Is FLASH the future of radiation therapy?

Since radiation therapy was first used to treat cancer over a century ago, clinicians have sought the right balance between maximizing the dosage for the best possible benefit and limiting damage to normal tissue. That research led to the current practice of fractioning, which is when a patient receives several partial treatments until the whole radiation dose is administered.

But in 2014, a breakthrough study showed that intense exposure to ultra-high levels of radiation allowed for the same anti-tumor effects but with significantly less damage to normal tissue. When used in radiation therapy, this method is now known as FLASH-RT.

Although these findings were initially met with skepticism, almost a decade later, they have been replicated in over 30 studies in different types of tissue, in different models and in different methods of radiation delivery. Now, researchers are working to understand the underlying mechanisms of how and why it works, and how to maximize the therapeutic potential of FLASH-RT in patients.

For the latest on FLASH-RT, we talked to radiation oncologist Steven Lin, M.D., Ph.D., who has authored several studies on FLASH, including work being presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting.

“There is still a lot to learn,” Lin says. “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.”

What exactly is FLASH-RT, and what is the benefit?

Currently, a patient receiving fractional radiation therapy undergoes several treatments, each taking several minutes. FLASH-RT delivers that same amount of radiation, but in higher intensity bursts usually lasting less than a second. This could mean fewer, and shorter, treatment sessions for patients, for some cases it could be as few as one session.

While this is more convenient for the patient, the major benefit is what is called the sparing effect. When the same dose of radiation is delivered at this intense rate, surrounding tissue is spared from the usual level of damage. 

Even on its own, this would be an important finding. It would allow for the same level of benefit while reducing side effects, but it also opens the door to higher doses of radiation than were previously possible.

“Sparing the normal tissue allows us to more effectively dose and kill the tumors themselves,” Lin says. “There is also some indication that FLASH-RT could impact the immune system in a positive way that could itself increase the effectiveness of cancer therapies.”

Clinicians are also excited about the potential to use FLASH in combination therapies. Because there is significantly less damage to surrounding immune cells, or lymphocytes, there is potential for a much stronger response to immunotherapies.

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

What are the risks or concerns about FLASH radiation therapy?

Even though there is overwhelming and still mounting evidence that FLASH-RT works, how it works is largely still a mystery. Several theories exist, and we think several factors likely contribute. 

“Understanding the mechanics and the biology more so that we can design approaches to ensure treatments are safe and effective is a major priority,” says Lin. “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.”

How close are we to being able to use FLASH-RT to treat more patients?

A natural question about FLASH is why it took this long to test the idea. Conceptually, the idea seems simple enough. But technically, it presents challenges, limiting its study to primarily major research institutions like MD Anderson.

“There are still lots of physics being worked on so that doses can be accurately measured and delivered to ensure safety,” Lin says. “We are fortunate to have access to multiple versions of FLASH-RT, including protons and electrons, which has allowed us to do significant preclinical experiments.”

One such study is being presented at ASTRO by Chike Abana, M.D., Ph.D., He will present preclinical findings of the short-term safety of FLASH on the surface of the skin.

Early-phase clinical trials are underway this year at MD Anderson, though at this point they’re exclusive to skin cancers. According to Lin, FLASH-RT for deeper tumors is on the way.

“It’s definitely a future goal to utilize not only proton FLASH, which is already being explored clinically, but also very high energy electrons and photons to allow translation to more deep-seated tumors, which would really open up the clinical uses for this technology,” Lin says.

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