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. 2017 Aug;9(8):2510-2520.
doi: 10.21037/jtd.2017.07.57.

Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer

Lina Li  1 , Shuimei Luo  1 , Heng Lin  1   2 , Haitao Yang  1 , Huijuan Chen  1 , Ziyuan Liao  1 , Wanzun Lin  1 , Weili Zheng  1 , Xianhe Xie  1
Affiliations

Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer

Lina Li et al. J Thorac Dis. 2017 Aug.

Abstract

Background: Lung cancer is the leading cause of cancer-related death worldwide. Numerous studies have been performed to investigate the correlation between epidermal growth factor receptor (EGFR) mutation status and the incidence of brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC), however, the outcomes were inconsistent. Thus, we performed this study to establish the role of EGFR mutation status in BMs.

Methods: Electronic databases PubMed, Embase, Cochrane Library, CBM, WanFang, CNKI were searched to identify relevant trials. The primary endpoint was the incidence of BMs in EGFR mutations or wild type NSCLC and the secondary endpoint was overall survival calculated from the BMs emerging (BMOS).

Results: Twenty-two studies incorporating 8,152 participants were eligible. EGFR mutations group possessed a significantly higher risk of BMs (OR =1.99; 95% CI, 1.59-2.48; P=0.000) than EGFR wild type group. In the stratified analysis, compared with EGFR wild type group, EGFR mutations group had a significant higher incidence (OR =2.01; 95% CI, 1.56-2.59; P=0.000) of subsequent BMs while only a trend of increasing the incidence of initial BMs (OR =1.38; 95% CI, 0.98-1.94; P=0.066). Moreover, exon 19 deletion had a trend of increasing the incidence of BMs 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 prolonged overall BMOS (HR =0.68; 95% CI, 0.47-0.98; P=0.038) and a longer BMOS in initial BMs (HR =0.50; 95% CI, 0.31-0.80; P=0.004) but no significant difference in NSCLC with subsequent BMs (HR =0.95; 95% CI, 0.42-2.15; P=0.901).

Conclusions: Patients with EGFR mutations were more susceptible to develop into BMs than those with EGFR wild type, especially during the course of disease.

Keywords: Brain metastases (BMs); epidermal growth factor receptor (EGFR); meta-analysis; non-small cell lung cancer (NSCLC).

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Flow diagram of included studies.
Figure 2
Figure 2
(A) Sensitivity analysis of the association of EGFR mutations and incidence of BMs; (B) funnel plot of incidence of BMs; (C) comparison of BMs between EGFR mutations group and EGFR wild type group; (D) subgroup analyses on incidence of BMs by study design. BMs, brain metastases; EGFR, epidermal growth factor receptor.
Figure 3
Figure 3
Subgroup analyses of incidence of BMs: (A) subgroup analysis on the incidence of BMs (EGFR mutations versus wild type) in patients with adenocarcinoma and stage IV respectively; (B) subgroup analysis on the incidence of subsequent and (C) initial BMs (EGFR mutations versus wild type); (D) subgroup analysis on the BMs incidence of exon 19 mutation versus exon 21 mutation. BMs, brain metastases; EGFR, epidermal growth factor receptor.
Figure 4
Figure 4
(A) Comparison of BMOS between EGFR mutations group and EGFR wild type group: BMOS in overall BMs (initial BMs + subsequent BMs); (B) BMOS in initial BMs; (C) BMOS in subsequent BMs. BMs, brain metastases; EGFR, epidermal growth factor receptor; BMOS, overall survival calculated from BMs emerging.
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