High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognosis and survival rates ranging from 15 to 35%. Approximately 10-12% of pediatric HGGs (pHGG) occur in children younger than five years of age at diagnosis, specifically infants (iHGG), with an unexpected overall survival rate (OS) in 60-70% of cases. In the literature, iHGGs include a large variety of heterogeneous lesions with different molecular profiles that likely explain their different outcomes. We report our single-institution experience of iHGG including 11 children under five years of age with newly diagnosed HGG between 2011 and 2021. All patients received surgery and adjuvant chemotherapy; only two patients received radiotherapy because their age at diagnosis was more than four years-old. Molecular investigations, including next generation sequencing (NGS) and DNA methylation, detected three NTRK-fusions, one ROS1-fusions, one MN1-rearrangement, and two PATZ1-fusions. According to the molecular results, when chemotherapy failed to control the disease, two patients benefited from target therapy with a NTRK-Inhibitor larotrectinib, achieving a complete remission and a very good partial response, respectively, and no severe side-effects. In conclusion, molecular investigations play a fundamental role in the diagnostic work-up and also in the therapeutic decision. Their routine use in clinical practice could help to replace highly toxic chemotherapy regimens with a target therapy that has moderate adverse effects, even in long-term follow-up.
Keywords: infants; larotrectinib; molecular profile; oncogenic fusions; pediatric high-grade gliomas; target therapy.