Hypo-Fractionated Stereotactic Radiosurgery for the Management of Brain Metastases

The increasing prevalence of brain metastases in cancer patients due to longer life expectancy and improvements in neuroimaging highlights the need for effective local treatments. Despite advancements in systemic targeted therapies, their low blood-brain barrier (BBB) penetrance limits their intracranial efficacy. Stereotactic radiosurgery (SRS) has largely supplanted whole-brain radiation therapy (WBRT) for patients with up to 10 brain lesions due to superior neurocognitive outcomes and high local control. While single-fraction SRS provides low radiation toxicity with smaller lesions, high-volume metastases necessitate doses above tolerance limits to achieve comparable local control. As tumor volume increases, the number of tumor cells also increases, requiring higher doses of radiation than the maximum tolerated doses reported in the RTOG 9005 study to achieve tumor control. Hypo-fractionated SRS (HySRS) permits the delivery of high radiation doses over 2-5 fractions, thus mitigating the risk of radiation toxicity while maintaining high local control. This review presents the available evidence and ongoing clinical trials on HySRS for the management of brain metastases.