S2618
Radiobiology - Translational radiobiology
ESTRO 2026
Seminars in Cancer Biology 98, 19-30 (2024)3. Eke, I. et al. Radiotherapy and Oncology 99, 271–278 (2011).4. Gilkes, D. M. et al. Nat Rev Cancer 14, 430– 439 (2015). Keywords: hypoxia, ECM, biomarker
p=0.0000054]; bladder [n=1,102, p=0.0027]; lung [n=764, p=0.0029]; pancreatic [n=271, p=0.00035]; prostate [n=689, p=0.035]). Unexpectedly, radiotherapy benefit was observed in patients with “low” (breast [n=751, p=0.0498]; head & neck [n=354, p=0.0085]) and “high” (bladder [n=1,102, p=0.00012]; cervix [n=91, p=0.043]) hypoxic-ECM scores, Patients benefiting from radiotherapy and exhibiting “high” scores had better metastasis-free survival (p<0.0001). Cross-validation using tertile stratification of Buffa, Ragnum, and Yang signatures confirmed that “high” hypoxia scores predicted radiotherapy benefit (breast, cervix, glioblastoma, pancreatic). In vitro, severe (0.2% O ₂ ), but not moderate hypoxia (1% O ₂ ), reduced migration and increased adhesion, effects enhanced by irradiation. Severe hypoxia decreased collagen fibres, while irradiation reduced cell/ECM interactions.
Poster Discussion 1860
High-salt diet increases gut toxicity in radiotherapy by enhancing intestinal radiosensitivity and driving dysbiosis with inflammatory Th17 responses Maximilian Giller 1 , Caroline N Walther 1 , Sophie M Nefzger 1 , Sarah Riedl 1 , Nicole A Schmid 1 , Sarah Diederich 1 , Tanja Groll 2 , Naziha Kruska 1 , Stephanie E Combs 1,3 , Thomas E Schmid 1,4 , Katja Steiger 2 , Markus Tschurtschenthaler 5,6 , Julius C Fischer 1 1 Department of Radiation Oncology, TUM School of Medicine and Health, TUM University Hospital Rechts der Isar, Munich, Germany. 2 Institute of Pathology, TUM School of Medicine and Health, Munich, Germany. 3 German Cancer Consortium (DKTK), Partner-site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany. 4 Institute of Radiation Medicine, Helmholtz Zentrum München, Neuherberg, Germany. 5 Zentralinstitut für translationale Krebsforschung (TranslaTUM), TUM School of Medicine and Health, Munich, Germany. 6 Institute of Translational Cancer Research and Experimental Cancer Therapy, TUM School of Medicine and Health, Munich, Germany Purpose/Objective: Identifying factors that contribute to intestinal radiotoxicity after radiotherapy (RT) of abdominal and pelvic tumors is crucial for improving the quality of life of cancer patients. A high-salt diet (HSD) is common in Western countries, yet the impact of increased sodium chloride (NaCl) intake on the development of intestinal side effects remains unclear. Material/Methods: Colony-formation assays using murine small intestinal ModeK cells, cultured under varying NaCl concentrations (103–200 mM), were performed to assess radiosensitivity. In addition, cell-cycle and cell- death analyses were conducted at multiple time points (30 min to 72 h post-irradiation). Murine small- intestinal organoids were cultivated in corresponding NaCl conditions and irradiated. Organoid growth and survival were quantified, DNA double-strand breaks were assessed by γ H2AX immunohistochemistry and flow-cytometric staining. C57BL/6 wild-type mice were fed either an HSD or a normal-salt diet (NSD) and treated with different RT regimens. Intestinal barrier integrity was evaluated by an in vivo FITC–dextran permeability assay. Fecal samples and tissue-adherent
Conclusion: Hypoxia-induced ECM remodelling is a prevalent pan- cancer process involving HIF1/HIF2-dependent and independent regulation. Severe hypoxia associates with radiotherapy benefit and reduced metastasis, likely due to reduced cell migration on highly hypoxic ECMs following irradiation. Further validation is warranted, as these findings could inform new therapeutic strategies. References: 1. Muz, B. et al. Hypoxia 83 (2015).2. Beckers et al.
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