Updated risk models demonstrate low risk of symptomatic radionecrosis following stereotactic radiosurgery for brain metastases

BACKGROUND: Improvements in systemic therapy continue to increase survival for patients with brain metastases. Updated dosimetric models are required to optimize long-term safety of stereotactic radiosurgery (SRS) for this indication. METHODS: Patients at a single institution receiving SRS from December 2011 to December 2014 were retrospectively reviewed. Patients with radiographic progression of at least one lesion, and with at least 6 months of follow-up from the start of SRS were included. Grade 3 necrosis was defined as requiring surgical intervention. This data were combined with two additional published datasets to construct logistic models describing necrosis risk as a function of dose and volume. RESULTS: From our institution, 294 brain metastases across 57 patients in 139 treatment plans met inclusion criteria. Primary histologies included non-small cell lung cancer (n = 19), melanoma (n = 13), breast carcinoma (n = 9), renal cell carcinoma (n = 7), and other (n = 9). Median follow-up from SRS of first cranial metastasis was 21.7 months (range: 6.3–56.6) and median overall survival was 25.6 months (range: 6.5–56.6). There were eight cases of Grade 1–2 and two cases of Grade 3 necrosis. As a useful clinical reference point, 20 cc of total brain receiving a single-fraction equivalent dose ≥14 Gy corresponded to 12.1% risk for Grade 1–3 (P < 0.003) and 3.4% risk for Grade 3 necrosis (P < 0.001). CONCLUSIONS: These results compare favorably with the QUANTEC brain tolerance estimates for radiosurgery, providing optimism for lower toxicity in the modern era. Additional studies are needed to determine dose tolerance parameters across a broad spectrum of patients.