ID #725 FGFR-altered pediatric low-grade gliomas (pLGG): clinical, morphological, and molecular characteristics

Abstract Introduction FGFR structural variations and mutations present rare actionable alterations in pLGG. Objective To investigate clinical and laboratory characteristics of FGFR-altered LGG in children. Materials and Methods Retrospectively 20 pediatric patients with LGG harboring FGFR alteration revealed by DNA or RNA sequencing diagnosed between 2017-2025 were evaluated. Results The male-to-female ratio was 1:1,5. Median age at diagnosis was 7.4 years (range: 1.1–16.8). Localization included midline structures (13), cerebral hemisphere (5) and cerebellum (2). Metastatic disease was in 5 patients. There were 4 cases of gross total resection (GTR), 11 of partial tumor resection (PR) and 5 biopsies. The initial morphological diagnoses: pilocytic astrocytoma (14), dysembryoplastic neuroepithelial tumor (2), low-grade glioma (2), polymorphous low grade neuroepithelial tumor of the young (1), and glioneuronal tumor (1). Molecular alterations were: FGFR fusions (n = 9, predominantly, FGFR1::TACC1), point mutations (n = 7) and internal tandem duplications (n = 4). Four cases of FGFR1 and PIK3CA co-mutations were observed. All 4 patients who underwent GTR and 4 of 11 patients after PR remained progression -free without further intervention. 7 patients received chemotherapy (carboplatin and vincristine) and 2 patients received focal radiation as firstline treatment. Disease progression was observed in 9 of 20 patients. Six patients received targeted therapy at the time of progression : FGFR inhibitor (erdafitinib) in 3 cases, combination of mTOR and MEK inhibitors (everolimus and trametinib) in 2 cases, and monotherapy with mTOR inhibitor (everolimus) in 1 case. No progression was detected in the targeted therapy cohort. At the time of followup, 18 patients were alive and 2 patients died from complications (tumor hemorrhage after radiation and pneumonia). Median followup time achieved 3.3 years (0.4–8.6). Conclusion FGFR-altered tumors exhibit morphological and clinical variability. In cases with GTR, observation may be sufficient. In case of progressive disease different types of targeted therapy could be effective treatment option.