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Review
. 2024 Feb 22;25(5):2546.
doi: 10.3390/ijms25052546.

FLASH Radiotherapy: Expectations, Challenges, and Current Knowledge

Andrea Borghini  1 , Luca Labate  2 , Simona Piccinini  2 , Costanza Maria Vittoria Panaino  2 , Maria Grazia Andreassi  1 , Leonida Antonio Gizzi  2
Affiliations
Review

FLASH Radiotherapy: Expectations, Challenges, and Current Knowledge

Andrea Borghini et al. Int J Mol Sci. .

Abstract

Major strides have been made in the development of FLASH radiotherapy (FLASH RT) in the last ten years, but there are still many obstacles to overcome for transfer to the clinic to become a reality. Although preclinical and first-in-human clinical evidence suggests that ultra-high dose rates (UHDRs) induce a sparing effect in normal tissue without modifying the therapeutic effect on the tumor, successful clinical translation of FLASH-RT depends on a better understanding of the biological mechanisms underpinning the sparing effect. Suitable in vitro studies are required to fully understand the radiobiological mechanisms associated with UHDRs. From a technical point of view, it is also crucial to develop optimal technologies in terms of beam irradiation parameters for producing FLASH conditions. This review provides an overview of the research progress of FLASH RT and discusses the potential challenges to be faced before its clinical application. We critically summarize the preclinical evidence and in vitro studies on DNA damage following UHDR irradiation. We also highlight the ongoing developments of technologies for delivering FLASH-compliant beams, with a focus on laser-driven plasma accelerators suitable for performing basic radiobiological research on the UHDR effects.

Keywords: CBMN assay; FLASH effect; FLASH radiotherapy; mitochondrial DNA; normal tissue response; nuclear DNA damage; tumor response; ultra-high dose rate; very high-energy electrons; γ-H2AX.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Overview of the preclinical and first-in-human clinical evidence about the ultra-high dose rate FLASH effect [1,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,38,39,40,41,42,43,44,45,47,48,50].
Figure 2
Figure 2
(A) Schematic illustration of depth dose distribution and DNA damage induction patterns for low and high LET beams; (B) timescales of physical, chemical, and biological phases of conventional and FLASH radiotherapy.
Figure 3
Figure 3
Schematic representation of the in vitro tests for ionizing radiation-induced DNA damage quantification.
See this image and copyright information in PMC

References

    1. Favaudon V., Caplier L., Monceau V., Pouzoulet F., Sayarath M., Fouillade C., Poupon M.F., Brito I., Hupé P., Bourhis J., et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice. Sci. Transl. Med. 2014;6:245ra93. doi: 10.1126/scitranslmed.3008973. - DOI - PubMed
    1. Farr J.B., Parodi K., Carlson D.J. FLASH: Current status and the transition to clinical use. Med. Phys. 2022;49:1972–1973. doi: 10.1002/mp.15401. - DOI - PubMed
    1. Vozenin M.-C., Hendry J.H., Limoli C.L. Biological Benefits of Ultra-High Dose Rate FLASH Radiotherapy: Sleeping Beauty Awoken. Clin. Oncol. 2019;31:407–415. doi: 10.1016/j.clon.2019.04.001. - DOI - PMC - PubMed
    1. Limoli C.L., Vozenin M.-C. Reinventing radiobiology in the light of FLASH radiotherapy. Annu. Rev. Cancer Biol. 2023;7:1–21. doi: 10.1146/annurev-cancerbio-061421-022217. - DOI - PMC - PubMed
    1. Friedl A.A., Prise K.M., Butterworth K.T., Montay-Gruel P., Favaudon V. Radiobiology of the FLASH effect. Med. Phys. 2022;49:1993–2013. doi: 10.1002/mp.15184. - DOI - PubMed

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