title: KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases.
abstract: BACKGROUND
  The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology.
  
  
  METHODS
  R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1-4, 5-9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wtKRAS) vs. mutated (mutKRAS)] was assessed.
  
  
  RESULTS
  A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7-66.7); most patients were male (n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wtKRAS tumors, although margin clearance of 1-4 mm or more was associated with improved OS compared to R1 (all P < 0.05), no difference in OS was observed when comparing margin clearance of 1-4 mm to the 5-9 mm and the ≥10 mm groups (all P > 0.05). In contrast, among patients with mutKRAS tumors, all three groups of margin clearance (1-4, 5-9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P > 0.05).
  
  
  CONCLUSIONS
  While a 1-4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status-including a 1 cm margin-did not improve survival among patients with mutKRAS tumors.
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.|Second Department of Propaedeutic Surgery, Laiko Hospital, University of Athens, Athens, Greece.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Margonis
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Andreatos
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Yuhree
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Katiuscha
authors.initials: K
authors.lastname: Merath
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Doris
authors.initials: D
authors.lastname: Wagner
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Buettner
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA.
authors.forename: Neda
authors.initials: N
authors.lastname: Amini
authors.affiliation: Second Department of Propaedeutic Surgery, Laiko Hospital, University of Athens, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Antoniou
authors.affiliation: Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. tpawlik1@jhmi.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary* / Q000601:surgery*; D008297:Male; D000072662:Margins of Excision; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)