Open Access

Michael Karremann, Tabea Gerdes, Gerrit H. Gielen, Robert Kwiecien, Thomas Perwein, Marion Hoffmann, Amedeo A. Azizi, Florian Babor, Carla Barrios-Bussmann, Lars Behrens, Martin Benesch, Luca Bertero, Veronica Biassoni, Brigitte Bison, Francesca R. Buttarelli, Gabriele Calaminus, Alexander Claviez, Felix Distelmaier, Martin Ebinger, Moatasem Elayadi, Jana Ernst, Matthias Eyrich, Gudrun Fleischhack, Carsten Friedrich, Lea L. Friker, Maria Luisa Garre, Nicolas U. Gerber, Johannes Gojo, Darren Hargrave, Svenja Häuser, Pablo Hernaiz-Driever, Stefan Holm, Marcus Jakob, Stephanie Knirsch, Christian Kratz, Jeanne Marie Krischer, Caspar Kühnöl, Ella Kumirova, Maura Massimino, Maria Vinci, Lisethe Meijer, Markus Metzler, Claudia Milanaccio, Andres Morales La Madrid, Giovanni Morana, Gunther Nussbaumer, Gianluca Piccolo, Bianca Pollo, Guido Reifenberger, Christian Reimann, Thorsten Rosenbaum, Elisabetta Schiavello, Jaroslav Sterba, Dominik Sturm, Elwira Szychot, Chiara Valentini, Stefano Gabriele Vallero, Eunike Velleuer-Carlberg, Miriam van Buiren, Angela Mastronuzzi, Dannis van Vuurden, André O. von Bueren, Maria Wiese, Claudia Zinke, Jozef Zlocha, Torsten Pietsch, Christof M. Kramm

• 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 prognosisBackground: 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.…