Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study
Authors: van Veldhuisen Eran , Klompmaker Sjors , Janssen Quisette P. , Hilal Mohammed Abu , Alseidi Adnan , Balduzzi Alberto , Balzano Gianpaolo , Bassi Claudio , Berrevoet Frederik , Bonds Morgan , Busch Olivier R. , Butturini Giovanni , Conlon Kevin C. , Frigerio Isabella M. , Fusai Giuseppe K. , Gagnière Johan , Griffin Oonagh , Hackert Thilo , Halimi Asif , Keck Tobias , Kleeff Jörg , Klaiber Ulla , Labori Knut J. , Lesurtel Mickael , Malleo Giuseppe , Marino Marco V. , Molenaar I. Quintus , Mortensen Michael B. , Nikov Andrej , Pagnanelli Michele , Pandé Rupaly , Pfeiffer Per , Pietrasz Daniel , Rangelova Elena , Roberts Keith J. , Cunha Antonio Sa , Salvia Roberto , Strobel Oliver , Tarvainen Timo , Wilmink Johanna W. , Koerkamp Bas Groot , Besselink Marc G. ,   on behalf of the Scientific Committee of the European-African Hepato-Pancreato-Biliary Association, Sauvanet Alain , Marthey Lysiane , Marthey Lysiane , Laurent Christophe , Régenet Nicolas , Coriat Romain , Taieb Julien , Turini Olivier , Dubray Vincent , Bourdariat Raphael , Bachet Jean Baptiste , Schwartz Lilian 
Published: December 2022

Abstract
Background
Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS.

Methods
This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012–2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression.

Results
The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5–8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34–42 months) for BRPC and 33 months (95% CI 27–45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20–2.20) and tumor differentiation (HR 1.43; 95% CI 1.08–1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS.

Conclusions
This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.