A 7-year-old female with recurrent midline pilocytic astrocytoma harboring a rare STRN3::NTRK2 fusion achieved sustained near-complete radiographic and clinical response to larotrectinib, a selective TRK inhibitor. Initial subtotal resection of the midbrain/thalamic tumor was followed by progression, prompting molecular profiling that identified the STRN3::NTRK2 fusion. Larotrectinib therapy initiated at recurrence resulted in a rapid reduction by 3 months, resolution of pontine extension by 6 months, and near-complete resolution by 15 months. This case highlights the potential of molecular diagnostics in pediatric neuro-oncology, particularly for BRAF-negative midline gliomas where NTRK fusions are rare but actionable. The durable response supports prioritizing larotrectinib over conventional chemotherapy in unresectable/progressive NTRK-driven gliomas. Routine fusion screening in BRAF-negative cases should be considered to identify candidates for targeted therapy. This report expands the known spectrum of NTRK2 partners in pilocytic astrocytoma and reinforces the use of TRK inhibitors as a treatment for molecularly defined subsets of pediatric glioma.
Keywords: Larotrectinib; NTRK2 fusion; midline glioma; pediatric glioma; pilocytic astrocytoma; targeted therapy.
Rare Molecular Fusion Identified: A 7-year-old girl with recurrent midline pilocytic astrocytoma was found to have a rare STRN3::NTRK2 gene fusion, expanding the known NTRK2 fusion partners.Exceptional Response to Targeted Therapy: Initiation of larotrectinib, a selective TRK inhibitor, resulted in rapid and near-complete radiographic and clinical tumor regression, with significant improvement observed within 3–15 months of therapy.Durable Remission Achieved: The patient’s tumor response has been sustained for at least 15 months, exceeding typical progression-free survival for similar pediatric CNS tumors.Favorable Safety Profile: Larotrectinib was well-tolerated, with only mild, transient side effects and no severe toxicities, which contrasts with the higher toxicity rates associated with conventional chemotherapy.Clinical Improvement Paralleled Imaging: The patient experienced notable improvements in neurological deficits, including balance, coordination, and eye alignment, alongside tumor shrinkage.Implications for Treatment Paradigm: This case supports the consideration of TRK inhibitors, such as Larotrectinib, over traditional chemotherapy for unresectable or progressive NTRK-driven gliomas in children.Importance of Molecular Diagnostics: The report emphasizes the crucial role of routine molecular screening for NTRK fusions in BRAF-negative pediatric gliomas, particularly in midline tumors where actionable fusions may be present.Potential to Avoid Morbidity: Early identification of NTRK fusions could enable the use of neoadjuvant TRK inhibitors, potentially reducing the need for high-risk surgery and the side effects of chemotherapy.