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 these lumps are actually lymph nodes and that many (if not 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; he simply has lumps.
The next step is a blood panel and urinalysis to 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 know the average life expectancy for a patient with untreated lymphoma is about two months from the time of diagnosis. If this is your dog's situation, you probably need some time to absorb the cancer diagnosis. You have many general questions and you know that a decision regarding chemotherapy must be made.
We will cover some commonly asked questions owners have at this point.
The spots indicate the location of peripheral lymph nodes in dogs. Illustration by Dr. Wendy Brooks.
How did my Dog get Lymphoma?
Most of the time, we do not know how dogs or people get cancer. There are many types of cancer and many possible causes of all those cancers (chemicals in our environment, especially cigarette smoke, 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. 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. When these abnormal cells escape our natural mechanisms, cancer develops.
It is important to realize that cancer is not contagious and that, as a pet owner, you should not feel that you somehow caused this or brought it on your pet. 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; furthermore, there is no way to verify cause. At this time, there is no way to know what caused lymphoma development in a given patient. Genetically predisposed breeds include the Basset hound, boxer, Golden retriever, and St. Bernard. It is best to concentrate on treatment.
Can my Dog be Cured?
Theoretically, yes, but practically speaking, no. It is best to focus on a realistic outcome that is the longest possible survival with a good quality of life. Different treatment protocols are associated with different disease-free intervals, meaning that the length of time your dog feels normal will vary depending on the protocol you choose. The disease-free interval also depends on patient factors (type of lymphoma, concurrent disease, prior treatment etc.). Obviously, the goal is to have as long a disease-free interval as possible.
Does my Pet Need Further Tests?
Most likely the answer is yes because there is a great deal more to know before treatment options can be determined. We need to know about the state of the patient's general health and if there are any medications that should not be considered. We need to know what type of lymphocytes are involved. We need to know how far the cancer has spread.
Basic blood work and a urinalysis will be needed to assess the patient's ability to take the medications needed. Obviously liver and kidney function will be relevant, but the blood calcium level is particularly worthy of scrutiny. Some types of lymphoma produce a hormone called PTH-rp (parathyroid hormone related protein) that is capable of creating dangerous elevations in the blood calcium level (see hypercalcemia for more details.) A dog with an elevated blood calcium level tends to have a poorer prognosis. Approximately 15 percent of dogs with lymphoma (and 40 percent of dogs with T-cell lymphoma) have elevated blood calcium levels, so screening is important from the beginning.
If a biopsy has not been performed, it may be a good idea to do one so as to get 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. Special staining of the sample, or even a test such as flow cytometry, is needed to distinguish the type of lymphocyte involved in the tumor. T-cell lymphoma, for example, is less responsive to medication than B-cell lymphoma. Luckily, B-cell lymphoma accounts for 75 percent of canine lymphoma.
Other tests that may be recommended include a bone marrow aspirate , ultrasound of the abdomen, and/or a spleen or liver aspirate. These tests are needed to stage the disease, which basically means determining how widespread the cancer is in the body. 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: bone marrow involvement, regardless of any other areas involved
Staging has less impact on therapy choices than one might think but it is true that patients in Stage V, the most advanced stage, have a poorer prognosis than those in the other stages.
How does Lymphoma Cause Death?
Lymphoma is a rapidly growing malignancy that is able to arise and/or travel to anywhere where there is lymph tissue. Of course, there is lymph tissue in 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 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 classified by the anatomic area affected. By far, the most common form in dogs is the multicentric form, which accounts for 84 percent of canine lymphoma. In this form, as in the hypothetical case we opened with, all peripheral lymph nodes are large and firm. There are three other forms of lymphoma:
- Gastrointestinal form (affecting only the GI tract) accounts for 5-7 percent of canine lymphoma
- Mediastinal (chest)
- Extranodal (skin, eye and other miscellaneous areas).
Lymphoma can occur anywhere in the body where there is lymph tissue. At this time, we will concentrate on multicentric lymphoma. Eventually further information on these rarer forms will be added.
The word chemotherapy conjures images of people losing their hair and suffering chronic nausea. It is unfortunate that many pets do not receive chemotherapy based upon these unpleasant images that do not truly represent the current state of treatment response in pets. Chemotherapy simply means therapy using medication (as opposed to using surgery or radiation). Decades of research has gone into patient comfort, minimizing side effects and maximizing response so it is important to keep an open mind. The following are common questions pet owners commonly have regarding chemotherapy for their dog.
The median survival time for most dogs on chemotherapy is approximately one year with 25 percent of dogs surviving two years.
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 is not. 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, depending on whether or not the patient is feeling ill or not. For example, a multicentric lymphoma dog who feels well is in stage IIIa compared to one 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.
Are there other factors that might suggest a better or worse response to treatment?
The goal is to achieve remission quickly and for the longest possible time. Factors that contribute to an individual dog's ability to do this include:
- Whether he is feeling sick at the time treatment is started. (Dogs that do not feel ill do best).
- Whether there is hypercalcemia (elevated blood calcium) on the blood panel. (Dogs with hypercalcemia do worse).
- Prior exposure (within the last week or so) to corticosteroid medications. (Steroids make the tumor resistant to chemotherapy - see below).
- Whether the lymphocytes involved are B-cells or T-cells. (T-cell lymphoma is more difficult to treat than B-cell lymphoma.)
- Whether there is intestinal involvement. (Intestinal lymphoma is very bad news for a dog.)
- Having Stage V lymphoma. (Most stages carry similar prognoses but Stage V is extra bad.)
- Indolent forms of lymphoma, small cell lymphoma, and low-grade lymphoma progress very slowly but are more resistant to chemotherapy.
Should we see an oncologist?
Lymphoma is a condition that not all veterinarians are comfortable treating. Discuss with your veterinarian whether referral to a specialist would be best for you and your pet.
Will chemotherapy make my dog sick?
Probably not. Nausea or infection are possibilities, but most dogs do not experience any such complications or they are readily controlled with medications. While approximately 25% will experience some kind of side effect, only 7% of patients experience side effects serious enough to require hospitalization. Human chemotherapy is generally much more aggressive, largely because survival goals are much longer, and as a result there is a larger side effect situation. In pets, goals are different — a year of remission versus a decade of remission for people — and protocols are less aggressive. The bottom line is that most pets on chemotherapy do not have significant side effect issues but if they do occur, they are usually manageable.
Will chemotherapy make my dog lose his hair or go bald?
While whiskers are commonly lost, substantial hair loss is not experienced by most dogs or cats on chemotherapy. There are some notable exceptions in those breeds that have synchronous hair follicle activity. Most breeds have hairs in all different stages of the growth-shed cycle at the same time. A few breeds have all hairs in the same stage at the same time. The breeds, including some of their mixed breeds, that have a baldness issue include Old English Sheepdog, poodle, Lhasa Apso, and 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. The chance of achieving remission is pretty good with most protocols: 50-80% depending on the protocol selected. The real differences in protocols concern how long the remission is likely to last. Obviously there are patient factors in play that influence this; see above.
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. (Seeking a second remission after the first remission has been lost 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:
- the disease-free interval (i.e., how long the patient is free from illness)
- survival time
- typical duration of remission
Commonly employed protocols are CHOP, single agent doxorubicin, doxorubicin and prednisolone, Tanovea® and doxorubicin and prednisolone monotherapy. See the links for more information on each drug and its associated side effects and issues. New protocols and new medications are constantly being developed and specialists have the most up to date information.
What is CHOP Therapy?
CHOP is an acronym for cyclophosphamide, doxorubicin HCI (hydroxydaunrubicin), vincristine (brand name Oncovin) and prednisolone/prednisone. The prednisolone/prednisone is typically given daily at home as a tablet while weekly injections/oral treatments are done in the hospital. There are several variations of this regimen but this multidrug format is probably the most common protocol employed regardless of the type of lymphoma. For B-cell lymphomas, 80-90 percent can be expected to achieve remission within the first month. The median survival time is 12 months with 25 percent of patients still alive at two years. Whether the protocol can be curtailed after a certain time or if it should be continued indefinitely is a subject of debate. For T-cell lymphoma, approximately 70 percent will achieve remission with a six to eight month median survival time. CHOP protocols involve drugs that have specific handling requirements and are generally performed with an oncology specialist.
What is Tanovea®?
Tanovea-CA1 is the brand name of a product called rabacfosadine. It is given as an IV infusion every 3 weeks for up to five treatments. It is one of the newest treatments in use for lymphoma. When it is combined with doxorubicin, 68% of dogs achieved remission with a median duration of 194 days while 16% achieved a partial remission. Tanovea-CA1 can be used alone but seems to work better with other medications. The main side effect of concern is pulmonary fibrosis (lung scarring), which is fatal in 5% of patients. West Highland White terriers are predisposed to pulmonary fibrosis and many experts feel this drug should not be used in this breed and should be used with warnings and extra monitoring in any terrier.
What if there are No Specialists or there are Financial Limitations?
If there are no oncology specialists in your area, it may be possible for your regular veterinarian to consult with a specialist to put together an appropriate protocol. There are also services where your veterinarian can not only consult with an oncologist but can also obtain needed medications. If a low income solution is needed, it may be worth considering prednisolone/prednisone monotherapy, which is a fancy term for giving prednisolone/prednisone alone with no other chemotherapy agents.
As chemotherapy goes, prednisolone/prednisone is quite benign and many, if not most, dogs have been on it one time or another for itchy skin. prednisolone/prednisone kills lymphocytes including malignant ones. As with other protocols, remission is frequently obtained within the first month but the remission is likely to be short (one to two months) unless other medications are added in. Furthermore, the use of prednisolone/prednisone makes the tumor resistant to other agents of chemotherapy so that it will be especially difficult to get a second remission after the first remission is lost.
The bottom line is that a remission will likely be possible at a low cost without seeing a specialist, but it will likely be a short one. This option is for patients for whom the other protocols are unavailable.
It should also be mentioned that funded research studies are periodically available. These are clinical trials examining an experimental protocol without cost to the pet owner after it has been determined that a patient is a candidate. See what clinical trials are available.
The Lymphoma Vaccine
An immunotherapy has been recently released in the form of a vaccine meant to extend the disease-free interval in conjunction with the CHOP chemotherapy protocol after remission. The vaccine is currently conditionally licensed, which means that it is believed to be safe and there is a reasonable expectation that it should work but full proof that it works is not available. It is new and somewhat controversial but studies so far are showing median survival times of over 730 days (a large improvement over one year with the CHOP protocol alone). If you are interested in this treatment, ask your veterinarian or veterinary oncologist.
VIN News Service commentaries are opinion pieces presenting insights, personal experiences and/or perspectives on topical issues by members of the veterinary community. To submit a commentary for consideration, email firstname.lastname@example.org.