Belly fat to treat brain cancer? Neurosurgeons test method to bypass blood-brain barrier
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Surgeons at Lenox Hill Hospital are recruiting patients for a first-in-human, single arm, open-label phase 1 clinical trial investigating the safety and feasibility of using belly fat to treat recurrent glioblastoma.
A team led by John A. Boockvar, MD, vice chair of neurosurgery and director of the Brain Tumor Center at Lenox Hill and director of the Laboratory for Brain Tumor Biology and Therapy at Feinstein Institutes for Medical Research, is testing the viability of the omental tissue in bypassing the blood-brain barrier and treating the fast-growing, aggressive brain cancer.
The trial, in its initial phase, is enrolling 10 participants with recurrent glioblastoma who will undergo standard surgical resection, after which the surgical cavity will be lined with a laparoscopically harvested omental free flap. Researchers will closely monitor each patient for adverse events, assessing for seizure, stroke, infection, tumor progression and death.
Two patients have already undergone successful laparoscopic omental-cranial transposition procedures.
“Glioblastoma is a universally fatal disease, and the FDA understands that in order to make progress, we’re going to have to take some significant leaps,” Boockvar told Healio.
The surgical procedure has been commonly used in head and neck cancers, but not for brain tumors. Boockvar said a brain tumor dog model was used for the omental-cranial transposition in 1990 at University of California, San Francisco.
Although the trial is in its infancy, researchers have concluded that it is feasible to put patients through the procedure of transplanting the omentum into the brain.
“What was shown in dogs in 1990 is able to be done in humans,” Boockvar said. “We learned that we can do this and that the graft survives.”
Boockvar addressed other concerns the research team is investigating.
“One of the risks of the operation is we’re putting in a very highly vascularized source of tissue,” Boockvar said. “What if the tumor grows faster because of all of the blood supply? What if the tumor grows along the graft instead of growing in the brain? And, obviously, I don’t want the tumor to hijack the blood supply that we’re giving it and maybe grow faster. That’s a risk that will be important to learn about if it were to happen.”
How the idea originated
Treatments for glioblastoma often run into the problem of the inability of drugs and molecules to penetrate the blood-brain barrier. Boockvar has been working on ways to solve this problem for 2 decades.
Boockvar said the omental-cranial transposition trial came about while working on another trial designed to navigate past the blood-brain barrier. The first trial, called the Temporal Parietal Fascial Flap trial, is for newly diagnosed patients with glioblastoma and uses a piece of scalp tissue called a pericranial flap, which is inserted into the resection cavity of patients. The idea for the trial came about as Boockvar was in surgery one day about 5 years ago.
“I was taking a big blood clot out of a patient, emergently. It was very, very large, like the size of a mango, and it ended up being a very large hemorrhagic brain tumor,” Boockvar said. “As I took out the brain tumor, I was elevating this flap called the pericranium, a tissue that sits between the skin and the skull. And I was able to elevate it.
“I said to myself, at that moment, what if I actually took out the brain tumor and then took the sheet of pericranium and laid it into the brain? The blood supply in that pericranium does not have a blood-brain barrier because it’s outside of the skull.”
Boockvar sent a medical student to dig into research papers, thinking it had to have been tested before. To his surprise, it had not been.
“We opened a trial, exploring this tissue, called temporoparietal fascia flaps, and the FDA allowed me to trial it in 10 patients,” he said. “We’re actually on our sixth patient, using temporoparietal fascia flaps to bypass the blood-brain barrier.”
Observing the success of the temporoparietal fascia flaps trial, Boockvar and his Lenox Hill colleagues, Peter Costantino, MD, craniofacial and cranial base tumor surgeon, and Robert Andrews, MD, vice chair of surgery, decided to “push the envelope even further” by using omental tissue.
“Omental [tissue] is like gold; it’s the like the plushest blanket you have, and it covers every organ in your abdomen,” Boockvar said. “My partner Peter Constantino and I hypothesized that, if we just showed that this flap trial was safe, we could take this omental [tissue], which is more vascular and more immunogenic in that it has lymph nodes in it and put that into the surgical cavity. Maybe those lymph nodes will recognize the brain cancer as foreign and help the body fight itself, the brain cancer.”
Progress thus far
Although it’s an extension of the temporoparietal fascia flaps trial, the omental trial is riskier, Boockvar said, since it requires more time in the operating room and a second surgical site. But so far, it’s working as they had hoped.
“We give the omental [tissue] its own blood supply by tying it into the artery in the neck, we tunnel it under the skin in front of the ear and then we place it in,” he said. “You’re basically creating another organ that’s surviving in the brain with its own blood supply, and then I can feed that organ and get drugs and chemicals into the microenvironment of the tumor.”
Because the trial is for patients with recurrent glioblastoma, the team at Lenox Hill must navigate carefully though the recruitment process; patients who are too sick may not have a strong enough performance status to qualify.
For those who qualify, Boockvar said the idea of using a tissue from belly fat to treat one of the most difficult-to-treat cancers is hopeful and early results are encouraging.
“My second patient was a physician,” Boockvar said. “He just sent me a picture of him rock climbing 6 weeks after surgery. This is what gets us motivated, when patients have the courage to do this, particularly a doctor who understands the scientific rationale and understands what the risks are. It’s very heartwarming.”
For more information:
John A. Boockvar, MD, can be reached at Department of Neurosurgery, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 130 E. 77th St., Black Hall Building, New York, NY 10075; email: jboockvar@northwell.edu.
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