Killing Tumor Cells in a “Flash”

Flash radiation may widen therapeutic window for radiation treatment.

A longstanding challenge for radiation oncologists is to deliver a sufficiently high dose of radiation to sterilize a tumor while minimizing off-target radiation, which is toxic and potentially fatal.

Flash radiation is a method of delivering a single pulse of radiation at ultrahigh dose-rates that has been shown to eliminate tumors and reduce the chance of complications arising from irradiating normal tissue. Pre-clinical studies are underway around the world testing its effectiveness for treating many types of cancer.

“Normal tissue could be spared by using these subsecond exposures.”

“This is suggesting that normal tissue could be spared by using these subsecond exposures,” said John Eley, Ph.D., radiation oncologist at Vanderbilt University of Medical Center. Eley, also a medical physicist, is conducting experiments testing flash radiation for the treatment of lung and brain tumors.

X-Ray Vs. Particle beam Therapy

X-ray radiation, one of the most common types of radiation therapies in the world, weakens as it travels through the body. Most of the energy of x-rays is released before reaching the tumor, Eley said.

Another method of radiation therapy is particle beam radiation, which uses charged particles like protons and carbon ions. The pattern of energy deposition is different if using x-rays versus charged particles; unlike an x-ray, a charged particle penetrates the body to a certain depth where it suddenly releases its maximum energy.

“You can control the energy of the beam so that it stops right in the tumor,” Eley explained. “As charged particles slow down, they give off more and more energy. Right before they stop, they give off the maximum amount of energy deposition. Globally, this puts a high energy deposition of radiation dose near the target, and almost no radiation beyond the depth of the target.”

Increasing Therapeutic Advantages

Pre-clinical studies have shown that delivering particle beam radiation using ultrahigh dose-rates is just as effective at treating tumors as conventional dose-rates, yet fewer side effects arise. Conventional radiation therapy is delivered at a dose rate of two to six gray per minute, Eley said. Flash radiation delivers radiation in a single, subsecond pulse at dose-rates of 40 to 100 gray per second.

“Flash radiation is appealing because you are combining two things at once. First, you are using proton therapy, which has some advantages over x-ray therapy already. Then you can increase the dose-rate to this potentially biological sparing dose-rate,” Eley said.

Flash radiation requires highly specialized equipment and is currently only be carried out with research-grade machines. Some standard-of-care linear accelerators are capable of operating at ultrahigh dose-rates, but significant modifications are required.

Understanding the Mechanism

Eley is currently testing the effectiveness of flash radiation for the treatment of malignant gliomas in a rodent animal model. Radiation toxicity in the brain can lead to treatment-induced side effects like neuroinflammation and cognitive impairment. Eley is testing whether radiation delivered at ultrahigh dose-rates can reduce these treatment-induced side effects while being equally as effective at treating brain tumors as radiation delivered at conventional dose-rates.

Eley is enthusiastic about the potential of flash radiation to improve cancer treatment. “You can escalate the dose and potentially have more curative treatments with the same side effects. Or you can give the same type of curative treatments that are given now, but with fewer side effects.”

“It’s exciting, but there’s not a clear mechanism that has been proven for why this ultrahigh dose-rate is sparing tissue.”

Added Eley, “It’s exciting, but there’s not a clear mechanism that has been proven for why this ultrahigh dose-rate is sparing tissue.” Eley hopes that better understanding of the mechanism will help elucidate whether the success of flash radiation is a general phenomenon or if ultrahigh dose-rates only work for a subset of tumor types.