FLASH Radiotherapy

“Cancer radiotherapy is a fast-evolving field, and a lot of research is currently being done to implement new technologies clinically,” says Magdalena Bazalova-Carter of the University of Victoria (UVic). “FLASH radiotherapy is currently one of the most exciting modalities and even though we don’t fully understand its mechanisms, it could revolutionize cancer radiotherapy.”

Bazalova-Carter will discuss the history of FLASH radiotherapy from the first in vitro experiments to contemporary ongoing clinical trials, at the SPIE Optics + Photonics symposium in San Diego.

What are some of your responsibilities as associate professor and Tier 2 Canada Research Chair in Medical Physics at the UVic?
As a Canada Research Chair, my primary responsibility is to conduct research in medical physics. I also teach undergraduate courses such as medical physics and nuclear physics and radioactivity, and I participate in university and professional organization committees. Additionally, I am the assistant director of our CAMPEP-accredited medical physics graduate program.

What led to your interest in physics and medical physics in particular?
I never enjoyed memorizing things in school and math and physics seem easy to me, so after high school I started my undergraduate degree at the Czech Technical University where I got my BSc and wrote a thesis in high-energy physics. While attending the Valencia Polytechnic University in Spain as an Erasmus student in my last year, I realized that my passion was in medical physics. I very much enjoyed Monte Carlo simulations of particle transport and knowing that my research could help treat cancer patients was extremely fulfilling.

How was FLASH radiotherapy developed?
Despite all letters being capitalized, FLASH is not an acronym; it simply means that radiation therapy is delivered in an ultrafast fashion.

FLASH radiotherapy was first observed in vivo by a group of scientists at Lausanne University Hospital (CHUV) in 2014. In their related paper in Science Translational Medicine, the authors demonstrated that, compared to conventional radiotherapy, ultrahigh dose-rate radiotherapy spares normal tissues and that its cancer-cell-killing potential is maintained. In later years, many other groups confirmed the effect, perhaps just not to the same magnitude as the first publication.

How would you describe “the FLASH effect?”
As mentioned above, the FLASH effect is described as the decrease in normal tissue toxicity, or radiation treatment side-effects, following ultrafast <500 ms radiotherapy delivery, while maintaining tumor control of conventional radiotherapy.

What are some of the challenges and advantages of FLASH?
There are many challenges in bringing FLASH radiotherapy into the clinic and perhaps this is one of the reasons why it’s such an exciting opportunity in cancer treatment. The first challenge is the ability to deliver radiation in an ultrafast fashion. Unfortunately, current clinical machines do not operate in the required ultrafast delivery mode, either at all or without significant modifications. Second, we need to make sure that FLASH is delivered safely. For example, if by accident the irradiation was longer than one second in conventional radiotherapy, this would likely result in a negligible increase in the delivered dose to the patient. In FLASH radiotherapy, however, a delay in terminating the beam of only one second could double or even triple the intended delivered radiation dose and potentially harm the patient. Another challenge of FLASH radiotherapy is that we are not certain if all cancer patients would benefit from it.

The main advantage of FLASH radiotherapy is the decreased normal-tissue toxicity. That could help in two scenarios. For those who are currently receiving curative doses of radiation, the magnitude of side effects could decrease, and patient’s quality of life would increase in return. Alternatively, cancer patients who currently cannot be treated with radiation due to the severe side-effects the treatment would cause, could become candidates for FLASH radiotherapy and their treatment options would improve.

How did you come to work with this project?
Somewhat surreptitiously, I would say. When the first FLASH study was published in 2014, I was working with Bill Loo at Stanford on treatment-planning optimization for rapid radiotherapy with very high-energy (VHEE) electron beams (>100 MeV). The goal was not FLASH radiotherapy, but to treat lung cancer patients within a single breath hold to ‘freeze’ respiratory motion. In 2015 I started my faculty position at UVic, and I was thinking about whether we could address the lack of FLASH radiation sources by means of VHEEs.

In discussions with researchers who had been developing a high-power 60 MeV electron beamline at TRIUMF, Canada's national particle accelerator center at University of British Columbia, I realized that there might be a potential to utilize their intermediate-energy 10 MeV beamline for FLASH research. Instead of working with low-energy electron beams that do not penetrate deep in tissue and cannot be used for treatments of most cancers, we decided we would try to convert the 10 MeV electron beam into a 10 MV photon beam that does reach deep-seated tumors.

In 2021, we built the first 10 MV photon ultrahigh dose-rate beamline in the world. As a by-product of this project, we also realized that we might be able to use conventional X-ray tubes for the delivery of FLASH radiotherapy with 160 kV X-rays and built a simple prototype system. This idea was implemented by XStrahl, Inc. who built a nice commercial product for preclinical FLASH research featuring two parallel-opposed X-ray tubes.

What do you see as the future for this technique?
We first need to be able to deliver ultrahigh dose-rate radiotherapy, and do so extremely accurately and safely. I am not fully convinced about the clinical importance of the decrease of side effects, however, I believe that ultrafast radiotherapy delivery, as long as it’s safe, will be beneficial to patients.

After proper setup, patients will be able to lay on the treatment table for a shorter time as the beam will be on for less than a second. Then, it’s possible that we will be able to create hypofractionated cancer treatments. This means that we could deliver radiation in a smaller number of sessions (5-10) compared to conventional radiotherapy that is in some cases delivered in up to 30 sessions over six weeks.