Second series by the Italian Association of Pediatric Hematology and Oncology of children and adolescents with intracranial ependymoma: an integrated molecular and clinical characterization with a long-term follow-up

BACKGROUND: A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We reanalyzed the series after a median 119 months, adding retrospectively patients’ molecular features. METHODS: Follow-up of all patients was updated. DNA copy-number analysis and gene-fusion detection could be completed for 94/160 patients, methylation classification for 68. RESULTS: PFS and OS at five/ten years were 66/58%, and 80/73%. Ten patients had late relapses (range 66-126 months), surviving after relapse no longer than those relapsing earlier (0-5 years). On multivariable analysis a better PFS was associated with grade 2 tumor and complete surgery at diagnosis and/or at RT; female sex and complete resection showed a positive association with OS. Posterior fossa(PF) tumors scoring ≥0.80 on DNA methylation analysis were classified as PFA (41) and PFB (8). PFB patients had better PFS and OS. Eighteen/32 supratentorial(ST) tumors were classified as RELA, and 3 as other molecular entities (anaplastic PXA, LGG MYB, HGNET). RELA had no prognostic impact. Patients with 1q gain or CDKN2A loss had worse outcomes, included significantly more patients >3 years old (p = 0.050) and cases of dissemination at relapse (p = 0.007). CONCLUSIONS: Previously-described prognostic factors were confirmed at 10-year follow-up. Late relapses occurred in 6.2% of patients. Specific molecular features may affect outcome: PFB patients had a very good prognosis; 1q gain and CDKN2A loss were associated with dissemination. To draw reliable conclusions, modern ependymoma trials need to combine diagnostics with molecular risk stratification and long-term follow-up.