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Possible mechanisms and simulation modeling of FLASH radiotherapy

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Abstract

FLASH radiotherapy (FLASH-RT) has great potential to improve patient outcomes. It delivers radiation doses at an ultra-high dose rate (UHDR: ≥ 40 Gy/s) in a single instant or a few pulses. Much higher irradiation doses can be administered to tumors with FLASH-RT than with conventional dose rate (0.01−0.40 Gy/s) radiotherapy. UHDR irradiation can suppress toxicity in normal tissues while sustaining antitumor efficiency, which is referred to as the FLASH effect. However, the mechanisms underlying the effects of the FLASH remain unclear. To clarify these mechanisms, the development of simulation models that can contribute to treatment planning for FLASH-RT is still underway. Previous studies indicated that transient oxygen depletion or augmented reactions between secondary reactive species produced by irradiation may be involved in this process. To discuss the possible mechanisms of the FLASH effect and its clinical potential, we summarized the physicochemical, chemical, and biological perspectives as well as the development of simulation modeling for FLASH-RT.

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Abbreviations

BED:

Biologically effective dose

CONV:

Conventional

DSB:

Double-strand break

GSH:

Glutathione

IRT:

Independent reaction time

LET:

Linear energy transfer

LPO:

Lipid peroxidation

LQ:

Linear-quadratic

MD:

Molecular dynamics

OER:

Oxygen enhancement ratio

ROS:

Reactive oxygen species

SBS:

Step-by-step

SSB:

Single-strand break

TOD:

Transient oxygen depletion

UHDR:

Ultra-high dose rate

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Acknowledgements

The authors thank Dr Hiroyuki Date (Hokkaido University) for helpful suggestions.

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  1. Graduate School of Health Sciences, Hokkaido University, N12 W5 Kita-Ku, Sapporo, Hokkaido, 060-0812, Japan

    Yuta Shiraishi

  2. Faculty of Health Sciences, Japan Healthcare University, 3-11-1-50 Tsukisamu-Higashi, Toyohira-Ku, Sapporo, Hokkaido, 062-0053, Japan

    Yuta Shiraishi

  3. Faculty of Health Sciences, Hokkaido University, N12 W5 Kita-Ku, Sapporo, Hokkaido, 060-0812, Japan

    Yusuke Matsuya & Hisanori Fukunaga

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Shiraishi, Y., Matsuya, Y. & Fukunaga, H. Possible mechanisms and simulation modeling of FLASH radiotherapy. Radiol Phys Technol 17, 11–23 (2024). https://doi.org/10.1007/s12194-023-00770-x

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