BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases

Author:

Bachet J-B12,Moreno-Lopez N3,Vigano L4,Marchese U5,Gelli M6,Raoux L7,Truant S8,Laurent C9,Herrero A10ORCID,Le Roy B11ORCID,Deguelte Lardiere S12,Passot G13ORCID,Hautefeuille V14,De La Fouchardiere C15,Artru P16,Ameto T17,Mabrut J Y18,Schwarz L19,Rousseau B20,Lepère C21,Coriat R22,Brouquet A2324,Sa Cunha A2524,Benoist S2324ORCID

Affiliation:

1. Sorbonne Université, University Pierre and Marie Curie, Paris, France

2. Department of Hepato-Gastroenterology, Hôpital Pitié Salpêtrière, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France

3. Department of Digestive Surgery, Dijon University Hospital, Dijon, France

4. Division of Hepatobiliary and General Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

5. Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France

6. Department of General Surgical Oncology, Gustave Roussy Institute, Villejuif, France

7. Department of Digestive Surgery, University Hospital of Toulouse, University Paul Sabatier, Toulouse, France

8. Department of Digestive Surgery and Transplantation, Lille University Hospital, Lille, France

9. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Saint André Hospital, Bordeaux, France

10. Department of General Surgery, Division of Transplantation, University of Montpellier – College of Medicine, Saint Eloi Hospital, Montpellier, France

11. Department of Digestive Surgery, Estaing University Hospital, Clermont-Ferrand, France

12. Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France

13. Department of Surgical Oncology, Centre Hospitalier Lyon Sud, Pierre Benite, France

14. Department of Gastroenterology, Amiens-Picardie University Hospital, Amiens, France

15. Department of Oncology, Centre Léon Bérard, Lyon, France

16. Department of Oncology, Hôpital Privé Jean Mermoz, Lyon, France

17. Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France

18. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, Hôpital Croix Rousse, Lyon, France

19. Department of Digestive Surgery, Hôpital Charles Nicolle, Rouen, France

20. Department of Oncology, Henri Mondor Hospital, AP-HP, Créteil, France

21. Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, AP-HP, Paris, France

22. Department of Gastroenterology and Digestive Oncology, Cochin Hospital, AP-HP, Paris, France

23. Department of Digestive Surgery and Surgical Oncology, Bicêtre Hospital, AP-HP, Paris–Sud University, Le Kremlin Bicêtre, France

24. Paris–Sud University, Le Kremlin Bicêtre, France

25. Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Paul Brousse Hospital, Villejuif, France

Abstract

Abstract Background BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. Methods The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. Results Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). Conclusion These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

Publisher

Oxford University Press (OUP)

Subject

Surgery

Reference28 articles.

1. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases;Vauthey;Ann Surg,2013

2. Meta-analysis of KRAS mutations and survival after resection of colorectal liver metastases;Brudvik;Br J Surg,2015

3. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study;Cremolini;Lancet Oncol,2015

4. Prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with leucovorin, fluorouracil, and oxaliplatin with or without cetuximab: a post hoc analysis of the PETACC-8 trial;Taieb;JAMA Oncol,2016

5. Prognostic value of BRAF and KRAS mutations in MSI and MSS stage III colon cancer;Taieb;J Natl Cancer Inst,2016

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3