Outcomes Following Proton Therapy for Pediatric Ependymoma

Abstract

Dosimetric studies show proton therapy can reduce the low/intermediate radiation dose delivered to uninvolved brain tissue in children with intracranial ependymomas, which may result in improved functional outcomes and fewer second malignancies in survivors. Based on this rationale, ependymoma has become the most common pediatric tumor treated with proton therapy worldwide yet clinical outcome data on efficacy and toxicity is limited. The purpose of this study is to report treatment outcomes of pediatric ependymoma patients following proton therapy. Between June 2007 and February 2017, 179 children (≤ 21 years old) with non-metastatic Grade II/III intracranial ependymoma were treated with proton therapy at a single institution. The median age was 3.5 years (range, 0.7-21) and 58% were male. The majority (65%) of tumors were located in the posterior fossa and classified as WHO grade III (67%). Twenty seven percent of patients underwent >1 operation to maximize the extent of resection; ultimately 85% had a gross total or near total tumor resection prior to radiotherapy. Thirty three percent of patients received pre-radiation chemotherapy. The median radiation dose in children ≤ 3 y/o was 54 Gy. Most (>90%) children over 3 years old received 59.4 Gy. Common patient and treatment variables were assessed for correlation with disease control. The median follow-up was 3.2 years. The 3-year actuarial rates of local control, progression free survival, and overall survival were 85.4%, 75.9%, and 90.4%, respectively. First site of progression was local, metastatic, or simultaneous in 14, 17, and 6 patients, respectively. On multivariate analysis, subtotal resection was associated with inferior local control (66.5% vs 88.4%, P = < 0.01) and progression free survival (59.4% vs 78.5%, P < 0.05). The 3-year actuarial rate of CTCAE Grade 2+ brainstem toxicity was 5.5% (95% CI: 2.9 to 10.2), including 1 case (0.5%) of grade 5 toxicity. This is the largest single institution series of children treated for ependymoma with any radiation modality. It confirms the impact of tumor resection on disease control. It also demonstrates that proton therapy can reduce the low/intermediate radiation dose to developing brain tissue without compromising disease control or producing unexpected toxicity.