title: Is hepatectomy justified for patients with RAS mutant colorectal liver metastases? An analysis of 524 patients undergoing curative liver resection.
abstract: RAS mutations are associated with limited overall survival after resection of colorectal liver metastases. Our aim was to determine criteria for considering hepatectomy for patients with RAS mutant colorectal liver metastases.
  
  
  
  Of 1,163 patients who underwent liver resection for colorectal liver metastases during 2005-2014, all patients operated on with curative intent who had known RAS mutation status were included. Factors associated with overall survival were determined using multivariate analysis.
  
  
  
  A total of 524 patients met the inclusion criteria; 212 (40%) had mutated RAS. Mutations were located on codon 12 in 128 patients (60%) and codon 13 in 29 (14%). At median follow-up of 38 months, median overall survival was 72.6 months for wild-type RAS and 50.9 months for mutated RAS (P < .001). Median overall survival for patients with codon 12 and 13 mutations was 51.9 and 50.9 months, respectively (P = .839), significantly worse than for patients with wild-type RAS (P = .005, and P = .038 for codon 12 and 13, respectively). For patients with RAS mutation, factors associated independently with worse overall survival were node-positive primary tumor, tumor >3 cm, and >7 cycles of preoperative chemotherapy. Major and 2-stage hepatectomy were not associated independently with overall survival. Median overall survival was 57, 41, and 21.5 months for patients with 1, 2, and 3 risk factors, respectively. There were no 4-year survivors in the highest-risk group.
  
  
  
  Patients with multiple risk factors had poor overall survival after curative resection of RAS mutant colorectal liver metastases. For such patients, hepatectomy may be ill advised, and alternative therapies or further systemic therapy should be considered.
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Guillaume
authors: G
authors: Passot
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Jason W
authors: JW
authors: Denbo
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Suguru
authors: S
authors: Yamashita
authors: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Scott E
authors: SE
authors: Kopetz
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Yun S
authors: YS
authors: Chun
authors: Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Dipen
authors: D
authors: Maru
authors: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Michael J
authors: MJ
authors: Overman
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Kristoffer Watten
authors: KW
authors: Brudvik
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Claudius
authors: C
authors: Conrad
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Thomas A
authors: TA
authors: Aloia
authors: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: jvauthey@mdanderson.org.
authors: Jean-Nicolas
authors: JN
authors: Vauthey
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000628:therapy; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006498:Hepatectomy / Q000379:methods / Q000401:mortality; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)