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A new procedure for radiation necrosis
LOUISVILLE, Ky.—A trial exploring a new procedure pioneered by Norton Healthcare physician-scientists, entitled “Low-dose Intra-arterial Bevacizumab for Edema and Radiation Necrosis Therapeutic Intervention (LIBERTI),” has discovered promising results to patients with radiation necrosis. The procedure directly targets radiation necrosis-affected brain tissue.
Alyssa Coffey was in the midst of training for an upcoming bodybuilding competition when she had her first seizure. A scan revealed that 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. Doctors in her home state were successful in using radiation therapy treat the AVM, but Coffey experienced the severe side effect of radiation necrosis.
Radiation therapy is effective at treating certain brain AVMs, but in up to 5 percent of cases it causes damage to the surrounding brain. This can result in radiation necrosis, as the nearby brain tissue becomes injured and dies. The condition can be disabling, and it can cause severe headaches, nausea and vomiting, seizures, cognitive issues and even death. Doctors use a variety of medications, such as steroids, to manage the symptoms. The medications are ineffective and all have serious side effects. There is currently no approved cure.
“It was miserable,” Coffey said. “The necrosis impacted my ability to work. Going to the gym was out of the question.”
Doctors in New Jersey suggested exploratory brain surgery, but Coffey felt it was too risky. Last year while using an online AVM support group, Coffey learned about a study at the Norton Neuroscience Institute and the University of Kentucky (UK) that sought to reverse radiation necrosis.
The trial, led by Shervin Dashti, M.D., Ph.D., endovascular neurosurgeon with Norton Neuroscience Institute and co-director of the Cerebrovascular & Endovascular Neurosurgery program, is the first worldwide to deliver a single small dose of the cancer drug Avastin directly to the necrosis-affected area of the brain. Tom Yao, M.D., endovascular neurosurgeon with Norton Neuroscience Institute, and Justin Fraser, M.D., neurosurgeon with UK HealthCare, are also treating patients in the study.
According to a news article by Joe Hall on Norton Healthcare’s website, Dashti coined the idea for the new treatment method over five years ago, when two preteen girls developed radiation necrosis and experienced severe side effects from steroid treatment. One patient experienced focal seizures, and the other patient needed hospitalization for fluid overload.
Dashti pointed out that “the imaging response was unbelievable … before the treatment, it looked like someone put a bomb in their brains. But it was like a miraculous recovery for both of them.”
Avastin has previously been used to effectively treat radiation necrosis. The medication is traditionally given through an IV; only a small percentage of the drug reaches the brain, and it has a hard time penetrating the blood-brain barrier. And exposing the body to Avastin can result in bad side effects like brain bleeds, clots and uncontrolled high blood pressure.
The new treatment method is innovative because it delivers a very small dose of Avastin directly into the artery going to the affected part of the brain. The smaller dose should significantly decrease the serious and life-threatening side effects of the drug. With targeted delivery, more of the drug will affect the desired brain area.
To increase the Avastin’s efficacy, Dashti infused a mannitol sugar solution into the carotid artery to open the blood-brain barrier. When done immediately before injecting Avastin, a much larger amount of the drug can reach the affected brain tissue, while minimizing drug exposure in the rest of the body.
“I felt this was my best option, and I was confident it was going to work,” Coffey stated.
Coffey flew to Louisville to receive her single-dose treatment. Dashti injected the Avastin into her brain through an artery in Coffey’s leg, and immediately began studying the effects.
It didn’t take long for Coffey to see a difference, either. “The headaches went away in a matter of weeks. I was able to go off my other medications and get back into the gym,” she noted.
Her scans were also positive. “The images showed great improvement in the area impacted by the necrosis,” Dashti mentioned. “We were very encouraged with what we were seeing.”
It’s been a year since Coffey first 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 show further improvement. Coffey 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 opined. “I’ve received tremendous care throughout. I feel like I have my life back.”
Dashti noted that other patients in the trial are also seeing similar results. “To this point, everyone who has received the Avastin has seen improvement in their condition. It’s very exciting.”
While the findings are encouraging, Dashti pointed 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. Hopefully, we’ll look to get funding for a larger, multicenter study in the future.” But for now he is excited about the treatment’s possibilities. “I think we have a chance to change the way we treat radiation necrosis and help more people,” Dashti concluded.