Developing an advanced risk stratification model for pediatric intracranial ependymoma based on the prospective trial E-HIT2000 and subsequent registries

Von Hoff K, Obrecht-Sturm D, Ghasemi DR, Wenning J, Mynarek M, Gerber NU, Benesch M, Juhnke BO, Bison B, Warmuth-Metz M, Timmermann B, Faldum A, Tippelt S, Fleischhack G, Grotzer M, Hernáiz Driever P, Beilken A, Ebinger M, Graf N, Frühwald MC, Schmid I, Slavc I, Koch A, Bergmann M, Hagel C, Coras R, Blümcke I, Reifenberger G, Felsberg J, Keyvani K, Harter PN, Prinz M, Staszewski O, Acker T, Stadelmann-Nessler C, Hartmann C, Von Deimling A, Sommer C, Hasselblatt M, Riemenschneider MJ, Monoranu CM, Rushing E, Haberler C, Kool M, Sill M, Pfister SM, Schüller U, Pietsch T, Kortmann RD, Kwiecien R, Witt H, Pajtler KW, Rutkowski S (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 28

Pages Range: 520-534

Journal Issue: 2

DOI: 10.1093/neuonc/noaf218

Abstract

BackgroundCurrent treatment strategies for pediatric intracranial ependymoma do not consider molecular heterogeneity. Here, we evaluated molecular group-specific determinants of outcome and developed an improved risk stratification model. Methods Patients aged 0-21 years with localized intracranial ependymoma were enrolled into the prospective clinical trial E-HIT2000. Treatment included maximum safe surgery, local radiotherapy, and chemotherapy, stratified according to age, histology and, following a major amendment, residual tumor. Clinical data were analyzed in a pooled molecularly annotated cohort with data from patients treated analogously within subsequent registries. Results For 291 trial patients, the 5-year progression-free survival (PFS) and overall survival (OS) were 62 ± 3% and 81 ± 2%, respectively. For the molecularly annotated pooled cohort (n = 228), 5-year PFS/OS were: posterior-fossa group A ependymoma (EPN-PFA) (n = 146): 45 ± 4%/77 ± 4%; posterior-fossa group B ependymoma (EPN-PFB) (n = 19): 90 ± 7%/100%; supratentorial ependymoma, ZFTA fusion-positive (EPN-ZFTA) (n = 59): 64 ± 7%/86 ± 5%; supratentorial ependymoma, YAP1 fusion-positive (EPN-YAP1) (n = 4): 50 ± 25%/100%. Patients with EPN-PFA without molecular risk factors (1q gain, and/or subtype EPN-PFA1c/d/e, 2a), with complete resection, and postoperative radiotherapy showed favorable outcomes (5-year PFS/OS 75 ± 10%/92 ± 7%). For patients with EPN-PFA with molecular risk factors, prognosis was poor irrespective of residual tumor status (5-year PFS/OS: 33 ± 6%/64 ± 6%). Among EPN-ZFTA, 11/59 tumors were classified as EPN-ZFTA with alternative fusions, associated with inferior PFS (5-year PFS/OS: 36 ± 15%/91 ± 9%). For EPN-ZFTA-RELA, homozygous deletions of CDKN2A were associated with unfavorable outcomes (4-year PFS/OS: 19 ± 16%/57 ± 18% vs. 79 ± 7%/97 ± 3%, P =. 0001). Finally, we developed a novel stratification model that discriminates standard and intermediate risk patients from those at high risk (P <. 0001 for PFS and OS). Conclusions These results strongly suggest the inclusion of molecular parameters into stratification and the use of distinct treatment strategies within future ependymoma trials.

Authors with CRIS profile

Involved external institutions

Universität Leipzig Germany (DE) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Hopp-Kindertumorzentrum Heidelberg - KiTZ Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitäts-Kinderspital Zürich Switzerland (CH) Medizinische Universität Graz Austria (AT) Universität Augsburg Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Essen Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Städtisches Klinikum Braunschweig Germany (DE) Universitätsklinikum Tübingen Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universitätsklinikum Augsburg Germany (DE) Klinikum der Universität München (LMU Klinikum) Germany (DE) Medizinische Universität Wien Austria (AT) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) Universitätsklinikum Düsseldorf Germany (DE) Albert-Ludwigs-Universität Freiburg Germany (DE) Justus-Liebig-Universität Gießen Germany (DE) Universitätsklinikum Göttingen Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Regensburg Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Universitätsspital Zürich (USZ) Switzerland (CH) Universitätsklinikum Bonn Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE)

How to cite

APA:

Von Hoff, K., Obrecht-Sturm, D., Ghasemi, D.R., Wenning, J., Mynarek, M., Gerber, N.U.,... Rutkowski, S. (2026). Developing an advanced risk stratification model for pediatric intracranial ependymoma based on the prospective trial E-HIT2000 and subsequent registries. Neuro-Oncology, 28(2), 520-534. https://doi.org/10.1093/neuonc/noaf218

MLA:

Von Hoff, Katja, et al. "Developing an advanced risk stratification model for pediatric intracranial ependymoma based on the prospective trial E-HIT2000 and subsequent registries." Neuro-Oncology 28.2 (2026): 520-534.

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