Immunotherapy Plus Stereotactic Radiosurgery: Building on the Promise of Precision Medicine for CNS Malignancies-PART 1: Principles of Combined Treatment.

The role of systemic therapy in the treatment of intracranial metastases has traditionally been limited by the blood-brain barrier, and radiation therapy-either with whole-brain treatment or stereotactic radiosurgery-has remained a primary treatment modality. Recent evidence has demonstrated that antigens released in the brain can inform the systemic immune system, and systemic antibodies can traverse into the brain. This has led to a renewed interest in investigating novel immunotherapy agents to treat both systemic and intracranial disease. Currently, several trials of immunotherapy, with or without sequential or concurrent radiation, have been performed in patients with brain metastases to evaluate the safety and efficacy of combined treatment. Combined use of stereotactic radiosurgery and checkpoint inhibitors appears safe and effective in the treatment of various brain metastases. Future studies will evaluate the optimal sequencing of radiosurgery and immunotherapy and assess the radiation doses and fractionations that will provide the best tumor response.