title: KRAS Mutation as a Biomarker for Survival in Patients with Non-Small Cell Lung Cancer, A Meta-Analysis of 12 Randomized Trials.
abstract: BACKGROUND
  Because there is no clear consensus for the prognostic implication of KRAS mutations in patients with non-small cell lung cancer (NSCLC), we conducted a meta-analysis based on 12 randomized trials to draw a more accurate conclusion.
  
  
  METHODS
  A systematic computer search of articles from inception to May 1, 2014 using the PubMed, EMBASE, and Cochrane databases was conducted. The enrollment of articles and extraction of data were independently performed by two authors.
  
  
  RESULTS
  Our analysis was based on the endpoints overall survival (OS) and progression-free survival (PFS). Nine records (All for OS, 7 for PFS) comprising 12 randomized trials were identified with 3701 patients who underwent a test for KRAS mutations. In the analysis of the pooled hazard ratios (HRs) for OS (HR: 1.39; 95% confidence interval [CI] 1.23-1.56) and PFS (HR: 1.33; 95% CI 1.17-1.51), we found that KRAS mutations are related to poor survival benefit for NSCLC. According to a subgroup analysis stratified by disease stage and line of therapy, the combined HRs for OS and PFS coincided with the finding that the presence of a KRAS mutation is a dismal prognostic factor. However, the prognostic role of KRAS mutations are not statistically significant in a subgroup analysis of patients treated with chemotherapy in combination with cetuximab based on the endpoints OS (P=0.141) and PFS (P=0.643).
  
  
  CONCLUSIONS
  Our results indicate that KRAS mutations are associated with inferior survival benefits for NSCLC but not for those treated with chemotherapies integrating cetuximab.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China E-mail : zhuxx01@126.com.
authors.forename: Min
authors.initials: M
authors.lastname: Ying
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Dian-He
authors.initials: DH
authors.lastname: Li
authors.forename: Long-Hua
authors.initials: LH
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)