EPEN-19. IMPACT OF MOLECULAR SUBTYPING ON PROGNOSIS IN CHILDREN AND ADOLESCENTS WITH SPINAL EPENDYMOMA

Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. Recent advances in subtyping the main molecular groups, myxopapillary ependymoma (MPE) and spinal ependymoma (SP-EPN), have successfully identified distinct risk groups among adult patients. This study aims at evaluating the prognostic impact of MPE subtypes A and B in a pediatric cohort.

Eighty-three patients with spinal ependymoma ≤22 years registered in the HIT-MED database between 1992 and 2022 were included. Forty-seven tumors were analyzed regarding global DNA methylation. In six cases, antibodies against HOXB13 and MYCN were used as surrogate markers for the methylation group. Twenty-eight MPE were further classified into subtypes by t-distributed stochastic neighbor embedding (t-SNE) analysis.

MPE (n=32, 63%) was the most common molecular type followed by SP-EPN (n=17, 33%) and MYCN-amplified ependymoma (n=2, 4%). One case remained molecularly unclear, and one was excluded due to reclassification as anaplastic pilocytic astrocytoma. MPE subtyping identified 18 MPE-A and 9 MPE-B (inconclusive: n=1). 5-year progression-free survival (5y-PFS) did not significantly differ between MPE and SP-EPN (65% vs. 78%, p=0.64). MYCN-amplification was associated with early relapses and with death in one patient. Patients with MPE-B may have a tendency towards superior 5y-PFS compared to MPE-A (86% vs. 56%, p=0.15), irrespective of the use of adjuvant treatment. MPE-A was more frequently disseminated at time of diagnosis (n=6/18) than MPE-B (n=1/8, not evaluable: n=1; p=0.28).

Molecular subtyping of spinal ependymoma in children does not allow to separate patients into distinct risk groups, yet. However, the potentially favorable PFS among patients with MPE-B prompts the consideration of treatment de-intensification for this group. Larger cohorts and further insights into the molecular heterogeneity of these tumors are needed to complete the basis for future clinical decision-making.