oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2025-24-4-43-53oncotomsk-3763Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESНепосредственные результаты применения неоадъювантной химиотерапии по схеме mFOLFIRINOX у больных резектабельным раком поджелудочной железыImmediate results of neoadjuvant chemotherapy with mFOLFIRINOX regimen in patients with resectable pancreatic cancerhttps://orcid.org/0000-0002-3036-9779ВервекинИ. В.VervekinI. V.

Вервекин Илья Валерьевич, онколог онкологического отделения № 1 

197022, г. Санкт-Петербург, ул. Льва Толстого, 6–8

Ilya V. Vervekin, MD, Oncologist, Oncology Department No. 1 

6-8, Lva Tolstogo St., Saint Petersburg, 197022

iivervekin@yandex.ruhttps://orcid.org/0000-0002-8514-5377ЗахаренкоА. А.ZakharenkoA. A.

Захаренко Александр Анатольевич, доктор медицинских наук, профессор 

197022, г. Санкт-Петербург, ул. Льва Толстого, 6–8

Aleksandr A. Zakharenko, MD, DSc, Professor 

6-8, Lva Tolstogo St., Saint Petersburg, 197022

ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава РоссииРоссияI.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of RussiaRussian Federation2025011020252444353Copyright © Вервекин И.В., Захаренко А.А., 20252025Вервекин И.В., Захаренко А.А.Vervekin I.V., Zakharenko A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/3763

Цель исследования – оценка эффективности и безопасности применения неоадъювантной химиотерапии (НАХТ) по схеме mFOLFIRINOX в лечении больных резектабельным раком поджелудочной железы. Материал и методы. С 2020 г. по настоящее время в ПСПБГМУ им. акад. И.П. Павлова проводится проспективное исследование II фазы, в котором изучается эффективность НАХТ по схеме mFOLFIRINOX с последующей радикальной операцией при резектабельном РПЖ по сравнению с радикальной операцией на первом этапе. В статье представлен предварительный анализ непосредственных результатов лечения. На сентябрь 2024 г. в исследование было включено 80 пациентов (группа стандартного лечения – n=41, группа НАХТ – n=39). В группе стандартного лечения проводилась радикальная операция с адъювантной полихимиотерапией (АПХТ) по схеме mFOLFIRINOX (оксалиплатин 85 мг/м2, внутривенно 120 мин; иринотекан 150 мг/м2, внутривенно 90 мин; кальция фолинат 400 мг/м2, внутривенно 120 мин; 5-фторурацил 2 400 мг/м2, внутривенная инфузия в течение 46 ч, каждые 2 нед) в объеме 12 циклов, в группе экспериментального лечения первым этапом выполнялась верификация опухоли (тонкоигольная аспирационная биопсия под контролем эндосонографии с последующим цитологическим исследованием или чрескожная трепанационная биопсия), после которой проводилось 6 циклов НАХТ по схеме mFOLFIRINOX, радикальная операция с АПХТ по схеме mFOLFIRINOX в объеме 6 циклов. В рамках данной статьи оценивались непосредственные хирургические результаты лечения, осложнения и летальность. Результаты. Выявлено значимое превосходство группы НАХТ над группой стандартного лечения по показателям: частота резекций воротной и/или верхней брыжеечной вены – 10,2 vs 21,9 % (ОР 0,44, 95 % ДИ [0,149–1,329] p=0,04), R0-резекция – 88,5 vs 73,2 % (ОР 0,6, 95 % ДИ [0,118–0,909], p=0,03), наличие лимфоваскулярной инвазии – 52,6 vs 14,8 % (ОР 0,28, 95 % ДИ [0,108–0,730] p=0,05), микроваскулярной инвазии – 55,2 vs 11,1 % (ОР 0,26, 95 % ДИ [0,1–0,669] p=0,01), периневральной инвазии – 65,7 vs 37 % (ОР 0,56, 95 % ДИ [0,327–0,969] p=0,01), частота отрицательного статуса лимфоузлов (pN0) – 73,1 vs 41,5 % (ОР 0,61, 95 % ДИ [0,331–0,969] p=0,009). Заключение. Неоадъювантная химиотерапия – перспективный и безопасный метод, способный улучшить непосредственные результаты лечения пациентов с резектабельным РПЖ.

The aim of the study was to evaluate of the efficacy and safety of neoadjuvant chemotherapy (nCT) with mFOLFIRINOX regimen for treating patients with resectable pancreatic cancer. Material and Methods. Since 2020, a prospective phase II clinical trial that tests the effectiveness of mFOLFIRINOX chemotherapy followed by radical surgery compared to surgery followed by chemotherapy has been conducted at Pavlov First Saint Petersburg State Medical University for patients with resectable pancreatic cancer. A preliminary analysis of the immediate treatment outcomes has been presented. As of September 2024, 80 patients were included in the study (standard treatment group: n=41, nCT group: n=39). Patients in the standard treatment group underwent radical surgery followed by mFOLFIRINOX aCT (oxaliplatin 85 mg/m2 IV for 120 min, irinotecan 150 mg/m2 IV for 90 min, calcium folinate 400 mg/m2 IV for 120 min, 5-fluorouracil 2400 mg/m2 IV infusion for 46 hours every 2 weeks) for 12 cycles; patients in the experimental treatment group underwent tumor verification at the first stage (endosonography-guided fine-needle aspiration biopsy with subsequent cytological examination or percutaneous biopsy), after which 6 cycles of mFOLFIRINOX nCT and radical surgery followed by mFOLFIRINOX aCT were performed for 6 cycles. The immediate surgical outcomes, complications and mortality rates were assessed. Results. A statistically significant superiority of the nCT group over the standard treatment group was revealed in the following indicators: frequency of portal and/or superior mesenteric vein resections – 10.2 vs 21.9 % (OR 0.44, 95 % CI [0.149–1.329] p=0.04), R0 resections – 88.5 vs 73.2 % (OR 0.6, 95 % CI [0.118–0.909], p=0.03), lymphovascular invasion – 52.6 vs 14.8 % (OR 0.28, 95 % CI [0.108–0.730] p=0.05), microvascular invasion – 55.2 vs 11.1 % (OR 0.26, 95 % CI [0.1–0.669] p=0.01), perineural invasion – 65.7 vs 37 % (OR 0.56, 95 % CI [0.327–0.969] p=0.01), frequency of negative lymph node status (pN0) – 73.1 vs 41.5 % (OR 0.61, 95 % CI [0.331–0.969] p=0.009). Conclusion. nCT is a promising and safe method that can improve immediate treatment outcomes in patients with resectable pancreatic cancer.

рак поджелудочной железынеоадъювантная химиотерапиярезектабельностьR0-резекцияхирургическое лечениепослеоперационные осложненияpancreatic cancerneoadjuvant chemotherapyresectabilityR0-resectionsurgical treatmentpostoperative complicationsReferencesSiegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1): 7–34. doi: 10.3322/caac.21551.Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1): 7–34. doi: 10.3322/caac.21551.Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–49. doi: 10.3322/caac.21660.Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209–49. doi: 10.3322/caac.21660.American Cancer Society. Cancer Facts & Figures 2020. Atlanta: American Cancer Society; 2020. [Internet]. [cited 06.05.2025]. URL: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.American Cancer Society. Cancer Facts & Figures 2020. Atlanta: American Cancer Society; 2020. [Internet]. [cited 06.05.2025]. URL: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.Neoptolemos J.P., Palmer D.H., Ghaneh P., Psarelli E.E., Valle J.W., Halloran C.M., Faluyi O., O’Reilly D.A., Cunningham D., Wadsley J., Darby S., Meyer T., Gillmore R., Anthoney A., Lind P., Glimelius B., Falk S., Izbicki J.R,. Middleton G.W., Cummins S., Ross P.J., Wasan H., McDonald A., Crosby T., Ma Y.T., Patel K., Sherriff D., Soomal R., Borg D., Sothi S., Hammel P., Hackert T., Jackson R., Büchler M.W.; European Study Group for Pancreatic Cancer. 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): 1011–24. doi: 10.1016/S0140-6736(16)32409-6.Neoptolemos J.P., Palmer D.H., Ghaneh P., Psarelli E.E., Valle J.W., Halloran C.M., Faluyi O., O’Reilly D.A., Cunningham D., Wadsley J., Darby S., Meyer T., Gillmore R., Anthoney A., Lind P., Glimelius B., Falk S., Izbicki J.R,. Middleton G.W., Cummins S., Ross P.J., Wasan H., McDonald A., Crosby T., Ma Y.T., Patel K., Sherriff D., Soomal R., Borg D., Sothi S., Hammel P., Hackert T., Jackson R., Büchler M.W.; European Study Group for Pancreatic Cancer. 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): 1011–24. doi: 10.1016/S0140-6736(16)32409-6.Conroy T., Hammel P., Hebbar M., Ben Abdelghani M., Wei A.C., Raoul J.L., Choné L., Francois E., Artru P., Biagi J.J., 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 J.L., Juzyna B., Gourgou S., O’Callaghan C.J., Jouffroy-Zeller C., Rat P., Malka D., Castan F., Bachet J.B.; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018; 379(25): 2395–406. doi: 10.1056/NEJMoa1809775.Conroy T., Hammel P., Hebbar M., Ben Abdelghani M., Wei A.C., Raoul J.L., Choné L., Francois E., Artru P., Biagi J.J., 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 J.L., Juzyna B., Gourgou S., O’Callaghan C.J., Jouffroy-Zeller C., Rat P., Malka D., Castan F., Bachet J.B.; Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018; 379(25): 2395–406. doi: 10.1056/NEJMoa1809775.Groot V.P., Rezaee N., Wu.W., Cameron J.L., Fishman E.K., Hruban R.H., Weiss M.J., Zheng L., Wolfgang C.L., He J. Patterns, Timing, and Predictors of Recurrence Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma. Ann Surg. 2018; 267(5): 936–45. doi: 10.1097/SLA.0000000000002234.Groot V.P., Rezaee N., Wu.W., Cameron J.L., Fishman E.K., Hruban R.H., Weiss M.J., Zheng L., Wolfgang C.L., He J. Patterns, Timing, and Predictors of Recurrence Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma. Ann Surg. 2018; 267(5): 936–45. doi: 10.1097/SLA.0000000000002234.Sauer R., Becker H., Hohenberger W., Rödel C., Wittekind C., Fietkau R., Martus P., Tschmelitsch J., Hager E., Hess C.F., Karstens J.H., Liersch T., Schmidberger H., Raab R.; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004; 351(17): 1731–40. doi: 10.1056/NEJMoa040694.Sauer R., Becker H., Hohenberger W., Rödel C., Wittekind C., Fietkau R., Martus P., Tschmelitsch J., Hager E., Hess C.F., Karstens J.H., Liersch T., Schmidberger H., Raab R.; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004; 351(17): 1731–40. doi: 10.1056/NEJMoa040694.Cunningham D., Allum W.H., Stenning S.P., Thompson J.N., van de Velde C.J., Nicolson M., Scarffe J.H., Lofts F.J., Falk S.J., Iveson T.J., Smith D.B., Langley R.E., Verma M., Weeden S., Chua Y.J., MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006; 355(1): 11–20. doi: 10.1056/NEJMoa055531.Cunningham D., Allum W.H., Stenning S.P., Thompson J.N., van de Velde C.J., Nicolson M., Scarffe J.H., Lofts F.J., Falk S.J., Iveson T.J., Smith D.B., Langley R.E., Verma M., Weeden S., Chua Y.J., MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006; 355(1): 11–20. doi: 10.1056/NEJMoa055531.van Hagen P., Hulshof M.C., van Lanschot J.J., Steyerberg E.W., van Berge Henegouwen M.I., Wijnhoven B.P., Richel D.J., Nieuwenhuijzen G.A., Hospers G.A., Bonenkamp J.J., Cuesta M.A., Blaisse R.J., Busch O.R., ten Kate F.J., Creemers G.J., Punt C.J., Plukker J.T., Verheul H.M., Spillenaar Bilgen E.J., van Dekken H., van der Sangen M.J., Rozema T., Biermann K., Beukema J.C., Piet A.H., van Rij C.M., Reinders J.G., Tilanus H.W., van der Gaast. A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012; 366(22): 2074–84. doi: 10.1056/NEJMoa1112088.van Hagen P., Hulshof M.C., van Lanschot J.J., Steyerberg E.W., van Berge Henegouwen M.I., Wijnhoven B.P., Richel D.J., Nieuwenhuijzen G.A., Hospers G.A., Bonenkamp J.J., Cuesta M.A., Blaisse R.J., Busch O.R., ten Kate F.J., Creemers G.J., Punt C.J., Plukker J.T., Verheul H.M., Spillenaar Bilgen E.J., van Dekken H., van der Sangen M.J., Rozema T., Biermann K., Beukema J.C., Piet A.H., van Rij C.M., Reinders J.G., Tilanus H.W., van der Gaast. A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012; 366(22): 2074–84. doi: 10.1056/NEJMoa1112088.Exarchakou A., Papacleovoulou G., Rous B., Magadi W., Rachet B., Neoptolemos J.P., Coleman M.P. Pancreatic cancer incidence and survival and the role of specialist centres in resection rates in England, 2000 to 2014: A population-based study. Pancreatology. 2020; 20(3): 454–61. doi: 10.1016/j.pan.2020.01.012.Exarchakou A., Papacleovoulou G., Rous B., Magadi W., Rachet B., Neoptolemos J.P., Coleman M.P. Pancreatic cancer incidence and survival and the role of specialist centres in resection rates in England, 2000 to 2014: A population-based study. Pancreatology. 2020; 20(3): 454–61. doi: 10.1016/j.pan.2020.01.012.Chiaravalli M., Reni M., O’Reilly E.M. Pancreatic ductal adenocarcinoma: State-of-the-art 2017 and new therapeutic strategies. Cancer Treat Rev. 2017; 60: 32–43. doi: 10.1016/j.ctrv.2017.08.007.Chiaravalli M., Reni M., O’Reilly E.M. Pancreatic ductal adenocarcinoma: State-of-the-art 2017 and new therapeutic strategies. Cancer Treat Rev. 2017; 60: 32–43. doi: 10.1016/j.ctrv.2017.08.007.Mokdad A.A., Minter R.M., Zhu H., Augustine M.M., Porembka M.R., Wang S.C., Yopp A.C., Mansour J.C., Choti M.A., Polanco P.M. Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis. J Clin Oncol. 2017; 35(5): 515–22. doi: 10.1200/JCO.2016.68.5081.Mokdad A.A., Minter R.M., Zhu H., Augustine M.M., Porembka M.R., Wang S.C., Yopp A.C., Mansour J.C., Choti M.A., Polanco P.M. Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis. J Clin Oncol. 2017; 35(5): 515–22. doi: 10.1200/JCO.2016.68.5081.Versteijne E., Suker M., Groothuis K., Akkermans-Vogelaar J.M., Besselink M.G., Bonsing B.A., Buijsen J., Busch O.R., Creemers G.M., van Dam R.M., Eskens FALM, Festen S., de Groot J.W.B., Groot Koerkamp B., de Hingh I.H., Homs M.Y.V., van Hooft J.E., Kerver E.D., Luelmo S.A.C., Neelis K.J., Nuyttens J., Paardekooper G.M.R.M., Patijn G.A., van der Sangen M.J.C., de Vos-Geelen J., Wilmink J.W., Zwinderman A.H., Punt C.J., van Eijck C.H., van Tienhoven G.; Dutch Pancreatic Cancer Group. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020; 38(16): 1763–73. doi: 10.1200/JCO.19.02274.Versteijne E., Suker M., Groothuis K., Akkermans-Vogelaar J.M., Besselink M.G., Bonsing B.A., Buijsen J., Busch O.R., Creemers G.M., van Dam R.M., Eskens FALM, Festen S., de Groot J.W.B., Groot Koerkamp B., de Hingh I.H., Homs M.Y.V., van Hooft J.E., Kerver E.D., Luelmo S.A.C., Neelis K.J., Nuyttens J., Paardekooper G.M.R.M., Patijn G.A., van der Sangen M.J.C., de Vos-Geelen J., Wilmink J.W., Zwinderman A.H., Punt C.J., van Eijck C.H., van Tienhoven G.; Dutch Pancreatic Cancer Group. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020; 38(16): 1763–73. doi: 10.1200/JCO.19.02274.Casadei R., Di Marco M., Ricci C., Santini D., Serra C., Calculli L., D’Ambra M., Guido A., Morselli-Labate A.M., Minni F. Neoadjuvant Chemoradiotherapy and Surgery Versus Surgery Alone in Resectable Pancreatic Cancer: A Single-Center Prospective, Randomized, Controlled Trial Which Failed to Achieve Accrual Targets. J Gastrointest Surg. 2015; 19(10): 1802–12. doi: 10.1007/s11605-015-2890-4.Casadei R., Di Marco M., Ricci C., Santini D., Serra C., Calculli L., D’Ambra M., Guido A., Morselli-Labate A.M., Minni F. Neoadjuvant Chemoradiotherapy and Surgery Versus Surgery Alone in Resectable Pancreatic Cancer: A Single-Center Prospective, Randomized, Controlled Trial Which Failed to Achieve Accrual Targets. J Gastrointest Surg. 2015; 19(10): 1802–12. doi: 10.1007/s11605-015-2890-4.Jang J.Y., Han Y., Lee H., Kim S.W., Kwon W., Lee K.H., Oh D.Y., Chie E.K., Lee J.M., Heo J.S., Park J.O., Lim D.H., Kim S.H., Park S.J., Lee W.J., Koh Y.H., Park J.S., Yoon D.S., Lee I.J., Choi S.H. Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial. Ann Surg. 2018; 268(2): 215–22. doi: 10.1097/SLA.0000000000002705.Jang J.Y., Han Y., Lee H., Kim S.W., Kwon W., Lee K.H., Oh D.Y., Chie E.K., Lee J.M., Heo J.S., Park J.O., Lim D.H., Kim S.H., Park S.J., Lee W.J., Koh Y.H., Park J.S., Yoon D.S., Lee I.J., Choi S.H. Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial. Ann Surg. 2018; 268(2): 215–22. doi: 10.1097/SLA.0000000000002705.Reni M., Balzano G., Zanon S., Zerbi A., Rimassa L., Castoldi R., Pinelli D., Mosconi S., Doglioni C., Chiaravalli M., Pircher C., Arcidiacono P.G., Torri V., Maggiora P., Ceraulo D., Falconi M., Gianni L. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018; 3(6): 413–23. doi: 10.1016/S2468-1253(18)30081-5.Reni M., Balzano G., Zanon S., Zerbi A., Rimassa L., Castoldi R., Pinelli D., Mosconi S., Doglioni C., Chiaravalli M., Pircher C., Arcidiacono P.G., Torri V., Maggiora P., Ceraulo D., Falconi M., Gianni L. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018; 3(6): 413–23. doi: 10.1016/S2468-1253(18)30081-5.Ghaneh P., Palmer D., Cicconi S., Jackson R., Halloran C.M., Rawcliffe C., Sripadam R., Mukherjee S., Soonawalla Z., Wadsley J., Al-Mukhtar A., Dickson E., Graham J., Jiao L., Wasan H.S., Tait I.S., Prachalias A., Ross P., Valle J.W., O’Reilly .DA., Al-Sarireh B., Gwynne S., Ahmed I., Connolly K., Yim K.L., Cunningham D., Armstrong T., Archer C., Roberts K., Ma Y.T., Springfeld C., Tjaden C., Hackert T., Büchler M.W., Neoptolemos J.P.; European Study Group for Pancreatic Cancer. Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2023; 8(2): 157–68. doi: 10.1016/S2468-1253(22)00348-X.Ghaneh P., Palmer D., Cicconi S., Jackson R., Halloran C.M., Rawcliffe C., Sripadam R., Mukherjee S., Soonawalla Z., Wadsley J., Al-Mukhtar A., Dickson E., Graham J., Jiao L., Wasan H.S., Tait I.S., Prachalias A., Ross P., Valle J.W., O’Reilly .DA., Al-Sarireh B., Gwynne S., Ahmed I., Connolly K., Yim K.L., Cunningham D., Armstrong T., Archer C., Roberts K., Ma Y.T., Springfeld C., Tjaden C., Hackert T., Büchler M.W., Neoptolemos J.P.; European Study Group for Pancreatic Cancer. Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2023; 8(2): 157–68. doi: 10.1016/S2468-1253(22)00348-X.Seufferlein T., Uhl W., Kornmann M., Algül H., Friess H., König A., Ghadimi M., Gallmeier E., Bartsch D.K., Lutz M.P., Metzger R., Wille K., Gerdes B., Schimanski C.C., Graupe F., Kunzmann V., Klein I., Geissler M., Staib L., Waldschmidt D., Bruns C., Wittel U., Fichtner-Feigl S., Daum S., Hinke A., Blome L., Tannapfel A., Kleger A., Berger A.W., Kestler A.M.R., Schuhbaur J.S., Perkhofer L., Tempero M., Reinacher-Schick A.C., Ettrich T.J. Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group. Ann Oncol. 2023; 34(1): 91–100. doi: 10.1016/j.annonc.2022.09.161.Seufferlein T., Uhl W., Kornmann M., Algül H., Friess H., König A., Ghadimi M., Gallmeier E., Bartsch D.K., Lutz M.P., Metzger R., Wille K., Gerdes B., Schimanski C.C., Graupe F., Kunzmann V., Klein I., Geissler M., Staib L., Waldschmidt D., Bruns C., Wittel U., Fichtner-Feigl S., Daum S., Hinke A., Blome L., Tannapfel A., Kleger A., Berger A.W., Kestler A.M.R., Schuhbaur J.S., Perkhofer L., Tempero M., Reinacher-Schick A.C., Ettrich T.J. Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group. Ann Oncol. 2023; 34(1): 91–100. doi: 10.1016/j.annonc.2022.09.161.Labori K,J., Bratlie S,O., Andersson B., Angelsen J.,H., Biörserud C., Björnsson B., Bringeland E.A., Elander N., Garresori H., Grønbech J.E., Haux J., Hemmingsson O., Liljefors M.G., Myklebust T.Å., Nymo L.S., Peltola K., Pfeiffer P., Sallinen V., Sandström P., Sparrelid E., Stenvold H., Søreide K., Tingstedt B., Verbeke C., Öhlund D., Klint L., Dueland S., Lassen K.; Nordic Pancreatic Cancer Trial-1 study group. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024; 9(3): 205–17. doi: 10.1016/S2468-1253-(23)00405-3.Labori K,J., Bratlie S,O., Andersson B., Angelsen J.,H., Biörserud C., Björnsson B., Bringeland E.A., Elander N., Garresori H., Grønbech J.E., Haux J., Hemmingsson O., Liljefors M.G., Myklebust T.Å., Nymo L.S., Peltola K., Pfeiffer P., Sallinen V., Sandström P., Sparrelid E., Stenvold H., Søreide K., Tingstedt B., Verbeke C., Öhlund D., Klint L., Dueland S., Lassen K.; Nordic Pancreatic Cancer Trial-1 study group. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024; 9(3): 205–17. doi: 10.1016/S2468-1253-(23)00405-3.Tempero M.A., Malafa M.P., Al-Hawary M., Behrman S.W., Benson A.B., Cardin D.B., Chiorean E.G., Chung V., Czito B., Del Chiaro M., Dillhoff M., Donahue T.R., Dotan E., Ferrone C.R., Fountzilas C., Hardacre J., Hawkins W.G., Klute K., Ko A.H., Kunstman J.W., LoConte N., Lowy A.M., Moravek C., Nakakura E.K., Narang A.K., Obando J., Polanco P.M., Reddy S., Reyngold M., Scaife C., Shen J., Vollmer C., Wolff R.A., Wolpin B.M., Lynn B., George G.V. Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021; 19(4): 439–57. doi: 10.6004/jnccn.2021.0017.Tempero M.A., Malafa M.P., Al-Hawary M., Behrman S.W., Benson A.B., Cardin D.B., Chiorean E.G., Chung V., Czito B., Del Chiaro M., Dillhoff M., Donahue T.R., Dotan E., Ferrone C.R., Fountzilas C., Hardacre J., Hawkins W.G., Klute K., Ko A.H., Kunstman J.W., LoConte N., Lowy A.M., Moravek C., Nakakura E.K., Narang A.K., Obando J., Polanco P.M., Reddy S., Reyngold M., Scaife C., Shen J., Vollmer C., Wolff R.A., Wolpin B.M., Lynn B., George G.V. Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021; 19(4): 439–57. doi: 10.6004/jnccn.2021.0017.Merkow R.P., Bilimoria K.Y., Tomlinson J.S., Paruch J.L., Fleming J.B., Talamonti M.S., Ko C.Y., Bentrem D.J. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014; 260(2): 372–77. doi: 10.1097/SLA.0000000000000378.Merkow R.P., Bilimoria K.Y., Tomlinson J.S., Paruch J.L., Fleming J.B., Talamonti M.S., Ko C.Y., Bentrem D.J. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014; 260(2): 372–77. doi: 10.1097/SLA.0000000000000378.Springfeld C., Ferrone C.R., Katz M.H.G., Philip P.A., Hong T.S., Hackert T., Büchler M.W., Neoptolemos J. Neoadjuvant therapy for pancreatic cancer. Nat Rev Clin Oncol. 2023; 20(5): 318–37. doi: 10.1038/s41571-023-00746-1.Springfeld C., Ferrone C.R., Katz M.H.G., Philip P.A., Hong T.S., Hackert T., Büchler M.W., Neoptolemos J. Neoadjuvant therapy for pancreatic cancer. Nat Rev Clin Oncol. 2023; 20(5): 318–37. doi: 10.1038/s41571-023-00746-1.Ahmad S.A., Duong M., Sohal D.P.S., Gandhi N.S., Beg M.S., WangGillam A., Wade J.L. 3rd, Chiorean E.G., Guthrie K.A., Lowy A.M., Philip P.A., Hochster H.S. 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. 2020; 272(3): 481–86. doi: 10.1097/SLA.0000000000004155.Ahmad S.A., Duong M., Sohal D.P.S., Gandhi N.S., Beg M.S., WangGillam A., Wade J.L. 3rd, Chiorean E.G., Guthrie K.A., Lowy A.M., Philip P.A., Hochster H.S. 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. 2020; 272(3): 481–86. doi: 10.1097/SLA.0000000000004155.Versteijne E., van Dam J.L., Suker M., Janssen Q.P., Groothuis K., Akkermans-Vogelaar J.M., Besselink M.G., Bonsing B.A., Buijsen J., Busch O.R., Creemers G.M., van Dam R.M., Eskens F.A.L.M., Festen S., de Groot J.W.B., Groot Koerkamp B., de Hingh I.H. Homs M.Y.V., van Hooft J.E., Kerver E.D., Luelmo S.A.C., Neelis K.J., Nuyttens J., Paardekooper G.M.R.M., Patijn G.A., van der Sangen M.J.C., de VosGeelen J., Wilmink J.W., Zwinderman A.H., Punt C.J., van Tienhoven G., van Eijck C.H.J.; Dutch Pancreatic Cancer Group. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022; 40(11): 1220–30. doi: 10.1200/JCO.21.02233.Versteijne E., van Dam J.L., Suker M., Janssen Q.P., Groothuis K., Akkermans-Vogelaar J.M., Besselink M.G., Bonsing B.A., Buijsen J., Busch O.R., Creemers G.M., van Dam R.M., Eskens F.A.L.M., Festen S., de Groot J.W.B., Groot Koerkamp B., de Hingh I.H. Homs M.Y.V., van Hooft J.E., Kerver E.D., Luelmo S.A.C., Neelis K.J., Nuyttens J., Paardekooper G.M.R.M., Patijn G.A., van der Sangen M.J.C., de VosGeelen J., Wilmink J.W., Zwinderman A.H., Punt C.J., van Tienhoven G., van Eijck C.H.J.; Dutch Pancreatic Cancer Group. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022; 40(11): 1220–30. doi: 10.1200/JCO.21.02233.

The authors declare that there are no conflicts of interest present.