Abstract
FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying mechanism(s) responsible for the FLASH effect are yet to be fully elucidated, but a prominent role for oxygen tension and reactive oxygen species production is the most current valid hypothesis. The FLASH effect has been confirmed in many studies in recent years, both in vitro and in vivo, with even the first patient with T-cell cutaneous lymphoma being treated using FLASH radiotherapy. However, most of the studies into FLASH radiotherapy have used electron beams that have low tissue penetration, which presents a limitation for translation into clinical practice. A promising alternate FLASH delivery method is via proton beam therapy, as the dose can be deposited deeper within the tissue. However, studies into FLASH protons are currently sparse. This review will summarize FLASH radiotherapy research conducted to date and the current theories explaining the FLASH effect, with an emphasis on the future potential for FLASH proton beam therapy.
Highlights
Radiotherapy using X-rays is a main treatment strategy employed to combat human tumors, with ~50% of all cancer patients receiving radiotherapy
FLASH radiotherapy is an exciting new treatment strategy that has the potential to change the future of clinical cancer treatment
The use of ultra-high dose rates several orders of magnitude higher than conventional dose rates generates a phenomenon known as the “FLASH effect”, through which sparing of normal healthy tissue is observed, while maintaining equivalent tumor control properties compared to conventional dose-rate radiotherapy
Summary
Radiotherapy using X-rays (photons) is a main treatment strategy employed to combat human tumors, with ~50% of all cancer patients receiving radiotherapy. The major drawback of radiotherapy treatment is that in order to deliver a lethal dose to cancerous cells, short- and long-term adverse side-effects are evident due to the irradiation of the surrounding normal healthy tissues that can severely impact the health and quality of life of the cancer patient [1,2,3]. This occurs because radiotherapy uses an external radiation beam where the dose decreases exponentially but which can deposit energy within a certain depth of the patient tissue [4]. Before this can happen though, it is critical that the underlying biological mechanisms and optimal beam delivery parameters are realized, as these currently remain largely uncovered
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