Alma L Moekotte1, Stijn van Roessel2, Giuseppe Malleo3, Rushda Rajak4, Brett L Ecker5, Martina Fontana3, Ho-Seong Han6, Mohamed Rabie6, Keith J Roberts7, Khalid Khalil7, Steven A White8, Stuart Robinson8, Asif Halimi9, Laura Zarantonello9, Giuseppe K Fusai10, George Gradinariu10, Adnan Alseidi11, Morgan Bonds11, Stephan Dreyer12, Nigel B Jamieson12, Nicholas Mowbray13, Bilal Al-Sarireh13, Vasileios K Mavroeidis14, Zahir Soonawalla14, Niccolò Napoli15, Ugo Boggi15, Tara S Kent16, William E Fisher17, Chung N Tang18, Louisa Bolm19, Michael G House20, Mary E Dillhoff21, Stephen W Behrman22, Masafumi Nakamura23, Chad G Ball24, Adam C Berger25, John D Christein26, Amer H Zureikat27, Ronald R Salem28, Charles M Vollmer5, Roberto Salvia3, Marc G Besselink2, Mohammed Abu Hilal29, Ra'ed Aljarrah30, Courtney Barrows16, Martha Navarro Cagigas17, Eric C H Lai18, Ulrich Wellner18, John Aversa19, Paxton V Dickson22, Takao Ohtsuka23, Elijah Dixon24, Richard Zheng25, Stacy Kowalski27, Mollie Freedman-Weiss28. 1. Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK; Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: a.l.moekotte@soton.ac.uk. 2. Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. 3. Department of Surgery, University Hospital of Verona, Verona, Italy. 4. Department of Histopathology, University Hospital of Southampton NHS Foundation Trust, Southampton, UK. 5. Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA. 6. Department of Surgery, Seoul National University Bundang Hospital, Seoul National University, College of Medicine, South Korea. 7. Faculty of Medicine, University of Birmingham, Birmingham, UK. 8. Department of Surgery, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK. 9. Pancreatic Surgery Unit, Division of Surgery, Karolinska University Hospital, Stockholm, Sweden. 10. Department of Surgery, Royal Free Hospital NHS Foundation Trust, London, UK. 11. Department of Surgery, Virginia Mason Medical Center, Seattle, USA. 12. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. 13. Department of Surgery, Morriston Hospital, Swansea, UK. 14. Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 15. Department of Surgery, Pisa University Hospital, Pisa, Italy. 16. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. 17. Department of Surgery, Baylor College of Medicine, Houston, USA. 18. Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. 19. Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. 20. Department of Surgery, Indiana University School of Medicine, Indianapolis, USA. 21. Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, USA. 22. Department of Surgery, University of Tennessee Health Science Center, Memphis, USA. 23. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 24. Department of Surgery, University of Calgary, Calgary, Alberta, Canada. 25. Department of Surgery, Jefferson Medical College, Philadelphia, USA. 26. Department of Surgery, University of Alabama School of Medicine, Birmingham, USA. 27. Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA. 28. Department of Surgery, Yale School of Medicine, New Haven, USA. 29. Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK; Department of Surgery, Istituto Fondazione Poliambulanza, Brescia, Italy. Electronic address: abuhilal9@gmail.com. 30. Department of Surgery, University Hospital of Southampton NHS Foundation Trust, Southampton, UK.
Abstract
INTRODUCTION: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. MATERIALS AND METHODS: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. RESULTS: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. CONCLUSION: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.
INTRODUCTION: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. MATERIALS AND METHODS: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. RESULTS: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. CONCLUSION: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.