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.

Risk factors for brain metastases in locally advanced non-small cell lung cancer patients treated with radical radiotherapy

“…Besides, the highly aggressive micropapillary subtype in adenocarcinoma with strong proliferation and migration ability was found to be associated with an increased BM risk ( 19 , 20 ). Recently, positive EGFR mutation in NSCLC patients was reported to have an impact on BM incidence in several studies ( 21 - 23 ). We also performed subgroup analysis in adenocarcinoma patients with known EGFR mutation status in our study and similar results were found.…”

Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer

“…Several issues need to be clarified regarding the TME and immunotherapy in NSCLC. For example, several reports showed that mRNA vaccine could be applied for cancer treatment via regulation of TME ( Zhong et al, 2021 ; Zhao W. et al, 2022 ; Huang et al, 2022 ). Proteomics, genomics, and metabolomics might be good approaches to explore the mechanism of gene mutation-driven lung cancer and TME ( Zhou et al, 2019 ; Bourbonne et al, 2022 ).…”

Osimertinib Plasma Trough Concentration in Relation to Brain Metastases Development in Patients With Advanced EGFR-Mutated NSCLC

“…Brain metastases (BM) are diagnosed in approximately 25% of all patients with a first diagnosis of metastatic EGFR-mutated ( EGFR m + ) NSCLC, and this can rise to more than 50% during the course of the disease. 1 , 2 , 3 Symptomatic BM are associated with a decrease in quality of life, and patients with BM have a worse prognosis compared with those without. 4 The percentage of patients diagnosed with having asymptomatic BM is increasing as baseline screening for (asymptomatic) BM in stages II to IV NSCLC is advised in the European Society of Medical Oncology and the National Comprehensive Cancer Network guidelines.…”