M. L. Rose1,2, R. Sachdeva1, Y. Mezgueldi1, R. Yen1,3, L. Serraj1, K. Corbett1,4, and T. I. Yock5; 1Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Hanover, NH, 2Department of Radiation Oncology and Applied Sciences, Dartmouth Cancer Center, Dartmouth Health, Lebanon, NH, 3Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, NH, 4Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 5Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Purpose/Objective(s): Ependymomas are the third most common brain tumors in children. The current standard of care for curative intent treatment is maximal safe resection followed by adjuvant radiotherapy. Controversy in the literature still exists over optimal radiotherapy dose. The most important prognostic factor for these tumors is the extent of resection followed by the addition of adjuvant radiotherapy. We completed a systematic review and meta-analysis of the available literature to determine the optimal radiotherapy dose regarding outcomes, including local control (LC), event-free survival (EFS), and overall survival (OS) in pediatric patients (=22y). Materials/
Methods: We searched MEDLINE (PubMed), Cochrane Database of Systematic Reviews, and Web of Science from inception to January 2024. We included cohort studies that compared adjuvant radiotherapy doses of =54Gy to >54Gy in pediatric patients (=22y) with non-metastatic intracranial ependymomas treated with curative intent therapy. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale of Cohort Studies. We quantitatively pooled studies using a random effects meta-analysis for hazard ratios (HR), 95% confidence intervals (CI), and statistical heterogeneity via I2. When HRs were unavailable, we transformed 3-year risks using established methods. We narratively summarized qualitative outcomes. Results: Seven cohort studies met our inclusion criteria, covering a combined 1321 pediatric patients. Studies included a range of doses from 45-66.6Gy. Compared with patients receiving adjuvant radiotherapy dose of >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%). Three studies methodically placed younger children in the lower dose cohorts due to concerns of late-effects of therapy. Two studies reported on the extent of resection by radiotherapy dose, with neither study reporting a statistical difference in LC, EFS, or OS, though the number of patients included in each study analysis was small (n=30). Five studies reported on late effects, with brainstem radionecrosis, radiation-induced vasculopathy, and secondary tumors being the most frequently reported toxicities. Toxicities were not reported in relation to the specific doses of radiotherapy received. Overall study quality was high, though lower scores were consistently seen in the comparability of cohorts. Conclusion: We found no difference in LC, EFS, or OS for those treated with =54Gy compared to >54Gy. Many of the children who were in the lower dose cohorts were younger in age, a group with historically worse outcomes, which may artificially increase rates of relapse, events, and mortality. There was insufficient data to complete a subgroup meta-analysis on radiotherapy dosing based on the extent of resection or molecular subgroups, an important question for future research.
.jpg "Melanie Rose, MD photo")