S2513
Radiobiology - Biology of novel irradiation techniques
ESTRO 2026
Conclusion: By changing the size of the boost in a single fraction hybrid protocol, we were able to detect the presence of tissue specific dose thresholds, below which the FLASH sparing effect is not observed. Precise characterization of these thresholds is crucial for implementation of FLASH-RT in the clinic. Fractionated hybrid regimens demonstrated that the increase in the number of CONV-RT fractions diminished the magnitude of the FLASH sparing effect. However, a substantial quantity of the FLASH sparing effect was still achieved when 1 out of 3 fractions was delivered by CONV-RT. In addition, our findings support the feasibility of hybrid irradiation approaches as a feasible pathway for translating FLASH-RT into future clinical applications. Keywords: FLASH-RT, Hybrid, Fractionation Correlating in vivo oygen concentration with histological response in hHNSCC after FLASH and conventional proton SOBP irradiation Manuel Bernabei 1,2 , Elisabeth Bodenstein 1,2 , Marina Guzman Hentschel 1,3 , Felix Horst 1,4 , So ň a Michlíková 1,4 , Jörg Pawelke 1,4 , Moritz Schneider 1,2 , Michael Schürer 1,5 , Marielle Wolf 1,2 , Mechthild Krause 1,6 , Antje Dietrich 1,3 , Elke Beyreuther 1,2 1 OncoRay, National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus- Technische Universität Dresden- Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 2 Institute of Radiation Physics, Helmholtz- Zentrum Dresden-Rossendorf, Dresden, Germany. 3 German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), Heidelberg, Germany. 4 Institute of Radiooncology - OncoRay, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany. 5 National Center for Tumor Diseases Dresden (NCT/UCC), Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany; Helmholtz-Zentrum Dresden- Rossendorf (HZDR), Dresden, Germany. 6 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Digital Poster 4416 Purpose/Objective: FLASH radiotherapy delivers radiation at ultra-high dose-rate (> 40 Gy/s). While normal tissue sparing effects are validated in different models, data on tumor treatment efficiency is still rare. In an ongoing preclinical trial, we aim to test non-inferiority of tumor control probability of conventional proton therapy
(CONV-PT) over FLASH proton therapy (FLASH-PT) in a heterogeneous cohort of three human head and neck squamous cell carcinoma (hHNSCC) xenograft models. Additionally, in this work, a cohort of xenograft tumors was excised for histological analyses to investigate the influence of oxygen availability and the tumor microenvironment on irradiated tumors, as well as the correlation between hypoxia and in vivo partial oxygen pressure (pO ₂ ) values in non-irradiated controls. Material/Methods: The heterogeneous hHNSCC cohort was established using UT-SCC14, FaDu, and UT-SCC5 tumor models subcutaneously transplanted into NMRI nude mice. When tumors reached 6–7 mm in diameter, mice of the histology arm were randomly assigned to FLASH- PT, CONV-PT, or control. 24 hours before irradiation, mice received an i.v. injection of Oxyphor PtG4 (75 μ L, 200 μ M/mL) to enable in vivo tumor pO ₂ measurement using the Oxyled system. Tumors were irradiated with a single proton fraction (UT-SCC14: 26.1 Gy; FaDu: 31 Gy; UT-SCC5: 35.7 Gy) using a spread-out Bragg peak (SOBP) with 100 Gy/s and 10 Gy/min, respectively. Mice were sacrificed 24 hours post-treatment following Pimonidazole (60–90 min) and Hoechst 33342 (60 s) injections. Tumors were excised, sectioned, stained and imaged. Image analysis in QuPath included pixel classification, intensity thresholding, and marker quantification via positive cell detection and trained classification. Results:
For the analyzed tumors (FLASH-PT n = 3; CONV-PT n = 3; Control n = 3), models were pooled to establish the QuPath analysis pipeline. Tumor pO ₂ values showed a positive trend with the perfused tumor fraction (Hoechst-positive regions; Spearman r = +0.82) and a negative trend with the necrotic tumor fraction
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