Top 5 tips for treating and beating lymphoma in dogs!

Lymphoma is a blood-borne cancer of lymphocytes, which are a specific type of white blood cell. It is the most common cancer diagnosed in dogs. There are several forms of lymphoma in dogs, the most common being high-grade lymphoblastic B-cell lymphoma, which closely resembles non-Hodgkin’s lymphoma in people. Lymphoma is one of the most treatable cancers in dogs, and recent developments in targeted therapies, monoclonal antibodies, and bone marrow transplantation could offer the hope of a cure in the future. Whether your dog was recently diagnosed, currently undergoing treatment, or you’re looking for information about disease prevention, you will find the following tips for treating and beating canine lymphoma valuable.

 

1. Pet your pup!

 

While you might expect a dog with cancer to show signs of illness, many dogs with lymphoma behave normally. Feeling enlarged lymph nodes may be the only sign something is wrong, and early detection is helpful for ensuring your dog is a good candidate for treatment. Lymph nodes are most readably felt under your dog’s chin, in front of his or her shoulders, and behind the knees. If you’re not sure about where to feel, here is a helpful video showing the location of lymph nodes in dogs. Don’t be afraid to ask your veterinarian for help. If you feel anything suspicious, contact your veterinarian so your dog can be evaluated as soon as possible.

 

2. Ask your vet for a referral to a board-certified oncologist.

 

If your primary physician was suspicious you had cancer, they would refer you to an oncologist. The same is true for your dog. Meeting with a veterinary oncologist does not mean you are committing to a specific treatment plan. Rather, this is your opportunity to ask questions about what to expect if your pet were to be treated for his disease versus if he were not, and to talk about what tests could be valuable for learning more about your dog’s cancer. Veterinary oncologists have extensive experience in the diagnosis and treatment of canine lymphoma. They will provide the most up-to-date information and have access to advanced treatment options beyond what is available to a general practitioner. For example, there is a newly approved drug for treating lymphoma in dogs that is currently only available to oncologists and could be an excellent option for your pet.

 

3. Purchase pet insurance.

 

While this is not an option to help pay for treatment following a diagnosis, many pet insurance companies will reimburse owners for a portion of the cost of cancer treatment for dogs insured prior to being diagnosed with cancer. Diagnostic tests and cancer treatment costs vary, but typically range from several hundred to several thousand dollars. Owners frequently admit discomfort with the impact that cost has on their decision to pursue treatment. Insurance can relieve some of this burden, allowing them to pursue options they would not have had without coverage. Some pet insurance companies offer “cancer riders” that provide additional reimbursement specifically for cancer care.

 

4. Don’t start treatment with prednisone/steroids before your appointment with your medical oncologist unless absolutely necessary.

 

Prednisone is frequently prescribed to dogs with lymphoma at the time of diagnosis, prior to consultation with a veterinary oncologist. Prednisone is a potent anti-inflammatory drug and can also help kill off a certain proportion of cancerous lymphocytes. While this may seem like a good thing to happen while you’re waiting for your referral appointment, there are two main concerns with this approach. One is prednisone administration prior to pursuing definitive treatment could interfere with tests your veterinary oncologist may recommend. Testing routinely includes labwork to look for cancerous lymphocytes in circulation, as well as imaging tests such as X-rays and abdominal ultrasound exams. If prednisone is started prior to executing these tests, the changes consistent with disease may improve or even completely resolve and your oncologist won’t be able to interpret the data correctly. This means they won’t be able to tell you an accurate stage of your pet’s disease.

 

Secondly, it is speculated that steroids can induce resistance to certain chemotherapy drugs used to treat lymphoma. This means dogs receiving steroids before chemotherapy could have less chance of responding to treatment, and their duration of response could be shorter.

 

Exceptions to this tip include dogs who are sick from lymphoma (e.g. not eating or having trouble breathing) and require more immediate treatment.

 

5. Don’t start your dog on any supplements, vitamins, nutraceuticals, or diet changes until you speak with your veterinarian.

 

It’s human nature to use the Internet to gather information about your pet’s health. A quick search for “canine lymphoma” returns nearly 500,000 hits. An impressive subset of this information is dedicated to the concept of treating dogs with lymphoma with homeopathy or other “natural” substances. Most sites lack evidence-based information proving such data is accurate. The rationale of “it may not help, but it can’t hurt” is false. The absence of a negative side effect does not imply safety—this is what FDA regulation is all about.

 

Some supplements could potentially negatively interfere with chemotherapy. For example, antioxidants may interfere with the mechanism of action of certain chemotherapy drugs as well as the normal physiologic way tumor cells are broken down by the body. There’s also evidence antioxidants may promote cancer growth. This doesn’t mean antioxidants don’t possess potential benefits, it simply reinforces that they must be used rationally and with appropriate research evidence to support their use.

 

While there are no known ways to prevent lymphoma in dogs, we do see this cancer in certain breeds more frequently (Golden Retriever, Labrador Retriever, Boxer, Bull Mastiff, Basset Hound, St. Bernard, Scottish Terrier, Airedale, and Bulldog). Owners of these breeds should talk with their veterinarian about what monitoring steps could be useful. Individuals considering owning one of the at-risk breeds should inquire with their breeder (if possible) about any known cancer patterns in their lines.

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Rescue me!

Lymphoma is a frequently diagnosed cancer in dogs. It is a cancer of lymphocytes, which are a type of white blood cell normally tasked with fighting infections. There are many different forms of lymphoma in dogs, with the most common type (multicentric lymphoma) bearing close resemblance to Non-Hodgkin’s lymphoma in people.

The recommended treatment plan for multicentric lymphoma in dogs is a 6-month course of a multi-drug injectable chemotherapy protocol. This treatment plan is extremely effective at achieving remission, which is a term used to describe when a patient no longer shows any visible, detectable evidence of their disease.

Remission rates are greater than 80%, and survival times can be extended well beyond what would be expected without any treatment.

Remission, unfortunately, does not equate with a cure. Cure would imply that treatment resulted in complete eradication of all of the cancer cells from the dog’s body. Remission indicates the disease is no longer detectable, but is still present.

Ninety-five percent of dogs treated for lymphoma will experience disease relapse (i.e., “come out of remission”). The timing of when this happens is variable.

Relapse typically manifests with the same clinical signs as were shown during the initial diagnosis. For example, if the initial signs of disease were enlarged peripheral lymph nodes that reduced to normal size during treatment, at relapse the lymph nodes would enlarge again.

If the patient was initially administered the multi-drug protocol mentioned above, this is usually considered the most successful plan in re-inducing remission once relapse occurs. The main exception to this recommendation would be a dog who experienced relapse in the midst of, or within a few short weeks of completing, the protocol. In those patients, rescue protocols are more appropriate and effective choices.

There are a many different rescue protocols for canine lymphoma. Amongst veterinary oncologists, owners are surprised to hear there is no one universally agreed upon “next best” way to proceed. Rescue protocols vary in terms of success of inducing remission, expected duration of remission, number of trips to the oncologist for treatment, chance of side effect, and cost.

Many owners are willing to treat their dog with lymphoma with chemotherapy once. Far fewer will embark on additional treatment once relapse is detected. The variables listed above also influence owner’s decisions about how they would next like to proceed.

For some, cost of treatment is not an issue, and efficacy is their primary goal. For others, the price tag associated with the drugs limits what they are able to pursue.

Even when finances do not play a role, aspects of treatment related to the emotional and time commitments required for appointments influence what an owner is, and is not, capable of.

When dogs with lymphoma experience relapse of disease it is a devastating reminder to owners of their pets’ vulnerability. It means their dog will not be a part of the 5% who are cured. It means revisiting the idea of continued chemotherapy. It means additional obligations they may be unprepared for. And it means genuinely facing their pet’s mortality, which is something they may have deeply buried during the time their dog was in remission.

From a clinician’s perspective, relapse evokes a similar set of emotions. These are owners and animals with which I’ve journeyed through diagnosis and six months of treatment. I’ve learned much about their lives, their families, and, of course, their dogs. When a dog comes out of remission, despite knowing the odds were never stacked in my favor, it still feels like a professional failure.

Once lymphoma resurfaces, it’s a harsh reminder that it was always there, lurking beneath the surface of a pet that otherwise behaves exactly the same as a healthy pet. Though I try to stress that relapse is simply an outward manifestation of the dog’s cancer and that there are many options available to re-induce remission, I remind owners that just because we can do something doesn’t mean we have to do anything.

Relapsed cases remind me that the palliative nature of veterinary oncology is a double-edged sword. I afford pets that have cancer with the chance to live longer and happier lives, which fulfills my goals to be an advocate for animals. But I cannot cure them because I must administer doses of drugs at levels designed to maintain a good quality of life during treatment rather than invoking a cure.

This is a bittersweet compromise I make as a veterinarian, who more than anything, must always ensure that I first do no harm.

What’s new for treating lymphoma in dogs?

Lymphoma is the most common cancer diagnosed in dogs and cats. It’s also an extremely common cancer in humans. This represents a unique opportunity where people can potentially benefit from treatment options developed for pets, and vice versa.

In people, lymphoma is usually classified as Hodgkin-like (HL) or Non-Hodgkin-like (NHL), with NHL being the most common form. Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL in people. Though many different forms of lymphoma exist in dogs, the most common form we diagnose in canine patients is similar to the DLBCL seen in humans.

Traditionally, in both people and animals, NHL is treated with chemotherapy using cytotoxic drugs in what is known as the “CHOP” protocol. The chemotherapy drugs in this protocol, though effective, are not specific for cancer cells, and this is the main reason for the adverse side effects seen with treatment.

The idea of using “targeted therapies” as anticancer weapons is not new, but it wasn’t until the late 1990s that this idea became a reality. Targeted therapies are designed to do exactly what their name implies: specifically target cancer cells while sparing healthy cells, thereby reducing side effects and, hopefully, also increasing efficacy.

Rituximab is an example of a targeted therapy in people; it is a “manufactured” antibody directed against a protein located on the outer surface of B-lymphocytes called CD20. After administration, one end of the rituximab antibody binds to the CD20 protein while the other end “sticks out” and signals the patient’s immune system to attack the lymphocyte and destroy it. Rituximab will bind to both cancerous and normal B-lymphocytes, but not to cells of other healthy tissues. making it a specific form of treatment for cancers (and other disorders) of B-lymphocytes, with limited toxicity to other tissues.

For humans with DLBCL, the combination of rituximab with traditional CHOP chemotherapy regimens essentially resulted in achievable cures in many cases, and this combination is now accepted worldwide as the standard of care people with lymphoma. Rituximab in combination with chemotherapy during the initial treatment of less aggressive variants of B-cell lymphoma (other than DLBCL) has also been documented in multiple clinical trials over the past decade.

Rituximab, unfortunately, is an ineffective treatment for canine lymphoma. The engineered antibody is specific only for the human version of CD20; it does not recognize the canine version of this same protein. However, the exciting results seen in people prompted intensive research towards developing monoclonal antibodies that would be effective for dogs.

After many years of study, several pharmaceutical companies have produced B-cell and T-cell monoclonal antibodies for use in dogs, and the veterinary oncology world is on the cusp of having such therapeutics available for widespread commercial use. Preliminary studies show the antibodies are safe and reasonably effective for the treatment of canine lymphoma. Studies are ongoing to determine the optimal timing of treatment, long-term benefit, and to better characterize any adverse effects.

Investigational studies examining the use of these therapeutics in greater detail are available at select veterinary hospitals across the United States. For example, the hospital where I work is one of only a handful of sites chosen to offer the T-cell monoclonal antibody as a treatment option for their patients.

If you would like to find out more information about monoclonal antibody therapy for your dog with lymphoma, please ask your veterinarian or contact your local veterinary oncologist for further information.

A new treatment for pets with cancer? Read here to find out more!

A few months ago I wrote an article describing a developing monoclonal antibody treatment option for treating B-cell lymphoma in dogs: (http://www.petmd.com/blogs/thedailyvet/jintile/2013/oct/new-treatment-for-dog-cancer-lymphoma-30979). Monoclonal antibody therapy represents a promising option for veterinary patients with a variety of tumors. This type of treatment capitalizes on the animal’s own immune system, using it to specifically target and attack cancer cells, while simultaneously affording a reduced risk of systemic side effects when compared to conventional chemotherapy drugs.

 

Since the time of publishing this article, a group of medical researchers in Vienna, Austria, have put forth the results of a small study describing a new and different monoclonal antibody for dogs. This antibody reacts with the canine version of a cell-surface protein called epithelial growth factor receptor (EGFR).

 

EGFR is mutated in many forms of cancers in both people and animals, and are most often found in epithelial cancers, which are tumors of the linings of different organs/tissues. Examples of epithelial tumors include mammary tumors, skin tumors, and lung tumors. Mutations in EGFR can lead to unregulated cell division and growth (e.g. formation of tumors) and can also help cancer cells figure out how to invade into other tissues and spread throughout the body (e.g. metastasize).

 

There are a variety of anti-EGFR monoclonal antibodies available for humans with cancer. One such “human” drug is called Cetuximab ®, which is structurally very similar to the newly developed canine anti-EGFR monoclonal antibody. Cetuximab ® is used to treat people with metastatic colorectal cancer, metastatic non-small cell lung cancer, and different forms of head and neck cancers.

 

Currently, veterinary patients with epithelial cancers (including those mentioned above treated with Cetuximab ®) have little treatment options beyond aggressive surgery and radiation therapy. Conventional injectable and/or oral chemotherapy protocols, though recommended, often lack evidence-based results to suggest their use substantially changes the outcome in pets.

 

Researchers showed the newly developed antibody was able to bind to the surface of canine cells overexpressing EGFR and that application of the antibody caused significant inhibition of canine tumor cell growth/proliferation. Moreover, the antibody was able to cause significant tumor cell killing via direct stimulation of other immune cells in petri dishes.

 

The next step will be establishing the safety and efficacy of the drug “in vivo”, meaning testing whether the results seen in the cells in the laboratory are translatable to live animals. This will usually entail safety trials, followed by efficacy trials, then potentially even larger-scale clinical trials. Each step requires a great deal of time and finances and compliance, which typically translates in to a long lag on knowing any further information while results of such studies are analyzed.

 

It’s interesting to note that while human oncologists have used monoclonal antibodies to treat many different cancers for over 20 years, this form of treatment is in it’s relatively infancy for veterinary oncologists.

 

This likely stems from 1) the astronomical costs associated with the development of such drugs and 2) the major limitations to the current manufacturing and purification processes necessary to mass-produce the antibodies. It’s not unusual for the costs associated with monoclonal antibody therapy to approach over $50,000 US dollars per year for individuals with cancers.  In the veterinary world, this is simply not a realistic option.
This latter point is one of my main concerns for the when/if monoclonal antibody therapy becomes a potential option for veterinary patients. Whether discussing the previously described treatment for lymphoma or the potential new option for epithelial cancers, we have to consider what measures can be taken to ensure the treatments won’t become cost-prohibitive for owners? How can we ensure all our patients have access to the drugs? Will this even be possible, given what we know from our human oncology counterparts?

 

It’s also important to keep in mind that in people, drugs such as Cetuximab ® are usually used in conjunction with other forms of chemotherapy, rather than as a single-agent treatment.   Therefore, monoclonal antibodies are unlikely to be a “magic bullet” for our patients. Veterinary oncologists will still recommend aggressive surgery, radiation therapy, and even injectable and/or oral chemotherapy, in combination with an immunotherapy option. Again, issues related to cost, owner concerns for their pet’s safety and quality of life, and other emotional factors will certainly come into play.

 

The take home message is progress is certainly being made in our field and exciting new options are likely to be available within the next few years.  It can be frustrating to recognize how my profession lags behind the advancements afforded to my human physician counterparts, but as Frederick Douglass said, “If there is no struggle, there is no progress.”

 

When we consider that veterinary oncology is truly still in the infancy of existence, learning about these new options suggests to me that overall, we are doing a pretty good job of progressing despite our struggles – with patients who tend to be much more tolerant of our shortcomings, and a whole lot cuter as a whole.

In memory of a weird dog…

This week marked the passing of a particularly special oncology patient and I wanted to use this entry as a means to tell his story.   It may sound cliché when we say each and every one of our patients are important to us, but it really is true. We do not discriminate, even when our patients literally try to kill us. But some find a way to squirm their way into our hearts just a little deeper than others, and Bear was one such dog. I’m not sure if it was his incredibly fuzzy and untamable hairdo, or his propensity to bolt out of our chemotherapy room and race down the hallway if you left the door open just a split second too long, or the way he would always find a way to position himself for a nap just behind the wheels of my desk chair. Maybe it was the fact Bear had an outstanding appointment with our service pretty much 3-4 times a month over the past year or so for various issues and clinical signs probably better served by a psychologist than a veterinarian.

 

Bear was only 5 years old when he was diagnosed with lymphoma, a blood-borne cancer that occurs all too commonly in dogs. Bear’s case was quite unusual: He was initially seen by our emergency service for the acute onset of a severe nosebleed. Nosebleeds can occur in dogs as a result of several reasons, and although cancer would be one potential cause, for a young dog such as Bear, it would certainly not be the top concern.

 

Bear’s bleeding was so severe he needed to be hospitalized for several days. During this time, he underwent many different tests to try and investigate why it occurred, including blood work, blood pressure testing, a CT scan of his nose, and a procedure called rhinoscopy. This is where a small camera located on the end of a flexible tube is inserted into the nose so the sinuses can be visually examined and evaluated. During these latter procedures, we discovered a mass in the left side of Bear’s nasal cavity and a very enlarged left tonsil. Surgery was performed to remove as much of the mass as possible, and biopsies of the affected tissue showed lymphoma.

 

Soon after, Bear’s owner met with me to discuss treatment options for his disease.   We performed further testing, and found no evidence of lymphoma anywhere else in his body. I talked with his owner about how unusual Bear’s presentation was, and how I was always taught by my mentor: “weird lymphomas behave weirdly”, simply meaning I wasn’t really sure how things were going to go for him. She elected to move forward with treatment, and Bear started on chemotherapy soon after.

 

Bear was a very quirky dog who liked to hide in corners, roll over for belly rubs, and refused to open his mouth for his exams, which was particularly irritating for me since I needed to pay close attention to his tonsils to monitor his disease state. He also loved to flop all 90+lbs of his body to the ground without warning, making it extremely difficult to perform basic tasks such as listening to his heart and lungs. It was also extremely fun to watch him spring from recumbency the second I exited a 2 foot radius from his body. Bear hated confinement, and it would literally take 3 people to manipulate his oversized body into a cage. Once located safely behind the confines of the metal bars, however, he would immediately fall asleep, snoring loudly and peacefully in his slumber. Bear was not a huge fan of other dogs, but for some reason they loved him and would constantly run up to greet him, while he patiently sat and started at the ceiling. I swear if he could whistle a tune and tap his paw in complete denial, he would have.

 

Bear was treated with 6 months of chemotherapy, and towards the end of his protocol, developed unusual wounds on his limbs, likely from an adverse reaction to medication. The wounds required regular care and monitoring, and through it all he never complained (other than the flopping) and spent his summer wearing decorated bandages and specialized braces for his front limbs.

 

This fall, during a routine “Bear checkup”, I noticed his left tonsil was slightly enlarged.   Since he was feeling great at home, we initially decided to monitor him but it wasn’t too long before he started showing signs of illness, and further testing confirmed relapse of his disease. As an oncologist, I know this happens in 95% of dogs with lymphoma, and the timing for when it occurred was exactly when it would be expected. Still, I think for Bear’s case I was hoping the adage of “weird lymphomas behaving weirdly” would hold out in his favor.

 

Bear’s owner elected to try further chemotherapy for him, and we were able to successfully treat his disease. As with most cases, Bear’s second remission was shorter than his first remission, and a few months after starting treatment, I found his stubborn tonsil was enlarged again. Despite additional treatments and short-lived responses, ultimately his disease proved too aggressive, and he crossed over the rainbow bridge this past weekend.

 

Bear wasn’t the most outgoing dog, or the smartest dog, or even the most attractive dog. He never performed tricks, he didn’t wag his tail, and I can’t recall him ever stooping so low as to lick a face or accept a treat. But he had so much personality and so many idiosyncratic behaviors; you couldn’t help but fall in love with him over and over again. And probably what I admire most about him was his ability to undergo his treatments and visits with dignity and patience. I never had the impression he was enduring things, but rather tolerating them. As if he possessed a greater understanding of what we were trying to do for him.

 

We will miss Bear a great deal, and I feel fortunate to have the opportunity to have known him and worked with him and learned from him. And although he may be a good example of how weird lymphomas happen to weird dogs, he still will remain a favorite in our hearts for many years to come.

 

 

 

 

 

Lymphoma

Lymphoma is a relatively common cancer in dogs and cats.  It is a cancer of lymphocytes, which are a type of white blood cell.  Here is a picture of a cytology sample from a fine needle aspirate from a lymph node of a dog with lymphoma.

 

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