Risk of late radiation necrosis more than 5 years after stereotactic radiosurgery

Radiation necrosis (RN) is a well-recognized late complication most commonly occurring within 2 years of stereotactic radiosurgery (SRS); however, late RN (LRN), RN occurring or recurring > 5 years after SRS, has been poorly described. This study analyzes the incidence of and risk factors for LRN occurring > 5 years after SRS.

This retrospective analysis included patients treated with linear accelerator-based SRS for tumors or arteriovenous malformations with > 5 years of clinical and serial MRI follow-up. LRN was defined as new neurological symptoms with neuroanatomically correlated imaging findings without disease recurrence. Univariate and multivariate analyses for LRN were performed using the Cox proportional hazards model.

The authors identified a cumulative 297 lesions in 219 patients treated to a median dose of 17 Gy with a median follow-up of 7.4 years. In total, 290 (97.6%) lesions were treated in a single fraction, and 64 (21.5%) were treated after resection. The LRN occurred in 19 (8.7%) patients and in 23 (7.7%) lesions at a median of 6.1 years (range 5.1-13.9 years) after SRS. Fifteen of the 23 (65.2%) lesions were managed with steroids, bevacizumab, and/or antiepileptic drugs. The remaining 8 (34.8%) were resected; histopathology confirmed necrosis without disease recurrence in each. On multivariate analysis, only > 5-cm3 volume of the brain receiving 12 Gy (brain V12Gy) (HR 6.01, 95% CI 1.77-20.48; p = 0.004) and a history of early, previously resolved RN (HR 9.53, 95% CI 2.00-45.61; p = 0.005) remained significantly associated with LRN.

RN risk persists well beyond 5 years after SRS, and recognizing LRN as an entity has important implications in managing these patients. LRN risk was highest in those with a brain V12Gy > 5 cm3 and a history of early RN after SRS, warranting close follow-up in perpetuity for select patients.