2025 American Academy of Neurology Abstract Website

Pouneh Amir Yazdani¹, Audrey-Anne Lamoureux¹, Michael J. Fisher², Lauriane Lemelle³, Pfaff Elke⁴, Stefan M. Pfister⁴, Daniel Orbach³, Scott Raskin⁵, Alexander Drilon⁶, Michal Zapotocky⁷, Uri Tabori⁸, Jordan R. Hansford⁹, Craig Erker¹⁰, Nicholas G. Gottardo¹¹, David S. Ziegler¹², Holly Lindsay¹³, Lindsey M. Hoffman¹⁴, Alvaro Lassaletta¹⁵, Nada Jabado¹⁶, Christina Coleman¹⁶, Sabine Mueller¹⁷, Nathan J. Robison¹⁸, Birgit Geoerger¹⁹, Christopher L. Moertel²⁰, Matthew Clarke²¹, Adam C. Resnick²², Mélanie Alves¹, François Doz²³, Theodore W. Laetsch², Sebastien Perreault¹
¹Department of Neurosciences, University of Montreal, CHU Sainte-Justine, ²Division of Oncology, Children's Hospital of Philadelphia, ³SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), PSL Research University, Institut Curie, ⁴Division of Pediatric Glioma Research, Hopp Children’s Cancer Center (KiTZ), ⁵Department of Pediatrics and Cincinnati Children's Hospital Medical Center, University of Cincinnati Medical School, ⁶Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, ⁷Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, ⁸Hospital for Sick Children, ⁹Michael Rice Centre for Hematology and Oncology; South Australia Health and Medical Research Institute; South Australia ImmunoGENomics Cancer Institute, University of Adelaide, SA, Australia. Children’s Cancer Centre, Royal Children’s Hospital; Murdoch Children’s Research Institute; Cancer Immunology Program, Peter MacCallum Cancer Centre; Department of Pediatrics, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia., ¹⁰IWK Health Centre, ¹¹Department of Pediatric Oncology and Hematology, Perth Children's Hospital, ¹²Children’s Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Sydney, NSW, Australia; School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, NSW, Australia; Kids Cancer Centre, Sydney Children’s Hospital, Randwick, NSW, Australia., ¹³Texas Children's Hospital, ¹⁴Phoenix Children's Hospital, ¹⁵Hospital Infantil Universitario Niño Jesús, ¹⁶Montreal Children's Hospital, ¹⁷University of California, ¹⁸Children’s Hospital Los Angeles, ¹⁹Gustave Roussy Cancer Center, Université Paris-Saclay, ²⁰Department of Pediatrics, University of Minnesota, ²¹The Institute of Cancer Research, ²²Division of Neurosurgery, Children's Hospital of Philadelphia, ²³SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), PSL Research University, Institut Curie. University Paris Cité.

Objective:

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.

Background:

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.

Design/Methods:

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.

Results:

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.

Conclusions:

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.