Some patients who receive brain tumor radiation develop radiation necrosis, causing debilitating effects. But a new clinical trial could change that.

UK and Norton partner in first-ever clinical trial for radiation necrosis

Radiation saves countless lives, but in rare cases, it causes a debilitating complication. Around 3 to 5 percent of patients who receive radiation for brain tumors, or arteriovenous malformations (AVM), develop radiation necrosis.

Radiation necrosis causes headaches, nausea and vomiting, cognitive problems, and neural dysfunction. Although a variety of medications has been used to manage symptoms, there is no approved cure. But a joint clinical trial at Norton Brownsboro Hospital in Louisville and UK HealthCare could change that.

The first trial of its kind that treats the brain directly

Led by Dr. Shervin Dashti and Dr. Tom Yao from the Norton Neuroscience Institute and Dr. Justin Fraser at UK HealthCare, the trial is the first in the world to deliver a dose of a cancer drug directly to the brain. This allows a larger amount of the drug to reach the brain, making treatment more effective.

Dashti has seen the effects of radiation necrosis on patients who have already experienced the trauma of brain cancer or AVM. In addition to the symptoms caused by the condition itself, patients suffer from side effects of steroids used to manage it: insomnia, mood changes and weight gain.

“There was nothing that worked for treating it, and people were devastated,” he said. “What we’re doing now is something completely different, and I think it has a chance to really change the way we treat this.”

More than three years ago, Dashti developed this treatment when two young patients were in desperate need. Only 12 and 13, both girls had developed radiation necrosis and were experiencing severe side effects from steroids. They had disabling headaches, gained 50 to 60 pounds each, missed significant amounts of school or withdrew entirely. One patient experienced focal seizures in her arm and leg; the other patient was hospitalized for fluid overload.

With no other treatment available, Dashti and Yao spoke to the first patient and her family about trying a low dose of Avastin directly to the brain. They agreed, and within 12 hours of the procedure, her headaches were gone. Brain scans over several months showed continuous improvement, her arm and leg had strengthened so she could walk without help, and she returned to school.

Jade Cain, now 16, was the second patient. She was 11 when the AVM was diagnosed and 13 when she met Dashti. According to her mother, Desiree Fischer, 75 percent of her brain was swollen by that time, and she was so depressed she didn’t want to leave the house.

“We’d been doing three or four months of steroids, and she ended up on all other kinds of other medications, too, because she developed thrush. So that’s what led us to this procedure. She spent a week in the children’s hospital because she was in fluid overload. She couldn’t do any more steroids because that was going to kill her.”

Fortunately, the treatment worked just as well for Cain. Her headaches went away, she was off steroids within four weeks, and she returned to school.

She had a final angiogram of her brain in March 2016, and everything was normal.

“It the most amazing, complete response after one treatment, and the imaging response was unbelievable. It was a miraculous recovery for both of them,” Dashti said.

Partnering with UK HealthCare

The success of these two patients motivated Dashti to start a clinical trial. He asked Fraser, director of cerebrovascular surgery and surgical director of the comprehensive stroke center at UK’s Kentucky Neuroscience Institute, to join them.

“We’re in this position of facing an uncommon complication of a treatment that is becoming more commonly used, and we don’t have a great way to fix it,” Fraser said. “What’s special about our procedure is that patients get the drug once, directly to the brain, as opposed to a complete course of the drug that can cause serious side effects.”

The trial is supported by both institutions and has received expert project management support from the UK Center for Clinical and Translational Science.

Showing gratitude and support

Cain’s family has raised more than $20,000 for the Children’s Hospital Foundation. At the decision of Cain and her mother, these funds are directed specifically to support research on radiation necrosis.

“From the steroid use, my child who weighed 105 pounds went up to 160 pounds in one month. Had this treatment already been approved, we could have omitted all that. She battled to get the weight off and to overcome poor body self-image,” Fischer said. “I wish it had been approved way before. And I hate that my child is the one who had to go through it, but I tell her, ‘You have no idea what you’ve done – you’ve paved the way so other people hopefully won’t have go through what you went through.’”

If you are interested in learning about participating in this study, please contact Elodie Elayi at elodie.elayi@uky.edu, or review the study information at ClinicalTrials.gov.


Next steps:

  • UK’s Center for Drug and Alcohol Research has recently made progress on a treatment for those with opioid use disorder. Learn more.
  • Clinical research helps develop the treatments and medications of the future. Learn how you can help.