New insights on clinical perspectives of FLASH radiotherapy: from low- to very high electron energy

Stefano Ursino; Giovanni Gadducci; Noemi Giannini; Alessandra Gonnelli; Taiushia Fuentes; Fabio Di Martino; Fabiola Paiar

doi:10.3389/fonc.2023.1254601

New insights on clinical perspectives of FLASH radiotherapy: from low- to very high electron energy

Front Oncol. 2023 Oct 23:13:1254601. doi: 10.3389/fonc.2023.1254601. eCollection 2023.

Authors

Stefano Ursino^{1

2

3}, Giovanni Gadducci^{1

2}, Noemi Giannini^{1

2}, Alessandra Gonnelli^{1

2}, Taiushia Fuentes^{1

2}, Fabio Di Martino^{2

4}, Fabiola Paiar^{1

2

3}

Affiliations

¹ Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
² Centro Pisano Multidisciplinare sulla Ricerca e implementazione clinica della Flash Radiotherapy (CPFR), University of Pisa, Pisa, Italy.
³ Center for Instrument Sharing University of Pisa (CISUP), University of Pisa, Pisa, Italy.
⁴ Unit of Medical Physics, S. Chiara University Hospital, Pisa, Italy.

Abstract

Radiotherapy (RT) is performed in approximately 75% of patients with cancer, and its efficacy is often hampered by the low tolerance of the surrounding normal tissues. Recent advancements have demonstrated the potential to widen the therapeutic window using "very short" radiation treatment delivery (from a conventional dose rate between 0.5 Gy/min and 2 Gy/min to more than 40 Gy/s) causing a significant increase of normal tissue tolerance without varying the tumor effect. This phenomenon is called "FLASH Effect (FE)" and has been discovered by using electrons. Although several physical, dosimetric, and radiobiological aspects need to be clarified, current preclinical "in vivo" studies have reported a significant protective effect of FLASH RT on neurocognitive function, skin toxicity, lung fibrosis, and bowel injury. Therefore, the current radiobiological premises lay the foundation for groundbreaking potentials in clinical translation, which could be addressed to an initial application of Low Energy Electron FLASH (LEE) for the treatment of superficial tumors to a subsequent Very High Energy Electron FLASH (VHEE) for the treatment of deep tumors. Herein, we report a clinical investigational scenario that, if supported by preclinical studies, could be drawn in the near future.

Keywords: FLASH radiotherapy; dose rate; low electron energy; normal tissue complication probability; tumor control probability; very high electron energy.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work is supported by the University of Pisa under the “PRA—Progetti di Ricerca di Ateneo” (Institutional Research Grants)—Project no. PRA_2022-2023_63 “DRIFT: DosimetRic and in vitro studies of Flash radioTherapy effect”.