Phd in NETWORK ONCOLOGY AND PRECISION MEDICINE

Thesis title: Pediatric Low-Grade Gliomas and Puberty: Recognizing the Subtle Hormonal Influence

Pediatric low-grade gliomas (pLGGs) are the most common central nervous system tumors in childhood, exhibiting marked heterogeneity in clinical course, molecular drivers, and anatomical distribution. Advances in molecular profiling have revolutionized management, enabling the introduction of targeted therapies for genetically defined subgroups, such as MEK and BRAF inhibitors. In parallel, the interplay between pubertal development and sex hormones is emerging as an important modulator of tumor dynamics, with evidence suggesting both clinical and biological relevance. This retrospective observational study analyzes the association between pubertal status, sex steroid hormones, and tumor progression in a cohort of 301 patients with pLGG, integrating clinical, endocrine, and molecular data. Patients with hypothalamic or optic pathway involvement presented a higher rate of precocious puberty and endocrine dysfunction. Notably, hormonal suppression with GnRH analogues in children with central precocious puberty showed a significant extension of event-free survival, supported by data from patient-derived organoid models demonstrating estrogen-driven proliferation in low-grade glioma cultures. Our findings suggest that pubertal status and sex hormones influence tumor behavior, advocating for a precision medicine approach that integrates endocrine profiling with molecular and radiological biomarkers. Future research directions include prospective studies on endocrine modulation in therapy and refined risk stratification in pediatric neuro-oncology, aiming to optimize both survival and long-term quality of life.