# Individualized therapeutic approaches for relapsed and refractory pediatric ependymomas: a single institution experience

## TL;DR

This study explores individualized treatments for relapsed pediatric ependymomas using molecular profiling and reports promising results with immunotherapy and other approaches.

## Contribution

The study demonstrates the feasibility and safety of individualized therapeutic approaches for relapsed pediatric ependymomas using comprehensive molecular profiling.

## Key findings

- Genomic analyses did not reveal actionable alterations, but immunotherapy and other agents showed prolonged progression-free survival in six patients.
- The 5-year overall survival was 88%, and the 2-year survival after relapse was 88%.
- Immunotherapy showed promising effects on ZFTA-positive ependymomas.

## Abstract

This retrospective study aims to show a real-life single-center experience with clinical management of relapsed pediatric ependymomas using results from comprehensive molecular profiling.

Eight relapsed ependymomas were tested by whole exome sequencing, RNA sequencing, phosphoproteomic arrays, array comparative genome hybridization, and immunohistochemistry staining for PD-L1 expression and treated with an individualized approach implementing targeted inhibitors, immunotherapy, antiangiogenic metronomic treatment, or other agents. Treatment efficacy was evaluated using progression-free survival (PFS), overall survival (OS), survival after relapse (SAR), and PFS ratios.

Genomic analyses did not reveal any therapeutically actionable alterations. Surgery remained the cornerstone of patient treatment, supplemented by adjuvant radiotherapy. Empiric agents were chosen quite frequently, often involving drug repurposing. In six patients, prolonged PFS after relapse was seen because of immunotherapy, MEMMAT, or empiric agents and is reflected in the PFS ratio ≥ 1. The 5-year OS was 88%, the 10-year OS was 73%, the 2-year SAR was 88%, and the 5-year SAR was 66%.

We demonstrated the feasibility and good safety profile. Promising was the effect of immunotherapy on ZFTA-positive ependymomas. However, further research is required to establish the most effective approach for achieving sustained remission in these patients.

The online version contains supplementary material available at 10.1007/s11060-025-05004-1.