Pediatric high-grade gliomas in patients with neurofibromatosis type 1 - A collaborative cohort study from the SIOPE HGG/DIPG working group

Karremann M, Gerdes T, Gielen GH, Kwiecien R, Perwein T, Hoffmann M, Azizi AA, Babor F, Barrios-Bussmann C, Behrens L, Benesch M, Bertero L, Biassoni V, Bison B, Buttarelli FR, Calaminus G, Claviez A, Distelmaier F, Ebinger M, Elayadi M, Ernst J, Eyrich M, Fleischhack G, Friedrich C, Friker LL, Garre ML, Gerber NU, Gojo J, Hargrave D, Häuser S, Hernaiz-Driever P, Holm S, Jakob M, Knirsch S, Kratz C, Krischer JM, Kühnöl C, Kumirova E, Massimino M, Vinci M, Meijer L, Metzler M, Milanaccio C, La Madrid AM, Morana G, Nussbaumer G, Piccolo G, Pollo B, Reifenberger G, Reimann C, Rosenbaum T, Schiavello E, Sterba J, Sturm D, Szychot E, Valentini C, Vallero SG, Velleuer-Carlberg E, Van Buiren M, Mastronuzzi A, Van Vuurden D, Von Bueren AO, Wiese M, Zinke C, Zlocha J, Pietsch T, Kramm CM (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 13

Pages Range: 71-85

Journal Issue: 1

DOI: 10.1093/nop/npaf104

Abstract

Background. We assessed clinical features, treatment, and survival of pediatric patients with neurofibromatosis type 1 (NF1) with high-grade glioma (HGG). Methods. Patients from this retrospective cohort study were identified through an international collaborative effort by the SIOPE HGG/DIPG working group. NF1 was diagnosed based on clinical presentation and confirmed by either a pathogenic germline NF1 gene alteration or the exclusion of mismatch repair deficiency. A control cohort without genetic cancer predisposition was matched in a 2:1-ratio from the HIT-HGG database. Results. We identified 29 pediatric patients with NF1-associated HGG. Median age at diagnosis of HGG was 11 years. All but 1 tumor arose outside the optic pathway and included circumscribed and diffuse HGG. Molecular analysis in a subset of tumors identified an enrichment of alterations in CDKN2A, TP53, and ATRX. Event-free and overall survival were as poor as in matched sporadic HGG patients. The prognosis was not superior with upfront radiotherapy compared with delayed radiotherapy. Conclusions. NF1-associated HGGs behave as aggressively as their sporadic counterparts. The relevance of delaying radiotherapy until the time of progression and adjuvant MEK inhibitor treatment needs further investigation.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Jena Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Essen Germany (DE) Carl von Ossietzky Universität Oldenburg Germany (DE) Universitätsklinikum Bonn Germany (DE) Istituto Giannina Gaslini Italy (IT) Universitäts-Kinderspital Zürich Switzerland (CH) Sana Kliniken AG Germany (DE) Ospedale Pediatrico Bambino Gesu Italy (IT) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Princess Máxima Center Netherlands (NL) University Hospital Brno Czech Republic (CZ) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Hopp-Kindertumorzentrum Heidelberg - KiTZ Germany (DE) Universitätsklinikum Göttingen Germany (DE) University College London (UCL) United Kingdom (GB) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Italy (IT) Medizinische Universität Lausitz - Carl Thiem (MUL - CT) Germany (DE) Universitätsklinikum Düsseldorf Germany (DE) Universitätsklinikum Ulm Germany (DE) Albert-Ludwigs-Universität Freiburg Germany (DE) HELIOS Kliniken Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Medizinische Universität Wien Austria (AT) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Tübingen Germany (DE) National Cancer Institute (NCI) United States (USA) (US) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) Medizinische Universität Graz Austria (AT) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Halle (UKH) / University Medicine Halle Germany (DE) Pirogov Russian National Research Medical University (RSMU / RNRMU) Russian Federation (RU) Universität Augsburg Germany (DE) University of Turin / Università degli Studi di Torino (UNITO) Italy (IT) Hospital Sant Joan de Déu Barcelona Spain (ES) Universitätsklinikum Regensburg Germany (DE) Foundation of the Carlo Besta Neurological Institute (IRCCS) Italy (IT) Klinikum Stuttgart Germany (DE)

How to cite

APA:

Karremann, M., Gerdes, T., Gielen, G.H., Kwiecien, R., Perwein, T., Hoffmann, M.,... Kramm, C.M. (2026). Pediatric high-grade gliomas in patients with neurofibromatosis type 1 - A collaborative cohort study from the SIOPE HGG/DIPG working group. Neuro-Oncology Practice, 13(1), 71-85. https://doi.org/10.1093/nop/npaf104

MLA:

Karremann, Michael, et al. "Pediatric high-grade gliomas in patients with neurofibromatosis type 1 - A collaborative cohort study from the SIOPE HGG/DIPG working group." Neuro-Oncology Practice 13.1 (2026): 71-85.

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