title: Effect of KRAS and BRAF Mutations on Survival of Metastatic Colorectal Cancer After Liver Resection: A Systematic Review and Meta-Analysis.
abstract: The purpose of the study was to evaluate whether the mutational status of Kirsten rat sarcoma viral oncogene homolog (KRAS) or b-viral oncogene homolog B1 (BRAF) could be an independent prognostic factor in the subset of patients with colorectal cancer liver metastases (CRLM) who undergo complete liver resection.
  
  
  
  A systematic literature review was performed to identify articles reporting relapse-free survival (RFS) and/or overall survival (OS) of patients who underwent complete liver resection for CRLM, stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis.
  
  
  
  Eleven studies, including 1833 patients, were eligible for the meta-analysis. Nine of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). Nine among 11 studies reported RFS stratified according to KRAS mutation and HRs in multivariate analysis were available in 7. In a pooled analysis, KRAS mutation was negatively associated with RFS (HR, 1.529; 95% CI, 1.287-1.817; P < .001). In 3 studies HRs of the multivariate analysis regarding the OS according to BRAF mutational status were also available, showing a negative association with OS (HR, 3.055; 95% CI, 1.794-5.204; P < .001).
  
  
  
  KRAS mutations are negatively associated with OS and RFS in patients who undergo complete liver resection for CRLM. A similar negative effect on OS was observed also for BRAF mutation, although fewer studies were included. These data support integration of KRAS and BRAF mutational status into a combined predictive score for prospective assessment of outcome after resection of CRLM in clinical studies.
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tosi
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Magni
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Amatu
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Mauri
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Bencardino
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Truini
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Veronese
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Milano, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: De Carlis
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Nichelatti
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy. Electronic address: andrea.sartorebianchi@ospedaleniguarda.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sartore-Bianchi
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy; Dipartimento di Oncologia e Emato-Oncologia, Università degli Studi di Milano, Milano, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary* / Q000601:surgery; D009154:Mutation; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; Colorectal cancer biomarkers; Colorectal cancer prognosis; KRAS; Liver metastases