ID #683 Clinical and Molecular Features of IDH1-Mutant Astrocytomas in AYA Patients: A 3- year Single-Center Experience
Antonella Cacchione, Federica D’antonio, Andrea Carai, Giovanna Stefania Colafati, Valentina Di ruscio, Vito Andrea Dell’anna, Fabiola Paoletti, Arturo Greco, Giada Del Baldo, Rossana Pavone, Angela MastronuzziAbstract
Background
IDH1-mutant astrocytomas are rare in pediatric and adolescent/young adult (AYA) patients, and their biological behavior and optimal management remain poorly defined. While pediatric gliomas are typically low-grade and driven by MAPK pathway alterations, adult diffuse gliomas frequently harbor IDH mutations. AYA patients represent a transitional biological and clinical population, yet treatment strategies are often extrapolated from pediatric or adult paradigms. We describe a single-center experience of IDH1-mutant astrocytomas in pediatric and AYA patients.
Methods
We retrospectively reviewed 10 consecutive patients aged 12–25 years diagnosed with IDH1-mutant astrocytoma at Bambino Gesù Children’s Hospital between 2022 and 2025. Clinical, radiological, histopathological, and molecular data were analyzed, including next-generation sequencing and germline testing when available. Treatment approaches and outcomes were evaluated.
Results
The cohort included 8 males and 2 females; one patient had an underlying cancer predisposition syndrome (Ollier/Maffucci). Tumors were located in the cerebral hemispheres (n = 6), pons (n = 3), and cervical medulla (n = 1). Nine tumors were WHO grade 2 and one grade 3. Gross total resection was achieved in four patients, followed by surveillance. Among six patients without gross total resection, four received upfront radiotherapy and two received an IDH1 inhibitor as first-line therapy. At progression, two patients treated initially with radiotherapy received IDH1 inhibitors. Overall, IDH1 inhibitors were administered in five patients. After a median follow-up of 10.2 months (range 6–16), disease stability was observed in all but one patient. Seizure control was satisfactory, and no treatment-related toxicities greater than grade 2 were reported.
Conclusions
IDH1-mutant astrocytomas in AYA patients appear to represent a distinct biological and clinical entity, supporting the need for age-specific, biology-driven treatment strategies and highlighting the importance of tissue diagnosis to guide targeted therapies.