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Tuesday, April 6, 2010

Tiny Drill Attacks Tough Tumors


A new approach to treating bone cancer is being tested in pet dogs.


In early February, Melissa Dauvalt noticed that her St. Bernard, Juno, had a lump on one of his front legs that was causing him to limp.


Tests confirmed that the dog had developed osteosarcoma, an aggressive and difficult-to-treat bone tumor that's found most commonly in adolescent children and large-breed dogs.

Dauvalt is a veterinarian, so she knew the most effective treatment would be amputation.

But she couldn't bear the thought of her 165-pound canine trying to walk on three legs.

"He's a big guy," says Dauvalt. "Amputation was not an option."

So Dauvalt and volunteered her dog for a clinical trial at Texas A&M University, where veterinarians are testing a new technology that delivers radiation directly to solid bone tumors. During a two-hour procedure on March 12, the vets used a drill roughly the size of an electric toothbrush to inject a radioactive isotope directly into the tumor, in the hopes of shrinking it without harming surrounding tissue.

The lessons they learn from Juno's experience--and that of other dogs in the trial--will help scientists determine if such highly targeted radiation treatments could also work in humans.

Osteosarcoma afflicts about 900 people per year in the United States, about half of whom are younger than 20, according to the American Cancer Society.

Some tumors can be removed effectively, but what makes the disease so devastating is its tendency to spread: One in four newly diagnosed cases have already metastasized, and the long-term survival rate is under 25 percent, says Crystal Mackall, chief of the pediatric oncology unit of the National Cancer Institute.

Osteosarcoma is genetically similar in dogs and humans, making the veterinary setting an important laboratory for researching human therapies.
"Dogs develop cancer naturally, and they share our environment," says Melissa Paoloni, a scientist at the NCI's Comparative Oncology Program.

That provides an opportunity to try potential new treatments in something other than rodents, which have to be engineered to develop cancer and therefore may not most accurately reflect the human experience.


About 6,000 new cases of canine osteosarcoma are diagnosed each year, according to the National Canine Cancer Foundation.

The drill was the brainchild of Stan Stearns, founder and president of Valco Instruments, a Houston-based maker of medical devices. Stearns lost his St. Bernard, Gabriel, to osteosarcoma in 2008. During the yearlong effort to save Gabriel's life, Stearns learned that external-beam radiation--the type commonly used to treat cancer--wasn't really effective for bone tumors, and presented too much of a risk to surrounding healthy tissues.

But after reading about experiments using biopsy tools to deliver medicine directly to bone, he had an epiphany.

"Valco had developed tubing that I thought could be the basis of a drill that would be flexible enough to go around corners," burrow into bone, and deliver radiation directly to tumors, Stearns says.

Valco's engineers developed the drill in a matter of months, and then partnered with startupIsoTherapeutics in nearby Angleton, TX, to formulate the radioactive solution.

IsoTherapeutics was founded in 2005 by two veterans of Dow Chemical who set out to develop "radiopharmaceuticals"--radioactive compounds designed to shrink tumors. They combined a radioisotope called yttrium-90 with a proprietary formula that prevents the compound from traveling beyond the tumor. The drill makes several tiny holes in the bone surrounding the tumor, and then delivers microscopic amounts of the compound into each hole. Because yttrium-90 emits high-energy beta particles, "we can cover the whole tumor with a minimal dose," says Keith Frank, cofounder of IsoTherapeutics.

And yttrium-90 does not emit gamma radiation, which greatly reduces the risk of radiation exposure to people working with the compound.

The Texas A&M veterinarians who performed Juno's procedure were guided by a high-powered PET/CT scanner. "We were able to see a perfect outline of the leg," Fossum says. After the team injected a contrast agent that binds to glucose in tumors, the PET/CT "showed us where to inject the radioisotope," says Theresa Fossum, a professor of veterinary surgery at the university.

Sixteen dogs have been treated with the experimental procedure at a handful of veterinary schools so far, Frank says. While it's too early to quantify the results, he says, "we always see pain palliation, and we definitely see an increase in survival

" He believes the procedure will work on other types of bone tumors, too.

IsoTherapeutics is currently in talks with researchers who want to test the technique in women with breast cancer that has metastasized to bone, Frank says.

As for Juno, he was walking without a limp 10 days after his treatment.
He'll undergo chemotherapy to attack any latent cancer cells, and then have a follow-up scan in about six months.

Owner Dauvalt says she has no regrets, regardless of what the outcome might be.

"We have to find different ways of treating cancer," she says. "I felt this was an opportunity not only to help my dog, but possibly to help people."
technologyreview

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