NTRK gene fusions are found in up to 2% of adults with gliomas and up to 40% of infants with non-brainstem gliomas. Selective TRK inhibitors (TRKi) are being investigated for the treatment of these tumors, but given their overall rarity, there is limited data on the clinical course of affected patients.

Our study describes the largest cohort of central nervous system (CNS) tumors with neurotrophic tyrosine receptor kinase (NTRK) gene fusions. We included 119 patients, detailing key demographic profiles, clinical characteristics and outcomes. 

We conducted a retrospective cohort study of pediatric and adult patients with CNS tumors with NTRK gene fusions. Patients diagnosed between 2000 to 2024 were identified through international oncologists and the Children’s Brain Tumor Network database. A standardized case report form collected patient demographics, pathology, tumor location, treatments, and outcomes. Progression free and overall survival were presented using Kaplan-Meier survival curves. Growth modulation index (GMI) was calculated to assess treatment efficacy.

119 patients were identified with NTRK fusion, with a median diagnosis age of 4.5 years (0-78.4 years). Histology was consistent with high-grade glioma (HGG) in 57.1% of patients and low-grade glioma (LGG) in 27.7%. Pediatric patients had a better prognosis with a median overall survival of 185.5 months (95% CI 99.5-229.3) compared to 24.8 months (95% CI 17.1-99.5I) in adults (p<0.0001). Patients with LGG also had a better outcome when compared to HGG (p=0.0012). The objective response rate was 68.8% with larotrectinib, compared to 38.1% for non-targeted treatment. In pediatric HGG, response to larotrectinib was evaluable for eight patients with an overall response rate of 100%. GMI was 2.1 (0.15-11.51) for pediatric patients treated with larotrectinib.

Children with LGG had a favorable outcome compared to adults and those with HGG. TRKi appear to improve tumor control in a subset of patients, most notably for pediatric HGG.