The effects of radiation therapy on the brain: implications for management

Radiation therapy (RT) plays a critical role in the management of intracranial malignancies, offering a potent and targeted approach to tumor control. The benefits of RT have been recognized for decades, and it is commonly employed in the management of both primary brain tumors and, especially, brain metastases. Through the induction of DNA damage and disruption of cellular integrity, RT promotes apoptosis and inhibits the proliferative capacity of cancer cells. Advances in imaging, dose planning, and delivery techniques have significantly enhanced the precision of RT, allowing for effective tumor eradication while minimizing harm to surrounding healthy tissue. As a result, RT improves local disease control and contributes to prolonged survival in patients with brain tumors. Nonetheless, intracranial RT may inadvertently damage surrounding healthy brain structures. The effects of RT can manifest as both acute and delayed toxicities, potentially compromising patient quality of life and long-term outcomes. For treating clinicians, a thorough understanding of these complications is necessary to design radiation treatment plans that properly balance the therapeutic efficacy of therapy with the risks of adverse treatment-related outcomes. In this review, we explore the distinct pathophysiological mechanisms, symptoms, and management strategies associated with acute, early delayed (one to six months), and late delayed radiation-induced brain toxicities. In particular, we discuss the risks of somnolence syndrome, peri-ictal pseudoprogression, radiation necrosis, vascular disorders, cognitive impairment, cranial neuropathies, endocrine dysfunction, the development of secondary malignancies, stroke-like migraine attacks after radiation therapy (SMART) syndrome, and acute late-onset encephalopathy after radiation therapy (ALERT) syndrome after brain RT.