Dose Escalation for Posterior Fossa Ependymomas: Analysis of Prospective Pediatric Proton/Photon Consortium Registry

Abstract

<h3>Purpose/Objective(s)</h3> A dose of 54 Gy is considered a minimum dose required for local control (LC) in an adjuvant setting for posterior fossa (PF) ependymomas; however, a higher dose may be more desirable given that the primary mode of relapse is local failure. Proton therapy (PT) may allow for safer delivery of higher radiation doses, although data on safety and efficacy of dose-escalation for posterior fossa tumors with PT are currently limited. We analyzed the Pediatric Proton/Photon Consortium Registry (PPCR), the largest United States database of pediatric patients treated with PT, to examine the safety and efficacy of dose-escalation (≥55.8 Gy) for PF ependymoma. <h3>Materials/Methods</h3> All consecutive patients enrolled on the PPCR with PF ependymomas who received adjuvant radiation with PT between 2002 and 2020 were assessed. Survival and toxicity outcomes between patients who received a standard dose (SD) of 54 Gy and a high dose (HD) ≥55.8 Gy were compared. Overall survival (OS), LC, and progression-free survival (PFS) were estimated using Kaplan Meier analysis. <h3>Results</h3> A total of 171 children with PF ependymoma were treated with PT: 111 (65%) received SD and 60 (35%) received HD. Of those in HD cohort, 43 (72%) received a dose of 59.4 Gy [range, 55.8-59.4]. The median follow-up time was 35.6 months. Median age was 3.2 years [range, 0.5-21.2]. Patients in the HD cohort were older (median 4.25 vs 2.73 years, p=0.008). A higher proportion of HD children had a subtotal resection of their primary tumor (30.5% vs 17.4%) although not statistically significant (p=0.112). More patients in the HD arm received chemotherapy following the completion of PT (83.3% vs. 45.5%, p=0.075). No statistically significant differences in neurologic (82.4% vs. 89.5%), auditory (30.6% vs. 29.8%), visual (50.5% vs. 45.6%), endocrine (15.7% vs. 15.8%), or cutaneous (86.1% vs. 75.4%) toxicities were noted between SD and HD patients, respectively. Median OS and median PFS were not reached for both cohorts. The 5-year OS were 78.4% (95% CI: 67.5-91.2) and 74.9% (95% CI: 61.2-91.7) for SD and HD, respectively (p=0.082). The 5-year LC were 79.9% (95% CI: 71.1-89.9) and 70.1% (95% CI: 57.5-85.4) (p=0.069), and the 5-year PFS were 58.4% (95% CI: 47.1-72.4) and 63.8% (95% CI: 50.8-80.2) (p=0.54) for SD and HD, respectively. Among the subset of HD patients receiving 59.4 Gy, there similarly was no LC, PFS, or OS advantage when compared to SD (all p>0.05). <h3>Conclusion</h3> Dose-escalation (≥55.8 Gy) did not result in higher rates of radiation-induced toxicities in children with PF ependymomas treated with PT on PPCR. At the same time, higher doses did not lead to superior LC or survival when compared to a standard dose of 54 Gy. Randomized studies are needed to provide a definitive answer on the value of dose-escalation in pediatric PF ependymoma and identify a subset of children who may benefit from higher RT doses.