Innovations in Whole Brain Radiation Therapy

Whole brain radiation therapy (WBRT) continues to play a critical role in managing patients with extensive brain metastases, but neurocognitive decline remains a significant limitation. This review examines the clinical presentation and underlying pathophysiology of radiation-induced neurocognitive impairment, which affects the majority of patients within a year of treatment. The mechanisms are multifactorial and include vascular injury, chronic neuroinflammation, impaired hippocampal neurogenesis, and disruption of white matter connectivity within key neural networks. Established neuroprotective strategies, such as memantine and hippocampal-avoidance radiation techniques, as well as emerging approaches, including memory-avoidance and genu-sparing WBRT that target broader limbic structures, are discussed. In addition, we review methods to improve local control through simultaneous integrated boosts and streamline treatment workflows using autosegmentation and simulation-free planning. Balancing tumor control with neurocognitive preservation is increasingly important as patients with brain metastases live longer with modern systemic therapies.