ESTRO 2025 - Abstract Book

S47

Invited Speaker

ESTRO 2025

In conclusion, advances in dose fractionation, target delineation, treatment sequencing, and tumor biology-driven personalization are revolutionizing RIT in head and neck and skin malignancies. Future clinical trials will refine these strategies, optimizing outcomes through precision radioimmunotherapy.

4725

Speaker Abstracts Focus on urological cancer Magdalena Stankiewicz Brachytherapy Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland

Abstract:

Combining brachytherapy (BT) and immunotherapy represents a promising improvement in treating urological malignancies. Thanks to highly conformal and heterogeneous dose distributions delivered directly to the tumour site, brachytherapy has the distinctive potential to augment the immunogenic effects of radiation. The conformal dose distribution allows for the sparing of normal tissues and lymphoid organs, potentially minimising off-target immunosuppressive effects. Additionally, the heterogeneous intra-tumoral radiation dose leads to various immunomodulatory effects. Lower doses cause immune cell infiltration, cytokine release, and a temporary depletion of tumour-infiltrating lymphocytes, while higher doses result in cell death and the release of tumour antigens. Harnessing the immunomodulatory effects of brachytherapy could provide strategies to address the challenges impeding the efficacy of immunotherapies in immunologically "cold" tumours while improving the response in immunologically "hot" tumours (1). Data from preclinical studies suggest that when combined with checkpoint inhibitors (ICIs), brachytherapy may induce an abscopal effect, though clinical evidence is still emerging. Nevertheless, integrating brachytherapy with ICIs presents an exciting opportunity to enhance antitumour responses. Irradiation leads to increased PD-L1 expression on tumour cells, which can be targeted by ICIs, preventing immune evasion. Moreover, the immune system may recognise the tumour antigens released as a result of irradiation, potentially acting as an "in situ" tumour vaccine. Checkpoint inhibitors enhance this effect. Clinical trials exploring the combination of brachytherapy with immunotherapies such as nivolumab, pembrolizumab, durvalumab and others are ongoing, with preliminary data indicating improved outcomes in patients with advanced prostate cancer (2,3). Additional concerns under examination include the analysis of immune biomarkers from baseline and post-radiation therapies, including brachytherapy, and exploring alterations in PD-L1 expression on regulatory T cells following brachytherapy (4). Several clinical trials are now exploring the role of combined radiation therapy and tumour vaccine regimens. Sipuleucel-T, an FDA-approved dendritic cell-based vaccine, has significantly reduced the risk of death by 21% compared to placebo in castration-resistant prostate cancer patients. While radiation therapy is not a part of currently approved cancer vaccine treatments, preclinical studies suggest combining radiation with vaccines might produce a synergistic effect. However, based on the results of phase II trials, no statistically significant improvement in oncological outcomes was observed in patients receiving both sipuleucel-T and radiotherapy (5). It is worth noting that in most of these trials, the radiation techniques consisted of external beam radiotherapy or stereotactic radiotherapy. Preclinical trials offer promising insights into future treatment approaches, such as injectable depots for sustained intra-tumoral delivery of iodine-131 radionuclides combined with immunostimulants (6). These depots are driven by elastin-like polypeptides undergoing a thermally sensitive phase transition. Such a delivery system has been shown to control both local and metastatic tumours effectively. Such an approach could offer a novel strategy for treating