Stereotactic Radiosurgery and Immunotherapy for Brain Metastases: Practical Integration, Timing, and Toxicity

Brain metastases remain a major cause of morbidity and mortality in patients with cancer, particularly melanoma and non-small cell lung cancer. Stereotactic radiosurgery (SRS) is a cornerstone of management for limited intracranial disease, offering high local control while minimizing the neurocognitive toxicity associated with whole-brain radiotherapy. Immune checkpoint inhibitors (ICIs) have also transformed systemic therapy for tumors with central nervous system involvement, creating increasing clinical need to define how best to integrate these modalities.The combined use of SRS and ICIs has raised an important question regarding optimal treatment timing. Retrospective evidence suggests that concurrent or near-concurrent administration, commonly defined as treatment within approximately 2–4 weeks, may improve local control and intracranial response. Several studies also suggest a potential survival advantage compared with sequential treatment, although these findings are limited by selection bias and require prospective validation. Most contemporary analyses do not show a significant increase in radionecrosis (RN) with concurrent single-agent ICI; however, emerging data suggest that dual checkpoint blockade may increase the risk of symptomatic RN.This narrative review synthesizes the biologic rationale, clinical evidence, and toxicity considerations for combining SRS and ICIs in patients with brain metastases. We emphasize differences between single agent and dual ICI strategies, highlight dosimetric predictors of RN such as V12 Gy, and propose a practical framework for treatment integration. Overall, concurrent SRS with single-agent ICI appears feasible and is associated with favorable intracranial outcomes in selected patients, whereas dual ICI warrants more cautious, individualized decision-making. Prospective studies are needed to define optimal sequencing, patient selection, and toxicity mitigation strategies.