Fractionated Stereotactic Intensity-Modulated Radiotherapy for Large Brain Metastases: Comprehensive Analyses of Dose-Volume Predictors of Radiation-Induced Brain Necrosis

Background: Dosimetric predictors of brain necrosis (BN) have not yet been established for fractionated stereotactic radiotherapy (SRT). Methods: Multivariate logistic models were developed for comprehensive analyses of dosimetric predictors in patients who received first-line fractionated SRT for brain metastases (BMs). The normal brain volume receiving a xx Gy biological dose in 2 Gy fractions (VxxGyE) was calculated from the retrieved dose-volume parameters. Results: Three-fraction SRT was delivered to 34 patients with 74 BMs (mean target volume, 4.3 cc), 5-fraction SRT to 58 with 106 BMs (15.4 cc), and 10-fraction SRT to 20 with 35 BMs (25.9 cc) according to protocols depending on the target volume (p <0.001). In the 5- and 10-fraction groups, the incidence of symptomatic BN was significantly higher in patients with a larger V50GyE (odds ratio: 1.07, p <0.02), V55GyE (1.08, p <0.01), or V60GyE (1.09, p <0.01). The incidence of BN was also significantly higher in cases with V55GyE >30 cc or V60GyE >20 cc (p <0.05). Conclusion: In 5- or 10-fraction SRT, at least V55GyE ≤30 cc or V60GyE ≤20 cc should be maintained to lower the risk of BN.