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Neoadjuvant Therapy in Borderline Resectable Pancreatic Cancer

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Abstract

In this perspective, we present our assessment of all of the known accumulated evidence on the role of neoadjuvant therapy in the management of borderline resectable pancreatic cancer highlighting the gaps in the data, the current regimens used and providing a brief insight into the way forward.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  Google Scholar 

  2. Maurer CA, Zgraggen K, Buchler MW (1999) Pancreatic carcinoma Optimizing therapy by adjuvant and neoadjuvant therapy? Zentralbl Chir 124:401–407

    CAS  PubMed  Google Scholar 

  3. Mehta V, Fisher G, Ford J, Poen J, Vierra M, Oberhelman H, Niederhuber J (2001) Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg 5:27–35

    Article  CAS  Google Scholar 

  4. Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, Lee JE, Pisters PW, Evans DB, Wolff RA (2006) Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol 13:1035–1046

    Article  Google Scholar 

  5. Al-Hawary MM, Francis IR, Chari ST, Fishman EK, Hough DM, Lu DS, Macari M, Megibow AJ, Miller FH, Mortele KJ, Merchant NB, Minter RM, Tamm EP, Sahani DV, Simeone DM (2014) Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the society of abdominal radiology and the american pancreatic association. Gastroenterology 146:291-304 e291

    Article  Google Scholar 

  6. Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC (2009) Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol 16:1727–1733

    Article  Google Scholar 

  7. Tempero M, Arnoletti J, Behrman S, Ben-Josef E, Benson AB 3rd, Casper E (2012) Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 10:703–713

    Article  CAS  Google Scholar 

  8. Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, Kindler HL, Alberts SR, Philip P, Lowy AM, Pisters PW, Posner MC, Berlin JD, Ahmad SA (2013) Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol 20:2787–2795

    Article  Google Scholar 

  9. Barreto S, Windsor J (2016) Justifying vein resection with pancreatoduodenectomy. Lancet Oncol 17:e118–e124

    Article  Google Scholar 

  10. Bockhorn M, Uzunoglu F, Adham M, Imrie C (2014) Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 155:977–988

    Article  Google Scholar 

  11. Bittoni A, Santoni M, Lanese A, Pellei C, Andrikou K, Stefano C (2014) Neoadjuvant therapy in pancreatic cancer: an emerging strategy. Gastroenterol Res Pract 2014:183852

    Article  Google Scholar 

  12. Windsor JA, Barreto SG (2017) The concept of “borderline resectable” pancreatic cancer: limited foundations and limited future? J Gastrointest Oncol 8:189–193

    Article  Google Scholar 

  13. Pingpank JF, Hoffman JP, Ross EA, Cooper HS, Meropol NJ, Freedman G, Pinover WH, LeVoyer TE, Sasson AR, Eisenberg BL (2001) Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg 5:121–130

    Article  CAS  Google Scholar 

  14. Kato H, Usui M, Isaji S, Nagakawa T, Wada K, Unno M, Nakao A, Miyakawa S, Ohta T (2013) Clinical features and treatment outcome of borderline resectable pancreatic head/body cancer: a multi-institutional survey by the Japanese Society of Pancreatic Surgery. J Hepatobiliary Pancreat Sci 20(6):601–610

  15. Barreto SG, Loveday B, Windsor JA, Pandanaboyana S (2019) Detecting tumour response and predicting resectability after neoadjuvant therapy for borderline resectable and locally advanced pancreatic cancer. ANZ J Surg 89:481–487

    Article  Google Scholar 

  16. Barenboim A, Lahat G, Geva R, Nachmany I, Nakache R, Goykhman Y, Brazowski E, Rosen G, Isakov O, Wolf I, Klausner JM, Lubezky N (2018) Neoadjuvant FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer: an intention to treat analysis. Eur J Surg Oncol 44:1619–1623

    Article  Google Scholar 

  17. Chuong MD, Frakes JM, Figura N, Hoffe SE, Shridhar R, Mellon EA, Hodul PJ, Malafa MP, Springett GM, Centeno BA (2016) Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer. J Gastrointest Oncol 7:221–227

    PubMed  PubMed Central  Google Scholar 

  18. He J, Blair AB, Groot VP, Javed AA, Burkhart RA, Gemenetzis G, Hruban RH, Waters KM, Poling J, Zheng L, Laheru D, Herman JM, Makary MA, Weiss MJ, Cameron JL, Wolfgang CL (2018) Is a pathological complete response following neoadjuvant chemoradiation associated with prolonged survival in patients with pancreatic cancer? Ann Surg 268:1–8

    Article  Google Scholar 

  19. Katz MH, Shi Q, Ahmad SA, Herman JM, Marsh Rde W, Collisson E, Schwartz L, Frankel W, Martin R, Conway W, Truty M, Kindler H, Lowy AM, Bekaii-Saab T, Philip P, Talamonti M, Cardin D, LoConte N, Shen P, Hoffman JP, Venook AP (2016) Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic c: Alliance for Clinical Trials in Oncology Trial A021101. JAMA Surg 151:e161137

    Article  Google Scholar 

  20. Mellon EA, Hoffe SE, Springett GM, Frakes JM, Strom TJ, Hodul PJ, Malafa MP, Chuong MD, Shridhar R (2015) Long-term outcomes of induction chemotherapy and neoadjuvant stereotactic body radiotherapy for borderline resectable and locally advanced pancreatic adenocarcinoma. Acta Oncol 54:979–985

    Article  CAS  Google Scholar 

  21. Mellon EA, Jin WH, Frakes JM, Centeno BA, Strom TJ, Springett GM, Malafa MP, Shridhar R, Hodul PJ, Hoffe SE (2017) Predictors and survival for pathologic tumor response grade in borderline resectable and locally advanced pancreatic cancer treated with induction chemotherapy and neoadjuvant stereotactic body radiotherapy. Acta Oncol 56:391–397

    Article  CAS  Google Scholar 

  22. Pietrasz D, Turrini O, Vendrely V, Simon JM, Hentic O, Coriat R, Portales F, Le Roy B, Taieb J, Regenet N, Goere D, Artru P, Vaillant JC, Huguet F, Laurent C, Sauvanet A, Delpero JR, Bachet JB, Sa Cunha A (2019) How does chemoradiotherapy following induction FOLFIRINOX improve the results in resected borderline or locally advanced pancreatic adenocarcinoma? An AGEO-FRENCH Multicentric Cohort. Ann Surg Oncol 26:109–117

    Article  Google Scholar 

  23. Rashid OM, Pimiento JM, Gamenthaler AW, Nguyen P, Ha TT, Hutchinson T, Springett G, Hoffe S, Shridhar R, Hodul PJ, Johnson BL, Illig K, Armstrong PA, Centeno BA, Fulp WJ, Chen DT, Malafa MP (2016) Outcomes of a clinical pathway for borderline resectable pancreatic cancer. Ann Surg Oncol 23:1371–1379

    Article  Google Scholar 

  24. Rose JB, Rocha FG, Alseidi A, Biehl T, Moonka R, Ryan JA, Lin B, Picozzi V, Helton S (2014) Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol 21:1530–1537

    Article  Google Scholar 

  25. Truty MJ, Kendrick ML, Nagorney DM, Smoot RL, Cleary SP, Graham RP, Goenka AH, Hallemeier CL, Haddock MG, Harmsen WS, Mahipal A, McWilliams RR, Halfdanarson TR, Grothey AF (2021) Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline/locally advanced pancreatic cancer. Ann Surg 273(2):341–349

  26. Javed AA, Wright MJ, Siddique A, Blair AB, Ding D, Burkhart RA, Makary M, Cameron JL, Narang A, Herman J, Zheng L, Laheru D, Weiss MJ, Wolfgang C, He J (2019) Outcome of patients with borderline resectable pancreatic cancer in the contemporary era of neoadjuvant chemotherapy. J Gastrointest Surg 23:112–121

    Article  Google Scholar 

  27. Paniccia A, Edil BH, Schulick RD, Byers JT, Meguid C, Gajdos C, McCarter MD (2014) Neoadjuvant FOLFIRINOX application in borderline resectable pancreatic adenocarcinoma: a retrospective cohort study. Medicine (Baltimore) 93:e198

    Article  CAS  Google Scholar 

  28. Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernandez-del Castillo C (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 261:12–17

    Article  Google Scholar 

  29. Kim SS, Nakakura EK, Wang ZJ, Kim GE, Corvera CU, Harris HW, Kirkwood KS, Hirose R, Tempero MA, Ko AH (2016) Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: is radiation necessary in the modern era of chemotherapy? J Surg Oncol 114:587–596

    Article  CAS  Google Scholar 

  30. Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, Buijsen J, Busch OR, Creemers GM, van Dam RM, Eskens F, Festen S, de Groot JWB, Groot Koerkamp B, de Hingh IH, Homs MYV, van Hooft JE, Kerver ED, Luelmo SAC, Neelis KJ, Nuyttens J, Paardekooper G, Patijn GA, van der Sangen MJC, de Vos-Geelen J, Wilmink JW, Zwinderman AH, Punt CJ, van Eijck CH, van Tienhoven G, G. Dutch Pancreatic Cancer (2020) preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the Dutch randomized phase III PREOPANC trial. J Clin Oncol 38:1763–1773

    Article  CAS  Google Scholar 

  31. Rangelova E, Wefer A, Persson S, Valente R, Tanaka K, Orsini N, Segersvard R, Arnelo U, Del Chiaro M (2021) Surgery improves survival after neoadjuvant therapy for borderline and locally advanced pancreatic cancer: a single institution experience. Ann Surg 273(3):579–586

  32. Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernandez-Del Castillo C, Ferrone CR, Hong TS (2018) Total neoadjuvant therapy with FOLFIRINOX followed by individualized chemoradiotherapy for borderline resectable pancreatic adenocarcinoma: a phase 2 clinical trial. JAMA Oncol 4:963–969

    Article  Google Scholar 

  33. Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Chone L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O’Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB, G. Canadian cancer trials, G.I.P.G. the Unicancer (2018) FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379:2395–2406

    Article  CAS  Google Scholar 

  34. Janssen QP, Buettner S, Suker M, Beumer BR, Addeo P, Bachellier P, Bahary N, Bekaii-Saab T, Bali MA, Besselink MG, Boone BA, Chau I, Clarke S, Dillhoff M, El-Rayes BF, Frakes JM, Grose D, Hosein PJ, Jamieson NB, Javed AA, Khan K, Kim KP, Kim SC, Kim SS, Ko AH, Lacy J, Margonis GA, McCarter MD, McKay CJ, Mellon EA, Moorcraft SY, Okada KI, Paniccia A, Parikh PJ, Peters NA, Rabl H, Samra J, Tinchon C, van Tienhoven G, van Veldhuisen E, Wang-Gillam A, Weiss MJ, Wilmink JW, Yamaue H, Homs MYV, van Eijck CHJ, Katz MHG, Koerkamp BG (2019) Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis. J Natl Cancer Inst 111(8):782–794

  35. Versteijne E, Vogel JA, Besselink MG, Busch ORC, Wilmink JW, Daams JG, van Eijck CHJ, Groot Koerkamp B, Rasch CRN, van Tienhoven G (2018) Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg 105:946–958

    Article  CAS  Google Scholar 

  36. Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd (2011) Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol 29:4105–4112

    Article  CAS  Google Scholar 

  37. Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L (2008) Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol 19:1592–1599

    Article  CAS  Google Scholar 

  38. Ahmad SA, Duong M, Sohal DPS, Gandhi NS, Beg MS, Wang-Gillam A, Wade 3rd JL, Chiorean EG, Guthrie KA, Lowy AM, Philip PA, Hochster HS (2020) Surgical outcome results from SWOG S1505: a randomized clinical trial of mFOLFIRINOX versus gemcitabine/nab-paclitaxel for perioperative treatment of resectable pancreatic ductal adenocarcinoma. Ann Surg 272(3):481–486

  39. Takahashi S, Ohno I, Ikeda M, Kobayashi T, Akimoto T, Kojima M, Konishi M, Uesaka K (2017) Neoadjuvant S-1 with concurrent radiotherapy followed by surgery for borderline resectable pancreatic cancer: study protocol for an open-label, multicentre, prospective phase II trial (JASPAC05). BMJ Open 7:e018445

    PubMed  PubMed Central  Google Scholar 

  40. Gao S, Zhu X, Shi X, Cao K, Bian Y, Jiang H, Wang K, Guo S, Zhang H, Jin G (2019) Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase II trial (BRPCNCC-1). Radiat Oncol 14:52

    Article  Google Scholar 

  41. Katz MHG, Ou FS, Herman JM, Ahmad SA, Wolpin B, Marsh R, Behr S, Shi Q, Chuong M, Schwartz LH, Frankel W, Collisson E, Koay EJ, Hubbard JM, Leenstra JL, Meyerhardt J, O’Reilly E (2017) Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas. BMC Cancer 17:505

    Article  Google Scholar 

  42. Motoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M, Honda G, Matsumoto I, Wada K, Furuse J, Matsuyama Y, Unno M, C. Study group of preoperative therapy for pancreatic, c. Japanese study group of adjuvant therapy for pancreatic (2019) randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol 49:190–194

    Article  Google Scholar 

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Correspondence to Bhawna Sirohi.

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Barreto, S.G., Shrikhande, S.V. & Sirohi, B. Neoadjuvant Therapy in Borderline Resectable Pancreatic Cancer. Indian J Surg Oncol (2021). https://doi.org/10.1007/s13193-021-01361-1

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