P10.18.A THE IMPACT OF PUBERTAL STATE ON THE ONSET AND PROGRESSION OF PEDIATRIC LOW-GRADE GLIOMAS: CAUSAL ASSOCIATION OR UNDERLYING BIOLOGICAL MECHANISM?

Abstract BACKGROUND Pediatric low-grade gliomas (pLGG) are the most common central nervous system tumors in children, with an incidence of 10-12 cases per million annually. Estrogen receptors (ER-α, ER-β, and GPER) are expressed in pLGG and have been implicated in the activation of the MAPK/ERK pathway, which may influence tumor behavior (Hirtz et al., 2020)(Tavares et al., 2018). Experimental studies have shown that estradiol stimulates astrocyte proliferation and gene expression associated with the cell cycle and angiogenesis(Madeshwaran et al., 2024). During puberty, there is an increase in estrogen levels not only in women but also in men, driven by the conversion of androgens to estrogens via aromatase. Several case reports have described children with precocious puberty and pLGG who experienced tumor reduction after hormone-blocking therapy alone or in combination with chemotherapy. These findings suggest that sex hormones may play a role in the behavior of pLGG(De Lucio Delgado et al., 2023)(Kang et al., 2024). METHODS Our study included patients with pLGG treated at Bambino Gesù Children’s Hospital in Rome between January 2015 and December 2025, for whom follow-up data were available. Demographic, clinical, surgical and histological data were collected. Clinical and radiological outcomes, including hormonal assessment with objective pubertal state (Tanner stage) were monitored during follow-up. RESULTS This retrospective observational study included 215 patients diagnosed with pLGG. The median age at diagnosis was 13.9 years (range 1-16 years), with 95 females (44.2%) and 120 males (55.8%). Among the entire cohort, 48 patients (22.3%) with Tanner stage >3 received a diagnosis of pLGG or experienced disease progression; of these, 12 patients (25.0%) had a diagnosis of precocious puberty. Among patients with precocious puberty, 10 (83.3%) were diagnosed with precocious puberty concurrently with or prior to the diagnosis of low-grade brain tumor, while 3 patients (25.0%) developed precocious puberty at the moment of tumor progression. CONCLUSIONS Our findings suggest that hormonal changes during puberty, particularly increased estrogen levels, may influence the development and progression of pLGG. The association between pubertal stage, precocious puberty, and tumor dynamics highlights the potential role of sex hormones in modulating tumor behavior. Further prospective studies are needed to better understand the biological mechanisms underlying this relationship and to explore potential therapeutic implications.