Systematic review and meta-analysis of adjuvant radiation dose for pediatric patients (≤22y) with non-metastatic intracranial ependymomas.

Abstract

Ependymomas are the third most common brain tumors in children. Standard of care is surgery followed by adjuvant radiotherapy. Controversy in the literature still exists over optimal radiotherapy dose. We completed a systematic review and meta-analysis to determine the optimal dose for local control (LC), event-free survival (EFS), and overall survival (OS) in pediatric patients. We searched MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and Web of Science through January 2024. We included cohort studies that compared adjuvant radiotherapy of ≤54Gy to >54Gy in pediatric patients (≤22 years) with non-metastatic intracranial ependymomas. We assessed study quality using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies. We pooled studies using a random effects meta-analysis for hazard ratios (HR), 95% confidence intervals (CI), and assessed statistical heterogeneity via I2. When HRs were unavailable, we transformed risks using established methods. We narratively summarized qualitative outcomes. Seven studies met our inclusion criteria, covering a combined 1321 patients. Studies included a range of doses from 45-66.6Gy. Compared with >54Gy, we found no difference in LC for those receiving ≤54Gy (HR=0.83, 95% CI 0.56-1.24, I2=49.1%), in EFS (HR=1.02, 95% CI 0.95-1.09, I2=0.00%), and OS (HR=0.99, 95% CI 0.82-1.20, I2=37.5%). Two studies reported on subtotal resection by radiotherapy dose, neither study reporting statistical differences in LC, EFS, or OS, though the number of patients was small (n≤30). Five studies reported on late effects, with brainstem radionecrosis, radiation-induced vasculopathy, and secondary tumors being the most frequent. Overall study quality was high, though lower scores were consistently seen in comparability of cohorts. No studies reported on molecular subgroups. We found no difference in LC, EFS, or OS for those treated with ≤54Gy compared to >54Gy. There was insufficient data to complete a subgroup meta-analysis on radiotherapy dosing based on extent of resection or molecular subgroups.