[author: Pam Koenig]
More than half of all cancer patients are treated with radiation therapy and may incur acute and chronic toxicities to normal tissue, leading to debilitating side effects. Researchers at the University of California-Irvine and Switzerland’s Lausanne University Hospital may have found an answer to this dilemma.
A cutting edge radiation therapy technique called FLASH radiotherapy has the potential to reduce the adverse effects of cancer radiation therapy while maintaining the therapeutic effects and survival benefits of conventional radiotherapy. FLASH radiotherapy involves the ultra-fast delivery of radiation treatment [RT] at dose rates several orders of magnitude greater than those currently used in clinical practice. The entire RT treatment, or large fraction doses, can be delivered in parts of a second, compared to several minutes for conventional-RT.
Montay-Gruel and colleagues found that in mice with glioblastoma, FLASH-RT was comparable to conventional-RT in treatment effectiveness and survival rates and was shown to significantly spare radiation-induced cognitive deficits in learning and memory. Scientists believe that the extremely short time of exposure made possible by FLASH-RT is the key: the fleeting burst of radiation from FLASH interacting with levels of oxygen in healthy tissues leads to an increase in radiation resistance and protects the normal tissues.
Thus, FLASH-RT opens the door to potentially deliver higher curative doses to tumor cells to overcome tumor radiation resistance — meaning that FLASH-RT may allow patients to receive a greater total dose of radiation before the really toxic side effects start.
The FLASH effect is not a new idea, but the technology has seen a resurgence of interest in the last few years. In addition to the current study, the FLASH effect has been confirmed recently by several additional studies. And while FLASH delivery technology does not yet exist for humans, low energy electrons and proton beam therapy methods are being investigated. Groups around the world are working on machines to deliver FLASH-RT; one device is awaiting approval in the U.S. and Europe, and there are plans to use it in two clinical trials at the Lausanne University Hospital early next year.
As with anything, there are limitations. It has only been significantly studied in preclinical settings, and randomized controlled trials with FLASH-RT and conventional-RT arms are needed.
But overall, the consistency of the normal tissue protection among animal species, the magnitude of this benefit, and the excellent anti-tumor effects observed so far, all suggest that the FLASH effect could also be reproduced in human patients and encourage the testing of this hypothesis in clinical trials. If its limitations can be overcome, FLASH-RT could be a powerful additional tool in cancer treatment management in the future, providing a revolutionary tumor treatment and a better quality of life for patients.
Links to Science Daily news article and cited study:
University of California — Irvine. Cancer treatment without side effects? Researchers eliminate brain tumors without damaging cognition. Science Daily. Copyright Oct. 27, 2020. https://www.sciencedaily.com/releases/2020/10/201027133715.htm
Montay-Gruel P, Acharya MM, Gonçalves Jorge P, et al. Hypo-fractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice. Clin Cancer Res. Oct. 12, 2020: Epub. https://clincancerres.aacrjournals.org/content/early/2020/10/15/1078-0432.CCR-20-0894
Links to other articles:
Bourhis J, Montay-Gruel P, Gonçalves Jorge P, et al. Clinical translation of FLASH radiotherapy: Why and how? Radiother Oncol. 2019; 139:11–17.
https://www.thegreenjournal.com/article/S0167-8140(19)30360-3/fulltext
Bourhis J, Sozzi WJ, Gonçalves Jorge P, et al. Treatment of a first patient with FLASH radiotherapy. Radiother Oncol. 2019; 139: 18–22.
https://www.thegreenjournal.com/article/S0167-8140(19)32959-7/fulltext
Hughes JR, Parsons JL. FLASH radiotherapy: Current knowledge and future insights using proton-beam therapy. Int J Molec Sci. 2020; 21(18): Epub.
https://www.mdpi.com/1422-0067/21/18/6492
Maxim PG, Keal P, Jing C. FLASH radiotherapy: Newsflash or flash in the pan? Med Physics. 2019; 46(10):4287–4290.
https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/mp.13685
Wilson JD, Hammond EM, Higgins GS, Petersson K. Ultra-high dose rate (FLASH) radiotherapy: Silver bullet or fool’s gold? Front Oncol. Oct. 17, 2020: Epub.
https://www.frontiersin.org/articles/10.3389/fonc.2019.01563/full
Corrigendum https://www.frontiersin.org/articles/10.3389/fonc.2020.00210/full
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