Physics and biology of ultrahigh dose-rate (FLASH) radiotherapy: a topical review

Published on Dec 4, 2020in Physics in Medicine and Biology2.883
· DOI :10.1088/1361-6560/ABAA28
Nolan Esplen3
Estimated H-index: 3
(UVic: University of Victoria),
Marc S. Mendonca24
Estimated H-index: 24
(IU: Indiana University),
Magdalena Bazalova-Carter12
Estimated H-index: 12
(UVic: University of Victoria)
Ultrahigh dose-rate (>40 Gy/s) radiotherapy, or "FLASH" therapy, has gained significant momentum since the publication by Favaudon et al. in 2014, in which reduced normal tissue toxicity and similar tumor control for ultrahigh dose-rate radiotherapy compared to conventional radiotherapy was demonstrated in vivo. A number of subsequent studies from this and other groups investigating FLASH normal tissue protection followed shortly and the literature has been since been inundated with FLASH publications. Today, FLASH therapy has been considered by some as being capable of "revolutionizing radiotherapy". The goal of this review article is to present the current state of this intriguing radiotherapy technique. We namely review existing publications on FLASH radiotherapy (RT) in terms of its physical and biological aspects. In the physics section, ultrahigh dose-rate electron, photon and proton radiation sources with their beam delivery parameters are thoroughly discussed. Next, the benefits and drawbacks of equipment suitable for dosimetry in FLASH-RT, such as ionization chambers, radiochromic films, semiconductor detectors and alanine dosimeters, are presented. The biology section begins with a summary of the first in vitro high dose rate irradiations performed in the late 1960s and early 1970s and continues with a description of the recent normal and tumor tissue response studies performed with electron, photon and proton beams. The section is concluded with possible mechanistic explanations of the FLASH normal tissue protection effect (FLASH effect). The challenges of clinical application of FLASH-RT and its future prospects are critically discussed in the last section. Specifically, proposed treatment machines and treatment planning publications geared towards FLASH-RT are reviewed.
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