ID #725 FGFR-altered pediatric low-grade gliomas (pLGG): clinical, morphological, and molecular characteristics
Ludmila Papusha, Artur Merishvavian, Alexander Druy, Ekaterina Salnikova, Margarita Zaytseva, Agnesa Panferova, Irina Vilesova, Andrey Flegontov, Igor Kasich, Andrey Sysoev, Vitaliy Degtyarev, Marina Koldasheva, Anton Artemov, Anastasia Protsvetkina, Alexander Karachunskiy, Galina Novichkova, Olga Zheludkova, Sabet Kazuhiro, Eugene Hwang, Roger Packer, Nikolay GrachevAbstract
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.