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Review
. 2020 Jan 17:9:1563.
doi: 10.3389/fonc.2019.01563. eCollection 2019.

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

Joseph D Wilson  1 , Ester M Hammond  1 , Geoff S Higgins  1 , Kristoffer Petersson  1   2
Affiliations
Review

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

Joseph D Wilson et al. Front Oncol. .

Erratum in

Abstract

Radiotherapy is a cornerstone of both curative and palliative cancer care. However, radiotherapy is severely limited by radiation-induced toxicities. If these toxicities could be reduced, a greater dose of radiation could be given therefore facilitating a better tumor response. Initial pre-clinical studies have shown that irradiation at dose rates far exceeding those currently used in clinical contexts reduce radiation-induced toxicities whilst maintaining an equivalent tumor response. This is known as the FLASH effect. To date, a single patient has been subjected to FLASH radiotherapy for the treatment of subcutaneous T-cell lymphoma resulting in complete response and minimal toxicities. The mechanism responsible for reduced tissue toxicity following FLASH radiotherapy is yet to be elucidated, but the most prominent hypothesis so far proposed is that acute oxygen depletion occurs within the irradiated tissue. This review examines the tissue response to FLASH radiotherapy, critically evaluates the evidence supporting hypotheses surrounding the biological basis of the FLASH effect, and considers the potential for FLASH radiotherapy to be translated into clinical contexts.

Keywords: FLASH; hypoxia; immune; normal tissue; radiotherapy.

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Figures

Figure 1
Figure 1
(Ideal) Pulsed FLASH-RT delivery. A schematic view of a pulsed beam delivery, specifying some parameters which seems to be important for inducing the FLASH effect.
Figure 2
Figure 2
The oxygen depletion hypothesis. The relationship between oxygen tension (horizontal axis) and radiation sensitivity (vertical axis) is shown schematically and has been widely reported (40, 41). In response to FLASH-RT, the physiological level of oxygen (physoxic) found in normal tissues decreases rapidly (pink arrow) and has an important impact on radiation sensitivity. This temporary or transient hypoxia protects the normal tissues as radiation resistance increases. In contrast, oxygen levels are low (hypoxic) in tumor tissues and consequently FLASH-RT has less of an impact on radiation sensitivity.
See this image and copyright information in PMC

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