Navigating the Critical Translational Questions for Implementing FLASH in the Clinic

Billy W Loo Jr; Ioannis I Verginadis; Brita Singers Sørensen; Anthony E Mascia; John P Perentesis; Albert C Koong; Emil Schüler; Erinn B Rankin; Peter G Maxim; Charles L Limoli; Marie-Catherine Vozenin

doi:10.1016/j.semradonc.2024.04.008

Navigating the Critical Translational Questions for Implementing FLASH in the Clinic

Semin Radiat Oncol. 2024 Jul;34(3):351-364. doi: 10.1016/j.semradonc.2024.04.008.

Affiliations

¹ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA. Electronic address: BWLoo@stanford.edu.
² Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
³ Danish Centre for Particle Therapy & Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
⁴ Division of Oncology, Cincinnati Children's Hospital and Departments of Pediatrics and Radiation Oncology, College of Medicine, University of Cincinnati, Cincinnati, OH.
⁵ Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
⁶ Department of Radiation Physics, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
⁷ Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA.
⁸ Department of Radiation Oncology, University of California, Irvine School of Medicine, Irvine, CA.
⁹ Secteur Radio-Oncologie et Radiobiologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland; LiRR - laboratory of innovation in radiobiology applied to radiotherapy, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Laboratory of Radiation Oncology, Radiation Oncology Service, Department of Oncology, CHUV Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

PMID: 38880544
DOI: 10.1016/j.semradonc.2024.04.008

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.

Publication types

Review

MeSH terms

Animals
Clinical Trials as Topic
Humans
Neoplasms* / radiotherapy
Radiation Oncology / methods
Translational Research, Biomedical*

Grants and funding

R01 CA233958/CA/NCI NIH HHS/United States