What is FLASH-RT and is it the Future of Radiation Therapy?

A compelling article, “Is FLASH The Future of Radiation Therapy?” was published in September 2023 by Aubrey Bloom, Communications Program Manager at MD Anderson Cancer Center.  

Radiation therapy has been used for over a century to treat cancer. Clinicians use fractioning to balance the benefits of administering high doses of radiation to the tumor while limiting damage to surrounding healthy tissue. In 2014, a study showed that ultra-high levels of radiation can produce the same anti-tumor effects as conventional radiation therapy with even less damage to normal tissue. This method is now known as FLASH-RT. It has been replicated in 30+ studies, and researchers are working to understand how to maximize its therapeutic potential.

Bloom’s article shares a fascinating encounter with radiation oncologist Steven Lin, M.D., Ph.D., who has written several FLASH studies and presented works at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting. Lin stated:

“There is still a lot to learn. We have to be careful and not let the excitement about the potential keep us from our careful approach in research. But if it continues to hold up, it could be a ‘holy grail’ of radiation therapy.”

How beneficial is FLASH-RT?

In his article, Bloom explains that a patient undergoing fractional radiation therapy needs to go through multiple treatments, each taking several minutes. But with FLASH-RT, the same amount of radiation can be delivered in higher-intensity bursts, often more than 300 times higher, than those which typically last less than a second. This means that patients may require fewer and shorter treatment sessions, and in some cases, just one session may suffice.

The major benefit of FLASH-RT is the “sparing effect,” which means that when the same dose of radiation is delivered at this intense rate, the surrounding tissue is saved from the typical level of damage while still killing the cancer cells at the tumor site. This not only reduces side effects for the patient but also opens up opportunities to administer higher doses of radiation than previously possible.

By sparing the normal tissue, clinicians can more effectively dose and kill the tumors. FLASH-RT may also have a positive impact on the immune system, potentially increasing the effectiveness of cancer therapies.

Electron beams were used in the earliest research on FLASH-RT; however, electrons do not penetrate deeply into tissue, and treatment was limited.  When proton beams were used for ultra-high dose-rate radiation, tumor penetration was sufficiently reached in most patients.

Clinicians are excited about the potential to use FLASH-RT in combination therapies. Since there is significantly less damage to the surrounding immune cells or lymphocytes, there is potential for a much stronger response to immunotherapies. This could significantly augment the benefits of treatments like immunotherapy for cancer patients. Lin says,

“There is tremendous potential for this to really augment the benefit of treatments like immunotherapy for cancer patients.”

 What are the risks of FLASH-RT?

Despite overwhelming evidence, the mechanism behind FLASH-RT remains a mystery, with multiple theories and contributing factors. Lin states,

“Understanding the mechanics and the biology more so that we can design approaches to ensure treatments are safe and effective is a major priority. There are many aspects of FLASH-RT that are still being tested and manipulated to understand how to make it more effective. There are still lots of unknowns about how ultra-high dose radiation impacts not only tumors but the tumor microenvironment. There are some potentially interesting implications to the entire body that expand beyond just the tumor itself.”

To read Aubrey Bloom’s full article, click here. Another article citing the first human trial at the University of Cincinnati can be found here.