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000274491 245__ $$aDo We Preserve Tumor Control Probability (TCP) in FLASH Radiotherapy? A Model-Based Analysis.
000274491 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2023
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000274491 520__ $$aReports of concurrent sparing of normal tissue and iso-effective treatment of tumors at ultra-high dose-rates (uHDR) have fueled the growing field of FLASH radiotherapy. However, iso-effectiveness in tumors is often deduced from the absence of a significant difference in their growth kinetics. In a model-based analysis, we investigate the meaningfulness of these indications for the clinical treatment outcome. The predictions of a previously benchmarked model of uHDR sparing in the 'UNIfied and VERSatile bio response Engine' (UNIVERSE) are combined with existing models of tumor volume kinetics as well as tumor control probability (TCP) and compared to experimental data. The potential TCP of FLASH radiotherapy is investigated by varying the assumed dose-rate, fractionation schemes and oxygen concentration in the target. The developed framework describes the reported tumor growth kinetics appropriately, indicating that sparing effects could be present in the tumor but might be too small to be detected with the number of animals used. The TCP predictions show the possibility of substantial loss of treatment efficacy for FLASH radiotherapy depending on several variables, including the fractionation scheme, oxygen level, and DNA repair kinetics. The possible loss of TCP should be seriously considered when assessing the clinical viability of FLASH treatments.
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000274491 650_7 $$2Other$$aDNA repair
000274491 650_7 $$2Other$$aFLASH
000274491 650_7 $$2Other$$aTCP
000274491 650_7 $$2Other$$aUNIVERSE
000274491 650_7 $$2Other$$adose-rate
000274491 650_7 $$2Other$$aionizing radiation
000274491 650_7 $$2Other$$amodeling
000274491 650_7 $$2Other$$atumor volume
000274491 7001_ $$0P:(DE-HGF)0$$aMein, Stewart$$b1
000274491 7001_ $$aTessonnier, Thomas$$b2
000274491 7001_ $$0P:(DE-He78)360c5bc2b71a849e35aca747c041dda7$$aAbdollahi, Amir$$b3$$udkfz
000274491 7001_ $$0P:(DE-He78)8714da4e45acfa36ce87c291443a9218$$aDebus, Jürgen$$b4$$udkfz
000274491 7001_ $$0P:(DE-He78)e24b607ded082a3089a1f6bf326a7a8e$$aDokic, Ivana$$b5$$udkfz
000274491 7001_ $$aMairani, Andrea$$b6
000274491 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms24065118$$gVol. 24, no. 6, p. 5118 -$$n6$$p5118$$tInternational journal of molecular sciences$$v24$$x1422-0067$$y2023
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