Predictive Factors for Survival and Radiation Necrosis in Patients with Recurrent High-Grade Glioma Treated with Re-Irradiation

Abstract

<h3>Purpose/Objective(s)</h3> To analyze the predictors of survival and radiation necrosis in adult patients (pts) with recurrent high-grade gliomas (rHGG) who have undergone re-irradiation (ReRT). <h3>Materials/Methods</h3> All adult pts with rHGG who had ReRT from 2009 to 2020 at one institution were retrospectively reviewed. Demographic, clinical, dosimetric, and radiological data were obtained from the electronic medical records. The primary outcome was to identify predictors of overall survival (OS) and radiation necrosis (RN). The secondary outcome was to identify patterns of failure after ReRT, which was defined as in-field, marginal or distant if >95% of the recurrence volume was in the 80% isodose line (IDL), between 80%-20% IDL, or outside 20% IDL, respectively. OS, progression-free survival (PFS), and RN were estimated by the Kaplan-Meier method. Toxicity was recorded according to CTCAE V5.0. <h3>Results</h3> Were included 79 pts with a median age of 52 yrs (range, 19-79), 62% were male, 85% had grade 4 glioma at presentation and 98% at ReRT. IDH was wildtype/mutated/unknown in 73%/11%/15% of pts. 92% had concurrent/adjuvant temozolamide at the primary treatment. 34% had re-resection prior to ReRT. 16% had concurrent bevacizumab at ReRT. The most common fractionation schedules at the primary treatment were 40 Gy/15Fx (9%) and 50-60 Gy/28-33Fx (91%), and at ReRT were 17-24 Gy/1Fx (9%), 20-35 Gy/5Fx (38%), 25-35 Gy/10Fx (48%) and 36-54 Gy/18-30Fx (5%). The median cumulative equivalent dose in 2 Gy fractions (EQD2, a/b=2) was 103 Gy (range, 81-216). The median OS and PFS were 9.9 (95% CI 8.3-11.6) and 4.1 mos (95% CI 3.6-5.4), respectively. The OS and PFS rate at 6/12 months were 69.6%/34.2% and 29.1%/7.5%, respectively. The prognostic factors for OS on multivariate analyses (MVA) were interval from initial treatment to first progression ≥16.3mos (HR=0.35, 95% CI 0.20-0.59, p<0.001), re-resection prior ReRT (HR=0.43, 95% CI 0.25-0.73, p=0.002), ECOG ≥1 at ReRT (HR=1.90, 95% CI 1.10-3.30, p=0.022) and PTV volume at ReRT ≥112cc (HR=2.63, 95% CI 1.55-4.44, p≤0.001). Toxicities G2 and G3 were 22% (8.8% RN) and 5% (2.5% RN), respectively. Concurrent use of bevacizumab (p<0.001) and EQD2 ≤98 Gy (p<0.001) were predictors for lower incidence of RN on MVA. Exploratory analysis suggested three risk groups for RNs based on cumulative EQD2: ≤100 Gy (RN = 4%), 100-111 Gy (RN = 13%), and ≥111 Gy (RN = 20%). The failures after ReRT were in-field, marginal or distant in 67%, 6%, and 27% of pts who had follow-up MRI, respectively. <h3>Conclusion</h3> Re-irradiation is a safe and effective treatment for GBM. We describe predictive factors for OS and RN to guide patient section. Focus on pts with the most favorable OS may aid in identifying pts most likely to benefit from ReRT.