October 12, 2018

Cancer-Sniffing Dogs: Where Are We Today?

Scientists are hard at work trying to harness dogs’ ability to detect cancer with their nose.
By Heather Millar
Dog Cancer DetectionWhen it comes to cancer detection, it appears that dogs have some pretty keen senses. Consider these seemingly unusual cases. The dog of a teacher in Kent, England, had become unusually interested in smelling her owner’s breath. When the woman went to her doctor for a checkup, she received a diagnosis of lung cancer. She believes it was because of her dog that her cancer was diagnosed at stage I.

A 40-year-old woman from Rochester, Minnesota, was studying for a test when her dog began nosing at her left side and acting strangely. When the woman brushed away the dog slobber, she felt a lump and subsequently received a diagnosis of breast cancer.

The dog of a woman from Amherst, New York, persistently sniffed a red spot on the woman’s nose, prompting her to get the bump checked. It turns out the bump was basal cell carcinoma that may have caused severe disfigurement if it had gone unchecked.

Google “my dog detected my cancer,” and you’ll find dozens of similar stories from around the world. Of course, there is no proof that any of these dogs—untrained in cancer detection—truly found the disease, but the topic is gaining a foothold in the mainstream, with research teams and nonprofit organizations worldwide taking a closer look.

These are early days for peer-reviewed research results, but studies have established that some dogs, after intensive training, can indeed detect many types of cancer (breast, lung, prostate, thyroid, and colon among them) from a variety of biological samples, including breath, urine, plasma, and blood.

The daunting challenge now is to replicate these studies. Then scientists must figure out how to translate dogs’ diagnostic skills into clinically useful, standardized protocols that can be scaled up from study samples of a few dozen or hundreds to the millions who are screened for cancer each year.

“I absolutely believe that [dogs] can detect cancer,” Cynthia M. Otto, DVM, PhD, director of the University of Pennsylvania School of Veterinary Medicine (Penn Vet) Working Dog Center, said. “The bigger question is how we will use them in the battle to fight cancer.” 
 

Why Dogs?

Estimates vary, but scientists think that a dog’s sense of smell may be 10,000 to 100,000 times better than that of humans. A dog’s anatomy allows it to sniff pretty much continuously, separating air into one stream for respiration and into ano-ther stream for smelling. Pro- portionally, the section of a dog’s brain that is devoted to analyzing smells is 40 times larger than that section in humans. It’s difficult to wrap your mind around a sense that powerful. Scientists offer this vision analogy: It’s as if we see a third of a mile away, while dogs can see 3000 miles away.

Add to this that current cancer detection methods are often less than accurate. In many cases, symptoms don’t appear until the disease is in its late stages. And many types of cancer, such as ovarian and prostate, can’t be detected reliably at early stages.
 

History of Disease-Sniffing Dogs

People noticed long ago that illness had a particular smell. In fact, Hippocrates famously sniffed his patients. Over the past several decades, medical investigators have found that dogs could smell maladies such as hypertension and malaria. 

The smells of disease come mostly from volatile organic compounds (VOCs). We ex- crete hundreds of VOCs in our sweat, breath, urine, and other bodily fluids, creating a signature smell. If we’re sick, it stands to reason that our cells’ metabolism changes, and
so does our odor signature. 

Scientists first identified can- cer VOCs in 1971. But it wasn’t until 1989 that someone put dogs and cancer VOCs together in a report in The Lancet in which the authors recounted the case of a dog that repeatedly sniffed a lesion on its owner’s thigh. That lesion turned out to be early-stage melanoma.1

Evidence was slow to build, however. Finally, in 2004, a research team in the United Kingdom conducted a study to see whether dogs could detect bladder cancer from urine samples.2 After 7 months of training, the dogs got it right 40% of the time. That may not seem amazing by some standards, but it was statistically significant and inspired others to conduct similar research. Positive studies began to accumulate, each of which inspired a flurry of media attention and public enthusiasm. But investigators caution that much work remains to be done.
 

Discrepancies Persist 

Not all studies of canine cancer sniffers have been suc-cessful, and experts need to figure out whether that’s due to the dogs’ cancer-smelling ability or some other factor that affected the results.

In a 2017 feasibility study, David C. Dorman, DVM, PhD, DABVT, DABT, and colleagues presented dogs with urine sam-ples from normal dogs and from dogs known to have cancer.3 “The dogs were trained to signal the odor by moving the scent container with their nose,” explained Dr. Dorman, a professor of toxicology at North Carolina State University College of Veterinary Medicine. A technician would provide the dog with a treat every time it correctly selected the urine from a dog with cancer. “Training kept becoming more complex,” Dr. Dorman said. “We started with 1 normal and 1 cancer urine sample and eventually moved to multiple samples of each from different dogs.” At the conclusion of the study, only 1 of the 4 dogs learned to identify urine from a dog with cancer.

The final study phase used double-blind tests to evaluate whether this single dog would generalize this behavior to novel urine samples. “As it turned out, the dog wasn’t able to reliably detect the cancer sample,” Dr. Dorman said. “Our results are similar to what some others have found using urine samples from men with prostate cancer.” 

Still, Dr. Dorman doesn’t dismiss the possibility that dogs can detect cancer. “I believe that we can train dogs to detect some cancers,” he said. “I doubt, however, that this training will apply to all forms of cancer because no 2 forms of cancer are necessarily identical.”

Although he has no studies related to cancer detection in his pipeline, Dr. Dorman suggested that future studies consider technical issues related to dog training, blinding technicians, and collection and storage of appropriate urine samples. “Another challenge could be that the chemical signals cancer makes could vary with time and may also vary from animal to animal or person to person,” he added.
 

Looking Ahead

Cancer Detection DogExperts at the Penn Vet Working Dog Center are currently focused on ovarian cancer detection. “Our first manuscript is under review in the Journal of Breath Research, and our goal is to continue to work with our collaborators to develop an early screening device for ovarian cancer,” said Dr. Otto, who is also an associate professor of critical care at Penn Vet. “We use the dogs as the gold standard and are actively working with the them to determine the minimum threshold of odor for detection.”

In a recent proof-of-concept study, a German research team determined that dogs could be a valuable tool for lung cancer diagnosis.4 The investigators obtained 9 breath samples from healthy individuals and 10 samples from patients with lung cancer who had not yet begun treatment. They also prepared 4 synthetic air samples containing several VOCs: 1-butanol, 2-butanone, 2-pentanone, and hexanal.

Only 2 dogs in the study, a Labrador retriever and a poodle, successfully completed training and were used for testing. Of the 9 samples from patients with lung cancer, the Labrador correctly identified all 9 and the poodle identified 8 as positive. Of 10 samples from healthy patients, the Labrador correctly identified 8 and the poodle identified 4 as negative. Next, the dogs attempted to distinguish between the synthetic air samples (n = 4) and samples from healthy patients (n = 10). Each dog correctly identified 3 synthetic air samples as positive.4 The investigators concluded that “specially trained detection dogs are a useful tool for finding the best possible biomarker for an effective diagnostic system for lung cancer.”

Even with research results that sway in either direction, there’s still the question of what to do with the knowledge that dogs may be able to smell cancer. Should an army of trained dogs be deployed to hospitals? In part, the In Situ Foundation in the United States and Medical Detection Dogs in the United Kingdom are working toward that.
“People call or email all the time, asking for our services,” said Dina Zaphiris, a dog trainer and CEO of the In Situ Foundation. “They might have lung plaques and be told to go home and wait 6 months. They say, ‘I’ll pay you anything.’ But it’s not that simple; we have to consider the science and also liability issues.”

Based in Chico, California, the In Situ Foundation runs cancer detection certification classes for dog trainers, drawing students from as far away as Finland, Canada, and Argentina. Several graduates of those programs are planning to set up partnerships with local hospitals, and In Situ is also in talks with a nearby California hospital.
In Canada, a service called CancerDogs is working with the Florida-based Fire Fighter Cancer Foundation to screen breath samples from firefighters throughout Canada and the United States. More than 40,000 men and women have been screened to date.5

Ultimately, it will be helpful to establish a system for verifying and validating what dogs find. This would control the rate of false-positives and prevent the sleepless nights that could come with positive findings by dogs that could not be confirmed by computed tomography or other tests.

A version of this article original appeared on CureToday.com
References
1. Williams H, Pembroke A. Sniffer dogs in the melanoma clinic? Lancet. 1989;333 (8640):734. doi: 10.1016/S0140-6736(89)92257-5.
2. Willis CM, Church SM, Guest CM, et al. Olfactory detection of human bladder cancer by dogs: proof of principle study. BMJ. 2004;329(7468):712. doi: 10.1136/bmj.329.7468.712.
3. Dorman DC, Foster ML, Fernhoff KE, Hess PR. Canine scent detection of canine cancer: a feasibility study. Vet Med Res Rep. 2017;8:69-76. doi: 10.2147/VMRR.S148594.
4. Fischer-Tenhagen C, Johnen D, Nehls I, Becker R. A proof of concept: are detection dogs a useful tool to verify potential biomarkers for lung cancer? Front Vet Sci. 2018;5:52. doi: 10.3389/fvets.2018.00052.
5. Blackwell T. Canadian firm uses dogs to screen thousands of U.S. firefighters for cancer, but critics see no proof it works. National Post. March 26, 2017. nationalpost.com/health/canadian-firm-uses-dogs-to-screen-thousands-of-u-s-firefighters-for-cancer-but-critics-see-no-proof-it-works. Accessed June 27, 2018.

 

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