By Tammy McCausland
This blog post is modified from an article that appeared in Radiation Oncology News for Administrators Vol 32 No 4.
In 1959, D. L. Dewey and J. W. Boag first reported FLASH radiotherapy (FLASH-RT), a novel radiotherapy technology defined as a single ultra-high dose-rate (≥ 40 Gy/s) radiotherapy.1 They called it the “flash effect.”1
Over the past decade early promising study results in the U.S. and abroad show that FLASH-RT has a sparing effect on normal tissue for reasons researchers don’t understand definitively. FLASH-RT appears to be a promising technology for its ability to limit damage to normal tissue.
The equipment being used to do FLASH-RT is registered as an investigation under the U.S. Food & Drug Administration (FDA) with an investigational device exemption (IDE). The FDA requires a 10-person limit for initial studies until the researchers gather sufficient preliminary data.
The Cincinnati Children’s Hospital Medical Center/University of Cincinnati Medical Center Proton Therapy Center conducted the world’s first human trial (FAST-01) of FLASH-RT.2 The FAST-01 trial, which included 10 patients, focused on feasibility and safety. “We chose patients with metastatic tumors in the extremities [the limbs] because they have known metastatic disease and, unfortunately, most have a fairly limited life expectancy,” says John C. Breneman, MD, medical director of the center, University of Cincinnati Cancer Center member, and professor emeritus in the Department of Radiation Oncology in the University of Cincinnati’s College of Medicine. “Harm that might be caused in a patient who has a limited lifespan isn’t as significant as harm in a person who’s going to live for 20 years. We chose the extremities because the harm that could be caused there would be limited to things like skin and bone and potentially muscle.”
The FAST-01 trial results were reported at ASTRO’s 2022 annual meeting. Breneman and his research team are conducting a similar follow-up trial—also with 10 patients—this time focused on treating tumors in the thorax.
Researchers at Penn Medicine’s Abramson Cancer Center are also investigating FLASH-RT. In March 2022, Penn Medicine received a $12.3 million, five-year National Institutes of Health
(NIH) grant to study ultra-fast, high-dose FLASH radiotherapy.3 Penn Medicine hopes to launch human clinical trials in a year or so, based on the preclinical work it’s doing with the NIH PO1 grant. “Most of the work being done under the PO1 grant is to understand what the mechanism of action is in different scenarios, with different types of tumors, in different types of animals,” says James Metz, MD, chair of Radiation Oncology and leader of the Roberts Proton Therapy Center at Penn. “We’re also looking at some effects of conventional, electron FLASH versus carbon FLASH versus proton FLASH, and comparing those things to see how we deliver the optimal treatment.”
FLASH-RT’s ultra-high dosage requires that clinical trials are designed carefully. FLASH-RT also requires extensive work regarding the physics, quality assurance and planning systems. “With dose rates like this being delivered in less than a second, a mistake can be catastrophic. We have to know exactly what we’re delivering and control the beam very carefully, and be convinced that we’re delivering the dose that we want to deliver,” says Dr. Metz.
With a conventional course of treatment it’s possible to course-correct for a small mistake or if something wasn’t delivered exactly as intended. With FLASH-RT, however, everything has to be perfect. “Imaging and soft tissue imaging have to be really good with FLASH to be able to see exactly where we’re delivering the treatment,” Dr. Metz explains.
As with any new technology or treatment, reimbursement for FLASH-RT has to be figured out with the Centers for Medicare and Medicaid Services and payers. Those discussions have already started with vendors and individual facilities. Given the more complicated work required for QA, controlling the beam and planning, Dr. Metz says, “I’m sure there’ll be different reimbursement ultimately for it, but that’s in the negotiation phase now.”
If FLASH-RT becomes feasible to use in a routine setting, Dr. Breneman says, “we’ll take a six-week course of radiation therapy and make it last a week. For patients with a tumor that is relatively resistant to radiation and can’t be treated more aggressively because of problems with surrounding normal tissue, we could potentially use FLASH to escalate the aggressiveness of the treatment and have a better chance of actually curing the tumor.”
Use of FLASH-RT in the clinic is likely five years away, Dr. Breneman estimates. Dr. Metz similarly anticipates it will be at least five years before there will be more widespread use of FLASH-RT off clinical trial.
“If it works out that we can deliver an entire radiation course in one, or a few treatments with fewer side effects, that completely changes the way patients experience their cancer treatment. It would be incredibly shortened treatment courses with much reduced toxicity,” says Dr. Metz. “It would really change the game in cancer care completely, not just in radiation oncology, but all of oncology.”
Dr. Breneman is more measured about the potential impact FLASH-RT will have. “Even in its most optimistic uses, FLASH will have some limitations. It does require higher dosage given each time you treat a patient, and there are some instances even with FLASH that a person just won’t tolerate it based on the location of their tumor or other factors,” he says. “FLASH
is going to be another tool that we’ll use, but it’s not going to replace conventional radiation.”
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