Safety and Efficacy of Reduced-Dose Stereotactic Radiosurgery Dose Administered With Concomitant Central Nervous System-Penetrant Systemic Therapy for Brain Metastases

Objectives: The reported rate of symptomatic radiation necrosis (SRN) in patients with brain metastases treated with immune checkpoint inhibitor therapy and concomitant single-fraction stereotactic radiosurgery (SRS) is as high as 20%. Previous work has piloted reduced-dose SRS as a potential solution. We present our experience with reduced-dose SRS to further assess its safety and efficacy for this patient population. Methods: Patients receiving SRS within 30 days of CNS-penetrant systemic therapy for brain metastases of 0 to 2 cm maximum diameter on MRI were treated with 18 Gy SRS and prospectively followed. The rates of 6-month local control and 6-month SRN were assessed. Results: Fifty-nine brain metastases were treated in 17 patients. The most common systemic therapy used was single-agent atezolizumab (25% of lesions) and single-agent pembrolizumab (19% of lesions). The most common primary tumors were small cell lung cancer, renal cell carcinoma, and lung adenocarcinoma (68% of lesions). The 6-month local control rate was 96%, with no 6-month SRN. Conclusions: In the largest series examining reduced-dose SRS with concomitant CNS-penetrant systemic therapy, our findings confirm previous reports of the safety and efficacy of single-fraction 18 Gy SRS for brain metastases with maximum diameter 0 to 2 cm receiving therapy within 30 days of SRS. The excellent local control with minimal SRN at this dose supports 18 Gy for patients with brain metastases 2 cm or smaller receiving CNS-penetrant systemic therapy as preferable to the traditionally higher SRS doses, which have represented the standard of care, while remaining preferable to systemic therapy alone.