OBJECTIVE: To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA) score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX. BACKGROUND: The PANAMA score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy. METHODS: This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association. Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy. RESULTS: Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. Discrimination in median overall survival (OS) was observed stratified by risk groups (48.5, 27.6, and 22.3 months, log-rank Plow-intermediate = 0.004, log-rank Pintermediate-high = 0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group [hazard ratio (HR): 1.50, 95% CI: 0.92-2.50], whereas improved OS was observed in the intermediate (HR: 0.58, 95% CI: 0.34-0.97) and high-risk groups (HR: 0.47, 95% CI: 0.24-0.94; P interaction = 0.008). CONCLUSIONS: The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available through pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefits associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS.

Cancer Center Amsterdam Amsterdam The Netherlands

Collegium Medicum University of Social Sciences Lodz Poland

Department of Diagnostics and Intervention Surgery Umeå University Umeå Sweden

Department of Digestive and Hepatobiliary Surgery Liver Transplantation University Hospital of Clermont Ferrand Clermont Ferrand France

Department of Digestive Surgery and Liver Transplantation Croix Rousse University Hospital Hospices Civils de Lyon University of Lyon Lyon France

Department of Gastroenterological Surgery Helsinki University Hospital Helsinki Finland

Department of General and HPB Surgery and Liver Transplantation Ghent University Hospital Ghent Belgium

Department of General and Pancreatic Surgery The Pancreas Institute University of Verona Hospital Trust Verona Italy

Department of General Surgery Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello Palermo Italy and Oncologic Surgery Department P Giaccone University Hospital Palermo Italy

Department of General Surgery Division of Visceral Surgery Medical University of Vienna Vienna Austria

Department of General Visceral and Thoracic Surgery University Hospital Hamburg Eppendorf Hamburg Germany

Department of General Visceral and Transplantation Surgery Heidelberg University Hospital Heidelberg Germany

Department of Hepato Biliary Pancreatic Surgery Liver Transplant Center Paul Brousse Hospital Université Paris Sud Université Paris Saclay Villejuif France

Department of Hepato Pancreato Biliary Surgery Oslo University Hospital Oslo Norway and Institute of Clinical Medicine University of Oslo Oslo Norway

Department of Medical Oncology Amsterdam UMC location University of Amsterdam Amsterdam The Netherlands

Department of Medical Oncology Odense University Hospital Odense Denmark

Department of Medicine and Technological Innovation Pancreas Unit Ospedale di Circolo Insubria University Varese Italy

Department of Pancreatic Surgery IRCCS San Raffaele Hospital Vita Salute University Milano Italy

Department of Surgery Amsterdam UMC location University of Amsterdam Amsterdam The Netherlands

Department of Surgery Charles University and Central Military Hospital Prague Czech Republic

Department of Surgery Erasmus MC Cancer Center Rotterdam The Netherlands

Department of Surgery Odense Pancreas Center Odense University Hospital Odense Denmark

Department of Surgery Oklahoma University Health Science Center Oklahoma City Oklahoma

Department of Surgery Pederzoli Hospital Peschiera Italy

Department of Surgery Trinity College Dublin Trinity Centre for Health Sciences Dublin Ireland

Department of Surgery University Hospital Birmingham Birmingham UK

Department of Surgery University Medical Center Schleswig Holstein UKSH Campus Luebeck Luebeck Germany

Department of Surgery University of California at San Francisco San Francisco

Department of Surgery University of Colorado Hospital Aurora

Department of Visceral Vascular and Endocrine Surgery Martin Luther University Halle Wittenberg Halle Germany

Division of Surgery and Oncology Department of Clinical Science Intervention and Technology Karolinska Institutet Karolinska University Hospital Stockholm Sweden

Hepatobiliary Surgery and Liver Transplantation Unit Royal Free Hospital London UK

National Surgical Centre for Pancreatic Cancer St Vincent's University Hospital Dublin Ireland

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