A FLASH of Insight: Breakthrough reveals that ultra-short, high-dose proton irradiation enhances cell survival

Osaka, Japan - Proton beam therapy, a type of radiation therapy, possesses a physical property known as the Bragg peak, which causes the beam to exert its strongest effect at a specific depth, with no effect beyond that point. This characteristic allows for a higher concentration of the dose on tumors located deep within the body, making it a promising cancer treatment method.

However, in some cases, the dose limit to surrounding healthy tissue necessitates a compromise in the tumor's radiation dosage or may even cause proton beam therapy to have to be abandoned altogether. Therefore, developing irradiation technologies that can further reduce the dose to normal tissues is a pressing issue.

In recent years, it has been reported that in radiation therapy, when the dose rate (the amount of radiation delivered per unit time) is extremely high, specifically more than 400 times the normal dose rate, a phenomenon occurs in which cell survival rate is increased, minimizing damage to normal tissues while maintaining local control of the tumor. This phenomenon, which results from the instantaneous delivery of radiation, is called the "FLASH effect" and has gained global attention.

Until recently, it was believed that increased cell survival rates with ultra-short proton beam irradiations only occurred under hypoxic conditions, as it had not yet been demonstrated whether cell survival rates increase with ultra-short proton irradiation under normal oxygen conditions.

However, a team of researchers from Kazuhiko Ogawa’s laboratory led by Osaka University was the first in the world to demonstrate that cell survival rates increase even under normoxic conditions with ultra-short irradiation by using Sumitomo Heavy Industries' new superconducting AVF cyclotron, which enables ultra-short, high-dose proton irradiation.

"There are very few experimental devices worldwide that can perform ultra-high dose rate irradiation, which made securing the necessary irradiation environment a significant challenge," says lead author Masashi Yagi. "The FLASH effect is a game-changer in radiation therapy, and unraveling its mechanisms will greatly advance the field of radiological science," says corresponding author Kazumasa Minami.

This research deepens the understanding of the mechanisms behind the FLASH effect and is expected to lead to the development of a cancer treatment method, known as FLASH proton therapy, that produces fewer side effects. FLASH proton therapy combines the physical characteristics of proton beams, which allow for high dose concentration on tumors, with the biological effects of the FLASH effect, which reduces damage to normal tissues. This synergy is anticipated to result in higher local control rates and lower side effect incidences than ever before.

“Our research group will continue to push forward with this work, contributing a new chapter to the 130-year history of radiation therapy from Japan as we strive to develop better radiation treatment methods." says senior author Shinichi Shimizu.

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The article, “Sparing Effect on Cell Survival Under Normoxia Using Ultra-high Dose Rate Proton Beams from a Compact Superconducting AVF Cyclotron,” was published in Anticancer Research at DOI: https://doi.org/10.21873/anticanres.17255

About Osaka University
Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Website: https://resou.osaka-u.ac.jp/en