Abstract Background Brain metastases (BM) significantly affect both prognosis and quality of life in patients with metastatic non-small cell lung cancer (NSCLC), highlighting the need for innovative therapeutic strategies. In this systematic review, we evaluated the prevalence and clinical significance of key genomic alterations in BM from NSCLC. Methods Comprehensive searches of PubMed, Web of Science, Embase, and the Cochrane Library identified 19 studies encompassing 3028 patients, 930 of whom had BM. Results Among BM patients, 50% harbored TP53 mutations, while 49% exhibited PD-L1 overexpression, and 30% demonstrated a tumor mutational burden (TMB) ≥10 mut/Mb. These alterations were associated with tumor progression, immune evasion, and increased mutational load. Additional actionable biomarkers, though less frequent, included ERBB2, BRAF, and NTRK alterations. Importantly, our findings revealed substantial intertumor heterogeneity between primary tumors and BM, underscoring the need of site-specific genomic profiling to inform treatment decisions. Conclusions Overall, this study underscores the critical role of genomic profiling in advancing precision medicine approaches and supports the integration of novel targeted and immunotherapeutic strategies to improve outcomes in NSCLC patients with brain metastases. The dynamic evolution of biomarker expression during disease progression and tumor heterogeneity remains major challenges to the development of durable treatment strategies.
Wang et al. (Fri,) studied this question.
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