Driver gene-specific prevalence and incidence of brain metastases in non-small cell lung cancer: a meta-analysis encompassing all disease stages.

BACKGROUND: Brain metastases (BM) in non-small cell lung cancer (NSCLC) are associated with a poor prognosis. Identifying relevant genomic alterations can facilitate the targeting of therapies. We conducted a systematic review and meta-analysis to assess the prevalence and incidence of these alterations in NSCLC patients. METHODS: PubMed, Embase and WOS were searched, from January 2000 to February 2024 using "lung", "met" and "incidence" as search phrases. We obtained data on the prevalence at diagnosis and the annual incidence of new BM in patients with EGFR, ALK, KRAS, and other genetic alterations. The pooled prevalence and incidence rates were calculated using a random effects model. This study is registered with PROSPERO (CRD42023491178). RESULTS: A total of 120 articles were included in the analysis. Prevalence data were derived from 94 studies (17,458 patients), while incidence data were obtained from 95 studies (13,323 patients). The pooled prevalence of BM at diagnosis was found to be 28.8% (95% [CI]: 0.263-0.313). This prevalence was highest among patients who were ALK-positive (31.6%) or had EGFR-positive (29.4%). The incidence rates were observed to be 0.086 in the EGFR group (95% CI 0.045-0.131), 0.062 in the ALK group (95% CI 0.003-0.122), 0.057 in the KRAS group (95% CI 0.000-0.188), 0.064 in the ROS1 group (95% CI 0.000-0.162), and 0.055 in the RET group (95% CI 0.000-0.224). INTERPRETATION: Comprehensive meta-analyses indicate prevalence and incidence of BM are higher in patients with specific genomic alterations and advanced disease. Brain imaging and targeted therapies for brain penetrance are important.