Is hepatectomy justified for BRAF mutant colorectal liver metastases?: A multi-institutional analysis of 1497 patients Journal Article


Authors: Gagnière, J.; Dupré, A.; Gholami, S. S.; Pezet, D.; Boerner, T.; Gönen, M.; Kingham, T. P.; Allen, P. J.; Balachandran, V. P.; De Matteo, R. P.; Drebin, J. A.; Yaeger, R.; Kemeny, N. E.; Jarnagin, W. R.; D'Angelica, M. I.
Article Title: Is hepatectomy justified for BRAF mutant colorectal liver metastases?: A multi-institutional analysis of 1497 patients
Abstract: Objective: To analyze clinical outcomes and prognostic variables of patients undergoing hepatic resection for BRAF mutant (BRAF-mut) colorectal liver metastases (CRLM). Background: Outcomes following hepatectomy for BRAF-mut CRLM have not been well studied. Methods: All patients who underwent hepatectomy for CRLM with complete resection and known BRAF status during 2001 to 2016 at 3 high-volume centers were analyzed. Results: Of 4124 patients who underwent hepatectomy for CRLM, 1497 had complete resection and known BRAF status. Thirty-five (2%) patients were BRAF-mut, with 71% of V600E mutation. Compared with BRAF wild-type (BRAF-wt), BRAF-mut patients were older, more commonly presented with higher ASA scores, synchronous, multiple and smaller CRLM, underwent more major hepatectomies, but had less extrahepatic disease. Median overall survival (OS) was 81 months for BRAF-wt and 40 months for BRAF-mut patients (P < 0.001). Median recurrence-free survival (RFS) was 22 and 10 months for BRAF-wt and BRAF-mut patients (P < 0.001). For BRAF-mut, factors associated with worse OS were node-positive primary tumor, carcinoembryonic antigen (CEA) >200'μg/L, and clinical risk score (CRS) ≥4. Factors associated with worse RFS were node-positive primary tumor, ≥4 CRLM, and positive hepatic margin. V600E mutations were not associated with worse OS or RFS. A case-control matching analysis on prognostic clinicopathologic factors confirmed shorter OS (P < 0.001) and RFS (P < 0.001) in BRAF-mut.Conclusions: Patients with resectable BRAF-mut CRLM are rare among patients selected for surgery and more commonly present with multiple synchronous tumors. BRAF mutation is associated with worse prognosis; however, long-term survival is possible and associated with node-negative primary tumors, CEA ≤ 200'μg/L and CRS < 4. © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: adult; cancer survival; controlled study; middle aged; primary tumor; gene mutation; major clinical study; overall survival; case control study; bevacizumab; lymph node metastasis; laparoscopic surgery; prospective study; carcinoembryonic antigen; wild type; cetuximab; risk assessment; irinotecan; scoring system; liver resection; liver surgery; hepatectomy; oxaliplatin; b raf kinase; braf mutation; colorectal liver metastases; recurrence free survival; metastatic colorectal cancer; clinical outcome; open surgery; cancer prognosis; clinical outcomes; long term survival; colorectal liver metastasis; prognosis; human; male; female; priority journal; article; high volume hospital; robot assisted surgery
Journal Title: Annals of Surgery
Volume: 271
Issue: 1
ISSN: 0003-4932
Publisher: Lippincott Williams & Wilkins  
Date Published: 2020-01-01
Start Page: 147
End Page: 154
Language: English
DOI: 10.1097/sla.0000000000002968
PUBMED: 29995686
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Ronald P DeMatteo
    637 DeMatteo
  2. Mithat Gonen
    1029 Gonen
  3. Peter Allen
    501 Allen
  4. William R Jarnagin
    903 Jarnagin
  5. Rona Denit Yaeger
    316 Yaeger
  6. T Peter Kingham
    609 Kingham
  7. Sepideh Gholami
    32 Gholami
  8. Nancy Kemeny
    543 Kemeny
  9. Jeffrey Adam Drebin
    165 Drebin
  10. Thomas Boerner
    71 Boerner