ESTRO 2024 - Abstract Book

S146 ESTRO 2024 risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. Key issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. Invited Speaker

These ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings.

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Single-cell analysis of lung responses to radiation injury

Charles Fouillade

Institut Curie, Radiation biology, Orsay, France

Abstract:

My talk will provide an overview of the dynamic molecular alterations and cellular changes characterizing at the single cell level acute and late pulmonary toxicities (i.e. pneumonitis and lung fibrosis) occurring after thoracic radiotherapy. To determine the transcriptional changes induced by radiation at the single cell level, we sequenced, by scRNAseq, over 100 000 lung cells from mice that were previously exposed to thoracic irradiation at either a fibrogenic (17 Gy) or a non fibrogenic (10 Gy) dose as well as non-irradiated control. We explored the dynamic of the underlying physiopathological processes by analyzing different timepoints covering from the early pneumonitis phase (i.e. from 1 to 3 months) to the late development of radiation-induced pulmonary fibrosis (i.e. 4 to 5 months). To document the cellular changes and spatial reorganization of the lung during fibrogenesis, we applied smFISH-based spatial transcriptomic to map the different lung cell types at 3, 4 and 5 months after radiation injury. This lung single cell atlas allowed us to identify transcriptional hallmarks of radiation-induced pulmonary fibrosis such as activation of epithelial to mesenchymal transition (EMT) program in specific alveolar epithelial cells (i.e. AT2), upregulation of matrix producing genes in a subset of lung fibroblasts as well as a predominant senescence profile in specific populations. These transcriptional alterations are associated with an important remodeling of the lung architecture during fibrogenesis. Particularly, lung spatial analysis revealed i) a drastic decrease in epithelial AT2 cells associated with a change in their morphology ii) a progressive accumulation of distinct subsets of pro inflammatory macrophages iii) an invasion of fibroblastic foci by dysmorphic capillaries. Interestingly, cell-cell communication analysis based on the single cell data confirmed an increased pro-angiogenic signaling from the