ESTRO 2024 - Abstract Book

S105 ESTRO 2024 loss of sexual confidence, low self-esteem and a loss of masculinity. Problems are particularly acute for men who undergo multiple treatments due to disease progression, and those on long-term androgen deprivation therapy. Men face significant barriers accessing help and interventions to address sexual wellbeing. Healthcare professionals often assume prostate cancer patients place a low level of importance on these issues due to cohort demographics and low sex drive associated with the common use of androgen-targeted agents. Further barriers to accessing care include age, disability, sexual orientation, ethnicity, and disease stage. Support for men managed in the oncological setting with radiotherapy and hormone therapy is also significantly worse than those who undergo surgery. When patients are able to access help, focus tends to be placed on penile rehabilitation through erectogenic interventions. There is less emphasis on neglected physical side effects and limited access to psychosexual support to address the long-term impact on men and their partners. More recently, a biopsychosocial approach to care has proposed offering men more holistic support. This approach recognises that the prospects of penile rehabilitation are often poor. More emphasis is placed on adapting and adjusting sex lives to ensure men and their partners are able to maintain intimacy despite loss of function. Invited Speaker

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Single-cell transcriptomics on salivary gland organoids after photon and proton radiotherapy

Rob P Coppes

University Medical Center Groningen, Radiation Oncology and Biomedical Sciences, Groningen, Netherlands

Abstract:

Proton therapy has a physical advantage over conventional photon-based radiotherapy. However, little is known about the differences in cell-autonomous biological mechanisms of radiation-surviving cells in healthy tissue. To investigate the potential differences between these radiation types, we used an adult salivary gland organoid (SGO) model, which closely resembles the normal tissue response to radiation. Single-cell RNA sequencing (scRNAseq) allows the study of gene expression changes in populations with a similar gene expression characteristic, depicting cell type. Although both radiation qualities showed a similar and dose-dependent decrease in cell survival, proton irradiated SGOs maintained a higher self-renewal capacity measured as secondary organoid forming efficiency (OFE), suggesting better stem cell functioning. A first characterization of SGO showed the presence of stem/progenitor, progenitor, basal, luminal duct and acinar precursor cells, indicating the reflection of the normal tissue. As expected, irradiation reduced the number of stem/progenitor populations with a relative increase in more differentiated ones. Pseudobulk and gene set enrichment analyses showed an upregulation of genes related to Notch signalling enrichment of development-related processes following irradiation, especially in the stem/progenitor population. Activation of the Notch pathway is important for stem cell maintenance and proliferation following irradiation. Moreover, cell-cell interaction analysis showed a higher upregulation of these processes in proton-irradiated SGO. Indeed, Notch inhibition or stimulation reduced or increased OFE, respectively, thus increasing stemness. Next to that, we observed that specifically in a subpopulation stem/progenitor cells showed an increased INF-β response after proton irradiation due to the derepression of transposable elements (TEs) derived cytoplasmic dsRNA. Again, up or down-regulation of INF-β showed improved or suppressed OFE, respectively. In conclusion, proton, compared to photon irradiation, improved the regenerative potential of SGO due to microenvironmental changes in interferon-beta (IFN-β) and Notch signalling. These data might point to a possible advantage of proton over photon radiotherapy.

This work was supported by the Dutch Cancer Society KWF Grant nr: 12092