Impact of molecular classification on prognosis in children and adolescents with spinal ependymoma: Results from the HIT-MED database

Neurooncol Adv. 2024 Oct 23;6(1):vdae179. doi: 10.1093/noajnl/vdae179. eCollection 2024 Jan-Dec.

Abstract

Background: Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims to evaluate the prognostic impact of molecular typing on pediatric spinal cord ependymomas.

Methods: Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database (German brain tumor registry for children, adolescents, and adults with medulloblastoma, ependymoma, pineoblastoma, and CNS-primitive neuroectodermal tumors) between 1992 and 2022 were included. Forty-seven tumors were analyzed by DNA methylation array profiling. In 6 cases, HOXB13 and MYCN proteins were detected as surrogate markers for specific methylation classes. Ten patients had NF2-related schwannomatosis.

Results: With a median follow-up time of 4.9 years, 5- and 10-year overall survival (OS) were 100% and 86%, while 5- and 10-year progression-free survival (PFS) were 65% and 54%. Myxopapillary ependymoma (SP-MPE, n = 32, 63%) was the most common molecular type followed by spinal ependymoma (SP-EPN, n = 17, 33%) and MYCN-amplified ependymoma (n = 2, 4%). One case could not be molecularly classified, and one was reclassified as anaplastic pilocytic astrocytoma. 5-year PFS did not significantly differ between SP-MPE and SP-EPN (65% vs. 78%, P = .64). MYCN-amplification was associated with early relapses (<2.3 years) in both cases and death in one patient. Patients with SP-MPE subtype B (n = 9) showed a non-significant trend for better 5 years-PFS compared to subtype A (n = 18; 86% vs. 56%, P = .15). The extent of resection and WHO tumor grades significantly influenced PFS in a uni- and multivariate analysis.

Conclusions: Molecular typing of pediatric spinal ependymomas aids in identifying very high-risk MYCN-amplified ependymomas. Further insights into the molecular heterogeneity of spinal ependymomas are needed for future clinical decision-making.

Keywords: DNA methylation; MYCN-amplification; molecular type; pediatric spinal ependymoma; radiotherapy.