ID #386 Real-world data: Next Generation Sequencing Analyses for Pediatric Brain Tumors and Access to Targeted Therapy in a resource-limited setting
Andrea M Cappellano, Natalia Dassi, Jessica Rodrigues, Sergio Cavalheiro, Patricia Dastoli, Daniela Almeida, Francine Gamba, Nasjla Silva, Silvia ToledoAbstract
Introduction
Global disparities in outcomes between low and high-income countries result from social, political, and economic factors. Despite advances in molecular characterization in neuro-oncology, the implementation in developing countries remains challenging.
Objective
To analyze the results and real-world applicability of the Next Generation Sequencing (NGS) OCCRA panel for pediatric brain tumors at GRAACC Hospital, São Paulo, Brazil.
Methods
Cross sectional study-database analysis.
Results
From 2018-2025, 626 patients were diagnosed with pediatric brain tumors: 241 (38.5%) low-grade gliomas (LGG), 112 (17.9%) medulloblastoma (MB), 106 (16.9%) high-grade gliomas (HGG), 42 (6.7%) ependymomas, 39 (6.2%) germ cell tumors (GCT), 34 (5.4%) craniopharyngiomas, 24 (3.8%) choroid plexus tumors (CPT), 11 (1.8%) atypical teratoid/rhabdoid tumors (AT/RT), 7 (1.1%) sarcomas, 7 (1.1%), pineoblastoma (PB) and 3 (0.48%) Embryonal Tumor with Multilayered Rosettes (ETMR). NGS was performed on 235 samples (37.5%), identifying 161 variants (68.5%). Alterations were detected in LGG (80/95; 84.2%), mainly BRAF–KIAA1549; HGG (32/35; 91.4%), including H3K27M (14), BRAFV600E (4), and ALK/ROS1/NTRK fusions in infants (4); DIPG (15) with H3K27M mutations; medulloblastoma (17/37); AT/RT (3/8); pineoblastoma (1/4); craniopharyngioma (3/3); ependymoma (7/11); CPT (2/3); sarcomas (2/2); and GCT (1/2). Fifteen patients with LGG and BRAF alterations received dabrafenib and trametinib, trametinib alone or tovorafenib. Two HGG patients and BRAFV600E received dabrafenib and trametinib and one patient with CDK4 amplification received palbociclib. Three patients with infant-type hemispheric gliomas and ALK/ROS/NTRK fusions received lolartinib/repotrectinib. In 11 cases, drugs were provided through expanded access, eight through clinical trials and two through private health insurance.
Conclusion
Despite molecular analysis being feasible in 37.5% of cases, targeted therapy was available to a small proportion of patients (3.3%), primarily through compassionate use and a recent but limited availability of clinical trials. This highlights that access to molecular diagnostics and targeted therapies remain challenging in less privileged countries.