title: Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis.
abstract: BACKGROUND
  Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status.
  
  
  METHODS
  Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected, according to the PRISMA guidelines. Pooled HRs were calculated for both the OS and/or RFS.
  
  
  RESULTS
  Seven eligible trials (1403 patients) were included. Pooled analysis showed that KRAS mutations predicted a significantly worse both RFS (HR: 1.65; 95% CI: 1.23-2.21) and OS (HR: 1.86; 95% CI: 1.51-2.30) in patients who underwent surgical resection of CLM. BRAF mutations were also associated with a significantly worse OS (HR: 3.90; 95% CI: 1.96-7.73) in this subgroup of patients.
  
  
  CONCLUSIONS
  This meta-analysis suggests both KRAS and BRAF mutations as poor, prognostic biomarkers, associated with worse survival outcomes, in patients undergoing hepatic resection of CLM.
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Passiglia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bronte
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galvano
authors.affiliation: Medical Oncology Department, Campus Biomedico, University of Rome, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy. Electronic address: antonio.russo@usa.net.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: BRAF; Colorectal cancer; KRAS; Liver metastasis; Prognostic biomarker