Extracellular vesicles and interventional radiotherapy (modern brachytherapy): a translational gap analysis of dose-gradient-driven biological responses

Abstract Extracellular vesicles (EVs) play a key role in radiation-induced biological responses and intercellular signaling. While extensively studied in external beam radiotherapy, their interaction with interventional radiotherapy (IRT, modern brachytherapy), characterized by steep and localized dose gradients, remains poorly explored. A qualitative literature-based gap analysis was conducted using PubMed and Scopus to identify studies investigating EVs in clinical or experimental settings involving IRT. Eligible publications included any form of EV analysis in patients or models treated with IRT alone or in combination with other therapies. Studies were qualitatively categorized according to treatment modality, EV characterization strategy, biological samples, and study endpoints. Only a limited number of original studies were identified. When IRT was delivered as a standalone treatment, localized irradiation was sufficient to induce measurable modulation of EV populations and cargo. In combined treatment settings, EVs were more commonly investigated as systemic biomarkers of treatment response or immune modulation, without isolating the specific biological contribution of IRT. Across studies, EV characterization approaches and clinical contexts were highly heterogeneous, and spatial dose–response relationships intrinsic to IRT were rarely addressed. Despite its intrinsic physical advantages, IRT remains underutilized as a platform for investigating EV-mediated radiation responses. The available evidence suggests that IRT can induce distinct EV modulation, but its biological potential is largely unexplored. Integrating EV analysis with IRT-specific dosimetry and spatial dose gradients represents a relevant translational opportunity for future radiobiological research.