Article, 2024

Navigating the Critical Translational Questions for Implementing FLASH in the Clinic

Seminars in Radiation Oncology, ISSN 1532-9461, 1053-4296, Volume 34, 3, Pages 351-364, 10.1016/j.semradonc.2024.04.008

Contributors

Loo, Billy Wiseman (Corresponding author) [1] Verginadis, Ioannis I 0000-0002-0755-4511 [2] Sørensen, Brita Singers 0000-0002-3955-4735 [3] Mascia, Anthony E 0000-0002-4819-3062 [4] Perentesis, John Peter 0000-0002-4237-8226 [4] Koong, Albert C 0000-0001-9824-1643 [5] Schüler, Emil [5] Rankin, Erinn Bruno 0000-0002-2045-2296 [1] Maxim, Peter Gregor [6] Limoli, Charles L 0000-0002-1321-4142 [6] Vozenin, Marie-Catherine 0000-0002-2109-8073 [7] [8] [9]

Affiliations

  1. [1] Stanford University
    2. [NORA names: United States; America, North; OECD];
  2. [2] University of Pennsylvania
    3. [NORA names: United States; America, North; OECD];
  3. [3] Aarhus University Hospital
    4. [NORA names: Central Denmark Region; Hospital; Denmark; Europe, EU; Nordic; OECD];
  4. [4] University of Cincinnati
    5. [NORA names: United States; America, North; OECD];
  5. [5] The University of Texas MD Anderson Cancer Center
    6. [NORA names: United States; America, North; OECD];

Abstract

The "FLASH effect" is an increased therapeutic index, that is, reduced normal tissue toxicity for a given degree of anti-cancer efficacy, produced by ultra-rapid irradiation delivered on time scales orders of magnitude shorter than currently conventional in the clinic for the same doses. This phenomenon has been observed in numerous preclinical in vivo tumor and normal tissue models. While the underlying biological mechanism(s) remain to be elucidated, a path to clinical implementation of FLASH can be paved by addressing several critical translational questions. Technological questions pertinent to each beam type (eg, electron, proton, photon) also dictate the logical progression of experimentation required to move forward in safe and decisive clinical trials. Here we review the available preclinical data pertaining to these questions and how they may inform strategies for FLASH cancer therapy clinical trials.

Keywords

FLASH effect, anti-cancer efficacy, beam, beam type, biological mechanism(s, cancer therapy clinical trials, clinic, clinical implementation, clinical trials, criticism, data, degree, dose, effect, efficacy, experimentation, flash, increased therapeutic index, index, irradiation, logical progression, magnitude, mechanism(s, normal tissue toxicity, order, phenomenon, preclinical data, questions, reducing normal tissue toxicity, scaling order, technological questions, therapeutic index, time, time scale orders, tissue toxicity, toxicity, translational questions, trials, tumor, type

Funders

  • National Cancer Institute
  • Oncosuisse
  • Siemens (United States)
  • Swiss National Science Foundation

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