Radiation therapy is an important component of cancer treatment, with about 50% of all cancer patients requiring it at some point through the course of their illness (Basker et al. 2012). Despite being critical in current cancer treatment schemes, it carries risks due to its tendency to damage nearby cells while destroying cancer cells. This means that the elimination of cancerous tissue is limited by the dose of radiation that the patient can receive without the risk of severe radiation-induced effects (Chow and Ruda 2023). Because of this limitation, a significant proportion of research in radiotherapy is aimed towards minimizing damage to nearby healthy tissue during the targeting of cancer cells (Majeed and Gupta 2023)).
Flash Radiotherapy (FLASH-RT) is an emerging technology that could overcome the limitations of conventional radiotherapy by delivering doses of radiation several orders of magnitude higher than that of conventional radiotherapy, at ultrafast speeds typically within a fraction of a second (Chow and Ruda 2023). The term FLASH was coined by a 2014 research paper by Fauvadon et al. that defined FLASH as irradiating dose greater than 40 Gray per second (Gy/s; a unit representing the delivery of one joule of ionizing radiation energy per kilogram of matter per second). In vitro studies suggest that ultrafast pulses of radiation elicit less genomic instability than continuous prolonged radiation with the same total dose, sparing normal tissues from radiation-related side effects like skin toxicity and damage to organs-at-risk (Fauvadon et al. 2014).
The main advantage of FLASH-RT is therefore its ability to selectively damage cancer cells while minimizing damage to surrounding local tissue (Matuszak et al. 2022). It does this by exploiting the difference in response to ultrahigh doses of radiation between tumour cells and normal tissue. This phenomenon called the Flash effect was initially observed in 1959 when Dewey and Boag observed that a species of bacteria (Serratia marcescens) exhibited lower radiosensitivity when exposed to ultrahigh dose rates of megavoltage X-rays in a nitrogen-oxygen mixture than a normal dose rate in 100% oxygen.
Bibliography
Baskar, Rajamanickam, Kuo Ann Lee, Richard Yeo, and Kheng-Wei Yeoh. 2012. “Cancer and Radiation Therapy: Current Advances and Future Directions.” International Journal of Medical Sciences 9 (3): 193–99. https://doi.org/10.7150/ijms.3635.
Chow, James C. L., and Harry E. Ruda. 2023. “Flash Radiotherapy: Innovative Cancer Treatment.” Encyclopedia 3 (3): 808–23. https://doi.org/10.3390/encyclopedia3030058.
DEWEY, D. L., and J. W. BOAG. 1959. “Modification of the Oxygen Effect When Bacteria Are Given Large Pulses of Radiation.” Nature 183 (4673): 1450–51. https://doi.org/10.1038/1831450a0.
Favaudon, Vincent, Laura Caplier, Virginie Monceau, et al. 2014. “Ultrahigh Dose-Rate FLASH Irradiation Increases the Differential Response Between Normal and Tumor Tissue in Mice.” Science Translational Medicine 6 (245). https://doi.org/10.1126/scitranslmed.3008973.
Majeed, H, and V Gupta. 2023. “Adverse Effects of Radiation Therapy.” Europepmc.Org, August 14. https://europepmc.org/article/nbk/nbk563259.
Matuszak, Natalia, Wiktoria Maria Suchorska, Piotr Milecki, et al. 2022. “FLASH Radiotherapy: An Emerging Approach in Radiation Therapy.” Reports of Practical Oncology and Radiotherapy 27 (2): 343–51. https://doi.org/10.5603/rpor.a2022.0038.
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