Next generation sequencing for cns tumors in children; does it add value in a middle-income country setup?

Abstract INTRODUCTION Advances in molecular diagnostics led to improved targeted interventions in the treatment of pediatric CNS tumors. However, the capacity to do these diagnostics is limited in LMICs, and consequently their value is questionable. METHODS We reviewed our experience of Next Generation Sequencing (NGS) testing (TruSight RNA Pan-Cancer seq panel) for pediatric CNS tumors at KHCC/Jordan (March/2022- April/2023). Paraffin blocks’ scrolls were shipped to Sickkids laboratory based on local multidisciplinary team recommendations. We reviewed patients’ clinical characteristics, tumor types and the impact on treatment. RESULTS There were 16 boys and 16 girls; median age at time of testing was 9.5 years (range, 0.9- 21.9 years). Twenty samples were sent at diagnosis and twelve upon tumor progression. Main diagnoses were Low-grade glioma (15), High-grade glioma (10), and other tumors (7). Reasons for NGS testing were: to find a molecular target (20), and to characterize more tumor/behavior (12). The median time from shipping the samples to receive the NGS result was 22 days (range, 15-49 days) at a cost of US$1000. Twenty (63%) tumors had targetable alterations (MAPK/PI3K inhibitors (16), NTRK inhibitors (2), check point inhibitors (2)). Two rare BRAF mutations were identified (BRAFp.G469A, BRAFp.K601E). One tumor diagnosed initially as undifferentiated round-cell sarcoma found to have NAB2::STAT6 fusion and re-diagnosed as aggressive metastatic solitary fibrous tumor. Eight patients received targeted therapy; Dabrafenib/Trametinib (5), Pembrolizumab (2), Entrectinib (1), while radio-chemotherapy was used in the others. Three patients died from disease progression (one used Entrectinib). CONCLUSIONS Sent abroad NGS testing was feasible, however local capacity building is necessary. In this highly selected tumor cohort, high percentage of targetable alterations were identified. NGS was helpful to characterize tumors more and to offer alternative therapies. Nevertheless, interpretation of the significance of NGS results and access to those “new” therapies continues to be a challenge in LMICs