The Impact Radiation Therapy Variables on Pediatric High-Grade Glioma (pHGG) Outcomes: A National Cancer Database Analysis

Abstract

Pediatric high-grade gliomas (HGGs) are a devastating disease with a poor prognosis. Radiation therapy (RT) is standard of care in the definitive treatment of pediatric HGG, yet data addressing the impact of varying RT variables on outcomes are lacking. The purpose of this analysis is to evaluate the impact of RT variables on outcomes of pediatric HGG patients in the National Cancer Database (NCDB). The NCDB participant user file including cases diagnosed between 2003-2015 was used to select patients age <22 with histologically proven WHO Grade III and IV high-grade gliomas, brain tumor location codes (ICD-O-3 C710-C719), and who received RT of dose ≥50Gy and <76Gy between 2004 and 2013. RT variables including RT dose, timing between diagnosis and RT initiation (<4 weeks, 4-6 weeks, or >6 weeks), and RT modality were analyzed along with baseline demographic, tumor and treatment variables to assess the impact on overall survival in Univariate and Multivariable analyses by the proportional hazards regression. Kaplan-Meier Curves were generated and compared by Log-rank tests for the covariates above. 498 pediatric HGG patients were included. The median age at diagnosis was 15 years (range 0-21), 54% of patients were male and 79% white. Histologies included glioblastoma (30%), astrocytoma (55%), oligogendroglioma (5%) and gliomas not otherwise specific (10%). Surgery was performed in 73.5% of patients and 90% of patients received chemotherapy. Chemotherapy was initiated either before or during radiation in 80% of patients, and after RT was completed in 5% of patients. The median RT dose was 59.4 Gy (SD 2.9 Gy) starting a median of 4.4 weeks from diagnosis (SD 2.5 weeks). Median follow-up was 19.6 months (Q1-Q3: 11.8 – 44.5) with 1- and 3-year OS (95% CI) of 78.4% and 40.4%, respectively. There was a non-significant trend between RT dose >59.4 Gy and longer overall survival (HR 0.80 (0.62-1.04), p = 0.092) on univariate analyses. On Multivariable analysis, female gender, older age, and private insurance remained independently associated with lower rate of overall death. Radiation delay of ≤4 weeks from diagnosis and glioblastoma histology were significantly associated with higher rate of overall death. There was no difference in OS according to whether RT was delivered with photons (IMRT or 3-D conformal) or proton therapy. Outcomes for pediatric HGG are poor. Delay of RT initiation beyond 6 weeks from diagnosis does not appear to negatively impact outcomes. Early initiation of RT within 4 weeks may be detrimental or related to unknown prognostic factors.Tabled 1Abstract 2552; Table. Multivariable Survival Analysis of Overall Survival Main EffectCovariateDescriptionHazard Ratio (95% CI)HR P-valueSexFemale0.71 (0.56 - 0.90)0.005Primary PayorPrivate insurance0.73 (0.56 - 0.96)0.025Radiation Delay<4 weeks from diagnosis1.55 (1.05 - 2.25)0.028HistologyGlioblastoma1.72 (1.33 - 2.24)<0.001 Open table in a new tab