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Genomic Alterations and the Incidence of Brain Metastases in Advanced and Metastatic NSCLC: A Systematic Review and Meta-Analysis

*June 2023*

Lung cancer is a major global health problem, with an estimated 2 million new cases every year and 1.8 million deaths.1 NSCLC is the commonest form and accounts for 85% of all lung cancers.2 Advanced (stage III) and metastatic (stage IV) NSCLC confer the worst prognosis, with 5-year survival rates of 15% and 5%, respectively.3 Survival is improving owing to a combination of novel targeted agents, earlier diagnosis, and other treatment advances such as immunotherapy.4 Recent trials have revealed improved overall survival (OS) with targeted therapies for tumors carrying specific genomic alterations, such as EGFR5 and ALK.6,7

Up to 60% of patients with NSCLC are expected to have central nervous system (CNS) involvement at some point during their disease.8 Development of brain metastases (BMs) specifically in NSCLC is associated with reduced OS, progression-free survival, and quality of life,9,10 although earlier detection seems to improve survival.10 Screening programs to detect asymptomatic BM and the use of prophylactic cranial irradiation (PCI) to reduce the risk of BM development remain controversial.11,12 There is a knowledge gap around the prevalence of BM, the rate at which they develop, and the factors that drive the process.13 Although the discovery of genomic alterations in NSCLC has facilitated the development of targeted agents, the impact of these alterations (such as EGFR, ALK, KRAS, ROS1, RET, and others) on BM development remains mostly unclear. Read more.