FLASH ultra-high dose rates in radiotherapy: preclinical and radiobiological evidence

Abstract

Purpose

Flash radiotherapy (FLASH-RT) is currently being regarded as the next breakthrough in radiation treatment of cancer, delivering ultrahigh radiation doses in a very short time, and sparing normal tissues from detrimental injury. Here we review the current evidence on the preclinical findings as well as the radiobiological mechanisms underlying the FLASH effect. We also briefly examine the scenario of available technologies for delivering FLASH dose-rates for research and their implications for future clinical use.

Conclusions

Preclinical studies report that the FLASH-RT reduces radiation-induced toxicity whilst maintaining an equivalent tumor response across different animal models. However, the molecular radiobiology underlying FLASH effect is not fully understood and further experiments are necessary to understand the biological response. Future studies also includes the design of a FLASH delivery system able to produce beams appropriate for treatment of tumors with ultra-high dose rates. All these research activities will greatly benefit from a multidisciplinary collaboration across biology, physics and clinical oncology, increasing the potential of a rapid clinical translation of FLASH-RT.

Keywords:

• Radiotherapy
• FLASH effect
• preclinical evidence
• radiobiology
• devices

Disclosure statement

The authors report no conflict of interest.

Additional information

Notes on contributors

Andrea Borghini

Andrea Borghini, MSc, PhD, is a Postodctoral Researcher at the Molecular Epidemiology and Genetics Unit, Institute of Clinical Physiology, National Research Council (CNR-IFC), Pisa, Italy

Cecilia Vecoli

Cecilia Vecoli, MSc, PhD, is a Researcher at the Molecular Epidemiology and Genetics Unit, Institute of Clinical Physiology, National Research Council (CNR-IFC), Pisa, Italy

Luca Labate

Luca Labate, MSc, PhD, is a Researcher at the Intense Laser Irradiation Laboratory, National Institute of Optics, National Research Council (CNR-INO), Pisa, Italy

Daniele Panetta

Daniele Panetta, MSc, MPE, is a Researcher at the Micro-PET/CT Imaging Laboratory of Institute of Clinical Physiology, National Research Council (CNR-IFC), Pisa, Italy

Maria Grazia Andreassi

Maria Grazia Andreassi, MSc, PhD, is a Research Director and Group Leader of the Molecular Epidemiology and Genetics Unit, Institute of Clinical Physiology, National Research Council (CNR-IFC), Pisa, Italy

Leonida A. Gizzi

Leonida A. Gizzi, MSc, PhD, is a Research Director and Group Leader of the Intense Laser Irradiation Laboratory at the National Institute of Optics, National Research Council (CNR-INO), Pisa, Italy