PURPOSE : Stereotactic radiosurgery (SRS) is the current standard of care in patients with brain metastases and controlled extracranial disease. Radiation necrosis (RN) is the dose-limiting side-effect of SRS but the dose constraints especially for fractionated SRS remain poorly defined. We assessed the risk of RN after 3-fraction SRS with a goal to identify specific dose -volume constraints associated with grade 3 or higher RN (G3RN).

METHODS : A single-institutional retrospective review of patients treated with 3-fraction SRS was performed. Primary endpoint was G3RN which was defined as severe symptoms with evidence of necrosis on MRI with perfusion and/or biopsy confirmation. Tissue volume around each target lesion was contoured and volumetric doses per lesion were recorded. Logistic regression models were used to estimate the relationship between RN and each volumetric dose, and NTCP modeling was performed using modified LKB model.

RESULTS : From 2015 to 2021, 434 patients, underwent 539 courses of Linac-based SRS treating 2518 lesions. Median SRS dose was 24Gy. Median follow-up after SRS was 7.9months, while the median overall survival was 9months. A total of 93(17.2%) patients and 123(4.9%) lesions developed any RN. Forty-two(7.8%) patients and 57(2.3%) lesions developed G3RN. On logistic regression, V20 and V23 were best predictors of any grade RN and G3 RN respectively, with cut-off values of 4cc, 10cc and 20cc associated with <5%, <7.5% and <10% risk of any RN and V23<15cc to be associated with <5% risk of G3RN. With constrained optimization of the NTCP LKB model for G3RN, we obtained a TD50 of 31.4Gy (95%CI 27.8-35.1Gy).

CONCLUSIONS : In patients receiving 3 fraction SRS, G3RN was seen in 7.8% patients and 2.3% lesions treated. V20 and V23 were most robust dosimetric parameters associated with RN. Further studies evaluating the outcomes and RN in patients treated with fSRS compared to single fraction SRS are warranted.