Modern brachytherapy in glioblastoma: overcoming clinical barriers to improve local control

Glioblastoma almost invariably recurs at the margin of the resection cavity despite maximal treatment combining surgery, external beam radiotherapy, and chemotherapy. More than 80% of recurrences arise locally, underscoring a persistent unmet need for improved locoregional control. Despite major advances in conformal external beam radiotherapy techniques, durable local control remains challenging because of diffuse tumor infiltration, biological resistance, and the need to preserve surrounding healthy brain tissue. Although internal radiotherapy has existed for decades and is supported by a compelling radiobiological rationale, its integration into routine neuro-oncological practice remains limited. In this narrative review, we examine why a technically established approach, based on a sound biological rationale, continues to play a limited role in glioblastoma management. We focus on dosimetric standardization as a major challenge specific to internal radiotherapy. Unlike external beam radiotherapy, which prescribes absorbed dose within a standardized planning framework, internal radiotherapy delivers radioactive activity, resulting in spatially and temporally evolving dose distributions that are difficult to reconstruct, compare, and biologically interpret. Recent advances in intracavitary implantable and injectable platforms, patient-specific modeling, and improved understanding of glioblastoma radiobiology may enable a shift toward biologically informed treatment planning. By integrating radiation physics, tumor biology, and clinical decision-making, modern brachytherapy may emerge as a structured complement to multimodal glioblastoma care aimed at achieving improved local control.