title: KRAS Mutation Status Predicts Site-Specific Recurrence and Survival After Resection of Colorectal Liver Metastases Irrespective of Location of the Primary Lesion.
abstract: The KRAS mutation status is reportedly correlated with poor survival outcome in patients with colorectal liver metastases (CLM); however, its true prognostic impact and the reason for the poor prognosis remain unclear.
  
  
  
  Data on 163 patients with a known KRAS mutation status who underwent curative resection for CLM were retrospectively reviewed. The long-term survival and site-specific incidence of recurrence were then compared between patients with a KRAS mutation (mtKRAS) and those without a mutation (wtKRAS).
  
  
  
  The mtKRAS group had a poorer 3-year disease-specific survival (DSS) rate (59.8 vs. 83.6 %, p = 0.016), 3-year recurrence-free survival (RFS) rate (0 vs. 20.2 %, p = 0.069), and median time to surgical failure (TSF) [18.8 vs. 39.7 months, p = 0.001] than the wtKRAS group. The cumulative incidences of liver recurrence and lung recurrence at 3 years were also higher in the mtKRAS group (76.2 vs. 54.7 %, p = 0.060; and 71.9 vs. 37.3 %, p < 0.001, respectively). A multivariate analysis confirmed that an mtKRAS status had a significant effect on the DSS rate (hazard ratio [HR] 2.9, p = 0.006), RFS (HR 2.0, p = 0.004), TSF (HR 2.4, p < 0.001), liver recurrence (HR 1.7, p < 0.001), and lung recurrence (HR 2.6, p < 0.001). Lung-related unresectable recurrences were more frequent (41 vs. 18 %, p = 0.048) and were associated with an earlier TSF (9.6 vs. 14.0 months, p = 0.14) in the mtKRAS group, regardless of the location of the primary lesions.
  
  
  
  mtKRAS is associated with poor survival outcome after CLM resection because of a relatively high incidence of lung recurrence and a relatively short TSF.
authors.affiliation: Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan. shindou-tky@umin.ac.jp.|Okinaka Memorial Institute for Medical Disease, Tokyo, Japan. shindou-tky@umin.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Shindoh
authors.affiliation: Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan.|Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Nishioka
authors.affiliation: Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Yoshioka
authors.affiliation: Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Sugawara
authors.affiliation: Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masaji
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. KOKUDO-2SU@h.u-tokyo.ac.jp.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy / Q000401:mortality*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)