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Review
. 2022 Jun;49(6):4099-4108.
doi: 10.1002/mp.15623. Epub 2022 Apr 25.

A roadmap to clinical trials for FLASH

Paige A Taylor  1 , Jean M Moran  2 , David A Jaffray  1 , Jeffrey C Buchsbaum  3
Affiliations
Review

A roadmap to clinical trials for FLASH

Paige A Taylor et al. Med Phys. 2022 Jun.

Abstract

While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As FLASH clinical trials are designed, it will be important to ensure we can deliver dose consistently and safely to every patient. Much like hyperthermia and proton therapy, FLASH is a promising new technology that will be complex to implement in the clinic and similarly will require customized credentialing for multi-institutional clinical trials. There is no doubt that FLASH seems promising, but many technologies that we take for granted in conventional radiation oncology, such as rigorous dosimetry, 3D treatment planning, volumetric image guidance, or motion management, may play a major role in defining how to use, or whether to use, FLASH radiotherapy. Given the extended time frame for patients to experience late effects, we recommend moving deliberately but cautiously forward toward clinical trials. In this paper, we review the state of quality assurance and safety systems in FLASH, identify critical pre-clinical data points that need to be defined, and suggest how lessons learned from previous technological advancements will help us close the gaps and build a successful path to evidence-driven FLASH implementation.

Keywords: FLASH; advanced technology; clinical trials; quality assurance; radiation therapy; ultra-high dose rate.

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Conflict of interest statement

Dr. Buchsbaum reports none.

Dr. Jaffray reports royalties from Beaumont Hospital/Elekta/Varian (RT cone‐beam CT), University Health Network/Elekta (SRS/SRT cone‐beam CT), University Health Network/Raysearch (deformation modeling), University Health Network/Modus (QA phantoms), and University Health Network/Precision X‐ray (small animal irradiator). He holds 26 US and 21 foreign patents (12 are/were licensed) and has another 8 inventions active in the patent process in the domain of radiation oncology and cancer treatment. He currently has no active research agreements and no consulting arrangements with industry.

Dr. Moran reports funding within the past year from the National Institute of Health, Blue Cross Blue Shield of Michigan, and Varian Medical Systems. Dr. Moran is part of a patent application related to dosimetry measurements (PCT/US2020/032385).

Ms. Taylor reports funding from the National Institute of Health grant CA180803.

Figures

FIGURE 1
FIGURE 1
For each of the technical components of FLASH RT, we provide guidance on whether standard RT tools and workflow are sufficient or new technology and processes need to be developed. For trials during the early stages of UHDR use, it may be prudent to expand credentialing activities and to capture time‐related data. (Adapted from AAPM Task Group 113 on Physics practice standards for (conventional) clinical trials).
FIGURE 2
FIGURE 2
A roadmap highlighting key components that will be needed to successfully conduct Phase II/III clinical trials in humans. Many of the technological issues are being actively addressed, while preclinical trials are still being organized and standardized. This is contingent on reasonable understanding of the tumor and normal tissue biology within the study
FIGURE 3
FIGURE 3
NCI annual funding support of FLASH related research can be viewed by the public on the website reporter.nih.gov. Shown are two screen captures from that website. Capture “a” is dated in June 2021 and “b” from January 2022. Both are from a search on keywords “FLASH” and “radiation therapy.” We defer to the reader to explore other global funding agencies’ data as publicly available
See this image and copyright information in PMC

References

    1. Montay‐Gruel P, Petersson K, Jaccard M, et al. Irradiation in a flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s. Radiother Oncol. 2017;124(3):365‐369. 10.1016/J.RADONC.2017.05.003 - DOI - PubMed
    1. Zhang Q, Cascio E, Li C, et al. FLASH investigations using protons: design of delivery system, preclinical setup and confirmation of FLASH effect with protons in animal systems. Radiat Res. 2020;194(6):656‐664. 10.1667/RADE-20-00068.1 - DOI - PubMed
    1. Cunningham S, McCauley S, Vairamani K, et al. FLASH proton pencil beam scanning irradiation minimizes radiation‐induced leg contracture and skin toxicity in mice. Cancers (Basel). 2021;13(5):1‐15. 10.3390/CANCERS13051012 - DOI - PMC - PubMed
    1. Sax K. The time factor in x‐ray production of chromosome aberrations. Proc Natl Acad Sci U S A. 1939;25(5):225. 10.1073/PNAS.25.5.225 - DOI - PMC - PubMed
    1. Kirby‐Smith JS, Dolphin GW. Chromosome breakage at high radiation dose‐rates. Nature. 1958;182(4630):270‐271. 10.1038/182270a0 - DOI - PubMed