TY  - JOUR
AU  - Liew, Hans
AU  - Mein, Stewart
AU  - Tessonnier, Thomas
AU  - Abdollahi, Amir
AU  - Debus, Jürgen
AU  - Dokic, Ivana
AU  - Mairani, Andrea
TI  - Do We Preserve Tumor Control Probability (TCP) in FLASH Radiotherapy? A Model-Based Analysis.
JO  - International journal of molecular sciences
VL  - 24
IS  - 6
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DKFZ-2023-00634
SP  - 5118
PY  - 2023
N1  - #EA:E210#
AB  - Reports 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.
KW  - DNA repair (Other)
KW  - FLASH (Other)
KW  - TCP (Other)
KW  - UNIVERSE (Other)
KW  - dose-rate (Other)
KW  - ionizing radiation (Other)
KW  - modeling (Other)
KW  - tumor volume (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36982185
DO  - DOI:10.3390/ijms24065118
UR  - https://inrepo02.dkfz.de/record/274491
ER  -