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

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.