Correlation Between EGFR Mutation And Incidence Of Brain Metastases In Non-small Cell Lung Cancer

Background and objective: Brain metastases are life-threatening complications of non-small cell lung cancer(NSCLC)during the course of disease.Currently,numerous studies have been performed to investigate the correlation between EGFR mutations and the incidence of brain metastases in NSCLC,however,the outcomes were inconsistent.Thus,we performed this meta-analysis aimed to identify the correlation between EGFR mutations and the incidence of brain metastases in NSCLC.Methods: Electronic databases Pub Med,Embase,Cochrane Library,CBM,CNKI,Wan Fang and VIP,were thoroughly searched to identify the observational studies which reported the correlation between EGFR mutation status and the incidence of brain metastases in NSCLC up to February 2017.Two reviewers identified the included studies and assessed the quality according to the Newcastle Ottawa Quality Assessment Scale(NOS)of each study independently.Then the data analyses were performed through the Stata/SE 12.0 and a fixed effect model(P>0.1 and I2?50%)or random effect model(P?0.1 or I2>50%)was adopted according to the result of Chi-square and I-square tests.Furthermore,sensitivity analysis and subgroup analysis were combined to test the heterogeneity.Publication bias was statistically analyzed using Egger's and Begg's test.The primary endpoint was the incidence of brain metastases and the secondary endpoint was overall survival post brain metastases(BMOS).Results: Twenty-two observational studies with 8152 participants,including 2664 with EGFR mutations and 5488 with EGFR wild type,were eligible.EGFR mutations group possessed a significantly higher risk of brain metastases(OR 1.99,95% CI 1.59-2.48,P=0.000)than EGFR wild type group.Moreover,we obtained the similar results in the subgroup of initial brain metastases(OR 1.38,P=0.066);subsequent brain metastases(OR 2.01,P=0.000);East Asia(OR=2.39,P=0.000); occident(OR=1.59,P=0.060);adenocarcinoma(OR=1.93,P=0.000);stage IV(OR=1.83,P=0.000).Furthermore,exon 19 deletion had a trend of increasing the incidence of brain metastases than exon 21 mutation(OR 1.44,95% CI 0.77-2.68,P=0.252).Compared with EGFR wild type group,EGFR mutations group possessed a longer BMOS in initial brain metastases(HR 0.50,95% CI 0.31-0.80,P=0.004)but no significant difference in NSCLC with subsequent brain metastases(HR 0.95,95% CI 0.42-2.15,P=0.901).Conclusions: Patients with EGFR mutations were more susceptible to develop into brain metastases than those with EGFR wild type during the course of disease;and both adenocarcinoma and stage IV with EGFR mutations hold a higher risk of brain metastases.