Only study of its kind in the world seeks to reverse effects of radiation necrosis — damaged or dead brain tissue caused by radiation therapy
“I started losing my sight and then passed out in the car,” Alyssa Coffey recalled about experiencing her first seizure.
She was in the midst of training for an upcoming bodybuilding competition. A scan revealed the then 23-year-old New Jersey resident had an arteriovenous malformation (AVM), a tangle of abnormal blood vessels connecting arteries and veins in the brain.
“It was extremely scary,” she said. “I’d been the picture of perfect health until that point.”
To treat the AVM, doctors in her home state used radiation therapy. The radiation therapy worked in treating the AVM, but unfortunately Alyssa experienced the severe side effect of radiation necrosis.
Radiation therapy is an effective way to treat certain brain AVMs. In up to 5 percent of cases, however, it can cause unwanted damage to the surrounding brain. This can result in radiation necrosis, which is when the brain tissue near the area that received radiation becomes injured and dies.
The condition can be disabling, causing severe headaches, nausea and vomiting, seizures, cognitive issues and nervous system dysfunction.
Doctors use a variety of medications, such as steroids, to manage the symptoms. None of the medications work very well, and all of them have serious side effects. Currently, there is no approved cure.
“It was miserable — I was having debilitating headaches constantly,” Alyssa said. “The necrosis impacted my ability to work, and going to the gym was out of the question. I gained weight from the medical steroids they had me on to treat the condition. This was even impacting my relationship with my boyfriend.”
Alyssa was at a crossroads. Doctors in New Jersey suggested exploratory brain surgery, but she felt it was too risky.
Norton Healthcare trial for radiation necrosis
Last year, while on an AVM support group website, Alyssa learned about a study at Norton Neuroscience Institute in conjunction with the University of Kentucky that sought to reverse radiation necrosis.
The trial, led by Shervin R. Dashti, M.D., Ph.D., endovascular neurosurgeon with Norton Neuroscience Institute, is the first in the world to deliver a single small dose of the cancer drug Avastin directly to the area of the brain affected by radiation necrosis. Tom L. Yao, M.D., endovascular neurosurgeon with Norton Neuroscience Institute, and Justin F. Fraser, M.D., neurosurgeon with UK HealthCare, also are treating patients as part of the study.
Avastin previously has been used effectively to treat radiation necrosis. The medication is given through an IV, which means that the drug has to circulate through the body before only a small percentage of it reaches the brain. When the drug does reach the brain, it has a hard time penetrating it because of a natural defense mechanism called the blood-brain barrier. Making matters worse, exposure of the body to Avastin can result in serious side effects, such as bleeding in the brain, clots forming in the veins of the leg or lungs, and uncontrolled high blood pressure.
What makes Dr. Dashti’s treatment innovative is that it delivers a very small dose of Avastin directly into the artery that goes to the affected part of the brain. The smaller dose should significantly decrease the serious and life-threatening systemic side effects of the drug. Also, with the targeted delivery of Avastin, a lot more of the drug will get to where it needs to go.
To make penetration of the drug into the necrosis even more effective, Dr. Dashti uses a special technique to open up the blood-brain barrier by infusing a mannitol sugar solution into the carotid artery. When this is done right before injecting the Avastin, a lot more of the drug will penetrate to where it needs to go in the brain.
In essence, this new, targeted method allows doctors to temporarily break down the blood barrier and deliver a much larger amount of the drug to the affected brain tissue, while minimizing exposure of the rest of the body to the drug. Dr. Dashti theorizes that delivering such a precise dose would amplify the drug’s benefits while reducing serious side effects.
Nearly five years ago, Dr. Dashti came up with the idea for this investigational treatment when two young girls developed radiation necrosis and experienced severe side effects from steroids, the prevailing treatment. One patient experienced focal seizures (formerly known as partial seizures) affecting her arm and leg. The other patient had to be hospitalized for fluid overload.
The treatment worked.
“The response was the most amazing complete response after one treatment, and the imaging response was unbelievable,” Dr. Dashti said. “It’s a very visual thing — before the treatment, it looked like someone put a bomb in their brains. But it was like a miraculous recovery for both of them.”
The radical success with these two young patients motivated Dr. Dashti to start the clinical trial. Alyssa became one of 10 patients from around the country to enroll. Five, including Alyssa, were chosen to participate at Norton Neuroscience Institute and the other five at UK.
“I felt this was my best option,” Alyssa said. “And I was confident it was going to work.”
Medication yields positive results
Alyssa flew to Louisville in September 2017 to receive her single-dose treatment. In a 45-minute procedure, Dr. Dashti injected the Avastin into her brain through an artery in her leg and immediately began studying the effects.
It didn’t take long for Alyssa to see a difference.
“The headaches went away in a matter of weeks,” she said. “I was able to go off my other medications and get back into the gym.”
Her scans also told a positive story.
“The images showed great improvement in the area impacted by the necrosis,” Dr. Dashti said. “We were very encouraged with what we were seeing.”
Norton Neuroscience Institute
Norton Neuroscience Institute is the leader in Louisville and Southern Indiana for neurology and neurosurgery.
Still going strong — and getting stronger
It’s been a year since Alyssa received her Avastin injection. She recently returned to Louisville for a follow-up exam. The headaches are now a distant memory, and her brain scans are showing further improvement. She said she’s feeling great and is even back to training for another bodybuilding competition.
“Participating in the trial was the best thing I could have done,” she said. “I’ve received tremendous care throughout. I feel like I have my life back.”
Dr. Dashti said other patients in the trial also are seeing similar results.
“To this point, everyone who has received the Avastin has seen improvement in their condition,” he said. “It’s very exciting.”
While the findings are encouraging, Dr. Dashti points out that the treatment is still a long way from becoming common practice.
“We studied a very small group of people, and we still have to determine if the benefits are long-term,” he said. “Hopefully, we’ll look to get funding for a larger, multicenter study in the future.”
For now, he’s excited about the possibilities.
“There was nothing that worked for treating radiation necrosis,” Dr. Dashti said. “I think we have a chance to really change the way we treat this and possibly improve the standard of care.”