ESTRO 2024 - Abstract Book

S126 ESTRO 2024 There are several factors to consider that likely influence efficacy and toxicity of prostate re-irradiation. Patient selection is an important factor in this setting. Especially prospective studies often define a minimum interval since initial radiotherapy or exclude patients with higher-grade toxicity after first irradiation. Although this seems to be reasonable, to date there is no clear evidence that either factor will significantly influence toxicity after re-irradiation. Target delineation in the published data, another factor that could possibly influence toxicity, has been inhomogeneous. Besides different CTV and PTV margins, there was no consensus whether the entire prostate or just the recurring lesion (usually defined with the help of an MRI or PET CT) was defined as target for re-irradiation. PTV size was identified as a factor influencing toxicity in one study. However, a Meta-Analysis no clear trend for pooled late toxicity depending on the target definition (for ≥G2 GI: 3% focal vs. 3% whole prostate; for ≥G2 GU: 20% focal vs. 9% whole prostate). Also the type of primary radiotherapy might be a factor to consider. To our knowledge however, there is only one study reporting data for SBRT for an initial LDR-only collective. A meta-analysis revealed that there are likely higher rates of toxicity (especially GU toxicity) in cohorts were patients received brachytherapy or EBRT and/or brachytherapy (≥G2 GI and GU 7% and 24%) compared to EBRT only cohorts (≥G2 GI and GU 3% and 14%). This confirms the findings by Fuller et al. that a more intensive first therapy results in higher toxicity rates after re-irradiation. Factors influencing the incidence of toxicity in the re-irradiation setting has been evaluated in some studies with no clear answer. There are prospective studies under way that will hopefully further offer guidance in patient selection, target delineation and treatment planning as the topic of prostate re-irradiation will likely become more important in the future with the rising life expectancy. Invited Speaker

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UniCAR T-cell combination with radiotherapy

Claudia Arndt

Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Department Radioimmunology, Dresden, Germany. Faculty of Medicine Carl Gustav Carus, TU Dresden, Mildred Scheel Early Career Center, Dresden, Germany

Abstract:

Adoptive transfer of T cells modified with tumour-specific chimeric antigen receptors (CARs) has proven to be an effective tool for the treatment of several haematological malignancies, as demonstrated by the approval of six different CAR-T products in Europe and the US. However, clinical translation to solid tumours is still limited, as evidenced by the suboptimal performance of CAR T cells in early in-human studies. Major challenges include the low intratumoral infiltration of CAR-T cells and the immunosuppressive tumour microenvironment. Combining advances in CAR-T cell therapy and radiotherapy may provide a promising approach to overcome these hurdles and increase therapeutic efficacy in cancer patients. This is underlined by our recent study demonstrating a synergistic effect of the combination of photon irradiation and CAR-T immunotherapy in HNSCC models. Our CAR-T approach is based on the adaptor CAR-T platform "UniCAR", in which CAR-T cell activity is controlled by a tumour-specific adaptor molecule called target module. In addition to their immunotherapeutic potential, UniCAR target modules have emerged as promising candidates for radiotheranostics. Following conjugation with chelators such as DOTAGA and NODAGA, they have been successfully labelled with diagnostic and therapeutic radionuclides. PET imaging in xenografted mice