Precision Medicine in Lung Cancer Brain Metastases: Integrating Novel Therapeutics and Radiotherapy for Optimal CNS Control

Abstract

Cerebral metastases develop in nearly half of patients with lung cancer, substantially impairing both survival and quality of life. Historically, poor blood–brain barrier penetration and modest intracranial activity of systemic agents limited treatment options. However, recent advances in immune checkpoint inhibitors and next generation CNS penetrant targeted therapies have reshaped the therapeutic landscape, achieving superior intracranial disease control and improved patient outcomes. Concurrently, stereotactic radiotherapy has emerged as a precise and effective local modality with a more favorable toxicity profile than whole brain irradiation. The integration of systemic and local approaches, guided by molecular profiling and clinical risk stratification, offers new opportunities to optimize CNS disease management. Nevertheless, these advances raise key challenges regarding treatment sequencing, patient selection, and risk adapted strategies. This review summarizes the contemporary management of lung cancer brain metastases and highlights future directions for clinical trial design, emphasizing the incorporation of multidimensional clinical, biological, and radiological tools to guide individualized treatment decisions