S1229
Clinical - Urology
ESTRO 2026
Our exploratory longitudinal study included 27 patients with prostate cancer in primary (n=4) and salvage (n=23) therapy settings. Stool samples were collected before RT, at the end of RT, 6 weeks post RT and 1 year post RT. Clinical symptoms were assessed using CTCAE v5.0. The microbial analysis was performed by purifying total microbial DNA, followed by amplification and Illumina MiSeq sequencing of the V3-V4 region of the bacterial 16S rRNA gene. The raw data was processed using Qiime2 and analyzed in R primarily with the phyloseq and vegan packages. Differential abundance analysis was performed using Linear Discriminant Analysis Effect Size (LEfSe) via the microbiomeMarker package. Functional genome prediction was performed using PICRUSt2. We divided our patients into two toxicity groups based on their maximum CTCAE diarrhea score: a high-toxicity group (score ≥ 2 at any timepoint and/or prolonged symptoms defined as ≥ 1 at 6 weeks post-RT) and a low-toxicity group (all other patients). Results: While alpha diversity (within-sample microbial richness and evenness) did not differ by toxicity group or timepoint, beta diversity (between-sample compositional differences) differed significantly between the high- and low-toxicity groups (PERMANOVA, p<0.05). Principal Coordinate Analysis (PCoA) showed distinct clustering for both phylogenetic and non-phylogenetic distances. LEfSe revealed that the low-toxicity group was significantly enriched in orders such as Bacteroidales, Enterobacterales, and Bifidobacterales. The high- toxicity group showed an enrichment of orders including Oscillospirales, Verrucomicrobiales and Christensenellales (LDA score ≥ 2, p <0.05). Functionally, these taxonomic differences correlated with the upregulation of metabolic pathways in the low-toxicity group. LEfSe identified the superpathway of L-tryptophan biosynthesis, the urea cycle, and the superpathway of arginine and polyamine biosynthesis as all being significantly more abundant (LDA score ≥ 2, p <0.05). Conclusion: Our analyses identified that increased bacterial L- tryptophan metabolism and arginine-to-polyamine pathways, including the urea cycle, are potential radioprotective factors during pelvic radiotherapy. Further analyses will be necessary to confirm the predictive and therapeutic relevance of our findings. References: 1. Lavelle A, Sokol H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol, 2020.2. Xiao HW, Cui M, Li Y, et al. Gut microbiota-derived indole 3- propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein. Microbiome, 2020. Keywords: gut microbiota, pelvic radiotherapy
472) and 130 (90, 472) days, respectively. Conclusion:
Our Bayesian mechanistic framework provides risk- based patient-specific forecasts of PSA dynamics under uncertainty. The results of this study further suggest that the combination of the α -superquantiles of our biomarkers and the DGBRD enable both early detection and individualized quantification of relapse risk, supporting more informed and personalized clinical decision-making in post-radiotherapy prostate cancer management. References: [1] G. Lorenzo, N. di Muzio, C.L. Deantoni, C. Cozzarini, A. Fodor, et al. (2022). Patient-specific forecasting of postradiotherapy prostate-specific antigen kinetics enables early prediction of biochemical relapse. iScience, 25(11), 105430.[2] T. Phan, S.M. Crook, A.H. Bryce, C.C. Maley, E.J. Kostelich, Y. Kuang. (2020). Mathematical modeling of prostate cancer and clinical application. Applied Sciences, 10(8), 2721.[3] A. Chaudhuri, G. Pash, D.A. Hormuth II, G. Lorenzo, M. Kapteyn, et al. (2023). Predictive digital twin for optimizing patient-specific radiotherapy regimens under uncertainty in high-grade gliomas. Frontiers in Artificial Intelligence, 6, 1222612. Keywords: tumor forecasting, biomechanistic model, prostate Microbial signatures and functional pathways associated with gastrointestinal toxicity after pelvic radiotherapy in prostate cancer patients Oliver C Holmes 1 , Sarah D Riedl 1 , Jonathan N Möller 1 , Kai Borm 1 , Klaus-Peter Janssen 2 , Stephanie E Combs 1,3 , Julius C Fischer 1 1 Department of Radiation Oncology, Technical University of Munich, Munich, Germany. 2 Department of Surgery, Technical University of Munich, Munich, Germany. 3 Institute for Radiation Medicine, Helmholtz Munich, Neuherberg, Germany Purpose/Objective: Gastrointestinal side effects during pelvic radiotherapy (RT) can limit therapeutic treatment options and impair the patients’ quality of life, yet the underlying mechanisms leading to interindividual differences in toxicity are poorly understood. Past studies suggest that host–microbiome interactions may contribute to Digital Poster 2466 radiation tolerance via immunomodulatory and metabolic pathways.1,2 This study investigates microbial and functional differences in the gut microbiota associated with the presence or absence of radiogenic intestinal toxicity in patients with prostate cancer undergoing pelvic RT. Material/Methods:
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