Introduction: The Growing Challenge of Intracranial Control in Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with a significant propensity for central nervous system (CNS) involvement. Approximately 25% of patients present with brain metastases at the time of diagnosis, and nearly 50% will develop them during the course of their illness. As systemic therapies—including targeted agents and immune checkpoint inhibitors (ICIs)—continue to improve extracranial survival, the brain has increasingly become a sanctuary site for disease progression, necessitating more effective and less toxic intracranial management strategies.
Historically, whole-brain radiation therapy (WBRT) was the standard for multiple metastases, but its association with significant neurocognitive decline led to a paradigm shift toward stereotactic radiosurgery (SRS). While SRS provides excellent local control for treated lesions, it does not address the risk of distant intracranial failure (the development of new lesions elsewhere in the brain). Consequently, there is an urgent clinical need for regional therapies that can extend the time to intracranial progression (TTIP) without the debilitating side effects of WBRT.