KEY POINTS
- This retrospective international cohort included 71 patients younger than 20 years treated with postoperative proton therapy for localized intracranial ependymoma at eight centers in Japan and China between 2000 and 2023. Median age at treatment was 5.4 years.
- Most tumors were clinically high risk: 73.2% were WHO grade 3, 59.2% were infratentorial, and gross total resection was achieved in 46/71 patients (64.8%). The typical proton prescription was 59.4 Gy(RBE) in 1.8-Gy(RBE) fractions.
- At median follow-up of 45.5 months, overall survival was 93.6% at 3 years and 76.9% at 5 years. Progression-free survival was 71.7% and 66.8%, respectively.
- Local control remained high at 88.4% at 3 years and 83.5% at 5 years. Twenty patients progressed: 4 had local failure alone, 9 distant failure alone and 7 both, corresponding to a local component in 15.5% and a distant component in 22.5% of the cohort.
- Multivariable analysis associated female sex with better overall survival (HR 0.15; p=0.006) and progression-free survival (HR 0.24; p=0.004). Supratentorial location was also favorable for overall survival (HR 0.193; p=0.017) and progression-free survival (HR 0.174; p=0.002); higher proton dose correlated with better overall survival (HR 0.857; p=0.045).
- Severe late toxicity was uncommon: no grade ≥3 late adverse events were recorded. Grade 2 events consisted of alopecia in two patients, hearing impairment in one and radiation necrosis in one; the grade 2 necrosis occurred after subsequent salvage reirradiation and cannot be attributed solely to the original proton course.
- Radiographic radiation necrosis of any grade was observed in 7 patients, mostly asymptomatic grade 1 changes. Two secondary malignancies (2.8%) were reported at 3.2 and 3.6 years, including one pathologically confirmed glioblastoma within the irradiated field. Interpretation is limited by relatively short and heterogeneous follow-up, incomplete molecular classification and non-standardized toxicity surveillance.
CLINICAL TAKEAWAY
Postoperative proton therapy provided durable local control with very little documented high-grade late toxicity in this multicenter pediatric ependymoma cohort. The results support protons as a reasonable postoperative modality, but do not establish superiority over modern photon RT, and longer standardized follow-up is particularly important for neurocognitive, endocrine and secondary-malignancy outcomes.