Vestibular schwannomas (VSs) are benign intracranial tumors that cause progressive hearing loss, vertigo, tinnitus, and, in some cases, symptomatic compression of the facial and trigeminal nerves or brainstem structures. Stereotactic radiosurgery (SRS) is a precise radiation technique and a cornerstone treatment for growing VSs. However, the unpredictable course of tumor growth and the risk of hearing loss after SRS continue to pose major challenges for clinical management.
To address these challenges, our clinical work focused on improving prediction and risk stratification in VS. We introduced vestibular end organs as distinct organs at risk during SRS planning, demonstrating that their dosimetric sparing is feasible without compromising tumor control. We developed automated tumor segmentation tools and advanced imaging analysis to forecast tumor growth, offering a scalable approach to personalize surveillance and intervention. Applying similar techniques, we were able to identify patients at high risk of developing hearing loss after SRS who could benefit from a preventive intervention.
The search for such a preventive intervention was pursued through basic research protocols. We established an image-guided mouse model of SRS-induced hearing loss that robustly reproduced the high-frequency, dose-dependent, and progressive pattern observed in patients. Using this model, we identified NADPH oxidase 3 (NOX3)-derived oxidative stress as a central driver of cochlear injury. Both genetic deletion of Nox3 and local small interfering RNA-mediated knockdown preserved auditory thresholds and cochlear structures, providing proof-of-concept with direct translational relevance for VS patients.
By bridging predictive imaging with targeted otoprotection, this thesis outlines a future paradigm for the management of VS. It opens new horizons where functional decline is no longer inevitable but can be anticipated and prevented, an unmet clinical need we will pursue in subsequent studies to translate this concept into therapeutic benefit for VS patients.
