Radiation Necrosis Following Five Daily Fractions of Stereotactic Radiotherapy for Surgical Cavities and Intact Brain Metastases

There is increasing use of hypofractionated stereotactic radiosurgery (HSRS) for the treatment of intact brain metastases and surgical cavities. Unlike single fraction stereotactic radiosurgery (SRS), limited data exist quantifying the risk of radiation necrosis (RN) specific to HSRS. We present our analyses of the risk of RN following 5 daily fraction HSRS to surgical cavities and intact metastases and respective predictors. 187 consecutively treated patients with 118 surgical cavities and 132 intact metastases were retrospectively reviewed. All patients were treated with thermoplastic mask immobilization using a cone-beam CT (CBCT) image-guided Linac with a multi-leaf collimator (MLC) and six-degrees-of-freedom treatment couch. All patients were treated with 5 daily fractions with a 2mm planning target volume (PTV) applied. Clinical and dosimetric variables were assessed to identify predictors of RN including the total volume of the brain minus the CTV (BMC) receiving 5 to 30 Gy in 5 Gy increments, where the CTV was the surgical cavity for resected lesions and equaled the GTV for intact lesions. The median total dose was 30 Gy (range, 20 to 35 Gy) and median follow-up was 13.5 months (range, 2 to 85). 144 patients (77%) received treatment to a single target; otherwise the median number of simultaneously treated targets was 2 per patient (range, 2 to 4). The most common histologies were lung cancer (48%), breast cancer (21%), and melanoma (10%). Median PTV volumes for cavity and intact metastases were 24.9cc and 7.7cc, respectively. RN was observed in 53 targets (21.2%) and the median time to RN was 8 months (range, 1 to 41). Time to RN was < 6 months for 20 (38%), 6 to 12 months for 23 (43%) and > 12 months for 10 (19%) targets. The rate of RN specific to cavities was 16%, of which 47% were symptomatic, and 26% for intact metastases of which 53% were symptomatic. RN was determined by surgical pathology in 29 cases (57%) and serial MRI in 23 cases (43%). Multivariable analysis (MVA) identified intact metastases vs cavities [OR 3.7 (95% CI, 1.33 to 10)] as a significant predictor of symptomatic RN. Specific to cavity HSRS, prior WBRT [OR 7.73 (95% CI, 1.67 to 35.69)] and prior SRS [OR 8.66 (95% CI, 1.14 to 65.7)] were significant predictors of symptomatic RN. For intact metastases, the BMC30Gy [OR 1.21 (95% CI, 1.02 to 1.43)] was a significant predictor of symptomatic RN and a threshold of 10.5cc was identified with an OR of 7.21 (95% CI, 1.31 to 39.45). The overall risk of RN with HSRS is modest and about half of affected patients are symptomatic. The risk of RN was greater for intact metastases compared to cavities following HSRS. In intact lesions, the BMC30Gy was predictive for symptomatic necrosis and a threshold of 10.5cc may guide treatment planning and/or dose selection.