title: KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases.
abstract: BACKGROUND
  The validity of the KRAS mutation as a predictor of recurrence-free survival (RFS) or overall survival (OS) is unclear. The current study investigated whether the presence of the KRAS mutation decreased RFS or OS in patients with colorectal cancer who underwent liver resection.
  
  
  METHODS
  Patients with resected colorectal liver metastases who received adjuvant hepatic arterial infusion plus systemic therapy and for whom KRAS data was available were evaluated. Correlation between KRAS and clinical factors was done using the Fisher exact test. Kaplan-Meier methods were used to estimate the median RFS and OS.
  
  
  RESULTS
  A total of 169 patients were evaluated, 118 of whom had KRAS wild-type (WT) and 51 had KRAS mutated (MUT) tumors. The 3-year RFS rate was 46% for patients with KRAS WT (95% confidence interval [95% CI], 35%-56%) and 30% (95% CI, 16%-44%) for patients with KRAS MUT (P =.005). The 3-year OS rate was 95% (95% CI, 87%-98%) and 81% (95% CI, 62%-95%), respectively, for patients with KRAS WT and KRAS MUT (P =.07). On multivariate analysis, KRAS remained a significant predictor of RFS (hazard ratio, 1.9). The 3-year cumulative recurrence rate by site of metastases was as follows: 2% versus 13.4% for bone (P≤.01), 2% versus 14.5% for brain (P =.05), 33.2% versus 58% for lung (P≤.01), and 30% versus 47% for liver (P =.10) in patients with KRAS WT versus KRAS MUT.
  
  
  CONCLUSIONS
  In the current study, among patients with resected colorectal liver metastases who were treated with adjuvant hepatic arterial infusion plus systemic therapy, patients with KRAS MUT were found to have a significantly worse 3-year RFS (30%) compared with KRAS WT (46%) p=.005. The cumulative incidence of bone, brain, and lung metastases was significantly higher for patients with KRAS MUT compared with those with KRAS WT.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Kemeny
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Chou
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Gewirtz
authors.forename: Andrea
authors.initials: A
authors.lastname: Cercek
authors.forename: T Peter
authors.initials: TP
authors.lastname: Kingham
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Yuman C
authors.initials: YC
authors.lastname: Fong
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Celina
authors.initials: C
authors.lastname: Ang
authors.forename: Efsevia
authors.initials: E
authors.lastname: Vakiani
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: KRAS mutation; adjuvant therapy; colorectal cancer; disease recurrence patterns; liver metastases