Dosimetric Factors Related to Radiation Necrosis after Five Fraction Radiosurgery for Patients with Resected Brain Metastases

Abstract Purpose Stereotactic Radiosurgery (SRS) is increasingly utilized in the management of patients with resected brain metastases (rBM). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation (RT) dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBM remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBM. Methods From 2008-2016, 55 rBM at a single institution that were treated post-operatively with five-fraction linear accelerator based SRS (25-35Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included RT dose to normal brain, location/magnitude of hot spots, CTV, and margin size. Hot spot location was stratified as within the tumor bed alone (CTV) or within the PTV expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence (LR). Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic. Results Median age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cc, the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed max hot spot (hazard ratio (HR): 3.28, p=0.045), volume of the hot spots within PTV expansion margin of relative magnitude 105%, 110%, 111%, and absolute magnitude 33.5Gy predicted for RN (p=0.029, p=0.04, p=0.038, and p=0.0488 respectively), but hot spots within the CTV did not. Conclusion To our knowledge, this is the first study that investigated dosimetric factors that predict for RN after five-fraction hypofractionated SRS for rBM. Hot spot location and magnitude appear important for predicting RN risk, suggesting these parameters should be carefully considered during treatment planning.