René Adam1, Bin Yi2, Pasquale F Innominato3, Eduardo Barroso4, Christophe Laurent5, Felice Giuliante6, Lorenzo Capussotti7, Réal Lapointe8, Jean-Marc Regimbeau9, Santiago Lopez-Ben10, Helena Isoniemi11, Catherine Hubert12, Jen-Kou Lin13, Thomas Gruenberger14, Dominique Elias15, Oleg G Skipenko16, Alfredo Guglielmi17. 1. Hepatobiliary Center, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Inserm U935, Villejuif, France. Electronic address: rene.adam@aphp.fr. 2. Hepatobiliary Center, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Inserm U935, Villejuif, France; Eastern Hepatobiliary Surgery Hospital/National Liver Cancer Center, Second Military Medical University, Shanghai, China. 3. Department of Oncology, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Inserm U935, Villejuif, France. 4. Department of HPB Surgery and Transplantation, Curry Cabral Hospital, Lisbon, Portugal. 5. Department of Digestive Surgery, Hôpital Saint André, Bordeaux, France. 6. Hepatobiliary Surgery Unit, Agostino Gemelli Hospital, Catholic University of the Sacred Heart, Rome, Italy. 7. Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy. 8. HPB Surgery and Transplantation Unit, Hôpital Saint-Luc, Centre Hospitalier de l'Université de Montréal, Montréal, Canada. 9. Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France. 10. Hepatobiliary and Pancreatic Surgery Unit, Department of Surgery, Dr. Josep Trueta Hospital, IdlBGi, Girona, Spain. 11. Department of Transplantation and Liver Surgery, Helsinki University Hospital, Helsinki, Finland. 12. Unit of HPB Surgery, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. 13. Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. 14. Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria. 15. Department of Oncologic Surgery, Institut Gustave Roussy, Villejuif, France. 16. Research Center of Surgery, Russian Academy of Medical Science, Moscow, Russia. 17. Division of Surgery A, Department of Surgery, GB Rossi Hospital, University of Verona, Verona, Italy.
Abstract
PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed. RESULTS: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2. CONCLUSION: CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.
PURPOSE:Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed. RESULTS: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2. CONCLUSION: CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.
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