S2559
Radiobiology – Normal tissue radiobiology
ESTRO 2026
into two half doses and varying the time between delivery showed that multi-pulse delivery could be spaced apart >5 sec and still see the observation of a FLASH sparing effect (9). Conclusion: Radiation damage in murine skin in vivo is a useful assay of FLASH sparing effect, and correlation with oxygen consumption. This Δ pO2 is likely from protein and lipid peroxyl radicals (i.e. DNA). It seems likely that oxygen consumption could be used as an in vivo quantitative assay of radiolytic damage, as a surrogate
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Optimization of FLASH split dose, fractionation, peak vs mean dose rate deliveries, by oxygen consumption measurement in vivo as a surrogate biomarker Brian Pogue 1,2 , Jacob Sunnerberg 1 , William Thomas 3 , David J Gladstone 1 , Harold M Swartz 2 , P Jack Hoopes 2 , Lesley A. Jarvis 2 , Rongxiao Zhang 4 1 Engineering, Dartmouth, Hanover, USA. 2 Radiation Oncology, Geisel School of Medicine at Dartmouth, Hanover, USA. 3 Medical Physics, University of Wisconsin, Madison, USA. 4 Radiation Oncology, University of Missouri, Columbia, USA Purpose/Objective: The FLASH effect is a reduction in damage to normal tissue, when ultra-high dose rates (UHDR) are used in radiotherapy as compared to conventional [low] dose rates (CDR)(1). Optimization of the dose delivery is a complex process given that the biological damage assays require long times, are labor intensive and have inherently high variability (2). In this study, we test the hypothesis that in vivo measurement of oxygen consumption ( Δ pO2) can be a surrogate biomarker of damage (3), and this can be used to quantitatively compare different UHDR delivery techniques. Material/Methods: Radiolytic Δ pO2 can be directly measured in skin by an observable drop in pO2 from before to after UHDR irradiation (3), sensed by molecular phosphorescence quenching of injectable Oxyphor (4). Murine studies have been used in normal skin to assess the relationship between this change in oxygen, and the macroscopic radiation damage to the skin, assessed by a visible damage score assay (5,6). Factors examined to date have been the total dose, dose fractionation, split dose delivery, and baseline tissue pO2 levels, directly comparing UHDR treatment effect to CDR treatment effects. Results: Measured changes on oxygen during UHDR irradiation were directly proportional to dose delivered in mice, showing dose dependence of radiolytic oxygen consumption in vivo. Doses greater than 16 Gy appear to be required to see differential skin damage sparing effect from UHDR versus CDR delivery for the assay used, although only UHDR delivery allows for pO2 measurement changes. The change in pO2 is correlated to initial oxygen at 0-16mmHg, but beyond 20 mmHg there was saturation of this and they are uncorrelated (7). Treatment of mice with intentionally varied skin oxygen demonstrated that mid level baseline oxygen was required for the FLASH effect, with is disappearing when skin was near zero or greater than 20 mmHg (8). Splitting the dose for FLASH
biomarker of delivery efficacy and a tool to systematically optimize FLASH delivery. References: 1.
Vozenin MC, et al, Vol. 139, Radiother Oncol.
2019. p. 1–3. 2.
Sorensen BS, et al, Vol. 175,
Radiother Oncol. 2022. p. 178–84. 3. Cao X, et al. Int J Radiat Oncol Biol Phys. 2021 Sept 1;111(1):240– 8. 4. Vinogradov SA, et al, Vol. 510, Adv Exp Med Biol. 2003. p. 181–5. 5. Pogue BW, et al, Front Oncol. 2024;14:1414584. 6. Cui F, et al, J Appl Clin Med Phys. 2024 Dec;25(12):e14508. 7. Sunnerberg JP, et al, Int J Radiat Oncol Biol Phys. 2025 Mar 15;121(4):1053–62. 8. Tavakkoli AD, et al, Front Oncol. 2025;15:1666489. 9. Sunnerberg JP, et al, Int J Radiat Oncol Biol Phys. 2025. p. (in press). Keywords: oxygen, radiation oncology, dermatology Impact of NRF2, KEAP1 and HO1 on Acute Side Effects in Rectal Cancer Patients Treated with Neoadjuvant Chemoradiation Hatice Kübra Gündüz 1 , Hilal Alkı ş 1 , Dilber Ramazan Çoban 2 , Goncagül Haklar 2 , Mustafa Adlı 1 1 Radiation Oncology, Marmara University, Istanbul, Turkey. 2 Biochemistry, Marmara University, İ stanbul, Turkey Purpose/Objective: Acute side effects is a challenge in rectal cancer patients treated with neoadjuvant chemoradiotherapy (CRT). Nuclear factor-erythroid 2 related factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1)/Heme oxygenase 1 (HO1) signaling pathway is Digital Poster Highlight 267
a part of antioxidant, anti-inflammatory, and detoxification processes and also involved in
resistance/toxicity of anti-cancer treatment. NRF2 plays active role in defense system against oxidation beside its prooxidant and tumorogenic effects. KEAP1 regulates expression and activation of NRF2. HO-1 has a dual effect on ferroptosis by inducing or inhibiting. Aim of this study was to evaluate the effect of NRF2/KEAP1/HO1 signaling pathway on acute side effects in rectal cancer patients treated with neoadjuvant CRT.
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