Clinical Significance Of Peripheral Blood Cell-free Tumor DNA-based EGFR Mutation Detection In Patients With Non-small Cell Lung Cancer: A Meta-analysis Of19Studies

Objective: To explore the likelihood of cell-free DNA(cfDNA) epidermalgrowth factor receptor (EGFR) mutation status in peripheral blood to assessEGFR mutation status in patients with non-small cell lung cancer(NSCLC) aswell as explore the association between cfDNA EGFR mutation and patients’clinicopathological features.Methods: A systematic search of the PubMed and Web of Sciencedatabases (up to July24,2013) was performed, with rigorous inclusive andexclusive criteria. Clinicopathological features of peripheral blood EGFRmutation as well as differences of EGFR mutations frequency betweenperipheral blood and matched tumor tissue samples were analyzed usingmeta-analysis method.Results: Final analysis of2256patients from19eligible studies wereperformed. Pooled relative risks (RRs) displayed that EGFR mutation-positivein cfDNA occurred more frequently from female, adenocarcinoma, non-smoker(RR=0.68,95%confidence interval [CI]:0.52-0.88, P=0.003; RR=0.43, 95%CI:0.32-0.57, P<0.00001; RR=0.62,95%CI:0.50-0.75, P<0.00001;respectively). EGFR mutations frequency in cfDNA were lower than matchedtumor tissue samples,30.00%vs36.38%(RR=0.80,95%CI:0.65-0.98, P=0.03),the concordance rate was79.02%(53.33%-95.74%). Subgroup analysis showedperipheral blood EGFR mutation rate was lower than tumor tissue detected byARMS assay, and also by non-ARMS assay (25.52%vs47.59%, P=0.18;26.88%vs35.39%, P=0.11; respectively); Serum EGFR mutation rate waslower than matched tumor tissue(19.76%vs33.25%, P=0.04), while there wasno significant difference between plasma EGFR mutation rate and matchedtumor tissue(33.21%vs37.36%, P=0.29); the concordance rate of EGFRmutation between peripheral blood and matched tumor tissue was higher inⅢB-Ⅳ stage patients compared toⅠ-ⅢA stage patients(77.99%vs65.89%,P=0.02).Conclusions: Peripheral blood cfDNA can be used to detect EGFRmutation especially when there are not enough tumor tissue for mutationanalysis in female, adenocarcinoma, non-smoking patients with advancedNSCLC. Compared to serum, plasma could reflect better the status of EGFRmutation. Thus, Plasma is the recommended optimizing specimen.