Epidermal growth factor receptor mutations and brain metastases in non-small cell lung cancer

Abstract

Studies have revealed that non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations has a high incidence of brain metastases (BMs). However, the association between EGFR mutations and BMs remains unknown. This review summarizes detailed information about the incidence of BMs, clinical and imaging characteristics of BMs, brain surveillance strategies, influence of treatments on BMs, prognosis after BMs, and differences in EGFR mutations between paired primary tumors and BMs in EGFR-mutated NSCLC. The prognostic results demonstrate that patients with mutated EGFR have a higher incidence of BMs, EGFR tyrosine kinase inhibitors (EGFR-TKIs) (afatinib and osimertinib) delay the development of BMs, and patients with mutated EGFR with synchronous or early BMs have better overall survival after BMs than those with wild-type EGFR. The EGFR mutation status of BM sites is not always in accordance with the primary tumors, which indicates that there is heterogeneity in EGFR gene status between paired primary tumors and BMs. However, the EGFR gene status of the primary site can largely represent that of BM sites. Among patients developing synchronous BMs, patients with mutated EGFR are less likely to have central nervous system (CNS) symptoms than patients with wild-type EGFR. However, the possibility of neuro-symptoms is high in patients with metachronous BMs. Patients with mutated EGFR tend to have multiple BMs as compared to patients with wild-type EGFR. Regarding very early-stage NSCLC patients without neuro-symptoms, regular neuroimaging follow-up is not recommended. Among advanced NSCLC patients with EGFR mutation, liberal brain imaging follow-up in the first several years showed more advantages in terms of cost.

Keywords: EGFR mutation; brain metastasis; characteristics; genetic heterogeneity; non-small cell lung cancer; prognosis.

Figure 1

(A–C) Comparison of the incidence of NSCLC BMs between EGFR+ (means EGFR mutation-positive) and EGFR− (means EGFR mutation-negative) patients according to overall BMs, synchronous BMs, and metachronous BMs. (D) Comparison of the incidence of BMs based on EGFR mutation subtype. (E) The data of median time to BM, which demonstrates that EGFR-TKIs have preventive effects against BMs. (F) The overall survival data after BMs (BMOS); most studies demonstrate that patients with mutated EGFR have better BMOS. The items in the vertical axis mean “author, published year, stage” in panels (A–E) and mean “author, published year, stage, metastatic type” in panels (D, F). Note. BMs, brain metastases; SC, synchronous BMs; MC, metachronous BMs; SC+MC, overall BMs; NSCLC, non-small cell lung cancer; EGFR, epidermal growth factor receptor; TKIs, tyrosine kinase inhibitors; NA, not available.