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NC State Neurologist Adapts Human Laser Therapy for Use in Dogs with Brain Cancer

Dr. Christopher Mariani’s work gives pet dogs a potential new treatment option and experts studying how to improve the technology their first naturally occurring, nonrodent research model.

Dr. Chris Mariani in blue scrubs and purple gloves kneels behind a white dog and examines him.
Dr. Christopher Mariani works with a client in the neurology lab at the NC State Veterinary Hospital.

A complicated, years-long project led by an NC State professor of veterinary neurology and neurosurgery and a former Duke University professor of neurosurgery has opened a pathway for more advanced brain cancer research and treatment for both humans and dogs. 

For the first time, Dr. Christopher Mariani and his team successfully employed laser interstitial thermal therapy or LITT to treat naturally occurring gliomas in pet dogs. The minimally invasive surgical technique, which the FDA approved for use in humans in 2009, uses thermal ablation to treat tumors and other brain abnormalities. 

Mariani’s work, recently published in Clinical Cancer Research, means that pet dogs now could be treated with LITT and that researchers studying new techniques and protocols for humans have a naturally occurring model in dogs, which often share the same environments, foods and activities as their owners. 

“The dog is really an important intermediate step because dogs develop a lot of brain tumors, and their brain tumors are actually quite similar to the types of tumors that humans get,” says Mariani, who has been at the NC State College of Veterinary Medicine for almost 20 years. “The main goal was to see whether we could actually get LITT to work in a dog so we would have a platform to improve upon it in the future.”

“The main goal was to see whether we could actually get LITT to work in a dog so we would have a platform to improve upon it in the future.” — Dr. Christopher Mariani

Mariani conducted the research in collaboration with the Duke Cancer Center and two industry partners: Brainlab, a digital medical technology pioneer, and Monteris Medical, a leader in image-guided thermal therapy. 

In 2017, Dr. Peter Fecci, a former professor of neurosurgery and director of the Duke Center for Brain and Spine Metastasis, approached NC State about collaborative research opportunities, including the need for a nonrodent model for studying ways to improve LITT outcomes in humans. The technology is useful for hard-to-reach areas of the brain, but it is limited in the size of tumors it can treat and in its ability to distinguish between healthy and unhealthy brain tissue.

Rodent Models Too Small

Fecci, now chairman of the Department of Neurosurgery at the University of Colorado Anschutz Medical Campus, is one of the world’s most experienced surgeons in using LITT, which has less risk and a shorter recovery time than traditional brain surgery because it requires only one small hole in the skull. He also extensively researches how to improve the technology.

Precisely locating where to drill and insert the laser probe requires surgeons to use a neuronavigational system, which allows them to use pointers at the surgical site to get a live 3-D orientation of the brain to compare with pre-operative CT or MRI images.

With rodent models too small to accommodate commercially available neuronavigation and LITT systems, Fecci asked Dr. Mike Nolan, the Randall B. Terry Jr. Distinguished Professor in Oncology at the NC State College of Veterinary Medicine, whether it might be feasible to use LITT for treating canine brain cancer.

Dr. Christopher Mariani consults with neurology resident Alejandra Mondino in the neurology treatment room.

“Dr. Fecci and I met and chatted a few times, and we knew there was a path forward — a way to make cutting-edge technologies available to pet owners via canine clinical trials and a way to leverage those trials to advance human cancer care as well,” Nolan says. “As the ideas percolated, it became obvious that the endeavor would benefit via addition of someone who had veterinary neurosurgical expertise and someone with expertise in canine brain tumor immunology. Dr. Mariani checks both of those boxes, so I looped him in.” 

First, someone would need to adapt a human neuronavigation system for use in dogs.

“The only reason we were able to do it was because of our industry partners,” Mariani says. “Brainlab loaned as a navigation system, which nobody’s ever really gotten to work consistently or well in dogs. And Monteris Medical installed a LITT system here at NC State, which is still here.”

Another challenge was that, unlike humans, dogs have thick muscles on their heads that have to be penetrated as well as the skull.

“It’s called the temporalis muscle, and it’s like a giant T-bone steak laying on top of their heads,” Mariani says. “We had to figure out a way to access it, because with humans, they do a little skin incision and they’re right there. With dogs, we have to get through this muscle.”

The Next Front

Once they perfected their techniques on cadavers, the researchers then needed to find and enroll pet dogs with naturally occurring gliomas smaller than 3 cm to treat and study.

That’s one of the unique benefits of the innovative research at the NC State College of Veterinary Medicine. Beloved pets often are the beneficiaries of cutting-edge technologies through the clinical trials needed to study and refine life-changing therapeutics.

LITT is considered a treatment, not a cure, because there are usually invasive cancer cells within seemingly normal brain beyond the main tumor margin.

Dr. Christopher Mariani leads the neurology service through morning rounds.
“The only reason we were able to do it was because of our industry partners,” Mariani says.

“With LITT, you place a laser probe into the middle of, in this case, a brain tumor, and the laser basically kills the tumor cells by heating them,” Mariani says. “But the technology isn’t sensitive to the tumor itself. If you just keep blasting it with heat, then you can damage other areas of the brain, and you aren’t going to eradicate all of the cancer cells.”

Oncologists likely need another technology to use in tandem with LITT, Mariani says, and current research focuses on two fronts: immunotherapy and gold nanostars. 

Immunotherapy would enhance the immune system’s ability to recognize and destroy any remaining cancer cells. The gold nanostars, which are injected in tumor tissue and act like tiny heat conductors, could help focus the thermal energy within the tumor tissue, improving the safety margin of the therapy

“They are experimenting with this in mice, but the problem is, you obviously can’t use the human neuronavigation system in a mouse,” Mariani says. “Plus, it’s an artificial system because you’re making artificial tumors in an immuno-compromised host. We’ll be treating pet dogs with naturally occurring tumors who have very few treatment options.”

Mariani is excited that the study made the cover of the print journal for clinical and translational cancer researchers.

“It’s actually a picture that Dr. Danielle Meritet, one of our pathologists, took that is on the cover, which is really cool and used to be a pretty prestigious thing back in the day,” he says. “I think it’s just a very cool ending to the project.”

This post was originally published in Veterinary Medicine News.