SIOP Ependymoma I: Final results, long-term follow-up, and molecular analysis of the trial cohort-A BIOMECA Consortium Study

Neuro Oncol. 2022 Jun 1;24(6):936-948. doi: 10.1093/neuonc/noac012.


Background: SIOP Ependymoma I was a non-randomised trial assessing event free and overall survival (EFS/OS) of non-metastatic intracranial ependymoma in children aged 3-21 years treated with a staged management strategy. A further aim was to assess the response rate (RR) of subtotally resected (STR) ependymoma to vincristine, etoposide, and cyclophosphamide (VEC). We report final results with 12-year follow-up and post hoc analyses of recently described biomarkers.

Methods: Seventy-four participants were eligible. Children with gross total resection (GTR) received radiotherapy, whilst those with STR received VEC before radiotherapy. DNA methylation, 1q, hTERT, ReLA, Tenascin-C, H3K27me3, and pAKT status were evaluated.

Results: Five- and ten-year EFS was 49.5% and 46.7%, OS was 69.3% and 60.5%. GTR was achieved in 33/74 (44.6%) and associated with improved EFS (P = .003, HR = 2.6, 95% confidence interval (CI) 1.4-5.1). Grade 3 tumours were associated with worse OS (P = .005, HR = 2.8, 95%CI 1.3-5.8). 1q gain and hTERT expression were associated with poorer EFS (P = .003, HR = 2.70, 95%CI 1.49-6.10 and P = .014, HR = 5.8, 95%CI 1.2-28) and H3K27me3 loss with worse OS (P = .003, HR = 4.6, 95%CI 1.5-13.2). Methylation profiles showed expected patterns. 12 participants with STR did not receive chemotherapy; a protocol violation. However, best chemotherapy RR was 65.5% (19/29, 95%CI 45.7-82.1), exceeding the prespecified 45%.

Conclusions: Participants with totally resected ependymoma had the best outcomes. RR of STR to VEC exceeded the pre-specified efficacy criterion. However, cases of inaccurate stratification highlighted the need for rapid central review. 1q gain, H3K27me3 loss, and hTERT expression were all associated with poorer survival outcomes.

Keywords: chemotherapy; ependymoma; radiotherapy; recurrence; resection.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Chromosome Aberrations
  • Cyclophosphamide
  • Ependymoma* / genetics
  • Ependymoma* / pathology
  • Ependymoma* / therapy
  • Etoposide
  • Follow-Up Studies
  • Histones* / genetics
  • Humans
  • Treatment Outcome
  • Vincristine


  • Histones
  • Vincristine
  • Etoposide
  • Cyclophosphamide

Supplementary concepts

  • Familial ependymoma