Ritzmann, Timothy A, Chapman, Rebecca J, Kilday, John-Paul, Thorp, Nicola, Modena, Piergiorgio, Dineen, Robert A, Macarthur, Donald, Mallucci, Conor 
ORCID: 0000-0002-5509-0547, Jaspan, Timothy, Pajtler, Kristian W et al (show 6 more authors)
(2022)
SIOP Ependymoma I: Final results, long-term follow-up, and molecular analysis of the trial cohort-A BIOMECA Consortium Study.
NEURO-ONCOLOGY, 24 (6).
pp. 936-948.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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%.<h4>Conclusions</h4>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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | chemotherapy, ependymoma, radiotherapy, recurrence, resection |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 06 Feb 2024 11:14 |
| Last Modified: | 06 Feb 2024 11:14 |
| DOI: | 10.1093/neuonc/noac012 |
| Open Access URL: | https://doi.org/10.1093/neuonc/noac012 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178449 |
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