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FLASH radiotherapy (FLASH-RT) is a technology that could modify the way radiotherapy is delivered in the future. This technique involves the ultra-fast delivery of radiotherapy at dose rates several ...orders of magnitude higher than those currently used in routine clinical practice. This very short time of exposure leads to the striking observation of relative protection of normal tissues that are exposed to FLASH-RT as compared with conventional dose rate radiotherapy. Here we summarise the current knowledge about the FLASH effect and provide a synthesis of the observations that have been reported on various experimental animal models (mice, zebrafish, pig, cats), various organs (lung, gut, brain, skin) and by various groups across 40 years of research. We also propose possible mechanisms for the FLASH effect, as well as possible paths for clinical application.
•FLASH radiotherapy (FLASH-RT) is a technology that could modify the way radiotherapy is delivered in the future.•Ultra-fast delivery of RT at dose rates several orders of magnitude higher than the ones currently used in clinical practice.•This very short time of exposure leads to the striking observation of relative protection of normal tissues after FLASH-RT.
The ultimate goal of radiation oncology is to eradicate tumours without toxicity to non-malignant tissues. FLASH radiotherapy, or the delivery of ultra-high dose rates of radiation (>40 Gy/s), ...emerged as a modality of irradiation that enables tumour control to be maintained while reducing toxicity to surrounding non-malignant tissues. In the past few years, preclinical studies have shown that FLASH radiotherapy can be delivered in very short times and substantially can widen the therapeutic window of radiotherapy. This ultra-fast radiation delivery could reduce toxicity and thus enable dose escalation to enhance antitumour efficacy, with the additional benefits of reducing treatment time and organ motion-related issues, eventually increasing the number of patients who can be treated. At present, FLASH is recognized as one of the most promising breakthroughs in radiation oncology, standing at the crossroads between technology, physics, chemistry and biology; however, several hurdles make its clinical translation difficult, including the need for a better understanding of the biological mechanisms, optimization of parameters and technological challenges. In this Perspective, we provide an overview of the principles underlying FLASH radiotherapy and discuss the challenges along the path towards its clinical application.
•FLASH-RT a paradigm-shifting method of delivering doses within an extremely short irradiation time.•FLASH-RT is a promising new tool to enhance the differential effect between tumors and normal ...tissues.•The consistency of the preclinical data clinical justifies transfer of FLASH-RT.•The most relevant parameters for FLASH are the combination of dose, dose-rate within the pulse, and overall time of irradiation.•A first proof of concept could be done with low-energy electrons and further tested with VHEE, protons and X-rays.
Over the past decades, technological advances have transformed radiation therapy (RT) into a precise and powerful treatment for cancer patients. Nevertheless, the treatment of radiation-resistant tumors is still restricted by the dose-limiting normal tissue complications. In this context, FLASH-RT is emerging in the field. Consisting of delivering doses within an extremely short irradiation time, FLASH-RT has been identified as a promising new tool to enhance the differential effect between tumors and normal tissues. Indeed, preclinical studies on various animal models and a veterinarian clinical trial have recently shown that compared to conventional dose-rate RT, FLASH-RT could control tumors while minimizing normal tissue toxicity.
In the present review, we summarize the main data supporting the clinical translation of FLASH-RT and explore its feasibility, the key irradiation parameters and the potential technologies needed for a successful clinical translation.