Abstract
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.