S2583
Radiobiology – Normal tissue radiobiology
ESTRO 2026
13 Department of Human Structure and Repair, Ghent University, Ghent, Belgium. 14 Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium. 15 MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy. 16 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 17 Cancer Epidemiology Group, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 18 Division of Genetics & Genome Biology, University of Leicester, Leicester, United Kingdom
Conclusion: Salsalate may be able to provide improvement in the therapeutic ratio of radiotherapy in HCC by improving radiotherapy response and mitigating radiation- induced hepatic fibrosis. This aligns with our previous work showing that the addition of salsalate to Lenvatinib therapy reduced MASH-associated fibrosis and improved survival in a metabolic HCC model. Collectively, these studies support the concept that targeting metabolism and inflammation with salsalate could simultaneously enhance therapeutic efficacy and protect the liver microenvironment during oncologic interventions. Keywords: Hepatocellular Carcinoma, Salsalate , Fibrosis Digital Poster Highlight 4501 Discovery and validation of whole blood microRNAs associated with late radiation toxicity in breast cancer patients Ester Aguado-Flor 1,2 , Lara Nonell 3 , Miguel E Aguado- Barrera 4,5 , Victor Navarro 6 , Victoria Reyes 7 , Manuel Altabas 7 , Ananya Choudhury 8,9 , David Gibon 10 , Alexandra Giraldo 7 , Maarten Lambrecht 11 , Tiziana Rancati 12 , Liv Veldeman 13,14 , Paolo Zunino 15 , Jenny Chang-Claude 16,17 , Jordi Giralt 7 , Xavier Maldonado 7 , Christopher Talbot 18 , Ana Vega 4,5 , Petra Seibold 16 , Sara Gutiérrez-Enríquez 1 1 Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain. 2 Programa de Doctorat en Biomedicina, Universitat de Barcelona (UB), Barcelona, Spain. 3 Bioinformatics Unit, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain. 4 Genetics in Cancer and Rare Diseases Group, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, Spain. 5 Fundación Pública Galega de Medicina Xenómica (FPGMX), Hospital Clínico Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain. 6 Biostatistics Unit, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain. 7 Department of Radiation Oncology, Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain. 8 Translational Radiobiology Group, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 9 Dept of Clinical Oncology, The Christie NHS Foundation Trust Hospital, Manchester, United Kingdom. 10 AQUILAB, by Coexya, Loos, France. 11 Department of Radiation Oncology, University Hospitals Leuven/KU, Leuven, Belgium. 12 Unit of Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Purpose/Objective: We aimed to identify differentially expressed
microRNAs (miRNAs) as potential biomarkers of late radiotherapy-induced side effects in whole blood from breast cancer (Bca) and prostate cancer (Pca) patients. Material/Methods: We analyzed clinical data and RNA prepared from whole blood samples taken beforeradiotherapy from Bca and Pca patients from the large and well- characterized REQUITE European cohort. Late RT- induced toxicities were monitored and documented by the physician using the CTCAE v4.0 toxicity grading system. In the context of the RADprecise European project, small RNA Illumina sequencing was performed in a discovery stage by matching patients with moderate or severe late toxicity to those without toxicity, two years after radiotherapy (74 cases and 62 controls for Bca; 61 cases and 61 controls for Pca). Validation of top candidate miRNAs was conducted using targetedNanoString technology in an independent REQUITE cohort (75 Bca patients with late toxicity vs. 198 without; 105 Pca patients with late toxicity vs. 203 without). Stepwise regression was applied in the discovery cohort to identify relevant clinical covariates, which were then included in both discovery and validation models. Differential expression was assessed using the DESeq2 framework. Functional enrichment of miRNAs was performed with the MiEAA web tool to identify molecular pathways associated with up- or downregulated miRNAs. Results: In Bca patients, 90 miRNAs were significantly differentially expressed between individuals with and without late toxicity (Figures 1A and 1B). Enrichment analysis indicated upregulation of pathways related to signal transduction, cellular senescence, and transcription in the toxicity group. Four miRNAs retained significant differential expression and consistent fold-change direction in association with late grade ≥ 2 atrophy/fibrosis in the validation cohort. In contrast, no differentially expressed miRNAs or enriched pathways were detected in the Pca cohort.
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