclitaxel (Nab-P) and gemcitabine (G) as preoperative therapy for potentially resectable pancreatic cancer (PC). JCO. 2013;31(15_suppl):4038–4038. doi:10.1200/jco.2013.31.15_suppl.4038.
  • Wei AC, Ou F-S, Shi Q, et al. Perioperative gemcitabine + erlotinib plus pancreaticoduodenectomy for resectable pancreatic adenocarcinoma: ACOSOG Z5041 (alliance) phase II trial. Ann Surg Oncol. 2019;26(13):4489–4497. doi:10.1245/s10434-019-07685-1.
  • Sohal D, Duong MT, Ahmad SA, et al. SWOG S1505: Results of perioperative chemotherapy with mFOLFIRINOX versus gemcitabine/nab-paclitaxel for resectable pancreatic ductal adenocarcinoma. JCO. 2020;38(15_suppl):4504–4504. doi:10.1200/JCO.2020.38.15_suppl.4504.
  • Lutfi W, Talamonti MS, Kantor O, et al. Perioperative chemotherapy is associated with a survival advantage in early stage adenocarcinoma of the pancreatic head. Surgery. 2016;160(3):714–724. doi:10.1016/j.surg.2016.05.029.
  • Versteijne E, Vogel JA, Besselink MG, 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):946–958. doi:10.1002/bjs.10870.
  • Kalser MH, Ellenberg SS. Pancreatic cancer: adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(8):899–903. doi:10.1001/archsurg.1985.01390320023003.
  • Klinkenbijl JH, Jeekel J, Sahmoud T, et 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. 1999;230(6):776–776. doi:10.1097/00000658-199912000-00006.
  • Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–1210. doi:10.1056/NEJMoa032295.
  • Smeenk HG, van Eijck CHJ, Hop WC, et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: long-term results of EORTC trial 40891. Ann Surg. 2007;246(5):734–740. doi:10.1097/SLA.0b013e318156eef3.
  • Van Laethem J-L, Hammel P, Mornex F, et al. Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. JCO. 2010;28(29):4450–4456. doi:10.1200/JCO.2010.30.3446.
  • Palta M, Godfrey D, Goodman KA, et al. Radiation therapy for pancreatic cancer: executive summary of an ASTRO clinical practice guideline. Pract Radiat Oncol. 2019;9(5):322–332. doi:10.1016/j.prro.2019.06.016.
  • Kim EJ, Ben-Josef E, Herman JM, 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):2692–2700. doi:10.1002/cncr.28117.
  • Shroff RT, Varadhachary GR, Crane CH, et al. Updated survival analysis of preoperative gemcitabine (gem) plus bevacizumab (bev)-based chemoradiation for resectable pancreatic adenocarcinoma. JCO. 2012;30(15_suppl):4051–4051. doi:10.1200/jco.2012.30.15_suppl.4051.
  • Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. JCO. 2008;26(21):3496–3502. doi:10.1200/JCO.2007.15.8634.
  • Talamonti MS, Small W, Mulcahy MF, et 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. 2006;13(2):150–158. doi:10.1245/ASO.2006.03.039.
  • Epelbaum R, Rosenblatt E, Nasrallah 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):138–143. doi:10.1002/jso.10159.
  • Joensuu TK, Kiviluoto T, Kärkkäinen P, et al. Phase I-II trial of twice-weekly gemcitabine and concomitant irradiation in patients undergoing pancreaticoduodenectomy with extended lymphadenectomy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;60(2):444–452. doi:10.1016/j.ijrobp.2004.03.026.
  • Small WJ, Berlin J, Freedman GM, 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):942–947. doi:10.1200/JCO.2007.13.9014.
  • Stessin AM, Meyer JE, Sherr DL. Neoadjuvant radiation is associated with improved survival in patients with resectable pancreatic cancer: an analysis of data from the surveillance, epidemiology, and end results (SEER) registry. Int J Radiat Oncol Biol Phys. 2008;72(4):1128–1133. doi:10.1016/j.ijrobp.2008.02.065.
  • Effenberger KE, Schroeder C, Hanssen A, et al. Improved risk stratification by circulating tumor cell counts in pancreatic cancer. Clin Cancer Res. 2018;24(12):2844–2850. doi:10.1158/1078-0432.CCR-18-0120.
  • Court CM, Ankeny JS, Sho S, et al. Circulating tumor cells predict occult metastatic disease and prognosis in pancreatic cancer. Ann Surg Oncol. 2018;25(4):1000–1008. doi:10.1245/s10434-017-6290-8.
  • Sivapalan L, Kocher HM, Ross-Adams H, Chelala C. Molecular profiling of ctDNA in pancreatic cancer: opportunities and challenges for clinical application. Pancreatology. 2021;21(2):363–378. doi:10.1016/j.pan.2020.12.017.
  • Botta GP, Abdelrahim M, Aushev VN, et al. Association of personalized and tumor-informed ctDNA with patient survival outcomes in pancreatic adenocarcinoma. JCO. 2022;40(4_suppl):517–517. doi:10.1200/JCO.2022.40.4_suppl.517.
  • Hackert T, Niesen W, Hinz U, et al. Radical surgery of oligometastatic pancreatic cancer. Eur J Surg Oncol. 2017;43(2):358–363. 10.1016/j.ejso.2016.10.023.
  • Adam R, Chiche L, Aloia T, et al. Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1,452 patients and development of a prognostic model. Ann Surg. 2006;244(4):524–535. doi:10.1097/01.sla.0000239036.46827.5f.
  • Shrikhande SV, Kleeff J, Reiser C, et al. Pancreatic Resection for M1 Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol. 2007;14(1):118–127. doi:10.1245/s10434-006-9131-8.
  • Gleisner AL, Assumpcao L, Cameron JL, et al. Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer. 2007;110(11):2484–2492. doi:10.1002/cncr.23074.
  • Ilmer M, Schiergens TS, Renz BW, et al. Oligometastatic pulmonary metastasis in pancreatic cancer patients: Safety and outcome of resection. Surg Oncol. 2019;31:16–21. 10.1016/j.suronc.2019.08.010.
  • Yamashita K, Miyamoto A, Hama N, et al. Survival impact of pulmonary metastasis as recurrence of pancreatic ductal adenocarcinoma. Dig Surg. 2015;32(6):464–471. doi:10.1159/000439545.
  • Ensminger WD. Intrahepatic arterial infusion of chemotherapy: pharmacologic principles. Semin Oncol. 2002;29(2):119–125. doi:10.1053/sonc.2002.31679.
  • Groot Koerkamp B, Sadot E, Kemeny NE, et al. Perioperative hepatic arterial infusion pump chemotherapy is associated with longer survival after resection of colorectal liver metastases: a propensity score analysis. JCO. 2017;35(17):1938–1944. doi:10.1200/JCO.2016.71.8346.
  • Beger HG, Gansauge F, Büchler MW, Link KH. Intraarterial adjuvant chemotherapy after pancreaticoduodenectomy for pancreatic cancer: Significant reduction in occurrence of liver metastasis. In. World Journal of Surgery. 1999;23(9):946–949. doi:10.1007/s002689900604.
  • Ohigashi H, Ishikawa O, Eguchi H, et al. Feasibility and efficacy of combination therapy with preoperative and postoperative chemoradiation, extended pancreatectomy, and postoperative liver perfusion chemotherapy for locally advanced cancers of the pancreatic head. Ann Surg Oncol. 2005;12(8):629–636. doi:10.1245/ASO.2005.05.028.
  • Wang Y, Xu Y, Zheng Y, Bao Y, Wang P. Postoperative hepatic arterial infusion chemotherapy improved survival of pancreatic cancer after radical pancreatectomy: a retrospective study. Onco Targets Ther. 2018;11:903–907. doi:10.2147/OTT.S153886.
  • Tajima H, Kitagawa H, Tsukada T, et al. Hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil or oral S-1 improves the prognosis of patients with postoperative liver metastases from pancreatic cancer. Mol Clin Oncol. 2013;1(5):869–874. doi:10.3892/mco.2013.152.
  • Sohal DPS, Kennedy EB, Cinar P, et al. Metastatic pancreatic cancer: ASCO guideline update. JCO. 2020;38(27):3217–3230. doi:10.1200/JCO.20.01364.
  • Casolino R, Paiella S, Azzolina D, et al. Homologous recombination deficiency in pancreatic cancer: a systematic review and prevalence meta-analysis. J Clin Oncol. 2021;39(23):2617–2631. doi:10.1200/JCO.20.03238.
  • Dalmasso B, Puccini A, Catalano F, et al. Beyond BRCA: the emerging significance of DNA damage response and personalized treatment in pancreatic and prostate cancer patients. IJMS. 2022;23(9):4709. doi:10.3390/ijms23094709.
  • Registry. APG. Pancreatic Cancer Genomic Distribution: Mutated Genes. https://www.aacr.org/professionals/research/aacr-project-genie/aacr-project-genie-data/11-most-common-cancer-types-in-the-aacr-project-genie-registry/pancreatic-cancer/. Published 2022.
  • Strickler JH, Satake H, Hollebecque A, et al. First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: A phase I/II study evaluating efficacy and safety. JCO. 2022;40(36_suppl):360490–360490. doi:10.1200/JCO.2022.40.36_suppl.360490.
  • Bekaii-Saab TS, Spira AI, Yaeger R, et al. KRYSTAL-1: Updated activity and safety of adagrasib (MRTX849) in patients (Pts) with unresectable or metastatic pancreatic cancer (PDAC) and other gastrointestinal (GI) tumors harboring a KRASG12C mutation. JCO. 2022;40(4_suppl):519–519. doi:10.1200/JCO.2022.40.4_suppl.519.
  • Golan T, Khvalevsky EZ, Hubert A, et al. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients. Oncotarget. 2015;6(27):24560–24570. doi:10.18632/oncotarget.4183.
  • Leidner R, Sanjuan Silva N, Huang H, et al. Neoantigen T-cell receptor gene therapy in pancreatic cancer. N Engl J Med. 2022;386(22):2112–2119. doi:10.1056/NEJMoa2119662.
  • Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the Phase II KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1–10. doi:10.1200/JCO.19.02105.
  • Chellakkan SB, Dinesh C, Wilber Q-T, et al. Listeria delivers tetanus toxoid protein to pancreatic tumors and induces cancer cell death in mice. Sci Transl Med. 2022;14(637):eabc1600. doi:10.1126/scitranslmed.abc1600.
  • Pishvaian MJ, Garrido-Laguna I, Liu SV, Multani PS, Chow-Maneval E, Rolfo C. Entrectinib in TRK and ROS1 fusion-positive metastatic pancreatic cancer. JCO Precis Oncol. 2018;(2):1–7. doi:10.1200/PO.18.00039.