Advancing cancer treatment

Dr. Stephen Withrow is a professor of surgical oncology and the Stuart Chair in Oncology at the College of Veterinary Medicine and Biomedical Sciences at Colorado State University in Fort Collins, Colo. He is also the associate director of the university's Animal Cancer Center, which he helped found. And he is the co-author of the textbook Small Animal Clinical Oncology (Saunders, 2006).

DVM: Your special interest is multimodal cancer treatments in animals as a model for humans with cancer. And I understand you initially became interested in that topic when you were an intern in New York City and then again while doing a fellowship at the Mayo Clinic in the 1970s. Can you tell us about those experiences?

Helping humans through animals: Dr. Stephen Withrow, with Angela, a cancer survivor, and Jacki, one of Dr. Withrow's Labrador retrievers.

Withrow: I graduated from the University of Minnesota in 1972 and was working as an intern at the Animal Medical Center in New York. We were encouraged to attend rounds in any of the area hospitals. I went to Memorial Sloan Kettering, and it was there that I became aware that veterinary medicine could have a significant influence on human health.

During this time, I had very good mentors, including my service chief, Dr. Bill DeHoff. My mentors encouraged me to take three months to complete an outside rotation. I chose the Mayo Clinic in Rochester, N.Y., and my time there was a real eye-opener. I learned that with surgical removal, chemotherapy and radiation therapy, there was no reason—short of money—why some of these human treatments couldn't be used in veterinary medicine. All we lacked was education on these techniques.

Eventually those of us interested in surgical oncology formed societies, and then we had certifications and clubs. Eventually, we helped to build this idea of translational medicine. A lot of people see translational medicine as something going from mice to people, but we know that oftentimes dogs and cats should be in the middle of those basic discoveries. So it should be from mice or rats, to dogs or cats, and then to humans.

DVM: You've been quoted as saying you realized back then that surgical oncology for pets needed standardization. What did you mean?

Withrow: In veterinary schools in the 1970s, there was a perception that cancer in animals was untreatable. Back then we rarely used aggressive surgery, radiation or meaningful chemotherapy on animal cancers. I helped develop the discipline of surgical veterinary oncology. We were able to change the paradigm from late detection and poor prognosis to early detection, aggressive interventions and better outcomes.

There also was a need to standardize surgical dosages, similar to how radiation and chemotherapy dosages are standardized. So we were able to help develop the standards of how to surgically treat different types of cancers at different stages. Oncologists began to understand that with these standards they could get extended survival rates, and we got more meaningful and predictive outcomes in an evidence-based fashion. Based on staging, anatomical site and species, we could be more accurate with both big and small interventions once we standardized the surgical dosing. Then we started publishing these techniques, indications and outcomes. We continue to "sell" this model to funding agencies and prove that animal models are relevant.

DVM: Tell us about the limb-sparing technique you developed to treat canine osteosarcoma. What inspired you? How has this been used in human cancer treatment?

Withrow: My specific interest is in bone cancer, osteosarcoma in particular. We see it a lot in dogs, but it's more rare in children. We were able to help develop ways for both animals and kids to keep their limbs. A lot of our early work was with allografts and intra-arterial chemotherapy. Eventually, we were able to prove the safety and efficacy of our limb-sparing practices. We did this work parallel to our physician counterparts and were able to make contributions along the way. Now most kids and some dogs will have their limbs spared.

DVM: You're the only veterinarian who's been admitted as a member to the Musculoskeletal Tumor Society. What are the advantages to joining a human medicine association?

Withrow: About 20 years ago, I was doing a sabbatical at Massachusetts General Hospital in Boston where they really embraced the idea that animal studies, when conducted humanely, can be beneficial to human medicine. At the time there were fewer than 100 people worldwide conducting concerted osteosarcoma research in humans.

I was doing a fellowship with Dr. Henry Mankin, and he was a member of the society. I attended a meeting as a guest. Henry nominated me for membership, and the group voted me in as the sole veterinarian in the group. From the society, I met Dr. Ross Wilkins, a Mayo Clinic-trained researcher who was doing very similar work with osteosarcoma in people as I was doing with animals. And he was based here in Colorado. We began a long friendship, and, through the years, we've collaborated on a lot of work. Through the society, I met the players in the field of sarcoma research and got access to intellects and ideas. And I was their check and balance with ideas relating to animals and pet animal studies. So it's been beneficial both ways.

DVM: The Animal Cancer Center (ACC) is the largest such facility in the world, and it's received 25 consecutive years of funding by the National Cancer Institute. Can you tell us about the center?

Withrow: When I came to Colorado State in 1978, I had an interest in cancer, but there was not much work being done in the field. At first I was doing orthopedics and neurosurgery. Eventually, I met Dr. Ed Gillette, a radiation researcher, and we built a partnership with me as the clinician. We were able to get the center started with some multiple and diverse funding sources. In time, I devoted myself exclusively to cancer.

The Animal Cancer Center grew into a full-service cancer treatment center, offering chemotherapy, radiation, surgery and clinical trials. By 2002, it had grown, and we moved into a 35,000-square-foot cancer research facility. Today, we have teaching facilities; we offer clinical services; and we conduct research and public outreach. We do about 3,000 consultations worldwide annually. And we have 10 labs and employ about 100 people. It's a small business with a diverse funding base. Our core areas of research include pharmacology, nutrition, immunology, genetics, imaging, trials, pathology, physics and musculoskeletal biology.

DVM: Are most of your clients from your area?

Withrow: Yes, about 75 percent of our patients are from Colorado, and about 25 percent of our patients come from all over the world. We see about 5,000 oncology appointments annually.

DVM: How prevalent is cancer in the pet population? Is that number growing or declining? Are certain breeds at risk?

Withrow: We make educated guesses about pet cancer numbers. In human medicine, cancer is a reportable disease, so researchers can get real numbers on incidence, location, type of cancer and that sort of thing. But we don't have that registration requirement yet in veterinary medicine.

The general numbers are these: one in two men, one in three women, one in four dogs and one in five cats will develop cancer at some point in their lives. That said, there are some breeds of animals in which we expect up to 50 percent to contract cancer. It's a moving target, with one of the highest-risk breeds being golden retrievers. We see more cancer in purebred dogs, but we're unsure if the causes are genetic, environmental or nutritional. There also seems to be a higher prevalence of cancer in breeds such as greyhounds, Bernese mountain dogs and flat-coated retrievers.

DVM: Are certain types of cancer more common now than in the past?

Withrow: We're not seeing an epidemic of any individual cancer. That said, we're seeing more vaccine-associated sarcomas in cats, but we're unsure if they're newly developed or they're just newly recognized. We've been able to make some recommendations for cats that get vaccinated regularly, such as using an alternate site or adjusting the timing of the vaccination. And in those cases, the incidence of feline vaccine-associated sarcomas has declined.

For a while, thyroid cancer in cats was seemingly epidemic, but in recent years, those numbers have fallen off. We're still unsure of what triggered the spike. Was it environmental? We don't know. We need more research on that. It's interesting to note that bone cancer is almost identical in dogs and people, but it's practically benign in cats. Certain mouth cancers are curable in dogs and humans, but not in cats.

DVM: What are the most difficult types of cancer for veterinarians to treat and why?

Withrow: Advanced and invasive local disease is hard to treat. These are cases when the pet owner didn't bring the animal in soon enough, or the veterinarian didn't recognize the lump as a problem and by the time we get them, the tumors are big and potentially bad. In addition, cancers we detect late and have spread beyond the initial site are always hard to treat.

DVM: When should a veterinarian recommend surgery for cancer patients?

Withrow: My challenge as a surgeon is to figure out how to stop the tumor growth at the initial site. This is often a formidable challenge. But we've found, as in human medicine, that individualized, customized treatments tend to work best. For example, while surgery is the cornerstone of veterinary oncology, we're also seeing more use of radiation, which is now limited only by the lack of training programs and equipment. Chemotherapy is gaining in popularity and accessibility and is limited only by the cost and potential for toxicity.

Then there are more experimental therapeutics available for clients to purchase and clinical trials that pet owners can enroll their pets in. This is a promising field. Currently, we have 22 clinical trials going at ACC, and two or three show real promise. Of course, it generally takes us one to two years to complete each one, and the trials themselves are not cheap.

DVM: How are the trials funded?

Withrow: We've been able to get some funding from sources that normally fund human medicine, such as the Bill and Melinda Gates Foundation. We're doing a nutrition intervention study with rice and beans that could alter the course or side effects of disease in humans. We're studying the influence of this diet on dogs and cats. The Gates Foundation wants to know if these data are transferrable to people in third-world countries. We also get some funding from the Morris Animal Foundation, which gets its donations mostly from pet owners who want to make an impact on certain diseases. The NIH, pharmaceutical companies and private individuals fund our other studies.

DVM: What types of cancer surgery tend to have the best and worst outcomes and why?

Withrow: The best outcomes are in patients whose cancer is localized and we've done aggressive removal in portions of the jaw, shoulder blade, rib cage and so on. This is where surgery has its role. But some surgeries are only one part of the treatment, and the patient needs a combination of therapies. For example, I might remove 99 percent of the tumor and the rest is treated with radiation or chemotherapy. We also have good surgical outcomes with mast cell tumors and breast cancer—but with a disease like hemangiosarcoma, not so much.

DVM: Any cancer prevention tips you can offer?

Withrow: I wish I knew! Less than 10 percent of animal cancers can be attributed directly to a heritable genetic cause. Cancer in animals is a multifactorial disease. Prevention, I'm afraid, is the elusive Holy Grail. By the way, that's not the case in human medicine. In humans, we know that if you reduce obesity or don't smoke you reduce the incidence of certain cancers. I suppose we could say that in some environments where ultraviolet light is high, light-pigmented or white dogs should get only limited time in the sun.

One thing in particular that's the single best way to prevent cancer in pets—spaying and neutering. If you spay a dog before she's 1 year old you can go a long way in preventing her from getting breast cancer. And in male dogs, you can reduce the risk of cancers of the reproductive system. With spaying and neutering there's a reasonably straightforward cause and effect.

DVM: To help detect early development of cancer in pets, what are some signs clients should watch for?

Withrow: We worked with the Veterinary Cancer Society to put together a list, which readers can find online. [Editor's note: The list is available at vetcancersociety.org/10-common-signs.html.]

DVM: Are there any promising new cancer treatments down the road?

Withrow: Yes. In the last 10 years, there's been a tremendous body of literature examining how cancer develops, how it escapes detection in the body, what cancer cells depend on to grow and much more. The most exciting thing to come out in recent years is the research on targeted pathways to prevent tumor growth. The haystack of information available today is just immense. It's finding the needles that can guide better therapies—that's still the hard part.

That said, the first two licensed drugs for animal cancer were recently released. They're molecularly targeted treatments that work on mast cell cancers, which are common skin tumors in dogs. The drugs are Palladia from Pfizer and Kinavet made by AB Science. While that's a terrific start, we have 200 different cancers to treat. We need help from our chemotherapy colleagues.

DVM: Any final thoughts on the topic of small-animal oncology?

Withrow: It's refreshing to see all of the oncology training and education programs available now, the quality of the care patients get, the availability of referral services and specialized veterinary care and how the private sector and clients have embraced veterinary oncology. Pet owners today are more engaged with their pets and willing to pay for these treatments to save their beloved animals.

DVM: I hear you're looking ahead to retirement. What do you plan to do when you have more time on your hands?

Withrow: I recently stepped down from the director's position at ACC and am now the associate director. Dr. Rod Page is the new director, and the transition has been seamless and exciting for me. That's freed up some time. I like fundraising for the ACC and probably will continue doing that. I will continue to teach surgical oncology and do research.

Loyle is a freelance medical editor and writer in Philadelphia and the former primary editor of the North American Veterinary Licensing Examination.