Multi-Institutional Investigation of Dose-Escalated Photon Radiotherapy for Intracranial Ependymoma

Abstract

<h3>Purpose/Objective(s)</h3> Adjuvant radiotherapy (RT) is an important modality of treatment for intracranial ependymoma. The most recently published Children's Oncology Group (COG) Study ACNS0121 recommended 54 Gy after gross total resection (GTR) for patients (pts) <18 months of age and 59.4 Gy for all other pts; however, the optimal RT dose remains unclear. Thus, we sought to characterize outcomes after dose-escalated photon radiotherapy (≥59.4 Gy) for intracranial ependymoma. <h3>Materials/Methods</h3> We conducted an Institutional Review Board-approved multi-institutional retrospective cohort analysis of pts who received surgery and radiation for grade II and III intracranial ependymoma between 1997-2021 before the age of 30 years. We recorded clinical and treatment characteristics, and outcomes. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and Tarone-Ware test. <h3>Results</h3> We identified 53 pts who were diagnosed at median age of 6.2 years (range: 0.9-29.9) and of which 20 (37.7%) were female. 20 (37.7%), 41 (77.4%), and 3 (5.7%) pts had anaplastic histology, infratentorial tumors, and metastatic disease at diagnosis, respectively. 15 (28.3%) pts received pre-RT chemotherapy and 10 pts (18.9%) had disease progression before RT. After median of 1 surgery (range: 1-5), 41 (77.4%) pts had a GTR before RT. 32 (60.4%) pts received ≥59.4 Gy. Median age at diagnosis was significantly lower for patients in the <59.4 Gy group compared to ≥59.4 Gy (3.9 vs. 8.7 years, p=0.01). Other factors were not significantly different between the two groups; however, fewer patients had anaplastic histology in the <59.4 Gy group compared to ≥59.4 Gy (23.8% vs. 46.9%, p=0.15). Median follow-up was 20.1 (range: 0.1-21.9) and 8.4 (range: 0.9-16.6) years for the <59.4 Gy and ≥59.4 Gy groups, respectively. PFS (8-year rates of 31.6% vs. 49.7%, p=0.24) and OS (8-year rates of 46.3% vs. 66.3%, p=0.19) were not significantly different between the <59.4 Gy and ≥59.4 Gy groups. Given anaplastic histology portends poor outcome, we examined outcomes for pts with grade 2 ependymoma, and found no significant difference in PFS (8-year rates of 40.0% vs. 61.5%, p=0.11) and OS (8-year rates of 46.7% vs. 64.8%, p=0.13) between the <59.4 Gy and ≥59.4 Gy groups. Median time to recurrence was 1.3 years (range: 0.3-14.7). Of the 29 recurrences in cohort, 7 (24.1%) occurred 5 years after RT. <h3>Conclusion</h3> In a modest sample size of pts undergoing photon-based RT for intracranial ependymoma, we found that there was a non-significant trend to PFS and OS being longer in pts receiving ≥59.4 Gy. Interestingly, 24.1% of recurrences in our cohort occurred 5 years or longer after RT, indicating that intracranial ependymoma can have a long disease course and long follow-up is important when studying outcomes. Future studies with larger cohorts and prospective design are still needed.