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MINI REVIEW article

Front. Oncol.
Sec. Radiation Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1414584
This article is part of the Research Topic Harnessing the Potential of FLASH: Questions We Must Address Prior to Effective Clinical Translation View all 8 articles

Major Contributors to FLASH Sparing Efficacy Emerge from Murine Skin Studies: Dose Rate, Total Dose per Fraction, Anesthesia and Oxygenation

Provisionally accepted
Brian W. Pogue Brian W. Pogue 1,2*Armin D. Tavakkoli Armin D. Tavakkoli 3William S. Thomas William S. Thomas 1P. Jack Hoopes P. Jack Hoopes 2,3Lesley A. Jarvis Lesley A. Jarvis 3
  • 1 University of Wisconsin-Madison, Madison, United States
  • 2 Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States
  • 3 Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States

The final, formatted version of the article will be published soon.

    Background: Normal tissue sparing from radiation damage upon ultra-high dose rate irradiation, known as the FLASH effect, has been widely reported in murine skin models, and translation of this type of radiotherapy to humans has already begun, with skin sparing being a primary outcome expected.This paper reviews the status of the field, focusing on proposed mechanisms and skin response assays, outlining what has become known in terms of input parameters that might control the magnitude of the FLASH effect.Results: Murine studies have largely focused on acute damage responses, developing over 3-8 weeks, to single doses of FLASH versus conventional irradiation (CONV), and data suggest that at dose rates above tens of Gray per second, with a total dose more than 20 Gy is where the induction of the FLASH effect occurs. Fractionated delivery appears possible, although fraction sizes of >17 Gy appear needed for sparing efficacy. The interplay between dose rate and total dose per fraction remains to be fully elucidated. Oxygen is a modulator of the efficacy, with both hypoxia and hyperoxia diminishing the FLASH effect. Measurements of transient changes in oxygen are possible and may be a marker of treatment efficacy.Taken together, the murine skin data provide important information for translational work, despite the associated limitations. Studies of later-term sparing effects as well as work on pig skin are needed to take the next step in assessing translational FLASH efficacy. Control of biological factors such as tissue oxygenation may be needed to understand and control the response.

    Keywords: Radiotherapy, Skin, FLASH radiotherapy, Dosimetry, Radiobiology, Radiation response biomarkers, radiation response

    Received: 09 Apr 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Pogue, Tavakkoli, Thomas, Hoopes and Jarvis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Brian W. Pogue, University of Wisconsin-Madison, Madison, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.