Site Editors

Alexander Drilon, MD

Gregory J. Riely, MD, PhD


Molecular Investigation of High-Grade Gliomas in Children

By: Lauren Harrison, MS
Posted: Monday, April 4, 2022

A group of physicians and researchers from Italy employed molecular investigations both to diagnose and choose therapeutics for a cohort of children with newly diagnosed high-grade gliomas. The team was led by Angela Mastronuzzi, MD, PhD, of Bambino Gesù Children’s Hospital in Rome, and the group published its single-center experience in Diagnostics.

A total of 11 patients younger than age 5 with high-grade gliomas presented to Bambino Gesù Children’s Hospital between 2011 and 2021. Patients underwent a series of magnetic resonance imaging studies at the time of diagnosis and during follow-up to monitor their response to therapy. Histologic diagnoses were confirmed for all patients; nine underwent next-generation sequencing studies, and nine had DNA-methylation profiling performed. Gross total resection was achieved in 6 of the 11 patients, whereas the other 5 patients had subtotal resection.

Among the nine patients who underwent next-generation sequencing, three tumors had NTRK fusions, two had PATZ1 fusions, and one had a ROS1 fusion. For those who had DNA-methylation analysis performed, the following matches were highlighted: one infant with high-grade glioma, two had IDH wild-type, one had BCOR internal tandem duplication, one had plexus tumor, and one had MN1 rearrangement. The samples were reanalyzed using a new classifier version, identifying two more tumors with PATZ1 fusions and one high-grade glioma RTK1 type.

Most patients (9 of 11) received adjuvant chemotherapy consisting of methotrexate, vincristine, etoposide, and cyclophosphamide. They then underwent autologous hematopoietic stem cell transplantation. Second-line regimens were administered in five of seven patients with relapsed or progressive disease. Within the entire cohort, four patients died of progressive disease, including one with BCOR internal tandem duplication, one with TRK1 type, and two without molecular investigation.

Patients with an identified NTRK fusion received treatment with the NTRK inhibitor larotrectinib as well. These patients achieved a complete remission and a very good partial response, respectively, and had no severe side effects.

Disclosure: The study authors reported no conflicts of interest.

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.