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Multicenter Study
. 2025 Apr;32(4):2809-2818.
doi: 10.1245/s10434-024-16735-2. Epub 2025 Jan 8.

Prognosis Associated with Complete Pathological Response Following Neoadjuvant Treatment for PancreaTic AdenOcarciNOma in the FOFLIRINOX Era: the Multicenter TONO Study

Pietro Addeo  1 , Milena Muzzolini  2 , Christophe Laurent  3 , Bruno Heyd  4 , Alain Sauvanet  2 , Jonathan Garnier  5 , Marie Sophie Alfano  5 , Sebastien Gaujoux  6 , Charles De Ponthaud  6 , Ugo Marchese  7 , Doris Da Silva  7 , Emmanuel Buc  8 , Regis Souche  9 , Jean Michel Fabre  9 , Pierre-Emanuel Colombo  10 , Lorenzo Ferre  10 , Maxime Foguenne  11 , Catherine Hubert  11 , Mehdi El Amrani  12 , Stephanie Truant  12 , Lilian Schwartz  13 , Nicolas Regenet  14 , Aurelien Dupre  15 , Raffaele Brustia  16 , Rim Cherif  16 , Julie Navez  17 , Benjamin Darnis  18 , Olivier Facy  19 , Robin Grellet  19 , Guillaume Piessen  20 , Julie Veziant  20 , Rami Rhaiem  21 , Reza Kianmanesh  21 , Elena Fernandez-De-Sevilla  22 , Maximiliano Gelli  22 , Abdelkader Taibi  23 , Pauline Georges  24 , Jean Yves Mabrut  24 , Mickael Lesurtel  2 , Alexandre Doussot  4 , Philippe Bachellier  25
Affiliations
Multicenter Study

Prognosis Associated with Complete Pathological Response Following Neoadjuvant Treatment for PancreaTic AdenOcarciNOma in the FOFLIRINOX Era: the Multicenter TONO Study

Pietro Addeo et al. Ann Surg Oncol. 2025 Apr.

Abstract

Background: The use of multiagent FOLFIRINOX chemotherapy for pancreatic adenocarcinoma in a neoadjuvant setting has been associated with an increased rate of complete pathological response (CPR) after surgery. This study investigated the long-term outcomes of patients with CPR in a multicenter setting to identify prognostic factors for overall survival (OS) and recurrence-free survival (RFS).

Methods: This retrospective cohort study examined biopsy-proven pancreatic adenocarcinomas with CPR after neoadjuvant chemotherapy or chemoradiotherapy and surgery, between January 2006 and December 2023 across 22 French and 2 Belgian centers. Cox analyses were used to identify prognostic factors of OS and RFS.

Results: There were 101 patients with CPR after chemotherapy (n = 58, 57.4%) and chemoradiotherapy (n = 43, 42.6%) followed by surgery. Neoadjuvant FOLFIRINOX was used in 90% of patients. The median OS after surgery was 177 months (95% confidence interval (CI) 58.9-177 months) with 1-, 3-, 5-, and 10-year OS rates of 93%, 75%, 63%, and 51%, respectively. The median RFS was 67.8 months (95% CI:34.4-NR) with 1-, 3-, 5-, and 10-year RFS rates of 83%, 58%, 54%, and 49%, respectively. The multivariate Cox analysis of OS and RFS showed that preoperative radiotherapy was an independent negative prognostic factor for OS (hazard ratio (HR) 2.51; 95% CI 1.00-6.30; p = 0.03) and RFS (HR 2.62; 95% CI 1.27-5.41; p = 0.009).

Conclusions: Complete pathologic response after neoadjuvant treatment is associated with remarkable long-term survival that is usually not seen after the resection of pancreatic adenocarcinomas. One-third of the patients still experienced disease recurrence, which was more common in those receiving preoperative chemoradiotherapy.

Keywords: Complete pathologic response; FOLFIRINOX; Neoadjuvant chemotherapy; Pancreatic adenocarcinoma; Radiotherapy.

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Conflict of interest statement

Disclosure: Guillaume Piessen BMS: consulting, board Nestlé: consulting Astellas pharma: consulting Medtronic: travel, accommodation MSD: travel, accommodation, consulting, lecture Daiichi: consulting Elivie : lecture Strycker: consulting

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