title: Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases.
abstract: The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status.
  
  
  
  Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed.
  
  
  
  On pathology, most patients (n = 380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n = 307, 63.3 %), while 36.7 % (n = 178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28-2.57; P = 0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42-3.30; P < 0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73-2.48; P = 0.348).
  
  
  
  The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis.
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Georgios Antonios
authors.initials: GA
authors.lastname: Margonis
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Yuhree
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Samaha
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Buettner
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, 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 University School of Medicine, Baltimore, MD, USA. tpawlik1@jhmi.edu.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000328:Adult; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000601:surgery*; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D008297:Male; D009154:Mutation; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016019:Survival Analysis
chemical_list: C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: CRLM; KRAS mutation; Tumor biology