Sen. John McCain, Sen. Ted Kennedy, Beau Biden and former N.Y. Mets catcher Gary Carter are just a few of the luminaries whose recent battles with one of the most deadly forms of brain cancer brought this disease into the public spotlight.
Indeed, about 25,000 people nationwide are diagnosed with deadly glioblastomas a year, according to the American Cancer Society.
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Despite this large number, progress in treating deadly brain tumors was minimal until recently, said Dr. Ricardo Komotar, a neurosurgeon at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, who heads the university’s Brain Tumor Initiative. The Initiative has more than 20 researchers, some of them brought in from institutions like Sloan Kettering in New York, to find a cure.
Today, doctors are using advanced techniques to perform neurosurgeries, including the awake craniotomy, laser ablation and biomarkers to light up the tumor. Combine that with new immunotherapies, which use the patient’s own body to fight off the disease, and innovative targeted incisionless techniques, and there’s new hope for patients where it once looked bleak. More than 600 clinical trials are underway nationwide targeting brain tumors and more than 400 of those are focusing on glioblastoma.
Much of the research — such as clinical trials at Sylvester and Nicklaus Children’s Hospital — point to this: targeted therapies and personalized medicine show much promise.
“The delivery of targeted therapies directly to the region with no damage to the healthy tissue around it — that will be the big potential of these kinds of treatments,” said Dr. John Ragheb, a neurosurgeon and director of neurology at Nicklaus Children’s Hospital. “Very exciting stuff.”
Here, then, is some of the clinical research that gives doctors and researchers much hope.
Devising new strategies
Dr. Noriyuki Kasahara, a gene therapy expert at Sylvester, is among the researchers looking at ways to activate the patient’s own immune system to fight the brain cancer. He developed a treatment using an engineered virus to infect cancer cells in the brain, killing the tumor cells from within. A clinical trial is showing promising results.
In Kasahara’s study, which is part of a multicenter clinical trial, a virus is injected into the tumor at the time of surgery. The virus then infects the tumor cells selectively. The patient takes a pill a couple of weeks later and the medication in the pill combines with the virus to destroy those cells, said Komotar.
In a clinical trial only at UM, Dr. Macarena De La Fuente, a neuro-oncologist, is also testing immunotherapy techniques but in a different way. Everyone has white blood cells that attack viruses and bacteria as part of their immune system. The question is how do you activate the white blood cells to fight the cancer?
“In this clinical trial, we take out the tumor, we isolate white blood cells from the patient, and then we mix the two outside the body so the white blood cells recognize the tumor and become activated against them, then reinject the activated white blood cells back into the patient so that they attack any remaining cancer cells,” Komotar explained.
Gregory Clark of Jupiter is part of the clinical study, and it has been going “very, very well,” he said. This was his second surgery; the first one was at another hospital and the cancer came back. This time the surgery to take out the cancer happened in February — far less “major” than the one before.
Another key difference: the after-treatments. The 72-year-old took the immunotherapeutic injections once a week for about a month and is now taking them once a month for six months, Clark said. “They think I will be fine."
Attacking brain cancer in kids
Brain cancer is the second most prevalent cancer in children, after leukemia.
Nicklaus Children's Hospital recently treated Nathalie Rivera of Miami, a 7-year-old whose benign brain tumor eventually regrew after surgery to remove it in 2015.
“Everyone wanted the tumor to disappear but it grew back and God knows why,” said her mother, Katherine.
Instead of another surgery, among the medical option was a tablet containing an inhibitor based on a specific mutation in her tumor. She takes the pill twice a day and her last MRI showed the tumor had shrunk considerably. Her only side effect has been sweating, her mother said.
"The doctor is always checking on how she is doing. It's not easy, but I feel confident she will not have it again when she grows.''
Nathalie is far from alone. Brain tumors in children number 2,000 to 3,000 in the United States. Nicklaus treats 50 to 60 brain tumors in children every year, said Dr. Ziad Khatib, director of neuro-oncology at Nicklaus.
Nicklaus was also part of a recent paper published in the journal Nature, in which the researchers found out that by doing this genetic analysis on tumors, they can classify different types of brain tumors into more precise groups, discovering new subtypes.
“The future of pediatric brain cancer is to have targeted treatment instead of blasting the brain with chemotherapy or radiation,” Khatib said. “Now we are understanding the genetic basis of the tumor more precisely and we are targeting that basis more specifically — with less side effects and better outcomes.”
Another promising form of targeted treatment being tested at Nicklaus is using focused ultrasound to destroy brain lesions.
Dr. John Ragheb, a neurosurgeon and director of neurology at Nicklaus, is leading a study using a new ultrasound technology — a form of incisionless surgery — that uses about 1,000 focused beams to remove a centrally located brain tumor.
It’s being tested now in a clinical trial at Nicklaus, and the treatment has been approved for adults for essential tremors. But the technology has the potential to do a great deal more, Ragheb said.
“Because we treat children and many of them have areas of abnormality in the brain, we need to reach it with as little trauma to the brain of the child as possible. This technology has great potential.”
Ragheb and Dr. Ian Miller are conducting a study of 10 children and young adults under 22 who have a lesion in the middle of the brain. Three people have been treated and 15 candidates screened. He said results have been promising but safety is the first priority.
“The beauty of this is that it lets you target an area of the brain causing the problem … and without opening the skin or skull or putting anything into the brain, you can destroy the part of the brain that’s sick. That’s a first. This involved no radiation,” Ragheb said. “When the children wake up [after the ultrasound treatment], they are normal — they sit up and have supper and go home the next day.”
The writers of "Grey’s Anatomy" apparently thought highly of the technology, too; they wrote it into the script of a recent episode.
“Our goal is to ultimately be able to use this for epilepsy and brain tumors,” said Ragheb.
Focused ultrasound could potentially disrupt the blood-brain barrier, which keeps certain substances in the bloodstream from reaching the brain. This would allow targeted therapy — whether it's chemotherapy, immunotherapy or even a biological agent like stem cells — to get into the brain.
“That would be a huge game changer for neurosurgery and neurology, just unbelievable potential,” Ragheb said.
The technology also has local ties. The Exablate Neuro MRI-guided focused ultrasound system is made by Insightec, an Israeli medical technology company with offices in Miami. Maurice R. Ferre, CEO and chairman of Insightec, was also co-founder of Broward-based Mako Surgical. Ferre is the son of former Miami Mayor Maurice Ferre.
The company recently received a $150 million investment and was named one of the world’s most innovative companies by Fast Company this year. A clinical trial in Maryland to study the technology for glioblastoma is planned.