Abstract
PURPOSE: We characterized the association between photon radiation dose (< 59.4 versus ≥ 59.4 Gy) and outcomes in intracranial ependymoma. We also examined factors associated with survival after relapse. METHODS: This multi-institutional retrospective study included patients age ≤ 21 years who received postoperative definitive-intent photon radiotherapy for posterior fossa ependymoma between 1997 and 2021. Clinical characteristics were obtained from medical records. Five-year overall (OS) and progression-free (PFS) survival were estimated using the Kaplan-Meier method. Factors associated with progression after radiotherapy, including dose < 59.4 versus ≥ 59.4 Gy, were analyzed using Fine and Gray's proportional subhazards model. Factors associated with post-relapse survival were explored using the Cox proportional-hazards model. RESULTS: We identified 45 patients meeting inclusion criteria; 48.9% received ≥ 59.4 Gy. There was no difference in 5-year OS or PFS between those who received < 59.4 Gy versus ≥ 59.4 (OS 49.0% vs. 82.9%, p = 0.11; PFS 36.4% vs. 63.9%, p = 0.08); however, there was a trend towards worse 5-year OS and PFS among patients with grade 2 ependymoma who received < 59.4 Gy (OS 48.8% vs. 88.9%, p = 0.06, PFS 40.0% vs. 83.1%, p = 0.08). Only age > 4 years at diagnosis (subdistribution hazard ratio [SHR]: 0.40, p = 0.03) was associated lower risk of progression. Following radiotherapy, 24 patients relapsed. Receipt of salvage systemic therapy was associated with worse post-relapse OS on multivariable analysis (HR = 2.84, p = 0.04). CONCLUSION: Underlying biological factors such as age and molecular subtype may hold greater prognostic significance than radiation dose in pediatric ependymoma. Regardless, recurrences are common and outcomes remain poor. Further research into optimal management of relapsed disease is critical.