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Original Investigation
September 10, 2020

Evaluation of Adjuvant Chemotherapy in Patients With Resected Pancreatic Cancer After Neoadjuvant FOLFIRINOX Treatment

Author Affiliations
  • 1Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, the Netherlands
  • 2Department of Radiology, St Antonius Hospital, Nieuwegein, the Netherlands
  • 3Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 4Department of Surgery, University Hospital Southampton National Health Service, Southampton, Hampshire, United Kingdom
  • 5Department of General Surgery, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy
  • 6Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
  • 7Department of Surgery, University of California at San Francisco, San Francisco
  • 8Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
  • 9Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Hospital, Milan, Italy
  • 10Department of General and Hepatobiliary Surgery, Gent University Hospital, Gent, Belgium
  • 11Department of Surgery, Pederzoli Hospital, Peschiera, Italy
  • 12Department of Surgery, University of Colorado Hospital, Aurora
  • 13Department of Surgery, Trinity College Dublin, Trinity Centre for Health Sciences, Dublin, Ireland
  • 14Hepatobiliary Surgery and Liver Transplantation Unit, Royal Free Hospital, London, United Kingdom
  • 15Department of Digestive and Hepatobiliary Surgery–Liver Transplantation, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France
  • 16Department of Surgery, Clermont-Auvergne University, Clermont-Ferrand, France
  • 17Department of General, Visceral and Transplantation Surgery, Universitätsklinikum Heidelberg, Heidelberg, Germany
  • 18Department of Surgery, Karolinska Institutet, Stockholm, Sweden
  • 19Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
  • 20General Surgery Department, Azienda Ospedaliera, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
  • 21Department of General Surgery, Hospital Universitario Marques de Valdecilla, Santander, Spain
  • 22Department of Surgery, Odense Pancreas Center, Odense University Hospital, Odense, Denmark
  • 23Department of Surgery, Charles University and Central Military Hospital, Prague, Czech Republic
  • 24Department of Digestive Surgery and Liver Transplantation, Croix Rousse University Hospital, Hospices Civils de Lyon, University of Lyon, Lyon, France
  • 25Department of Surgery, Universitaet zu Luebeck, Luebeck, Germany
  • 26Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany
  • 27Department of Surgery, University Hospital Birmingham, Birmingham, United Kingdom
  • 28Department of Medical Oncology, Odense University Hospital, Odense, Denmark
  • 29Department of Hepato-Biliary-Pancreatic Surgery, Liver Transplant Center, Paul Brousse Hospital, Université Paris-Sud, Université Paris-Saclay, Villejuif, France
  • 30Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland
  • 31Department of Clinical Epidemiology, Amsterdam University Medical Center, University of Amsterdam, the Netherlands
  • 32Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, the Netherlands
JAMA Oncol. Published online September 10, 2020. doi:10.1001/jamaoncol.2020.3537
Key Points

Question  Do patients who underwent resection of pancreatic cancer after neoadjuvant combination folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy benefit from adjuvant chemotherapy?

Findings  This international cohort study of 520 patients with resected pancreatic cancer found that adjuvant chemotherapy was significantly associated with improved survival in 254 patients with pathology-proven node-positive disease but not in 256 patients with node-negative disease.

Meaning  Adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease.

Abstract

Importance  The benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.

Objective  To assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.

Design, Setting, and Participants  This international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded.

Exposures  The association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise.

Results  We included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73).

Conclusions and Relevance  These results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.

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