Related Experiment Video
Updated: Oct 2, 2025
Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions
Published on: November 17, 2021
Molecular Landscape in Infant High-Grade Gliomas: A Single Center Experience
Valentina Di Ruscio1, Andrea Carai2, Giada Del Baldo1
1Department of Onco-Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Reasearch, Hospitalization and Healthcare (IRCCS), 00165 Rome, Italy.
Insights
Molecular investigations are crucial for diagnosing infant high-grade gliomas (iHGG). Targeted therapies, like NTRK-inhibitors, offer effective treatment with fewer side effects than traditional chemotherapy.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Molecular Diagnostics
Background:
- High-grade gliomas (HGG) are aggressive pediatric brain tumors with poor survival rates.
- Infant HGG (iHGG) comprises a distinct subgroup with variable molecular profiles and outcomes.
- Current treatments often involve toxic chemotherapy and radiotherapy.
Purpose of the Study:
- To report a single-institution experience with iHGG.
- To highlight the role of molecular profiling in diagnosis and treatment selection.
- To evaluate the efficacy of targeted therapy in iHGG.
Main Methods:
- Retrospective analysis of 11 iHGG patients diagnosed between 2011-2021.
- Surgical resection and adjuvant chemotherapy were standard treatments.
- Next-generation sequencing (NGS) and DNA methylation analyses were performed for molecular characterization.
Main Results:
- Molecular testing identified actionable fusions, including NTRK, ROS1, and PATZ1.
- Two patients with NTRK-fusions responded dramatically to NTRK-inhibitor therapy (larotrectinib).
- Targeted therapy resulted in complete remission and very good partial response with no severe side effects.
Conclusions:
- Molecular investigations are essential for accurate iHGG diagnosis and treatment planning.
- Targeted therapies offer a promising alternative to conventional chemotherapy, improving outcomes and reducing toxicity.
- Routine implementation of molecular diagnostics can guide personalized treatment strategies for iHGG.
Abstract:
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.
