Flash radiotherapy (Flash-RT) is an innovative technique used in radiotherapy for cancer treatment because it delivers an extremely high dose of radiation (>40 Gy/s) to the tumour in a very short period of time, typically within a fraction of a second. This ultra-fast delivery of radiation distinguishes Flash-RT from conventional radiotherapy, which typically involves the delivery of radiation over a longer time period, often several minutes. Studies conducted in cell and preclinical models suggested that Flash-RT may spare normal tissues from radiation-related side effects, such as skin toxicity, gastrointestinal complications, and damage to organs-at-risk. This is believed to be due to the unique normal tissue response to the ultra-high dose rate. Nevertheless, while Flash-RT shows promising results in preclinical and early clinical studies, one should note that the technique is still in the early stages of development. This entry provides a comprehensive exploration of the immense potentials of Flash-RT, covering its background, mechanisms, radiation sources, recent experimental findings based on cell and preclinical models, and future prospects. It aims to provide valuable insights into this innovative radiotherapy technology for anyone interested in the subject.
The dose rate, which refers to the amount of radiation delivered per unit of time, is significantly different between the two approaches. Conventional radiotherapy typically operates at a dose rate ranging from 0.001 to 0.4 Gy/s, while Flash radiotherapy surpasses this with a much higher dose rate of over 40 Gy/s. This disparity in dose rate has implications for the irradiation time required. Conventional radiotherapy typically demands an irradiation time exceeding 120 seconds, whereas Flash radiotherapy achieves its therapeutic effect in less than 1 second. Both conventional and Flash radiotherapy demonstrate efficient tumor control, indicating their effectiveness in targeting and treating cancerous cells. However, there is a notable difference in the potential for normal tissue complications. Conventional radiotherapy carries a higher risk of normal tissue complications, while Flash radiotherapy is associated with a lower incidence of such complications. The mechanisms underlying the two techniques also differ. Conventional radiotherapy operates through mechanisms such as repair, re-oxygenation, redistribution, repopulation, oxygen depletion, and the generation of reactive oxygen species (ROS). In contrast, Flash radiotherapy relies on mechanisms such as oxygen depletion, the generation of ROS, and immunoinflammatory responses.
|Conventional Radiotherapy||Flash Radiotherapy|
|Radiation type||X-ray, gamma-ray, electron, proton, heavy-ion||X-ray, electron, proton, heavy-ion|
|Dose rate (Gy/s)||0.001–0.4||>40|
|Irradiation time (s)||>120||<1|
|Normal tissue complication||High||Low|
|Mechanism||Repair, re-oxygenation, redistribution, repopulation, oxygen depletion, ROS||Oxygen depletion, ROS, immunoinflammatory response|
Flash-RT is a relatively new concept in the field of radiotherapy. Its history can be traced back to the early 20th century when researchers observed certain notable effects of high-dose radiation . One of the earliest observations related to Flash-RT occurred in the late 1950s. Dewey and Boag reported on the phenomenon known as the Flash effect, which is now referred to as Flash-RT [. They conducted an experiment using ultra-high-dose-rate megavoltage X-rays to irradiate Serratia marcescens. The study demonstrated that the bacteria, when exposed to ultra-high dose rates (UHDRs) (10–20 krads/2 μs), exhibited lower radiosensitivity in a nitrogen–oxygen mixture compared to the situation when irradiated at normal dose rates (1 krads/min) in 100% nitrogen. This lower radiosensitivity corresponded to the response typically observed under anaerobic conditions. Such findings indicated that the radiosensitivity of Serratia marcescens was influenced by both the oxygen content and the dose rate of the radiation. Town  discovered that mammalian cells irradiated at an UHDR of 3.5 × 106 krad/s showed interesting results. When the cells received a dose of up to 1 krads, a single pulse had a higher survival rate compared to two pulses. The result from Town is supported by Berry et al.  who observed similar outcomes in their experiments with hamster and HeLa cells, using ultra-high-dose-rate irradiation of 1 krads for a 15 ns pulse.