Incidence of radionecrosis in single-fraction radiosurgery compared with fractionated radiotherapy in the treatment of brain metastasis

Introduction Radiation-induced brain necrosis ["radionecrosis" (RN)] is a relatively uncommon but potentially severe adverse effect of stereotactic radiosurgery (SRS) for brain metastasis. Although dose, volume, and hypofractionation have been suggested to affect RN rates, patient and treatment variability in this population make it difficult to clearly delineate the risk. We set out to establish the effect of fractionation on RN rates by reviewing patients receiving simultaneous multi-fraction and single-fraction treatment at our centre. Methods Patients receiving simultaneous (within 1 month) 1-fraction (SSRS) and 3-fraction (fSRS) radiosurgery treatments during 2012-2015 were identified in our institution's database. Serial post-SRS magnetic resonance imaging (MRI) was reviewed to determine RN and local recurrence. The effect of maximum dose, volume, whole-brain radiotherapy (WBRT), and fractionation on RN development was assessed using logistic regression for paired data. Results are reported using odds ratios (ORS) and corresponding 95% confidence intervals (CIS). Results Of 90 patients identified, 22 had at least a 6-month MRI follow-up. Median follow-up was 320 days. The most common primary tumour type was non-small-cell lung cancer, followed by breast and rectal cancer. Radionecrosis developed in 16 patients [21 of 62 lesions (34%), with 4 being symptomatic (20%)]. Of the 21 lesions in which RN developed, 11 received 3 fractions, and 10 received 1 fraction. The OR for the association between the incidence of RN and maximum dose was 1.0 (95% CI: 0.9 to 1.1); for fractionation it was 1.0 (95% CI: 0.3 to 3.6); for previous WBRT, it was 0.4 (95% CI: 0.2 to 1.2); and for a 10-unit increase in volume, it was 3.1 (95% CI: 1.0 to 9.6). Local recurrence developed in 8 patients (12%), 6 of whom belonged to the SSRS group. Conclusions Our results indicate that patients receiving SRS for multiple brain metastases experience a higher rate of RN than is reported in the literature and poorer survival despite having equivalent local control. Maximum dose did not appear to be associated with RN risk in our cohort, but volume was significantly associated with RN risk. Although fractionated treatment did not directly lower the rate of RN in this population, it might have played a role in reducing the magnitude of the RN risk in large-volume lesions. Further investigation will help to delineate optimal dose and fractionation so as to minimize RN while maintaining local control in this group.