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.