Imagen de Portada

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

Current 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.Patients aged 0-21 years with localized intracranial ependymoma were enr...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Hoff, Katja von (Autor) , Obrecht-Sturm, Denise (Autor) , Ghasemi, David R. (Autor) , Wenning, Janna (Autor) , Mynarek, Martin (Autor) , Gerber, Nicolas U (Autor) , Benesch, Martin (Autor) , Juhnke, Björn O (Autor) , Bison, Brigitte (Autor) , Warmuth-Metz, Monika (Autor) , Timmermann, Beate (Autor) , Faldum, Andreas (Autor) , Tippelt, Stephan (Autor) , Fleischhack, Gudrun (Autor) , Grotzer, Michael (Autor) , Hernáiz Driever, Pablo (Autor) , Beilken, Andreas (Autor) , Ebinger, Martin (Autor) , Graf, Norbert (Autor) , Frühwald, Michael C (Autor) , Schmid, Irene (Autor) , Slavc, Irene (Autor) , Koch, Arend (Autor) , Bergmann, Markus (Autor) , Hagel, Christian (Autor) , Coras, Roland (Autor) , Blümcke, Ingmar (Autor) , Reifenberger, Guido (Autor) , Felsberg, Jörg (Autor) , Keyvani, Kathy (Autor) , Harter, Patrick N (Autor) , Prinz, Marco (Autor) , Staszewski, Ori (Autor) , Acker, Till (Autor) , Stadelmann-Nessler, Christine (Autor) , Hartmann, Christian (Autor) , Deimling, Andreas von (Autor) , Sommer, Clemens (Autor) , Hasselblatt, Martin (Autor) , Riemenschneider, Markus J (Autor) , Monoranu, Camelia-Maria (Autor) , Rushing, Elisabeth (Autor) , Haberler, Christine (Autor) , Kool, Marcel (Autor) , Sill, Martin (Autor) , Pfister, Stefan (Autor) , Schüller, Ulrich (Autor) , Pietsch, Torsten (Autor) , Kortmann, Rolf D (Autor) , Kwiecien, Robert (Autor) , Witt, Hendrik (Autor) , Pajtler, Kristian Wilfried (Autor) , Rutkowski, Stefan (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: February 2026
In: Neuro-Oncology
Year: 2026, Volumen: 28, Número: 2, Pages: 520-534
ISSN:1523-5866
DOI:10.1093/neuonc/noaf218
Acceso en línea:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/noaf218
Enlace del recurso
Notas de Autor:Katja von Hoff, Denise Obrecht-Sturm, David R Ghasemi, Janna Wenning, Martin Mynarek, Nicolas U Gerber, Martin Benesch, Björn O Juhnke, Brigitte Bison, Monika Warmuth-Metz, Beate Timmermann, Andreas Faldum, Stephan Tippelt, Gudrun Fleischhack, Michael Grotzer, Pablo Hernáiz Driever, Andreas Beilken, Martin Ebinger, Norbert Graf, Michael C Frühwald, Irene Schmid, Irene Slavc, Arend Koch, Markus Bergmann, Christian Hagel, Roland Coras, Ingmar Blümcke, Guido Reifenberger, Jörg Felsberg, Kathy Keyvani, Patrick N Harter, Marco Prinz, Ori Staszewski, Till Acker, Christine Stadelmann-Nessler, Christian Hartmann, Andreas von Deimling, Clemens Sommer, Martin Hasselblatt, Markus J Riemenschneider, Camelia-Maria Monoranu, Elisabeth Rushing, Christine Haberler, Marcel Kool, Martin Sill, Stefan M Pfister, Ulrich Schüller, Torsten Pietsch, Rolf D Kortmann, Robert Kwiecien, Hendrik Witt, Kristian W Pajtler, and Stefan Rutkowski, on behalf of the Austrian and Swiss HIT-Network the German
Descripción
Sumario:Current 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.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.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).These results strongly suggest the inclusion of molecular parameters into stratification and the use of distinct treatment strategies within future ependymoma trials.
Notas:Gesehen am 12.06.2026
Descripción Física:Online Resource
ISSN:1523-5866
DOI:10.1093/neuonc/noaf218

Ejemplares similares