title: PCR-based assays versus direct sequencing for evaluating the effect of KRAS status on anti-EGFR treatment response in colorectal cancer patients: a systematic review and meta-analysis.
abstract: BACKGROUND
  The survival rate of colorectal cancer (CRC) patients carrying wild-type KRAS is significantly increased by combining anti-EGFR monoclonal antibody (mAb) with standard chemotherapy. However, conflicting data exist in both the wild-type KRAS and mutant KRAS groups, which strongly challenge CRC anti-EGFR treatment. Here we conducted a meta-analysis in an effort to provide more reliable information regarding anti-EGFR treatment in CRC patients.
  
  
  METHODS
  We searched full reports of randomized clinical trials using Medline, the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO). Two investigators independently screened the published literature according to our inclusive and exclusive criteria and the relative data were extracted. We used Review Manager 5.2 software to analyze the data.
  
  
  RESULTS
  The addition of anti-EGFR mAb to standard chemotherapy significantly improved both progression-free survival (PFS) and median overall survival (mOS) in the wild-type KRAS group; hazard ratios (HRs) for PFS and mOS were 0.70 [95% confidence interval (CI), 0.58-0.84] and 0.83 [95% CI, 0.75-0.91], respectively. In sub-analyses of the wild-type KRAS group, when PCR-based assays are employed, PFS and mOS notably increase: the HRs were 0.74 [95% CI, 0.62-0.88] and 0.87 [95% CI, 0.78-0.96], respectively. In sub-analyses of the mutant KRAS group, neither PCR-based assays nor direct sequencing enhance PFS or mOS.
  
  
  CONCLUSIONS
  Our data suggest that PCR-based assays with high sensitivity and specificity allow accurate identification of patients with wild-type KRAS and thus increase PFS and mOS. Furthermore, such assays liberate patients with mutant KRAS from unnecessary drug side effects, and provide them an opportunity to receive appropriate treatment. Thus, establishing a precise standard reference test will substantially optimize CRC-targeted therapies.
authors.affiliation: Department of Mathematics, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Mathematics, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Mathematics, College of Basic Medical Sciences, China Medical University, Shenyang, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Huidan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D016032:Randomized Controlled Trials as Topic; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins