PURPOSE: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Center for Precision Medicine University Hospital Brno Brno 62500 Czech Republic

Department of Biology Faculty of Medicine and Central European Institute of Technology Masaryk University Brno 62500 Czech Republic

Department of Pathology University Hospital Brno and Faculty of Medicine Masaryk University Brno 62500 Czech Republic

Department of Pediatric Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno 62500 Czech Republic

International Clinical Research Center St Anne's University Hospital Brno 60200 Czech Republic

Laboratory of Tumor Biology Department of Experimental Biology Faculty of Science Masaryk University Brno 62500 Czech Republic

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