Distinct relapse pattern across molecular ependymoma types

Neuro Oncol. 2025 Jan 12;27(1):267-276. doi: 10.1093/neuonc/noae166.

Abstract

Background: Ependymoma (EPN) is not a uniform disease but represents different disease types with biological and clinical heterogeneity. However, the pattern of when and where different types of EPN relapse is not yet comprehensively described.

Methods: We assembled 269 relapsed intracranial EPN from pediatric (n = 233) and adult (n = 36) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information.

Results: The cohort comprised the following molecular EPN types: PF-EPN-A (n = 177), ST-EPN-ZFTA (n = 45), PF-EPN-B (n = 31), PF-EPN-SE (n = 12), and ST-EPN-YAP (n = 4). First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.4 years; P < .01). Metastatic or combined recurrences in PF-EPN-B and -A more often involved the spinal cord than in ST-EPN-ZFTA (72.7% and 40.0 vs. 12.5%; P < .01). No distant relapses were observed in ST-EPN-YAP (n = 4) or PF-EPN-SE (n = 12). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5% ± 4.4%/47.8% ± 9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5% ± 7.1%/90.0% ± 9.5% (P = .03). However, 10-year PRS for PF-EPN-B dropped to 45.8% ± 17.3%. Neither between the radiation field and relapse pattern nor between the radiation field and spinal involvement at relapse an impact was identified. Notably, all patients with relapsed ST-EPN-YAP did not receive upfront radiotherapy but were successfully salvaged using irradiation at relapse.

Conclusions: Relapse patterns of specific EPN types are different. Future clinical trials, treatment adaptions, duration of surveillance, and diagnostics should be planned to incorporate entity-specific relapse information.

Keywords: ependymoma; metastatic; recurrence; relapse.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Child
  • Child, Preschool
  • DNA Copy Number Variations
  • DNA Methylation*
  • Ependymoma* / genetics
  • Ependymoma* / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / genetics
  • Neoplasm Recurrence, Local* / pathology
  • Prognosis
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor