Henrik Petrowsky1, Michael Linecker1, Dimitri A Raptis2, Christoph Kuemmerli1, Ralph Fritsch3, Onur E Kirimker4, Deniz Balci4, Francesca Ratti5, Luca Aldrighetti5, Sergey Voskanyan6, Federico Tomassini7, Roberto I Troisi7,8, Jan Bednarsch9, Georg Lurje9,10, Mohammad-Hossein Fard-Aghaie11,12, Tim Reese11,12, Karl J Oldhafer11,12, Omid Ghamarnejad13, Arianeb Mehrabi13, Mauro E Tun Abraham14, Stéphanie Truant15, Francois-René Pruvot15, Emir Hoti16, Patryk Kambakamba16, Ivan Capobianco17, Silvio Nadalin17, Eduardo S M Fernandes18,19, Philipp Kron1,20, Peter Lodge20, Pim B Olthof21, Thomas van Gulik21, Carlos Castro-Benitez22, René Adam22, Marcel Autran Machado23, Martin Teutsch24, Jun Li24, Marcus N Scherer25, Hans J Schlitt25, Victoria Ardiles26, Eduardo de Santibañes26, Roberto Brusadin27, Victor Lopez-Lopez27, Ricardo Robles-Campos27, Massimo Malagó2, Roberto Hernandez-Alejandro14,28, Pierre-Alain Clavien1. 1. Swiss HPB and Transplantation Center, Department of Surgery, University Hospital Zurich, Zurich, Switzerland. 2. Department of HPB- and Liver Transplantation Surgery, University College London, Royal Free Hospitals, London, UK. 3. Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland. 4. Department of Surgery, Ankara University, Ankara, Turkey. 5. Hepatobiliary Surgery Division, Department of Surgery, IRCCS San Raffaele Hospital, School of Medicine, Milan, Italy. 6. Department of Surgery, A.I. Burnazyan FMBC Russian State Scientific Center of FMBA, Moscow, Russia. 7. Department of Human Structure and Repair, Ghent University Faculty of Medicine, Ghent, Belgium. 8. Department of Clinical Medicine and Surgery, Division of HPB, Minimally Invasive and Robotic Surgery, Federico II University Hospital Naples, Naples, Italy. 9. Department of General, Visceral and Transplantation Surgery, University Hospital Aachen, RWTH Aachen, Germany. 10. Department of Surgery, Charité Universitätsmedizin Berlin, Campus Charité Mitte and Campus Virchow Klinikum, Berlin, Germany. 11. Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Hamburg, Germany. 12. Semmelweis University Budapest, Campus Hamburg, Hamburg, Germany. 13. Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. 14. Department of Surgery, Division of HPB Surgery and Liver Transplantation, London Health Sciences Centre, London, Ontario, Canada. 15. Department of Digestive Surgery and Transplantation, University Hospital, Lille, France. 16. Department of Hepatobiliary and Liver Transplant Surgery, St. Vincents University Hospital, Dublin, Ireland. 17. Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Germany. 18. Department of General Surgery and Transplantation, Hospital Adventista Silvestre, and Department of Surgery, Faculty of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 19. Department of Surgery, Rio de Janeiro Federal University, Rio de Janeiro, Brazil. 20. HPB and Transplant Unit, St. James's University Hospital, Leeds, UK. 21. Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands. 22. Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France. 23. Department of Surgery, University of São Paulo, São Paulo, Brazil. 24. Department of Hepatobiliary Surgery and Transplantation University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 25. Department of Surgery and Transplantation, University Hospital Regensburg, Regensburg, Germany. 26. Department of Surgery, Division of HPB Surgery, Liver Transplant Unit, Italian Hospital of Buenos Aires, Buenos Aires, Argentina. 27. Department of Surgery and Liver and Pancreas Transplantation, Virgen de la Arrixaca Clinic and University Hospital and IMIB, Murcia, Spain. 28. Division of Transplantation, Hepatobiliary Surgery, University of Rochester, Rochester, New York.
Abstract
OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.
OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.
Authors: S Acciuffi; F Meyer; A Bauschke; R Croner; U Settmacher; A Altendorf-Hofmann Journal: J Cancer Res Clin Oncol Date: 2021-12-16 Impact factor: 4.553