Immunotherapy Plus Stereotactic Radiosurgery: Building on the Promise of Precision Medicine for CNS Malignancies-PART 2: Existing Experience and Considerations for Future Trials.

The brain has long been considered an immunologically privileged site, and the role of immunotherapy in treating intracranial disease has only recently been revived-with preclinical evidence showing that the systemic immune system responds to immunotherapy for intracranial disease, and with clinical evidence demonstrating improved locoregional control and survival compared with historical outcomes when immune-directed therapies are combined with radiation. Pharmaceutical industry-supported multi-institutional drug efficacy studies routinely exclude patients with brain metastases, so current evidence for treatment of brain metastases using stereotactic radiosurgery combined with immunotherapy comes from single-institution studies. Many studies of combinations of immune checkpoint blockade (with anti-cytotoxic T-lymphocyte-associated antigen 4 and anti-programmed death 1 antibodies) with stereotactic radiosurgery have demonstrated promising improvements in intracranial control and survival. In addition to evaluating the optimal combination of these therapies, future studies will likely search for predictive biomarkers to better select patients whose disease is most appropriately managed with this combined-modality approach.