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The “typical” canine lymphoma patient is a middle-aged dog brought to the veterinarian because one or more lumps have been found. The veterinarian rapidly determines that all of the peripheral lymph nodes (those near the skin surface) are enlarged and firm. Usually the dog has not been showing any signs of illness. The next step is a blood panel and urinalysis to more completely assess the patient’s health and one or more lymph nodes are aspirated or biopsied to confirm the diagnosis of lymphoma.

So here we are. We have confirmed lymphoma and we know the average life expectancy for a patient with untreated lymphoma is about 2 months from the time of diagnosis. If this is your dog you probably need some time to absorb the import of the cancer diagnosis. You have many general questions and you know that a decision regarding chemotherapy must be rendered.

We will attempt to cover commonly asked questions owners have at this point.

How did my dog get lymphoma?
We do not know how dogs (or people for that matter) get cancer most of the time. There are many types of cancer and many possible causes of cancer (chemicals in our environment, sun exposure, assorted viruses and infections). There are important genetic factors as well. Cancer starts with one or a small group of cells that have “gone wrong.” It appears that such cells arise in our bodies all the time and we have an assortment of natural mechanisms to destroy these cells before they get out of hand. Sometimes these cancer cells escape our natural mechanisms and cancer develops. It is important to realize that cancer is not contagious and that, as a pet owner, you should not feel that you caused this or brought it on your pet somehow.

Many people feel a need to find blame and latch onto the idea that a household cleaner or pesticide was the cause. This is a natural part of grieving but it is important not to focus on cause unduly. Cause is not relevant to treatment; further, there is no way to verify cause. It is best to concentrate on treatment. At this time, there is no way to know what caused lymphoma development in a given patient.

Can my dog be cured?
Theoretically, yes, but practically speaking no. It is best to focus on a realistic outcome which is the longest possible survival with good quality life. Different treatment protocols are associated with different disease-free intervals.

Does my pet need further tests?
If a biopsy has not been performed, it is a good idea to have one done so as to gain the maximum information about the tumor (whether it is slow or fast growing, what type of lymphocytes are involved etc.) as this information can help predict the response to chemotherapy. In cats, due to the effects of the feline leukemia virus on the bone marrow, a biopsy is absolutely necessary to diagnose lymphoma as there are many other blood diseases that can mimic lymphoma. In the dog, however, a lymph node aspirate is frequently adequate to make the lymphoma diagnosis. Many oncologists will require a biopsy prior to referral.

Other tests that may be recommended include a bone marrow aspirate and/or a spleen or liver aspirate. These tests are needed to stage the disease. Lymphoma is classified by stage:

Stage I: - only one lymph node involved

Stage II: - several lymph nodes in the same general area involved

Stage III: - all peripheral lymph nodes involved

Stage IV: - all peripheral lymph nodes plus the spleen, liver, and/or anterior mediastinum in the chest involved

Stage V: - everything in stage IV plus bone marrow involvement

In cases of lymphoma that are not as straightforward as the classical multicentric lymphoma described above, staging may be more important. Staging used to be done regularly after the initial diagnosis of lymphoma but it has since been found that stage of disease does not impact upon the response to chemotherapy (i.e., it is not true that a stage II will have a better response than a stage IV). The exception is Stage V, the most advanced stage. Patients with stage V lymphoma tend to have a poor response to chemotherapy.

How does lymphoma cause death?
Lymphoma is a rapidly growing malignancy that is able to go and grow anywhere where there is lymph tissue. This is virtually every organ in the body. Eventually, the cancer will infiltrate an organ to such an extent that that organ fails (often this is the bone marrow or the liver). The patient loses his/her appetite, vomits or gets diarrhea, weakens and dies. At some point the tumor becomes resistant to therapy and no further remissions can be obtained.

My dog does not fit the above scenario at all. What are other forms of lymphoma?
Lymphoma is classifed by anatomic area affected. By far, the most common form in the dog is the multicentric form as described above. There are other forms:

Skin form (also called mycosis fungoides)
 
Gastrointestinal form (affecting only the GI tract)
 
Leukemia (bone marrow form)

Lymphoma can occur anywhere in the body where there is lymph tissue. At this time, I will concentrate on multicentric lymphoma. 

Chemotherapy
The word chemotherapy conjours images of the bald Elizabeth Perkins from The Doctor or the bald and vomiting Campbell Scott in Dying Young. It is unfortunate that many pets (and probably people, too) do not receive chemotherapy based upon these unpleasant images that do not truly represent the current state of treatment response. Chemotherapy simply means therapy using medication, as opposed to therapy using surgery or radiation. We hope that you will open your mind to what decades of research and clinical experience tells us about chemotherapy rather than listening to what Hollywood has to say on the subject. The following are common questions pet owners commonly have regarding chemotherapy for their dog.

My dog is not acting sick in any way. Shouldn’t I wait until she at least feels sick before beginning chemotherapy?
This might seem like a reasonable approach at first glance but let us assure you that it really isn’t. One of the most important factors in determining the quality of remission (i.e., how fast we get remission and how long it lasts) is whether or not the patient is feeling sick at the time chemotherapy is started. When lymphoma patients are staged (see above under “does my pet need further tests”), stages are subcategorized as “a” or “b” (for example, a multicentric lymphoma dog who feels well is in stage IIIa while a multicentric lymphoma dog who is vomiting or not eating is in stage IIIb). You will have a much better chance for long term quality survival if lymphoma is treated while the patient is an “a.”

Should we see an oncologist?
It is never wrong to see a specialist. Lymphoma is such a common malignancy in humans that there are always new drugs, new protocols and experimental therapy that your regular veterinarian may not be familiar with. Seeing a specialist may be the best way to present you with all of your options. If you are interested, ask your veterinarian for a referral.

Will chemotherapy make my dog sick?
Probably not. Nausea or infection are possibilities but most dogs do not experience any such complications. Only 7% of patients require hospitalization due to side effects of chemotherapy. The bottom line here is to know that animals rarely get sick from chemotherapy but that you should know what to do in case of a problem (see later)

Will chemotherapy make my dog lose his hair or go bald?
While whiskers are commonly lost, substantial hair loss is not experienced by animals on chemotherapy for cancer. There are some notable exceptions: breeds that have synchronous hair follicle activity. Most breeds have hairs in all diffferent stages of the growth-shed cycle at the same time. A few breeds have all hairs in the same stage of growth-shed at the same time. The breeds that can have a baldness issue include: the Olde English Sheepdog, the poodle, the lhasa apso, the shih tzu.

How will I know when we have achieved remission?
A patient in remission is indistinguishable from a completely cancer-free patient. The lymph nodes will go down to normal size and if there were any signs of illness related to the cancer, these should resolve. There is approximately a 75% chance of achieving remission regardless of protocol selected.

How will I know when we have lost remission?
The most obvious sign will be that the lymph node enlargement has returned. This means that the cancer is now resistant to the drugs being used and new drugs must be chosen. (This is called a rescue.)

How long will my dog have quality life on chemotherapy?
This depends on what protocol you choose and there are many. There are also many factors that influence how an individual will do relative to the “average” response. Important parameters to note when reviewing a protocol are: 1) the disease-free interval (i.e., how long the patient is free from illness); 2) survival time; 3) typical duration of remission; 4) expense; and 5) scheduling.

Protocols and Studies
Combination chemotherapy with L-asparaginase, lomustine, and prednisone for relapsed or refractory canine lymphoma:  Saba, C.F., Thamm, D.H., Vail, D.M.  Journal of the American College of Veterinary Internal Medicine. Jan/Feb 2007; 21: 127-132.

This study looked at 31 dogs with the multicentric form of lymphoma, all of whom had either relapsed after the CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) protocol or did not  respond to it in the first place. Of these dogs, 52% achieved remission and overall 87% showed at least some response. The median time to achieve a response was 3 weeks. For dogs achieving remission, the disease began to progress again after a median of 111 days. For dogs achieving only a partial response, disease began to progress again after a median of only 42 days). Side effects occured in most dogs but were described as mild and generally required no treatment.

Chemotherapy followed by half-body radiation therapy for canine lymphoma: Williams, L.E., Johnson, J.L., Hauck, M.L. Ruslander, D.M., Price, G., and Thrall, D.E. Journal of the American College of Veterinary Internal Medicine. Sept/Oct 2004; 18: 703-709

Half-body radiation involves irradiating the front of the dog's body two days in a row, waiting 3 weeks, and then irradiating the rear half of the dog's body for two days in a row. In this study 94 dogs with lymphoma received an 11 week chemotherapy induction using prednisone, L-asparaginase, vincristine, doxorubicin, and cyclophosphamide.  Of the 94 dogs receiving chemotherapy, 78% (73 dogs) achieved remission. Of these 73 dogs, 52 underwent half-body radiation as above. Only dogs that had achieved remission were allowed to have radiation. The median remission time for these 52 dogs was 311 days.  Thirty-one of these 52 dogs lost remission during the time of the study and twenty of them repeated chemotherapy induction, followed by maintenance chemotherapy (without more radiation).  Seventeen out of twenty were able to achieve a second remission.  It is not entirely clear whether or not this protocol increased the median remission duration over more routine chemotherapy but the relatively short (11 week) chemotherapy protocol may provide substantial convenience factor for an owner. Another important advantage was the fact that 85% of dog seeking a second remission were able to obtain one. The disadvantage of this protocol is the expense of radiation and the fact that the necessary equipment may not be readily available.

Obviously it is important for a cancer patient to maintain appetite. A good appetite and enjoyment of food is one of the four criteria of life quality that are considered when deciding on euthanasia. Beyond maintaining body condition and getting proper nutrients, however, there are actual nutrients and nutritional strategies that have anti-cancer properties.

Low Carb Diet
Cancer is particularly efficient at using carbohydrates. The low carb diet theory is that a diet restricted in carbohydrates will be inhibitory to tumor growth. This theory plus work with omega 3 fatty acids has led to the production of Hills N/D diet (N/D stands for neoplasia diet, as neoplasia is the scientific term for cancer). See the next section for details regarding omega 3 fatty acids in the treatment of cancer.

Omega 3 Fatty Acids
What is A Fatty Acid?
Biochemically, a fatty acid is what we colloquially fat. When we talk about different types of fatty acids we are talking about different types of fat. A fatty acid consists of a long carbon chain (say 20 or so carbons in length) with a biochemical acid group at one end.

 
Saturated Vs. Unsaturated
Each carbon atom has four binding sites. In the carbon chain, two sites will be taken up by other carbons (i.e., the two adjacent carbons on the chain). In a saturated fat, the other two sites are taken up by hydrogen atoms. Saturated fats are typically sold at room temperature (like lard and butter) and are generally of animal origin. Saturated fats are generally burned as fuel by our bodies.

Unsaturated fats have two adjacent carbons held together by a biochemical double bond. These fats are generally liquid at room temperature and are of plant origin (olive oil, corn oil etc.).

Unsaturated fats can be classified as omega three fatty acids or omega six fatty acids, depending on the location of the double bond relative to the acid group at the end of the chain. These types of fatty acids are essential, meaning that our bodies cannot make them; instead, in order to get them we must eat them in our diet. These fats are not burned for fuel. Instead they are used as structural components. The omega six fatty acids are used as the main structural components in our cells. Omega three’s are used in the structure of the retina and central nervous system.

For healthy skin and coat, the diet must contain adequate
omega six fatty acids as these make up the very surface of the skin.

Examples of omega six fatty acids (also called n-6 fatty acids): Linoleic acid, gamma linolenic acid, and Arachidonic acid.

An excellent source would be evening primrose oil.
 
 

Examples of omega three fatty acids (also called n-3 fatty acids): Alpha linolenic acid, Eicosapentaenoic acid, docosahexanoic acid.

An excellent source is cold water fish oils.

Omega-3 fatty acids have been shown to inhibit the growth and spread of cancer plus they have anti-inflammatory properties. In the study that launched Hills N/D diet, 32 dogs with lymphoma were divided randomly into two groups: one that received a diet heavy in menhaden fish oil and one that received a diet heavy in soy bean oil. Both groups also received chemotherapy with doxorubicin. The dogs that received this omega 3 fatty acid diet went into remission sooner and stayed in remission longer than dogs that received the soy bean oil diet.

Both the low carb and omega three fatty acid therapies are incorporated into Hills N/D diet, which is available as a canned food and is available for dogs only.

Should My Dog Use This Diet?
This diet may be of tremendous benefit to a dog with lymphoma but there are a few caveats:

• This diet was tested on dogs who received BOTH dietary therapy AND chemotherapy. If you are planning to use this diet INSTEAD of chemotherapy, keep in mind that the effectiveness of this strategy remains untested.
• This diet is very expensive as food goes but, of course, very inexpensive as cancer therapy goes.
• This diet is frequently found unpalatable by dogs. Remember that enjoyment of food is an important life quality parameter. If a dog eats N/D diet poorly and loses body condition due to poor appetite, it is probably best to use a different diet which is more palatable.

Hollywood Brand Safflower Oil
The ingredient that is said to be beneficial here is linoleic acid. There are two major brands of safflower oil on the market: Hain and Hollywood. Apparently Hollywood is the brand with the most linoleic acid and is the brand of choice in this somewhat controversial treatment. In one study using eight dogs with Mycosis fungoides (the skin T-cell form of lymphoma), six dogs achieved remission with no other therapy.

In 1999, at the annual American College of Veterinary Dermatology meeting, two case reports were presented: one dog out of remission for mycosis fungoides after chemotherapy, and the other having had no other therapy for mycosis fungoides. The first dog had a partial response to the safflower oil and the other achieved prolonged remission.

Minimal adverse effects come with the use of this oil (if too much oil is used there is a possibility of pancreatitis but, in general, obesity from the fat is the only problem). Safflower oil is inexpensive and readily available.

So what is the catch? Should all lymphoma patients be on this oil? Safflower oil is an omega 6 fatty acid. Omega 6 fatty acids have been shown in other studies to have properties that actually support cancer growth. At this point, safflower oil seems to be a reasonable option only for mycosis fungoides and not other forms of lymphoma.

References
Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma:a double-blind, randomized placebo-controlled study. Cancer 88[8]:1916-28 2000 Apr 15 Ogilvie GK, Fettman MJ, Mallinckrodt CH,Walton JA,Hansen RA,Davenport DJ,Gross KL,Richardson KL, Rogers Q, Hand MSCancer Lett 1992 May 30;64(1):17-22Linoleate produces remission in canine mycosis fungoides.Iwamoto KS, Bennett LR, Norman A, Villalobos AE, Hutson CA Department of Radiological Sciences, University of California, Los Angeles 90024.The Use of Safflower Oil for the Treatment of Mycosis Fungoides in Two Dogs. Peterson, A., Wood, S., and Rosser, E. Dept of Small Animal Clinical Sciences, D208 Veterinary Medical Center, Michigan State University, East Lansing, MI.