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Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol


Pierre Leblond

Maura Massimino

Martin English

Clinical Assistant Professor (Nihr Clinical Lecturer) in Paediatrics

Lorenza Gandola

Gabriele Calaminus

Sophie Thomas


Julien Gautier

Professor of Paediatric Neuro-Oncology

Didier Frappaz


Background: The clinical management of ependymoma in childhood and adolescence is complex and the clinicobiopathological correlates of outcome remain poorly understood. This international SIOP Ependymoma II (SIOP EPII) trial aims to improve the outcome of patients with ependymoma. Methods: SIOP EPII includes any patient <22 years at diagnosis with ependymoma, stratified by age, tumor location, and outcome of the initial surgery. Centralized pathology and imaging is required for diagnosis confirmation. SIOP EPII included three randomized studies according to age, postoperative residue, and suitability to receive radiotherapy. Patients ineligible for interventional strata are followed-up in an observational study. The staging phase aims to determine if central neurosurgical and radiological postoperative MRI reviews increase the resection rate. Patients ?12 months with (i) no residual disease are randomly assigned in a phase III trial to evaluate the efficacy of post-radiation 16-week chemotherapy (VEC + CDDP) on PFS (stratum I); (ii) centrally confirmed measurable inoperable residual disease are allocated to randomized frontline chemotherapy phase II study (VEC vs. VEC + high-dose methotrexate) and considered for a second-look surgery (stratum II). If second-look surgery is not feasible or tumor residuum remains, patients receive 8 Gy-boost radiotherapy after conformal radiotherapy (phase I). (iii) Patients < 12 months (18 months in the UK) or not eligible to receive radiotherapy are randomized in a phase II study to receive chemotherapy (alternated myelosuppressive and nonmyelosuppressive chemotherapy), with or without valproate (stratum III). To overcome the limitations encountered in the preliminary conclusions of the ACNS-0831 study, a SIOP EPII dedicated on-study amendment has been planned to definitively conclude the relevance of maintenance chemotherapy in stratum I. Secondary outcomes include overall survival, quality of life, neuropsychological and neuroendocrine outcomes, safety, and identification of key prognostic biomarkers (BIOMECA). Clinical Trial Registration:, identifier: NCT02265770.


Leblond, P., Massimino, M., English, M., Ritzmann, T. A., Gandola, L., Calaminus, G., …Frappaz, D. (2022). Toward Improved Diagnosis Accuracy and Treatment of Children, Adolescents, and Young Adults With Ependymoma: The International SIOP Ependymoma II Protocol. Frontiers in Neurology, 13, Article 887544.

Journal Article Type Article
Acceptance Date Apr 19, 2022
Online Publication Date Jun 2, 2022
Publication Date Jun 2, 2022
Deposit Date Jul 18, 2022
Publicly Available Date Jul 19, 2022
Journal Frontiers in Neurology
Electronic ISSN 1664-2295
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 13
Article Number 887544
Keywords Neurology (clinical); Neurology
Public URL
Publisher URL


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