ESTRO 2023 - Abstract Book

S478

Sunday 14 May 2023

ESTRO 2023

numbers of Lgr5+ cells and Paneth cells. In addition, we found that I3A activated AHR to promote IL-10 expression to regulate Wnt signaling pathway. Furthermore, there was no radiological protection of I3A in the germ-free mice, indicating that the function of I3A was dependent on the gut microbiota. Conclusion Collectively, our findings suggested that microbiota-derived I3A protects against RIII by promote the proliferation and differentiation of Lgr5+ intestinal stem cells via AHR-IL10-Wnt signaling pathway. OC-0597 Gut Microbiota is Predictive of Radio-induced Gastrointestinal Toxicity in Prostate Cancer Patients J. Iacovacci 1 , T. Rancati 1 , E. Gioscio 1 , L. De Cecco 2 , B. Avuzzi 3 , B. Noris Chiorda 3 , F. Badenchini 1 , T. Giandini 4 , A. Cicchetti 1 , N. Zaffaroni 5 , V. Doldi 5 , E. Mancinelli 6 , M.S. Serafini 2 , A. Devecchi 6 , L. Andreoli 3 , E. Orlandi 7 , R. Valdagni 1,8,3 1 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Prostate Cancer Program, Milan, Italy; 2 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Experimental Oncology Department, Milan, Italy; 3 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Division of Radiation Oncology, Milan, Italy; 4 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Division of Medical Physics, Milan, Italy; 5 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Division of Molecular Pharmacology, Milan, Italy; 6 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Department of Applied Research and Technology Development, Milan, Italy; 7 National Center for Oncological Hadrontherapy, Radiation Oncology, Milan, Italy; 8 Università degli Studi di Milano, Department of Oncology and Hemato-oncology, Milan, Italy Purpose or Objective The search for factors beyond radiation dose that could improve the identification of prostate cancer patients (PCa) more at risk of toxicity is of extreme interest for personalized RT aiming at ameliorating quality-of-life of all survivors. To investigate the role that the intestinal microbiota (MB) might play in the development of RT-induced toxicity in the bowel, the MicroLearner study collected faecal samples from 136 (discovery) and 79 (validation) consecutive PCa pts treated with conventional (78Gy @2Gy/fr) or hypofractionated (65Gy @2.6Gy/fr) VMAT+IGRT in 5 fr/week before and after RT. Materials and Methods Gastrointestinal (GI) toxicity was assessed weakly during RT using CTCAE. Average grade > 1.3 over time points was used to identify a group of 16/136 (discovery) and 8/79 (validation) pts that suffered from acute form of GI toxicity. Operational Taxonomic Units abundances were extracted using 16S rRNA amplicon sequencing and Metagenomic 16S Thermo Fisher bioinformatics pipeline. A core MB at the genus level was extracted in the discovery cohort by selecting taxa found with a relative abundance greater or equal to 2% in at least 10% of the samples. Using the core MB, we developed a clinical decision-tree that evaluates the relative abundance of specific genera and tested its ability to predict the risk of toxicity both in internal and external (MARS population, Ferreira 2019) validation cohorts. Results Hierarchical clustering of the core profiles (Fig. 1a) revealed 8 clusters of pts in the discovery cohort displaying toxicity rates ranging from 0 to 60% (Fig. 1b). The cluster with the highest rate (10 pts, 7% cohort, 38% toxicity population) was significantly enriched for toxicity (Fisher’s exact test P<0.005). The high-risk MB composition was translated in the decision tree (Fig. 2 top), which can assess the MB-related risk of a patient to develop toxicity. We validated the model using the internal validation cohort and the external MARS early cohort (Fig. 2 bottom). A higher rate of toxicity is observed in all cohorts for pts with high-risk MB.