FLASH radiotherapy may show promise as a potential treatment for hard-to-kill tumors

FLASH radiotherapy, which delivers a therapeutic dose of radiation in a fraction of a second, may hold promise as a potential treatment for difficult-to-lethal tumors in a small number of bone cancer patients suggested in the first human study that The technology, which was previously tested on animals, was shown to be as safe and effective as conventional radiation without causing any unexpected side effects. will be presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

Our study demonstrates that FLASH radiotherapy with protons is a viable modality for pain relief. It may reduce the side effects associated with conventional radiotherapy and deserves further study. “

Emily C. Daugherty, MD, lead author of the study and Assistant Professor of Clinical Radiation Oncology, University of Cincinnati Cancer Center

FLASH radiotherapy (RT) delivers radiation at dose rates 300 times or more higher than those used in conventional radiotherapy. This triggers a phenomenon known as the flash effect, which kills cancer cells at the tumor site while reducing the harm that can occur to normal tissue around the tumor during conventional radiation therapy.

“Because FLASH radiotherapy is delivered at very high dose rates, it appears to damage normal tissue less. Cure rates may increase for patients with cancer, said John Breneman, MD, FASTRO, principal investigator of the trial and professor of radiation oncology and neurosurgery at the University of Cincinnati Cancer Center.

Most of the early studies on FLASH RT used electron beams to deliver the radiation, but these beams do not penetrate deep into tissue, limiting their applicability to this therapeutic approach. The use of proton beams for ultra-high dose rate radiation allows sufficient penetration to reach tumor sites in most people. Although preclinical studies in animals suggested that FLASH-RT safely delivered high doses of radiation with few adverse side effects, prior to the FAST-01 trial, the treatment was not feasible in humans. has never been tested in a clinical trial.

In this study, ultrahigh-dose-rate radiation was applied to 10 patients aged 27 to 81 years, each with 1 to 3 painful bone metastases in the extremities. Treatments were given to a cumulative 12 metastatic sites on the patient’s arms and legs. The patient received 8 Gy of radiation delivered at >40 Gy per second via a FLASH-enabled proton therapy system, he was given in one fraction. Pain, analgesic use, and adverse events were measured on the day of treatment, 15 days after treatment, and 1, 2, and 3 months after treatment. The researchers continued to measure these results every two months for up to 13 months. Median follow-up was 4.8 months.

Researchers selected patients who would have received conventional radiation therapy at the same dose as FLASH RT. “We used the exact same regimen, but with FLASH dose-rate radiation. says Dr.

After FLASH RT, 7 out of 10 patients experienced complete or partial pain relief. Six of her 12 treated sites had complete pain relief, and he had two sites with partial pain relief. Temporary flare-ups of pain occurred in 4 of the 12 sites treated.

Side effects from treatment were mild. Four patients had mild skin hyperpigmentation (darkened skin), one had skin discoloration, two had mild limb edema (swelling or swelling), and two had pruritus (itching). , 1 experienced fatigue, 1 experienced erythema (redness of the skin), and 1 experienced extreme pain.

Each FLASH treatment takes about 3/10th of a second, explained Dr. Daugherty. After treatment, “both the pain relief and side effects were consistent with what might have occurred with conventional radiation. We found no unexpected additional toxicities with significantly shorter treatments.”

FLASH RT may be most useful in treating hard-to-kill cancers in the brain, lungs, or gastrointestinal regions, where the healthy tissue surrounding the tumor is particularly susceptible to radiation exposure, Dr. Breneman said. . However, clinical trials at these sites will not be approved until studies show that ultra-high dose rate radiation is safe and effective in other less sensitive areas. The FDA limited approval for this study to adults with bone metastases in their arms and legs, areas at much lower risk if complications develop.

“From a practical standpoint, this is not the type of cancer FLASH was designed to treat, but we need human data to see if there are any unexpected side effects.” It’s not as dangerous as treating someone’s brain or lungs,” said Dr. Brenneman, who is also medical director of the Proton Therapy Center at the Cincinnati Pediatrics/University of California Medical Center.

Ultimately, FLASH RT could also help treat childhood cancers because children are more sensitive to the side effects of radiation therapy, he said. But more research needs to be done before that happens.

Researchers don’t fully understand why FLASH RT kills tumors with fewer side effects than conventional radiation, and more research is needed to determine the biological mechanisms driving FLASH’s effects, he said. Dr. Daugherty said.

The research team will then test it for safety and security. effectiveness of FLASH RT for patients with metastases closer to the lungs and heart. The FAST-02 trial (NCT05524064) is currently enrolling adult patients with thoracic bone metastases.