Feline Lymphoma

Lymphosarcoma, commonly called lymphoma, is one of the most common cancers diagnosed in cats. It is a cancer of the lymphocytes (a type of white blood cell) and lymphoid tissues. Lymphoid tissue is normally present in many places in the body including lymph nodes, spleen, liver, gastrointestinal tract and bone marrow.

Unlike lymphoma in dogs, viral causes of feline lymphoma are well defined. Infection with the feline leukemia virus (FeLV) has been shown to cause a significant (~60 fold) increase in risk for development of lymphoma in cats. Cats with the feline immunodeficiency virus (FIV) are also at increased risk of developing lymphoma (7 fold) and infection with both viruses confers a 77 fold increase in risk. Cats of any age, breed and of either sex can be affected. We typically see lymphoma in younger cats that are infected with the feline leukemia virus, and in older cats that are not infected with the virus. Other possible risk factors include exposure to second hand tobacco smoke, chronic immunosuppressive therapy, as well as chronic inflammatory diseases.

Types of Lymphoma
Lymphoma can be subdivided into several different forms, depending on the primary or predominant site of the tumor. Some cats have multiple sites of involvement and do not fit well into just one category. These are usually animals with very advanced disease.

1. Gastrointestinal Tract: The most common form is involvement of the gastrointestinal (GI) tract. This includes the stomach, intestines and liver; as well as some of the lymph nodes surrounding the intestines. Cats with this type of lymphoma often have clinical signs consisting of vomiting, diarrhea, weight loss or a decreased appetite.

2. Mediastinal: The mediastinum is a term used for a special aggregation of lymphoid tissue in the chest. Cats with this type of lymphoma often are seen because of difficulty breathing due to a large mass in the chest or an accumulation of fluid around the lungs.

3. Renal: The kidneys may be the primary sites of involvement. Cats that have this type are often seen because of signs related to kidney failure (increased thirst, increased urination, loss of appetite, vomiting).

4. Bone Marrow: If the cancer were confined to the bone marrow, it is considered leukemia. The signs that we see in cats are usually related to the decreased numbers of normal cells such as red blood cells that carry oxygen, white blood cells that fight infection and platelets that help with clotting - all of which are made in the bone marrow. Anemia (low red blood cell counts), infections and bleeding are common problems.

5. External Lymph Nodes: In a few cats, the only site of involvement is the external lymph nodes. These cats may be seen because of problems such as vomiting and loss of appetite or because the owner found “lumps” (enlarged lymph nodes) on their cat.

6. Other Sites: We will occasionally see other sites such as the skin, nose, brain and spinal cord as the primary site of involvement

Diagnosis and Initial Evaluation
A biopsy (tissue) or cytology sample is required in order to make a diagnosis of lymphoma. In some cases, we can obtain a diagnosis by a fine needle aspirate but sometimes a biopsy to obtain a larger piece of tissue is necessary to confirm the diagnosis. The ease with which a diagnosis can be obtained depends upon where the tumor is located.

A complete evaluation of a cat suspected of having lymphoma includes determining the extent of the cancer (i.e. looking for spread of the cancer to other sites) which is known as staging. A complete blood count (CBC), serum chemistry profile (which looks at things such as liver and kidney function, protein levels, blood sugar and electrolytes), urinalysis and FeLV/FIV testing are always recommended and provide important information regarding the effects of the cancer on body functions as well as the ability of the patient to handle chemotherapy or other treatments. Additional tests may include radiographs, abdominal ultrasound, bone marrow aspirate and CT/MRI. Chest radiographs (x-rays) allow us to look for internal lymph nodes, lung involvement, an enlarged mediastinum or fluid around the lungs. An abdominal ultrasound allows us to evaluate the liver, spleen, internal lymph nodes and intestinal tract for possible tumor involvement. A bone marrow aspirate allows us to look for tumor cells in the bone marrow as well as to evaluate the marrow’s ability to produce normal blood cells. Once we know the extent of disease, we can then decide on the best treatment for each individual patient.

Treatment and Prognosis
Chemotherapy is the mainstay of treatment for lymphoma; however, there may be situations when surgery and/or radiation are also indicated. Radiation therapy may be recommended if the cancer is localized to one site such as the nasal cavity. Often surgery or radiation therapy is used in addition to chemotherapy. Specific recommendations will be discussed based on your pet’s particular situation.

Lymphoma is very responsive to chemotherapy and 50-60% of treated cats will go into remission. The definition of remission is the complete disappearance of detectable cancer; however, microscopic amounts of tumor cells can remain hidden in the body. A remission is NOT a cure but it does allow your pet to experience a good quality of life without clinical signs associated with their disease. The length of the remission depends upon many factors including the primary site, how sick an animal is at the start of treatment and the extent of disease. In most situations, the average remission and survival times (with chemotherapy) are between six to twelve months; with about 30% of cats experiencing disease control for greater than one year and approximately 10-15% of cats living longer than two years.

Solitary lymphoma such as nasal is generally treated with radiation +/-chemotherapy. The radiation can be considered definitive with the intent for long term control or palliative for symptom relief in order to improve/maintain the patient’s quality with minimal negative impact. The prognosis for solitary lymphoma such as nasal lymphoma is generally better with many cats achieving local control for 1-1.5 years although there is still a concern that the cancer may spread within 3-6 months. If solitary lymphoma is treated with radiation and the cancer spreads later in life chemotherapy can be considered at that time.

The exact chemotherapeutic drugs and schedule will depend upon how aggressively the cancer is behaving, how sick an animal is at the start of treatment and any abnormalities in organ function, particularly kidneys and liver as well as the goals of treatment. Chemotherapy is more effective when we use a combination of drugs; therefore, most protocols generally consist of 4-6 different drugs. This is called a multi-drug protocol. Initially, treatments are given more frequently (i.e. once weekly) and then, depending upon the response and protocol used, are gradually spread out and/or discontinued. Other options for therapy may consist of using a single chemotherapy drug (single agent therapy) at 3- week intervals, or palliative care which is simply designed to keep your pet comfortable at home for as long as possible. While palliative care with drugs may provide comfort it generally only yields 1-2 month survival times. A disadvantage to single agent therapy is that remission rates and expected survival times are much more difficult to predict with these protocols. Bloodwork and/or radiographs and ultrasounds are generally repeated at regular specified intervals to monitor for side effects (such as a low white blood cell count) and to determine the pet’s response to treatment.

If a patient comes out of remission or relapses, we can try to put them back into remission using either new combinations of the same drugs or different drugs. Unfortunately, the chances of obtaining a second remission are lower; however, there are some cats that do respond and have additional time with a good quality of life.

Side effects
Most cats tolerate chemotherapy very well and experience minimal side effects. Serious side effects are only seen in 5-10% of the patients we treat. If side effects are serious or intolerable, we can consider either lowering the dose of the offending drug or substituting a different drug. Side effects include nausea, vomiting and loss of appetite, diarrhea, extreme tiredness or rarely infection. Certain chemotherapy agents can affect organ function over time. Cats do not lose their hair but may lose their whiskers and have a different texture to their fur secondary to chemotherapy.

Infiltrative Bowel Disease in Cats

What does Infiltrative Bowel Disease mean?
The small intestinal tract is a remarkable organ. It has to neutralize acid from the stomach, apply digestive enzymes and emollients, absorb and conduct away the microscopic nutrients, and move its contents from one end of our body to the other. There is also the matter of housing a variety of bacteria without allowing them to access the interior of our body, immunological reactivity, hormonal activity and response, and more. Its layers act as both a barrier and gateway, plus it must have muscle strength for tone and motion. Proper function depends in part on normal thickness of all the delicate layers.

Diseases of Infiltration:
Disease can lead to an influx of inappropriate cells into the layers of the intestine. This infiltration of the bowel by abnormal cells creates thickening and puffiness, which hampers function. The thick intestine does not contract properly, which leads to food pooling and sludging. Pooling and sludging leads to the sensation of nausea and malaise. The thick intestine also cannot absorb nutrients properly, which leads to weight loss and diarrhea. Frequently there is ulceration and bleeding as the membranes become unhealthy.

Dysbiosis:
Bacterial populations become altered when the nutrients available to them change in composition. In other words, what sort of bacteria live in the bowel depends on what nutrients are in abundance around them. Different nutrients promote different bacterial populations for better or worse. Abnormal nutrient absorption can lead to an overgrowth of bacteria or at least an alteration in the proportions of different populations of bacteria, creating a bad neighborhood in the bowel. Toxic bacterial products can be produced. Bacteria can overpower natural barriers, allowing them to crawl up the pancreatic duct or bile duct where they create inflammation in organs that are normally sterile (pancreas and liver).

Fixing it Depends on Knowing the Nature of the Infiltration
There are two common diseases that involve infiltration, intestinal lymphoma and inflammatory bowel disease (IBD). Both diseases involve lymphocytes infiltrating the delicate bowel. In lymphoma, these are malignant cancerous lymphocytes. In IBD, they are active lymphocytes reacting inappropriately to an immunological trigger (such as a food or bacterial waste product). Biopsy is necessary to distinguish these two diseases and distinguishing between the two conditions, allowing for the most effective treatment.

Treating Lymphoma
There are two forms of lymphoma, one associated with a rapid and sustained response to therapy with remissions of one year or longer being common, and the other type being nearly untreatable. Biopsy will determine which type a cat has. Confirmation of lymphoma also allows for a more tailored protocol so as to maximize the quality of remission.

Treating Inflammatory Bowel Disease
IBD is an immune-mediated disease and treatment centers on suppressing the inappropriate immunological response so that the bowel can recover. Special diets may be employed to minimize inappropriate reactions to food in long-term management. It is theoretically possible, eventually, to recover from this disease completely, though most patients need long-term medications to control the inflammation.

The possibly good news here is that because both conditions involve lymphocyte infiltration, there is a great deal of overlap in therapy, so it is possible to make up a treatment plan that will cover both possibilities with a reasonable chance of success. This is not optimal but provides a route to less expensive therapy.

Diagnostics Start with Ultrasound
The normal diagnostic sequence involves basic examination, lab work to rule out metabolic issues, and abdominal ultrasound followed by either endoscopy to obtain intestinal biopsies or exploratory surgery to obtain biopsies. A great deal of information can be obtained by ultrasound. Ultrasound allows for evaluation of tissue not accessible during endoscopy or even surgery. Further, it may even be possible to get the diagnosis without the expense and stress of intestinal biopsy if tissue can be obtained by ultrasound guidance.

That said, there are some caveats to the use of ultrasound as the final diagnostic. For example, there is a great deal of over-lap in bowel thickness between what normal patients have, what IBD patients have, and what lymphoma patients have. Normal patients will not have abnormal layering but sick patients can have completely normal layering. More severe disruptions in layering are more typical of lymphoma, especially when they occur in separate segments, but less severe wall thickness change is not very specific.

Some diagnostic considerations with abdominal ultrasound are as follows:

  • Severe bowel layer distortion implies (but does not confirm) malignancy
  • Milder bowel layer changes could be from either IBD or lymphoma
  • If any lymph nodes are enlarges, they may be aspirated with guidance from the ultrasound. If lymphoma is found, the diagnosis is made. If the node is immunologically reactive only, this does not rule out lymphoma but implies benign disease
  • If no lymph nodes are enlarged, the liver may be aspirated. If lymphoma is found, the diagnosis is made. If lymphoma is not found in the liver, it is not ruled out in the intestines
  • Growths or masses may be discovered that are best managed with surgical removal
  • Disease in other organs may be discovered

If ultrasound findings are not specific and the diagnosis remains ambiguous, in a perfect world referral for endoscopy follows, biopsy samples are taken, and a tailored therapy can initiate, or at least informed decisions can be made. Not every patient is stable for anesthesia, however, and not every owner is financially able to pursue a specialized procedure.

Because there is a great deal of overlap between the treatment for IBD and the treatment for lymphoma, a therapy plan can be designed that covers both possibilities reasonably well. Typically this involves corticosteroids, immunosuppressive medications, special diet, probiotics and nutritional supplements. Response to medication is generally rapid (within a week or two) for IBD, and a common lymphoma statistic is that 75% will achieve remission within three weeks regardless or protocol. Longer remissions can be obtained with more tailored protocols.

Vaccine Associated Sarcomas in Cats (VAS)

Dr. Gail Mason, DVM, MA, DACVIM
Kathi Smith, RVT, Internal Medicine & Oncology Technician

Vaccinating domestic cats against serious infectious disease is an important step in good quality health care. The diseases that are vaccinated for can cause serious illness and/or death. Vaccination against rabies is an important pet health, public health, and legal issue as well. However, due to statistical association between some vaccines and subsequent sarcoma development which was noted over the last decade, vaccine types and protocols are under heavy scrutiny.

Sarcomas
Injection site sarcomas, as the name implies, can develop in areas of the body where vaccination has taken place. This typically is between the animal's shoulder blades (interscapular) or on a hind limb. These tumors are aggressive in nature and are associated with significant tissue inflammation and decay. They tend to infiltrate the normal tissues with malignant tendrils making surgical excision difficult. Although they are considered to be in the class of "soft tissue sarcomas," they have a higher metastatic rate than other tumors of this class.

Staging
Current recommendations suggest that masses noted at vaccine sites which are present 3 or more months post-vaccinations, are greater than 2cm or are rapidly growing should be dealt with in a timely fashion. An incisional biopsy can confirm a VAS. Matastasis can occur to local lymph nodes and to the lungs.

Staging of the patient to evaluate the extent of the disease may include: 
• Chest radiographs (x-rays) 
• Abdominal radiographs
• Routine blood screening
• Ultrasonography or a CT scan

Treatment
Patients have longer survival times when an aggressive, initial resection is performed and is followed by radiation therapy. If the tumor is located on a limb, it may be necessary to perform a limb amputation. As unpleasant as this idea is, it is well-documented that patient recovery is rapid and quality of life can be excellent. Chemotherapy has also been used in the treatment of VAS but its exact efficiency remains to be determined. Most published veterinary medical reports have described use of either doxorubicin and/or carboplatin.

Prognosis
Unfortunately, cats with VAS may have a guarded to poor long term prognosis. Remission times are variable, but most often reported as being between 8 months to 1.6 years. Initial aggressive and complete resection appear to positively influence outcomes and longer, excellent quality remissions have been documented.

Transitional Cell Sarcomas in Dogs

Dr. Gail Mason, DVM, MA, DACVIM
Kathi Smith, RVT, Internal Medicine & Oncology Technician

Primary cancer of the bladder in dogs is relatively uncommon. Of those occurring in that location, transitional cell carcinoma (TCC) accounts for 50-80% of all reported cases.


Diagnosis of Transitional Cell Carcinomas
The clinical signs of bladder cancer in dogs are generally similar to those of urinary tract infections (cystitis) and urinary stones (cystic calculi). For this reason diagnosis by cytology of biopsy is required. Tests used in diagnosing TCC include:

• Urinalysis
• Cytology (urine or tissue aspirate)
• ultrasonography (+/- guided needle biopsy)
• abdominal radiographs (x-rays)
• routine bloodwork
• cystoscopy (fiberoptic exam of bladder/urethra)

Treatment for TCC
The overall metastatic rate for TCC is approximately 50%, and unfortunately, at this time there is no know cure of this disease. Control of local disease and its clinical signs are the main goal of therapy.

Surgery for TCC
Surgery can be a viable option for TCC patients but often the extent and tumor location provide multiple challenges. Surgery is generally considered palliative (vs. curative) for this tumor and may include:
• partial bladder removal (cystectomy)
• urinary tract diversion (catheter placement)
• bladder reconstruction

The risks and benefits expected with surgical treatment of TCC are worthy of a detailed discussion with a veterinary surgical specialist to determine if it is a reasonable option for a particular patient.

Chemotherapy for TCC
Systemic chemotherapy for bladder or urethral TCC has produced varying results. Drugs that have been employed include:
• Doxorubicin
• Mitoxantrone
• Cisplatin
• Cyclophosphamide

Though these drugs are relatively well tolerated in animals, most all reported survival times of less than one year. A recent retrospect study of 25 dogs with inoperable urinary bladder carcinoma suggested a survival advantage might exist when dogs receive doxorubicin (or mitoxantrone) in addition to a platinum-based compound (cisplatin or carboplatin). Similar combinations warrant further investigation. The drugs do, however, frequently abate the patientÕs symptoms.

Piroxicam
Interestingly, though not anticancer drugs per se, piroxicam and other non-steroidal anti-inflammatory drugs (deracoxib, metacam) have shown activity against TCC in dogs. They can be used alone or in combination with chemotherapeutic agents.

Anti-inflammatory drugs can exert antitumor activity by several mechanisms. They appear to include reduction of swelling, pain, formation of new blood vessels in tumor tissue, and perhaps direct antitumor effects on malignant cells.

Piroxicam can be extremely useful in the management of TCC in dogs. It works rapidly to reduce tumor swelling and obstruction to urine outflow. As a single agent, it is known to control TCC for at least as long as multiple-drug protocols.

These drugs can be used safely in many dogs and cats. However, adverse reactions in the gastrointestinal tract (gastritis, vomiting, bleeding ulcers) and in renal (kidney) function have been reported. If your pet is taking such a drug, monitor him/her for signs of decreased appetite, vomiting, or dark black stools, which may necessitate drug withdrawal.

Prognosis
Early diagnosis and intervention in patients with TCC are likely to produce the most favorable prognosis. Currently, recommended combination therapy with surgery, anti-inflammatory agents, and chemotherapeutics offer the best chance of tumor control. The long-term prognosis still remains guarded to poor as remission times uncommonly exceed 1 year. However, remission time can be good quality time for both pet and owner.

Thyroid Tumors in Dogs

Thyroid tumors arise from the thyroid tissue located in the neck.  The majority (80 to 90 %) of thyroid tumors are malignant (carcinomas).  The majority of dogs with thyroid tumors have normal thyroid function.  Decreased thyroid gland production can occur due to tumor destruction of normal thyroid tissue.  Thyroid carcinomas have a moderate potential for metastases (spreading of the cancer), with approximately 33% of patients having evidence of metastases at the time diagnosis.  The most common organ for this tumor to spread (metastasize) to is the lungs. 

Diagnosis

Most dogs will present for a mass or swelling in the neck. Difficulty swallowing, eating or a dry cough are also common.  Tumors may be discrete and freely moveable or may cause a large diffuse swelling of the neck.  Diagnosis may be made with either a fine needle aspirate or incisional biopsy.  Because these tumors have a large blood supply, blood contamination may prevent identification of cancer cells in samples with limited tissue or fine needle aspiration.  For small, moveable tumors, removal with biopsy will yield a definitive diagnosis.  Ultrasound evaluation is often helpful with large masses to determine the degree of invasion and possibility of surgical removal. Once a thyroid tumor has been diagnosed, chest x-rays are recommended to evaluate for possible metastases (spread) to the lungs.   Routine blood work, including a thyroid level is also recommended to evaluate your pet’s overall health, including thyroid function.

Treatment

Surgery:

Treatment recommendations for thyroid tumors are dictated by the size of the mass, degree of invasion, and whether the tumor is functional.  For small, moveable masses, surgical removal is recommended.  If the tumor is contained within the capsule of the gland, is completely removed, and low grade, no further therapy may be needed.  For tumors where surgery is unable to remove all of the tissue or there is evidence of invasion into blood and lymphatic vessels, additional therapy is warranted. A board-certified veterinary surgeon can determine the optimal surgical treatment plan for your pet.  

Radiation Therapy:

Definitive (curative intent)- Definitive course radiation therapy is recommended for patients whose tumors have been “debulked” with surgery, but surgery fails to remove all microscopic tumor tissue.  Radiation therapy is administered in order to kill any remaining tumor cells at the surgical site.  Chemotherapy is often recommended in combination with radiation to try to prevent or delay metastatic disease. 

Chemotherapy:

Chemotherapy is recommended for patients whose tumors exhibit characteristics of aggressive behavior such as invasion into blood or lymphatic vessels.  Chemotherapy is also used in combination with radiation therapy for patients whose tumors have been removed or for patients undergoing palliative radiation for large unresectable tumors.  Chemotherapy without surgery or radiation is useful for controlling thyroid carcinoma, even in cases of metastatic disease.  Most patients can be managed well for months to up to two years.  Carboplatin and doxorubicin chemotherapies appear to have some efficacy in thyroid carcinomas.  Chemotherapy is administered intravenously every 3 weeks for 4 to 5 treatments.  Low-dose oral chemotherapy (metronomic) is another option which is cost effective, provides excellent quality of life and delays regrowth and metastasis by interfering with the tumors ability to form new blood vessels. 

Prognosis

The prognosis for benign thyroid tumors (adenomas) is good, as most benign tumors can be cured with surgery.  The prognosis for thyroid carcinomas is dependent on size of the tumor, grade (differentiation), degree of local invasion, and presence of lymphatic and/or vascular invasion.  For small tumors, surgery alone may yield survival times of 2 to 3 years or longer. 

For tumors that cannot be completely removed with surgery or tumors that have evidence of lymphatic and/or vascular invasion, additional therapy (radiation and/or chemotherapy) is recommended. Ultimately, most patients with thyroid carcinomas will develop metastatic disease; however, with combination therapy, many patients will enjoy cancer-free, good quality of life for 1 to 2 years. 

For large, invasive tumors that cannot be removed with surgery, combination chemotherapy and radiation therapy will often result in decrease of the size of the tumor and a significant improvement in your pet’s quality of life. 

 

 

 

 

 

 

 

 

 

 

Soft Tissue Sarcomas

Soft Tissue Sarcomas (STS) in Cats and Dogs

Soft tissue sarcomas

Soft tissue sarcoma is a general term that refers to a group of tumors that form in tissues of mesenchymal origin such as the connective tissue (e.g. fat, smooth-muscle, blood vessels, lymph vessels, skeletal muscle, etc.) They tend to have similar histologic appearance and biological behavior, and can be either benign (noncancerous) or malignant (cancerous). Soft tissue sarcomas can arise in any part of the body although skin and subcutaneous (the layer of tissue directly underlying the skin) tumors are the most commonly observed.

Soft tissue sarcomas (STS) behave in a locally invasive manner. The incidence of metastasis (spread to different sites) varies from about 8% to 20%. This rate is generally lower than other types of tumors in animals; therefore, aggressive local control of the disease is the key goal.

Diagnosis

The individual STS tumor types can be challenging to distinguish between. Fine-needle aspirates or tissue biopsies are required to confirm a diagnosis. Not infrequently, additional pathology tests are required to more precisely determine the tissue of origin. Also, additional tests are performed in order to evaluate how advanced the disease is. The tests will depend on the type of soft tissue sarcoma but generally involve blood and serum biochemical tests, chest X-rays and imaging.

Disease Staging

Imaging studies of the local tumor may be recommended prior to planning the surgical removal of the tumor and/or radiation therapy, especially in animals with suspected intra-abdominal soft-tissue sarcomas. Advanced imaging techniques such as CT (computed tomography) and MRI (magnetic resonance imaging) are especially useful due to their high level of resolution and detail.

Diagnostic tests that evaluate whether the tumors have spread to other organs include chest X-rays (to check for metastasis to the lungs), abdominal ultrasound (to check for metastasis in the spleen, liver, etc.) and fine-needle aspirates/biopsy of regional lymph nodes (to check for lymph node metastasis). At the very minimum, chest X-rays should be performed prior to initiating treatment since soft tissue sarcomas commonly spread to the lungs. Lymph node metastasis is not common for typical soft tissue sarcoma but their biopsy/cytology should be assessed in animals whose lymph nodes appear abnormal and/or whose specific tumor type is suspected to have a high metastatic potential.

Treatment Options

Surgery

Invasive STS can be challenging to treat as they expend into surrounding structures and require extensive surgery to achieve complete removal. The first surgery is the key opportunity to achieve complete excision. A general principle for removing such tumors is that the tumor should be removed with a significant margin of normal tissue around it (in all directions) to ensure complete removal of all malignant cells. An experienced, board-certified veterinary surgeon is recommended for STS resections.

Some STS appear in locations in which complete resection is difficult without disturbing normal tissue. Depending upon the tumor location, such surgeries as limb amputation, rib resection, and nasal/jaw reconstructions may be required. It is important to note that veterinary patients recover quickly and cosmetically even from these more extensive surgeries.

Radiation Therapy

Radiation therapy can be combined with surgery in either a pre or post-surgical manner. If given prior to surgery, the tumor may decrease in size and be subsequently easier to remove. If radiation therapy is given after surgery, it is intended to eradicate tumor cells which may have left behind during an incomplete excision.





Veterinary patients are quite tolerant of this form of cancer treatment and it can increase the changes for successful long term disease management. This is a highly specialized form of cancer treatment and is provided by veterinary radiation oncologists at:

  • New England Veterinary Oncology Group (NEVOG), Waltham, MA. 781-684-8688

  • Angell Memorial Animal Hospital, Boston, MA. 781-522-7282

  • Tufts University School of Veterinary Medicine, N. Grafton, MA. 508-839-5395

Chemotherapy

The benefit of chemotherapy in the treatment of soft tissue sarcomas has not been quantified. However, recent research has shown that chemotherapy can delay regrowth or spread of aggressive soft tissue sarcomas. Chemotherapeutic agents used include doxorubicin, carboplatin, and certain alkylating agents. Low-dose daily metronomic chemotherapy is also showing promise as treatment for STS. In general, chemotherapy is recommended in patients deemed to have an aggressive tumor (high grade), metastatic disease, and/or intra-abdominal tumors.

Prognosis

The prognosis for soft tissue sarcoma is variable, though long term control or cure is possible. Local control of the tumor is very challenging and local tumor recurrence rates after surgery (with or without radiation) range from 7% to 32%. Poor prognostic factors for local tumor recurrence include large tumor size, incomplete surgical removal and high histologic tumor grade (high grade corresponds with aggressive tumor behavior). Management of recurrent soft tissue sarcomas is usually more difficult than the original tumor, emphasizing the need for aggressive treatment of the initial tumor. Because the median time for tumor recurrence is 368 days, the pets should undergo long term follow-up and frequent check-ups. The metastatic rate for soft tissue sarcomas varies from 8% to 17% with a median time to metastasis of 1 year, depending on the tumor’s properties. The median survival time for dogs with soft tissue sarcomas is 1416 days with surgical treatment and 2270 days with surgical and radiation treatment. Overall, up to 33% of dogs eventually die of tumor related causes.

Types of Soft Tissue Sarcomas

Tissue of origin

Benign tumor

Malignant tumor

Primary sties

Risk of malignant tumor metastasis

Organ of metastasis

Adipose (fat) tissue

Lipoma

Liposarcoma

Limbs, abdominal or chest cavity

Low to moderate

Lungs, liver, spleen, bone

Fibrous tissue

Fibroma

Fibrosarcoma

Limbs, oral cavity

Low to moderate

Lungs

Histiocytic cells

Histiocytoma

Histiocytic sarcoma

Limbs

Moderate to high

Lymph nodes, lungs, spleen, liver, kidneys

Lymph vessels

Lymphangioma

Lymphangiosarcoma

Limbs

Moderate

Lymph nodes

Blood vessels

Hemangioma

Hemangiosarcoma

Spleen, heart, liver, muscle, bone, kidneys

High

Lungs, liver, lymph nodes, distant dermal sites

Nervous tissue

-

Peripheral nerve sheath tumor

Limbs

Low to moderate

Lugns

Skeletal muscle

Rhabdomyoma

Rhabdomyosarcoma

Tongue, larynx, heart, bladder

Low to moderate

Lungs, liver, spleen, kidneys

Synovial tissue

Synovioma

Synovial cell sarcoma

Joints

Moderate to high

Lymph nodes, lungs

Myxoma tissue

Myxoma

Myxosarcoma

Limbs, joints

Low to moderate

Lungs

Source: Withrow Stephen J, and David M. Vail. Small Animal Clinical Oncology, St. Louis: Saunders Elsevier, 2007.

Radiation Therapy

Portland Veterinary Specialists


Radiation, at levels thousands of times the amount used to produce a chest x-ray, can be used medically to kill cells.  Both normal cells and cancer cells are affected, but radiation treatment is designed to maximize tumor effect and minimize normal tissue damage.  This is one reason that radiation treatments are given as a series of small doses rather than one large dose.
Radiation therapy is used to treat localized disease either in a palliative or definitive protocol.  It can be used in the management of cancers that cannot be treated successfully by surgery or chemotherapy alone.  Typically, it is employed following surgery when there are tumor cells remaining after excision, either because of the nature of tumor growth or because complete surgical removal is not possible.  Radiation therapy can offer, in some instances, permanent control of a tumor.

Radiation Therapy Risks
    There are some risks involved with any type of cancer treatment.  In addition to cancer cells, some normal cells will also be damaged by the radiation potentially resulting in side effects. Usually these side effects are outweighed by the benefits of killing the cancer cells. In addition, radiation therapy requires the animal to be perfectly still during treatment.  Thus, general anesthesia is necessary for each treatment and this carries some small but potential risk.  The anesthetic agents used at NEVOG are very safe and short acting since the radiation treatment typically lasts only a few minutes and does not cause any pain or discomfort.  Risk under general anesthesia is higher if the animal is experiencing disease related the lungs, heart, liver or kidneys weather caused by cancer or some other disease process.  

How is the therapy given?
    In veterinary radiation oncology, a machine directs a radiation beam toward the cancer and some normal tissues around it.  At NEVOG, a linear accelerator with electron capabilities is used.  Radiation therapy is given in a series of treatments that encompass several weeks.  A definitive protocol consists of 15-20 treatments (called fractions) given daily Monday-Friday.  This schedule helps reduce long-term radiation side effects in normal tissues by giving smaller daily doses over a period of time.  The treatment area is calculated to include all of the cancer and as little normal tissue as possible.  The total dose used and the number of treatments depends on many factors including the size and location of the cancer, the general health of your pet, and the type of cancer present.  The most important consideration is the total amount of radiation that can be administered to a patient without compromising the ability of healthy tissue to heal.  The treatment area may be marked with ink to enable the treatment to be directed to the same area every time.  Please maintain the marks as directed.  Sometimes radiographs or a CT scan of the treatment area are necessary to develop the appropriate radiation plan and for some patients, we use specific stabilization devices (ie. mask or mold of the head for brain tumors).
Even when long-term control is not possible, radiation therapy may improve a patient’s quality of life.  This is called palliative treatment.  This protocol consists of 3-5 large fractions of radiation given on a weekly, daily or every other day protocol depending on the cancer.  The side effects with this protocol are mild as it is designed to improve the patient’s comfort and quality of life while minimizing the negative impact.

Is radiation therapy ever used in combination with chemotherapy or surgery?
    Yes.  In situations where it is unlikely that any one method of cancer treatment will be effective, radiation therapy can be combined with surgery or chemotherapy.  In some situations a combination of all three types of treatment may be recommended.

How long does the entire treatment last, and what is the treatment schedule?
At NEVOG, most patients receive treatments on a Monday-Friday schedule for a total of 15-20 treatments over the course of 3-4 weeks for definitive treatment or 3-5 weekly, daily or every other day treatments for palliative treatment.  Treatment does not occur on weekends, this is a rest period.  Patients may board in the hospital for the entire treatment period, go home on weekends, be dropped-off daily or treated as an outpatient (1 hour appointment).  Because of the anesthesia required, outpatients should not eat anything before a treatment from midnight the night before. Water may be provided throughout the night.  They can eat about 1-2 hours after the treatment.  Pets may be sleepy for several hours following each treatment.  You may also notice that your pet appears more tired towards the end of the treatment course.

What are the side effects of treatment?
    During treatment the oncologist will monitor the effect of the radiation on the cancer as well as on normal tissue.  Most side effects that occur during radiation therapy, although unpleasant, are usually not serious, and are almost always limited to the area being treated.  Many animals develop skin changes in the area being treated.  Redness of the skin may develop near the end of, or after, radiation therapy.  This may progress to a dry or moist skin reaction, which resembles a severe sunburn or blistering rash.  This "radiation dermatitis" may cause your pet to rub or scratch.  It is important to keep your pet from causing self-trauma, as this will delay the healing phase.  In many cases we use an E. Collar or bandage to prevent self-trauma.  Ointments should be avoided during the moist (raw) phase as this may also delay healing.  You can clean the area with a warm compress and a mild soap.  Medications may also be prescribed to help manage the side effects.  Hairloss in the treated area is common and may persist for some time after the skin effects resolve.  Regrowth generally occurs in most patients and the color of the hair is usually white or gray.  The skin in the treatment field may also become darkly pigmented with time.
    It is unusual for animals to become nauseated and have vomiting or diarrhea as a result of radiation therapy.  This will usually only occur if portions of the abdomen are irradiated.  Some patients may experience diarrhea as a result of stress.  This usually resolves with diet or medical management.  Side effects involving other tissues that may be within the radiation treatment area (such as the eye, skin in the mouth, salivary glands of the oral cavity and bone) will be discussed with you on an individual basis.  The time from first appearance of acute side effects (those that happen in the immediate treatment period) until their resolution is usually 2-3 weeks.  Other side effects, if they occur, develop gradually over months to years and will be discussed as needed on an individual basis.

What happens after the treatment is over?
    It is important for your veterinarian or oncologist to examine your pet periodically after radiation therapy.  This will allow normal tissue side effects to be monitored and the effect of the radiation on the tumor to be evaluated.  It is the goal of definitive radiation therapy to completely eradicate the cancer.  In some pets this happens and no evidence of the tumor persists.  In other pets the tumor may never completely disappear, but growth is stopped and the tumor is essentially controlled.  The specific results to be expected depend on many factors.  Details on the likelihood of success will be provided to you on an individual basis by the radiation oncologist.

Quality of Life

Portland Veterinary Specialists

  Quality vs. quantity

The goal of cancer treatment in the veterinary patient is to achieve a good quality of life for as long as possible. Quantity of life is meaningless without quality. But quality issues are vague and changeable so it is easy to focus instead on quantity because that is a specific, well-defined goal. It is important to keep these two factors in balance. Your veterinarian should provide perspective and be objective and well informed about cancer, its treatment and how it is likely to affect your pet. On the other hand, you know your pet the best, and criteria for determining one animal’s quality of life may not fit for another.

 

  Assessing quality of life

Quality of life means different things to different people. For some people it is their pet chasing a ball or greeting them at the door. For others, it is knowing that pets are eating and sleeping through relaxing, painless days. One of the difficulties in evaluating your pet’s quality of life is that it can decline gradually. For someone living with a pet there may be no obvious daily changes, while to someone who only sees your pet every few weeks or months there could be dramatic change. Because of this, we encourage owners to establish and document their own personal “minimum standards” of quality of life for their pet at the start of cancer treatment. For example, it might be a pet’s lack of interest in eating or going on walks. It might be a pet’s struggling to breathe or inability to “get comfortable”.

Because we cannot ask our pets how they feel, we have to rely on their behavior and from this infer quality of life. Veterinary oncologists have developed measurements of quality of life. The ‘quality of life’ scale developed by Dr. Alice Villalobos (pawspice.com) allows both the pet’s family and the veterinarian to assess overall quality of life. It considers factors that affect an animal’s ability to carry on its normal activities. They are: alertness/mental status, appetite, weight/body condition, activity/exercise tolerance and elimination behaviors. Not only is this assessment a good indicator of how your pet feels overall, it also provides useful medical information. In general, animals that score high (i.e., have close to normal behaviors) tend to tolerate treatments well and do better overall than animals who score lower on the scale.

 

  Balancing cancer treatment and side effects

Cancer treatment usually involves side effects that can affect a pet’s quality of life. The degree of side effects that are tolerable depend on the goal and expected outcome of treatment. If our hope is for a cure or control of cancer (which in veterinary medicine usually means one year or longer), then we may be willing to tolerate treatment side effects with a higher risk, severity and duration. Some risk of temporary decreased quality of life seems reasonable in exchange for many months of good quality of life. Every owner and veterinarian will have their own opinion as to what constitutes acceptable and unacceptable risks and side effects. It is important to thoroughly discuss these concerns with your veterinarian so that together you can work toward a common goal.

 

 

  Palliative treatment

If we believe a cancer is incurable or impossible to control, then our goal becomes one of palliation, which is an attempt to maintain or improve quality of life without attempting to prolong it. We are unwilling to accept anything but minimal treatment side effects because the treatment should not be worse than the disease. Palliative care focuses on supportive measures such as controlling pain and infection and providing adequate nutrition.

 

  End of life

There often comes a point in the treatment of our veterinary cancer patients when we have exhausted all reasonable treatment options, and there is a low probability for quality of life in the future. We must remember that just because a treatment is technically possible does not mean that it is the best thing for our patient. We are then faced with euthanasia as the last treatment option. Just as we have intervened in the pet’s life by providing aggressive medical care in an effort to improve and prolong quality of life, we intervene when these methods are no longer effective so that we do not prolong needless suffering. It is the last act of kindness we can offer.

 

Quality of Life Scale

(The HHHHHMM Scale)

Pet caregivers can use this Quality of Life Scale to determine the success or Pawspice care. Score patients using a scale of 0 to 10 (10 being ideal).

Score

Criterion

0-10

HURT – Adequate pain control and breathing ability is of top concern. Trouble breathing outweighs all concerns. Is the pet’s pain well managed? Can the pet breathe properly? Is oxygen supplementation necessary?

0-10

HUNGER – Is the pet eating enough? Does hand feeding help? Does the pet need a feeding tube?

0-10

HYDRATION – Is the pet dehydrated? For patients not drinking enough water, use subcutaneous fluids daily or twice daily to supplement fluid intake.

0-10

HYGIENE – The pet should be brushed and cleaned, particularly after eliminations. Avoid pressure sores with soft bedding and keep all wounds clean.

0-10

HAPPINESS – Does the pet express joy and interest? Is the pet responsive to family, toys, etc.? Is the pet depressed, lonely, anxious, bored or afraid? Can the pet's bed be moved to be close to family activities?

0-10

MOBILITY - Can the pet get up without assistance? Does the pet need human or mechanical help (e.g. , a cart)? Does the pet feel like going for a walk? Is the pet having seizures or stumbling? (Some caregivers feel euthanasia is preferable to amputation, but an animal with limited mobility yet still alert, happy and responsive can have a good quality of life as long as caregivers are committed to helping their pet.)

0-10

MORE GOOD DAYS THAN BAD - When bad days outnumber good days, quality of life might be too compromised. When a healthy human-animal bond is no longer possible, the caregiver must be made aware that the end is near. The decision for euthanasia needs to be made if the pet is suffering. If death comes peacefully and painlessly at home, that is okay.

TOTAL

A total of 35 points represents acceptable life quality to continue with pet hospice (Pawspice).

 

Feline Quality of Life Scale

The HHHHHMM Quality of Life Scale

Feline caregivers can use this scale to evaluate the success of their Pawspice program. Grading each criterion using a scale of 0 to 10 (10 being ideal) will help caregivers determine Quality of Life for sick cats.

0-10

HURT – Adequate pain control, including breathing ability, is the first and foremost consideration. Is the cat’s pain successfully managed? Is oxygen necessary?

0-10

HUNGER – Is the cat eating enough?  Does hand feeding help?  Does the patient require a feeding tube?

0-10

HYDRATION – Is the patient dehydrated? For cats not drinking or eating foods containing enough water, use subcutaneous fluids once or twice daily to supplement fluid intake.

0-10

HYGIENE – The patient should be kept brushed and cleaned. This is paramount for cats with oral cancer. Check the body for soiling after elimination. Avoid pressure sores and keep all wounds clean.

0-10

HAPPINESS - Does the cat express joy and interest? Is the cat responsive to things around him (family, toys, etc.)? Does the cat purr when scratched or petted? Is the cat depressed, lonely, anxious, bored, and afraid? Can the cat’s bed be near the kitchen and moved near family activities so as not to be isolated?

0-10

MOBILITY – Can the cat get up without help? Is the cat having seizures or stumbling? Some caregivers feel euthanasia is preferable to a definitive surgery, yet cats are resilient. Cats with limited mobility may still be alert and responsive and can have a good quality of life if the family is committed to providing quality care.

0-10

MORE GOOD DAYS THAN BAD – When bad days outnumber good days, quality of life for the dying cat might be too compromised. When a healthy human-animal bond is no longer possible, caregivers must be made aware that their duty is to protect their cat from pain by making the final call for euthanasia. The decision needs to be made if the cat has unresponsive suffering. If death comes peacefully and painlessly at home, that is okay.

TOTAL

A total score of >35 is acceptable Quality of Life for maintaining a good Feline Pawspice.

 

Original concept, Oncology Outlook, by Dr. Alice Villalobos, Quality of Life Scale Helps Make Final Call, VPN, 09/2004; scale format created for author’s book, Canine and Feline Geriatric Oncology; Honoring the Human-Animal Bond, Blackwell Publishing, 2007. Revised for the International Veterinary Association of Pain Management (IVAPM) 2011 Palliative Care and Hospice Guidelines. Feline Scale created by Villalobos and adapted for Feline Internal Medicine

 

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Palladia Treatment

Palladia (toceranib phosphate) tablets

Client Information Sheet

This summary contains important information about Palladia. You should read this information before you start giving your dog Palladia and review it each time the prescription is refilled as there may be new information. This sheet is provided only as a summary and does not take the place of instructions from your veterinarian. Talk with your veterinarian if you do not understand any of this information or if you want to know more about Palladia.

What is Palladia?
Palladia, a tyrosine kinase inhibitor, is a drug used to treat mast cell tumors, a common
form of cancer that affects dogs.

Palladia works in two ways:
    • By killing tumor cells.
    • By cutting off the blood supply to the tumor.

Your veterinarian has decided to include Palladia as a part of your dog’s treatment plan
for mast cell tumor. Other types of treatment, such as surgery, drug treatment and/or
radiation may be included in the plan. Be sure to speak with your veterinarian about all
parts of your dog’s treatment plan.

What do I need to tell my veterinarian about my dog before administering Palladia?
Tell your veterinarian about all other medications your pet is taking, including: prescription drugs; over the counter drugs; heartworm, flea & tick medications; vitamins and supplements, including herbal medications.

Tell your veterinarian if your dog is pregnant, nursing puppies, or is intended for breeding purposes.

How do I give Palladia to my dog?
Palladia should be given to your dog by mouth (orally).

Palladia may be hidden inside a treat; be certain your dog swallows the entire tablet(s).

Follow your veterinarian’s instructions for how much and how often to give Palladia.
See the Handling Instructions section below in order to administer Palladia safely to
your dog.

How will Palladia affect my dog?
Palladia may help shrink your dog’s tumor. Like other cancer treatments, it can be
difficult to predict whether your dog’s tumor will respond to Palladia, and if it does
respond, how long it will remain responsive to Palladia. Regular check ups by your
veterinarian are necessary to determine whether your dog is responding as expected,
and to decide whether your dog should continue to receive Palladia.


What are some possible side effects of Palladia?
Like all drugs, Palladia may cause side effects, even at the prescribed dose. Serious
side effects can occur, with or without warning, and may in some situations result in death.
    • The most common side effects which may occur with Palladia include diarrhea,
    decreased or loss of appetite, lameness, weight loss and blood in the stool.

Stop Palladia immediately and contact your veterinarian if you notice any of the following changes in your dog:
   • Refusal to eat
   • Vomiting or watery stools (diarrhea), especially if more frequent than two times in 24 hours
   • Black tarry stools
   • Bright red blood in vomit or stools
   • Unexplained bruising or bleeding
   • Or if your dog experiences other changes that concern you

There are other side effects which may occur. For a more complete list, ask your veterinarian.

HANDLING INSTRUCTIONS

What do I need to know to handle Palladia safely?
Because Palladia is an anti-cancer drug, extra care must be taken when handling the
tablets, giving the drug to your dog and cleaning up after your dog.

Palladia is not for use in humans.

You should keep Palladia in a secure storage area out of the reach of children. Children should not come in contact with Palladia. Keep children away from feces, urine, or vomit of treated dogs.

If you are pregnant, a nursing mother, or planning to become pregnant and you choose to administer Palladia to your dog, you should be particularly careful and follow the handling procedures described below.

Palladia prevents the formation of new blood vessels in tumors. In a similar manner Palladia may affect blood vessel formation in the developing fetus and may harm an unborn baby (cause birth defects). For pregnant women, accidental ingestion of Palladia ay have adverse effects on pregnancy.

If Palladia is accidentally ingested by you or a family member, seek medical advice immediately. It is important to show the treating physician a copy of the package insert or label. In cases of accidental human ingestion of Palladia, you may experience gastrointestinal discomfort, including vomiting or diarrhea.

The following handling procedures will help to minimize exposure to the active ingredient in Palladia for you and other members of your household:

Anyone who administers Palladia to your dog should wash their hands after handling
tablets.

When you or others are handling the tablets:
• Do not split or break the tablets to avoid disrupting the protective film coating.
• Palladia tablets should be administered to your dog immediately after they are removed from the bottle.
• Protective gloves should be worn if handling broken or moistened tablets. If your dog spits out the Palladia tablet, the tablet will be moistened and should be handled with protective gloves.
• If the Palladia tablet is “hidden” in food, make sure that your dog has eaten the entire dose. This will minimize the potential for exposure to children or other household members.

Cleaning up after your dog:
• Because Palladia is present in the stool, urine and vomit of dogs under treatment, you must wear protective gloves to clean up after your treated dog.
• While your dog receives Palladia, place the stool, feces or vomit, and any disposable towels used to clean up in a plastic bag which should be sealed for general household disposal. This will minimize the potential for exposure to people in contact with the trash.
• You should not wash any items soiled with stool, urine or vomit from your dog with other laundry.

This client information sheet gives the most important information about Palladia. For more information about Palladia, talk with your veterinarian.

To report a suspected adverse reaction call Pfizer Animal Health at 1-800-366-5288.

Made in Italy
Distributed by Pharmacia & Upjohn Company
Division of Pfizer Inc, New York, NY 10017
Issued March 31, 2009

Osteosarcoma/Canine

CANINE OSTEOSARCOMA (Bone Cancer)

Osteosarcoma is the most common primary bone tumor in dogs. Large and giant dog breeds have the highest risk of this malignancy. This tumor is locally destructive to normal body tissues, and has a high metastatic rate (tendency to travel to distant sites in the body). It is one of the cancers in dogs that can be painful when in its active stages. Bones in the limbs that are affected by osteosarcoma can be weakened to the point of fracturing (called a pathological fracture). Osteosarcoma is an aggressive cancer that can develop in any bone of the body but the majority is seen in the limbs (e.g. elbow or the knee) where it is referred to as “appendicular osteosarcoma”. This is a very aggressive tumor that can cause lysis (disintegration of bone) and /or bone production, and it becomes more painful as it progresses. The lameness goes from intermittent to constant over 1 to 3 months. Obvious swelling becomes evident as the tumor grows and normal bone is replaced by the cancerous growth.

If no treatment is rendered, the animal usually succumbs to the disease within 1-2 months from the time of diagnosis. Surgical resection of the tumor and/or limb amputation are key to treatment of osteosarcoma. Though many owners are at first hesitant about surgery, they frequently observe that their dogs improve dramatically after this treatment. This is by and large because a source of constant pain has been removed. Patients generally make a dramatic recovery with 10-14 days of surgery. It is important to note, however, that surgical resection alone does little to prolong the dog’s survival time.

Diagnosis:

The initial evaluation of possible osteosarcoma involves x-rays of the affected site. The x-rays often reveal a characteristic bone pattern that, combined with history and breed, may indicate the presence of an osteosarcoma. While the history, physical examination and x-ray findings may all point to the diagnosis of osteosarcoma, the only bay to confirm the diagnosis is by biopsy.



What evaluation is needed for a pet with bone cancer?

In order to prepare a treatment plan for the pet, it is important to evaluate whether the cancer has spread to other organs. Osteosarcomas are known to metastasize to the lungs so chest x-rays are typically done to check if such spread occurred. Recently, advanced imaging techniques such as CT and MRI are being used to assess lung metastases and to evaluate the pet’s condition in more detail. The malignant growth in the bone may also be due to cancer that spread from other parts of the body. Common sites for these metastases are the lumbar and sacral vertebrae, pelvis and the shaft of long bones. Assessment of the overall health and any co-existing medical conditions is critical to determine the appropriate course of treatment.



What about chemotherapy?

Osteosarcoma is always considered to have spread microscopically in the dog's body by the time the diagnosis is made. This is the reason that surgery alone fails to control the disease. To attack the cancer cells both locally and systemically, chemotherapeutic agents can be used. The goals of therapy are to preserve a good to excellent quality of life for the dog, eliminate pain, and provide as long of a remission time as possible. Cure is not a reasonable goal at this time, and this fact must be realized by the owner prior to initiating therapy. The two most common chemotherapy agents used for osteosarcoma are doxorubicin (Adriamycin©), and platinum compounds such as carboplatin . Doxorubicin and the platinum compounds act synergistically against this type of cancer and they are used together for this purpose.

A total of 3 to 6 treatment sessions are scheduled at approximately 3 week intervals. The first treatment ideally begins about the time the surgical site sutures are removed. Although this protocol mirrors that used in humans, it is usually extremely well-tolerated. The patient’s quality of life is generally good to excellent as well as pain free.

Other Medications:

After chemotherapy, using a daily anti-inflammatory drug such as piroxicam or meloxicam (Metacam®), along with a low dose of antibiotic doxycycline is recommended. Together, these agents have been shown to reduce the growth rate of metastatic tumors. Side effects are uncommon with this combination, but if you detect that your dog has a decreased appetite, an increase in vomiting, or has dark, tar-like stools then stop the medications and alert us.

Side Effects of Therapy?

Healing from surgery is usually rapid and complete. The results in terms of cosmetics, function, and owner acceptance is excellent in most cases. All chemotherapeutic agents have potential side effects, which should be understood by the owner so that proper intervention can occur if the need arises.

Other Therapy:

Radiation therapy is reserved primarily for relieving bone pain at the site when removal is not possible or elected. It is well-tolerated, but not curative.

Post-Therapy

After therapy sessions are completed, your dog should be monitored by us or your local veterinarian about every three months. Chest radiographs (x-rays) are generally done at these times to detect possible disease metastasis. As importantly, doctors love to see how their K-9 and feline survivors are enjoying life.

What is Life Like for Chemotherapy Patients?

Chances are that you, or someone you know, have experienced chemotherapy for the treatment of cancer. Veterinarians who treat animals for cancer use many of the same chemotherapy agents that human oncologists use. Yet, in many ways the experience for pets seems very different. Why? For one thing, dosages of chemotherapy agents used in animals tend to be much lower than those used in people. Humans are given the highest doses possible, the consequences of which may require bone marrow transplantation, extended hospitalization, and numerous costly medications-all with good cause. However, for veterinary patients, this process would be unacceptable and cost prohibitive for most owners. The general quality of life for many veterinary cancer treatment patients can be surprisingly good and very close to normal. Most of the time they can maintain their normal activities, travel, and have fun with the families that love and care for them.

Most currently used anti-cancer agents do not specifically target cancer cells. Rather, they target and damage or kill rapidly growing cells. For the patient, this means cells lining the stomach and intestine (high turnover rate), cells of the bone marrow that make up the immune system (white blood cells, in particular), and cancer cells. It then is little surprise that the most common side effects of chemotherapy agents include mild to moderate nausea, vomiting, diarrhea, and increased risk of infection. Hair loss, in contrast to humans, is uncommon in dogs and cats on chemotherapy. In most animals, hair does not grow continually throughout their lives like it does in people. Some breeds, however, are susceptible to at least some hair loss (especially poodles, sheepdogs, Scotties and schnauzers). If your pet requires a groomer to trim its hair coat – then some hair loss can be anticipated. Pets, however, are not bothered much by this – and they seem to enjoy stylish polar-tec jackets as gifts. The good news is that the normal cell lines can almost always regenerate themselves, while the less well organized malignant cells suffer great damage. However, even at higher dosages, microscopic malignant cell clones remain alive, albeit dormant in the body. Eventually these give rise to drug-resistant cell lines. This is the biological basis of recurrent or metastatic cancers.

Although there is a risk of side effects, the majority of patients complete their therapies without major complications. If they do occur, however, you should be prepared to recognize them and take appropriate action. Over time, the tendency is to have less frequent side effects, as the individual animal’s sensitivity to the drug agents become known, the treatments are less frequent, and the cancer is in remission.

Risks to People Living with Chemotherapy-treated Pets

The anti-cancer drugs are excreted from the animal’s body via urine and feces. This usually happens in the 48 hours following treatment, but can be as long as 5 days for Adriamycin. If it is possible, you should try to have the animal eliminate in an area away from the immediate yard or play area. Cat boxes should be changed regularly, and waste material handled with a scoop. If urine or feces must be handled, use heavy rubber or latex gloves and disposable wipes/towels. Place all waste/towels in a plastic bag and seal it, before disposal. Smooth surfaces may be washed with a dilute bleach solution (1/4 c. to 1 gallon of water). Humans and other household pets living with treated pets are generally thought not to be at any health risk, just as in the case with humans. Pregnant women and children under the age of 18 should not handle ANY animal waste or anti-cancer medications. If any family member living with the pet has a condition that would suppress his/her immune system, it would be prudent to let the veterinarian know.

Prognosis:

Unfortunately virtually all animals diagnosed with osteosarcoma will eventually lose their battle with this disease. However, with appropriate intervention, most patients experience a high-quality of life during their disease remission.

The median survival times (MST) are as follows (used as guidelines only):

Treatment

MST (Days)

% alive at 1 year

% alive at 2 years

Surgery & Chemotherapy

262-540

32-62

10-28

Surgery Only

101-175

11-21

0-4

Radiation Therapy

122-313

-

-

Pain Control Only

107

-

-

Is It Worth It?

This is a difficult question to answer. Every situation and client-pet relationship is different and must be dealt with individually. If it were ever obvious that therapy was not working, or that the pet was indeed experiencing pain or discomfort, we are ethically obligated to inform you. What we can say is that most pets do indeed appear to enjoy their extended life period and do not even realize that they are "ill." However, the owner(s) must believe that they are doing the right thing for their pet and for their situation.

                         ________________________________________________________________



Colorado State University’s Flint Animal Cancer Center has created a series of videos that answer common questions about limb amputation.  The videos illustrate expectations two weeks before, during and after limb amputation.  To view the videos, please click on the link below:

www.csuanimalcancercenter.org/amputation


Pain Management for Cancer Patients

Portland Veterinary Specialists

Cancer pain

One of the biggest concerns you may have concerning your pet’s diagnosis with cancer is whether or not he or she is in pain. Pain associated with cancer in animals is fairly common although we may not always be able to detect it. Whether or not your pet is feeling pain depends on the type and location of the cancer as well as the therapy used to treat the cancer.

Treating pain in our animals with cancer is important not only from a humane perspective but also because chronic, untreated pain can negatively impact important physiologic functions such as wound healing, immunologic defenses and the even the ability to respond to pain treatment. The earlier pain is treated, the easier it is to manage over time and the better quality of life experienced by our animal companions.

Signs of pain in dogs

Some obvious signs of pain include limping, crying out, guarding the area of the body, reluctance to move, decreased or loss of appetite, change in behavior (becoming more aggressive or more submissive), sleeping more, lack of interest in normal activities and for cats, decreased grooming and change in litter box habits.

There may be other more subtle signs, so it is important for you as your pet’s voice to express your concern to your oncologist or veterinarian if you feel your pet is experiencing pain.

Examples of Tumors That Cause Pain in Veterinary Patients

Tumor Type

Expected Severity of Pain

Comments

Primary Bone Sarcoma

Moderate to Severe

Osteosarcoma is the most common (80%), followed by other sarcomas. Most are painful and cause a combination of lytic (destruction of bone) and blastic changes

Joint Tumors

Moderate to Severe

Stretching of the capsule and invasion into bone by primary joint tumors (synovial cell sarcoma, histiocytic sarcoma) or rumors invading around joints (oral tumor invading temporomandibular joint) can be very painful

Metastatic Bone Cancer

Moderate to Severe

Primary carcinomas are from the mammary gland, prostate, anal sac apocrine glands, lungs (cats), and bladder transitional cells. A common site is the spine (especially the lumbar region), but long bones can also be affected. In cats, digit metastasis from pulmonary carcinoma is well-reported. Most metastatic bone tumors are painful, and they most commonly are lytic (destruction of the bone)

Multiple Myeloma

Moderate to Severe

A common feature is osteolytic lesions (spine, long bones), with a risk of pathologic fractures. They can also compress nervous tissue (spinal cord)

Oral Tumors

Mild to Severe

Many will cause bone destruction and soft tissue inflammation. The most common oral tumors in dogs are melanoma, squamous cell carcinoma, and fibrosarcoma. In cats, squamous cell carcinoma is the most common (70%)

Nasal Tumors

Mild to Severe

Nasal tumors can cause considerable destruction and invasion of surrounding tissues, leading to pain

Urinary Tumors

Mild to Severe

Pain can be from invasion of tissues and inflammation, spasms, urinary obstruction, or renal capsule stretching.

Prostate Tumors

Mild to Severe

Pain is from similar causes as those in urinary tumors

Vaginal Tumors

Moderate to Severe

Pain if from similar causes as those in urinary tumors

Mammary Gland

None to Severe

Inflammatory carcinoma is the most painful, associated with pain in nearly 100% of cases. Lymphatic obstruction can be painful

Carcinomatosis

Moderate to Severe

The carcinomatosis is from various tumors (carcinomas, mesothelioma, sarcomas), and diffuse body cavity pain occurs secondary to serosal involvement. Pleural pain can be severe.

Mast Cell Tumors

None to Severe

Mast cell tumors are especially painful when degranulation and peritumor inflammation are present. Some ulcerated and inflamed carcinomas can be painful.

Pancreatic Carcinoma

Moderate to Severe

Pancreatic carcinomas are very painful in people; probably an important component in veterinary pancreatic carcinoma patients as well

Liver & Splenic Tumors

None to Moderate

Stretching the capsule, from primary or metastatic neoplasia can cause considerable visceral pain

Orbital Tumors

Moderate to Severe

Tumors can be primary orbital tumors or secondary to invasion by oral or sinonasal tumors; can cause pain upon opening the mouth

Central Nervous Tumors

Moderate to Severe

The tumors can be primary CNS tumors, or disseminated neoplasia (lymphoma, carcinomas, melanoma, and sarcomas) and can involve the meninges and nerves, or sinonasal tumors can involve the cranial vault. Headaches are common in people with brain tumors

Ear Tumors

Mild to Severe

Ear canal tumors can be painful, especially when secondary infection is present. Middle ear tumors, although uncommon, can be very painful, with bone destruction and pain upon opening the mouth

Brachial Plexus Tumors

Moderate to Severe

These tumors are uncommon but are most often very painful from direct neuropathic and neurogenic pain

Above table is from Understanding and Recognizing Cancer Pain in Dogs and Cats; May 1, 2005: By Lousi-Phillippe de Lormier DVM DACVIM (oncology) and Timothy M. Fan, DVM PhD DACVIM (internal medicine, oncology)

Options for treating pain

The first step in treating cancer pain is treating the cancer. If the therapies are not recommended in your pet’s particular case or you have decided not to pursue these treatments then the next step is to start pain medications.

There are many different types of pain medications or analgesics, as they are sometimes known. Most of these medications are safe and effective with some negative side effects. They include: non-steroidal anti-inflammatories (NSAIDs), opioids, corticosteroids, anticonvulsants (used for their analgesic properties), antidepressants, NMDA receptor blockers and local anesthetics.

The most common side effects from these medications are decreased appetite, vomiting, diarrhea and sedation. Your oncologist or veterinarian may periodically run blood work to monitor kidney and liver values. Any time you feel your pet may be experiencing a side effect from any medication you should call your veterinarian.

Pain management as a dynamic process

It is important to keep in mind that individual animals respond differently to pain medication. This means that frequent reassessment is key to good pain control. Your doctor will ask you regularly about how you feel your pet is responding to the pain medications. We often start with lower doses and fewer types of pain medications and increase them over time as needed.

Regardless of your pet’s diagnosis or treatment plan, the main goal is to improve or maintain a good quality of life. Many people worry that they will not be able to tell when their pet is feeling pain. We will do our best to help guide you and determine the best pain management plan for your pet’s particular situation.

Nasal Cavity Cancer

Cancer of the Nasal Cavity

  • Common symptoms include nasal discharge, nose bleeds, “snorting”, or facial deformity.

  • Radiation therapy is the current standard of care for nasal tumors.

  • Median survival time after full course of radiation treatment ranges from 8 to 19.7 months.

  • Median survival time with surgery alone ranges from 3 to 6 months.

Nasal cavity tumors:

The nasal cavity is a large air-filled space above and behind the nose. Paranasal sinuses are air-filled spaces that communicate with the nasal cavity. The most common type of cancers affecting this region are carcinomas and sarcomas, both of which are locally destructive. Carcinomas form in the lining of the nose and include adenocarcinomas, squamous cell carcinoma and undifferentiated carcinoma subtypes. Sarcomas form in the cartilage, bone or connective tissue within the nose. Although less frequent, other tumor types have been reported in the nasal cavity including melanoma or mast cell tumors. The metastatic rate (spread to other organs) is considered low at the time of diagnosis but can be as high as 50% at the time of death. The most common organs to which the tumors spread are the lymph nodes and the lungs, but can also include other sites like bone, kidneys, liver, skin, or the brain.

Symptoms of nasal cavity tumors in dogs:

The average duration of symptoms before diagnosis is 3 months and include bleeding from the nose, nasal discharge, facial deformity from bone erosion and tumor growth, sneezing, difficulty breathing, or eye discharge due to tumor obstruction of the ducts. Nasal bleeding or discharge will often occur in one nostril but may affect both sides over time. Some of these symptoms overlap with other medical conditions such as fungal infection, foreign body, or inflammation but as the tumor grows, signs such as facial deformity, swelling or eye protrusion may be observed. In cases where the nasal tumor is close to the brain, the dog may suffer from seizures or behavior changes.

Diagnosis of nasal cavity tumors:

To confirm a diagnosis of nasal tumors, the veterinarian will typically perform a physical exam, imaging and biopsy. Advanced imaging techniques such as CT scan and MRI are superior tools for evaluating the extent of tumors in the nasal cavity as well as for planning radiation therapy treatment. In order to definitively confirm the presence of a nasal tumor, a tissue biopsy should be obtained. This can usually be completed with a small fiberoptic instrument in a procedure called a rhinoscopy. Once diagnosis is confirmed as cancer, it is usually recommended to stage the disease (determining how extensive it is) so that an appropriate treatment plan can be developed by the veterinary oncologist. Staging of nasal tumors usually includes lymph node aspiration (to determine whether the tumor spread to the nearby lymph nodes), chest radiographs (to determine whether the tumor spread to the lungs) and blood tests/urinalysis (to determine the overall health of the pet and if the pet is well enough to undergo treatment).

Does cancer cause pain in dogs?

Pain is common in pets with cancer, with some tumors causing more pain than others. In addition to pain caused by the actual tumors, pets will also experience pain associated with cancer treatments such as surgery, radiation therapy or chemotherapy. Untreated pain decreases the pet’s quality of life, and prolongs recovery from the illness, treatment or injury. It is, therefore, essential that veterinary teams taking care of pets with cancer should also play a vital role in educating pet owners about recognizing and managing pain in their pets. The best way to manage cancer pain in pets is to prevent it, a term referred to as preemptive pain management. This strategy anticipates pain ahead of time and administers pain medication before the pet actually experiences pain, thus ensuring the pet’s maximum comfort.

Treatment options for nasal cavity tumors:

Because nasal cancer begins to invade the bone early, surgery (called rhinotomy) alone is not sufficient to control the cancer and is not usually recommended. Radiation therapy directly to the affected area is currently the treatment of choice for nasal tumors and has been shown to improve survival times. The advantage of radiation therapy is that it treats the entire nasal cavity together with the affected bone and has shown the greatest improvement in survival. At this time, it is uncertain whether surgical removal of the tumor prior to radiation therapy provides even better benefit to the patient. The radiation therapy is typically delivered in 10 to 18 treatment sessions over the course of 2 to 4 weeks, thus requiring commitment from the pet owners to complete the course of radiation treatment. More recent protocols involving one treatment per week for 3 weeks has demonstrated efficacy as well. It has been shown that megavoltage radiation therapy results in better survival compared to cobalt radiation therapy. The use of CT imaging prior to initiating radiation therapy can be of tremendous help for effectively directing radiation only toward the affected area while sparing normal healthy tissue. It should be emphasized that radiation therapy is remarkably well-tolerated in animals and usually can reduce or resolve disease symptoms in a short period of time.

For pets unable to undergo radiation therapy, chemotherapy is an option, but one with limited efficacy that does not improve overall survival times. If the tumor is small and did not invade surrounding tissues, surgical removal may be an option; however, very few dogs meet this criteria at the time of diagnosis. As mentioned above, surgical removal of large and/or invasive tumors does not provide any substantial benefit.

 

What are the side effects of radiation therapy?

Unfortunately, radiation therapy will affect some normal tissues that cannot be excluded from the radiation field (the area scheduled for irradiation). The amount of damage will depend on the daily dose of radiation, total radiation and how much of the tissue is being treated. Immediate side effects of radiation therapy usually include inflammation of the oral cavity (mouth), inflammation of the nasal cavity, shedding of the skin, and eye dryness. It is very important to prevent any additional damage to the area caused by the pet’s pawing or licking so Elizabethan collars should be used as needed. The majority of animals tolerate this therapy surprisingly well.

Prognosis for dogs with nasal cavity tumors:

One study of 139 dogs showed that without treatment, the average survival time is 95 days. Another study showed that dogs that underwent surgery alone had a median survival of 3 to 6 months, which is comparable to that reported for no treatment. Prognosis of dogs who show symptoms of nasal bleeding appears to be worse (medial survival of 88 days) compared to those without it (medial survival of 224 days). The median survival time after a full course of radiation treatment alone ranges from 8 to 19.7 months and 43 to 60% of dogs are alive 1 year after radiation and 11 to 44% are alive 2 years after radiation. The use of CT imaging to plan radiation treatment can increase the survival range to 11 to 19.7 months. Although radiation therapy alone is able to provide local control of nasal tumors for approximately 10 months, and thus prolong the patients’ overall survival, most dogs will eventually die or are humanely euthanized as a result of local disease progression.

 

Several characteristics are associated with poorer outcomes (shorter survival) in dogs with nasal tumors such as the patient being over 10 years old, having a tumor-induced facial deformity, presence of lymph node or other organ metastasis, or lack of resolution of clinical signs after radiation therapy.

 

Canine Melanoma Vaccine

Portland Veterinary Specialists

The oncologist recommended Canine Melanoma Vaccine for my dog.  What will it do?  How does it work?

Canine Melanoma Vaccine alerts the immune system to the presence of melanoma proteins, which results in the immune system fighting the cancer cells.  In conjunction with surgery and/or radiation to treat the initial tumor, this immune response may help extend the survival time for most dogs.  The melanoma vaccine is not meant to replace surgery and/or radiation therapy but is intended to be used along with these therapies


Since this is a vaccine, does that mean my dog can get it as a preventative?  Should my dog receive it every year with other vaccinations?

Currently, this vaccine has only been tested as a therapeutic vaccine, for use with dogs that have oral melanoma.  Most experts believe that the incidence of canine melanoma is too low to justify preventive melanoma vaccines for all dogs.


How and where is the vaccine administered?  Why are four doses of the vaccine necessary?

The vaccine is administered into the inner thigh muscle of the dog with by a needle-free injection.  Initial treatment requires administration of four doses of vaccine, one every two weeks.  After this initial series, dogs receive one booster dose every six months.  Each time dogs receive a dose, their immune response becomes stronger in the fight against melanoma.


Is injection of the therapeutic vaccine with the device painful for my dog?

Based on observations made during administrations, dogs do not react to the vaccine in a way that would suggest the vaccine is any more painful than a traditional injection.


What are the risks and side effects associated with my dog receiving Canine Melanoma Vaccine?

A temporary, low-grade fever or redness and swelling at the injection site may be observed in some dogs.  These side effects do not require any treatment and resolve quickly.  No other clinically significant safety issues were observed in safety studies used to support product licensure.


Will this therapeutic vaccine extend my dog’s life?  By how long?

Dogs with advanced melanoma (stages II, III and IV) have a reported survival time of less than five months when treated with standard therapies.  While the effect of therapeutic vaccines varies from one animal to another, most dogs with Stage II (tumors between 2-5 cm) and III (tumor with metastasis to local lymph nodes and/or greater than 5 cm) disease, that have participated in vaccine studies, have recorded improved survival times of one year or more.

Melanoma - Malignant

Oral tumors in dogs and cats are among the most commonly occurring cancers encountered in our patients.  The most common location for oral melanoma is the gum (gingiva) or the buccal mucosa (inside of the cheek), but other locations have been reported such as the inner lining of the lips, palate and tongue.  Oral melanomas are locally aggressive and also have a high likelihood (80%) of metastasis (spread) to other organs such as the regional lymph nodes and lungs.  Although most oral melanomas are very aggressive, there may be a small subset of these tumors, possibly including lingual (tongue) melanomas that may be less metastatic.

Symptoms of Oral Melanoma

Most cats and dogs with oral cancer have a mass in the mouth noticed by the owner.  Pets with oral tumors will typically have symptoms of increased salivation (drooling), facial swelling, bleeding from the mouth, weight loss, foul breath, oral discharge, difficulty swallowing, or pain when opening the mouth.  Loose teeth could be indicative of bone destruction due to the tumor.

Diagnosis

A thorough diagnostic evaluation of oral tumors is critical due to the variety of different tumors that could be present.  Sedation or anesthesia is often required in order to examine the pet’s mouth, especially if the suspected tumors are located in the back of the mouth or involve the tongue.  If the tumor is suspected to be malignant, chest X-rays can be done prior to biopsy to check for metastasis (spread) to the lungs.  Bone destruction is not typically seen on X-rays of the jaw until greater than 40% of the bone is destroyed so what appears to be a normal X-ray cannot exclude the tumor’s bone invasion. Advanced imaging such as CT (computed tomography) or MRI (magnetic resonance imaging) can be valuable tools in staging the disease (determining how advanced it is), especially for evaluating bone invasion and the potential extension of the tumor into the nasal cavity, pharynx or the eye.  The use of CT may eliminate the need for regular X-rays but CT/MRI imaging is more expensive.

Regional lymph nodes should be carefully assessed for any abnormalities, although lymph node size is not an accurate predictor of metastasis.  In a study of 100 dogs, 40% showed normal sized lymph nodes despite being positive for cancer cells, and 49% of dogs who showed lymph node enlargement did not actually have lymph node metastasis.  Lymph node aspirates (isolation of cells for microscopic analysis to check for the presence of any cancer cells) are recommended for pets with oral cancers.

The final diagnostic step, which is done under anesthesia, is incisional biopsy.  Biopsy is preferred over cytology to definitively differentiate between benign (noncancerous) and malignant (cancerous) tumors and determine the exact type of the tumor present.

Treatment Options

Surgery

Surgical removal of oral melanoma is always the primary method of treatment whenever possible.  Since many oral melanomas invade the bone, the surgery will aim to remove not only the tumor itself but also any associated boney structures.  For oral melanomas, an aggressive surgery is usually recommended given the aggressive nature of these tumors.  Cosmetic appearance is generally good after most upper or lower jaw surgeries but can be challenging when both sides have to be surgically treated.  While surgery can reduce the risk of local recurrence (tumor coming back), unfortunately, most dogs will eventually succumb to the tumor’s spread to other organs without further treatment.  In a published study of 37 dogs whose oral melanomas in the lower jaw were removed by partial mandibulectomies (surgery where part of the lower jaw was removed), median survival time was 9.9 months (range 1-36 months), and 21% of dogs were alive after one year.  Twenty of the 37 dogs were euthanized due to recurrent or metastatic disease. 

Types of Surgical Intervention

Mandibulectomy (lower jaw)                          Maxillectomy (upper jaw)

    Classified according to the portion(s) excised

A.     Unilateral rostral                                    A/B. Unilateral premaxillectomy

B.     Bilateral rostral                                      C. Bilateral premaxillectomy

C.     Central                                                   D. Central

D.     Caudal                                                    E. Caudal hemimaxillectomy

E.      Total hemimandibulectomy

F.      ¾ mandibulectomy


Radiation Therapy

Radiation therapy is second to surgery in terms of success of local tumor control.  It is usually reserved for oral tumors that are unable to be removed completely.  It is a well-tolerated form of therapy in animals.

Melanoma Vaccine

Malignant melamonas have a high metastatic rate (spread of cancer to other organs) in both human and veterinary medicine.  For patients with malignant melanoma, the Oncept® Canine Melanoma Vaccine produced by Merial® has proven to be a successful innovation in extending remission up to three times longer than those previously achievable.  This vaccine is administered into the inner thigh muscle of the dog with a needle-free transdermal device, and requires four initial injections at two-week intervals, followed by boosters every six months.  The vaccine has an extremely low incidence of side effects. 

The Canine Melanoma Vaccine treatment is new veterinary oncology but has been fully approved.  The vaccine works by alerting the patient’s own immune system to the presence of melanoma proteins.  This is a novel approach in cancer medicine which results in the immune system fighting the cancer cells that remain in the body. 

Prognosis

Oral melanoma is an aggressive disease with a high potential to metastasize to other organs, usually the lungs.  The median survival of dogs with no treatment is 65 days.  The median survival for dogs treated with surgery alone varies from 150 to 318 days with less than 35% of dogs surviving one year post-diagnosis.  The median survival time for dogs treated with radiation therapy is 211 to 363 days and for cats 66 to 224 days.  Other factors such as the tumor size, stage and success of the first treatment can also predict how well or poorly the pet will do.  Dogs with tumors smaller than 2 cm diameter have a median survival time of 511 days compared to 164 days for those with tumors greater than 2 cm diameter or lymph node metastasis.  This is in contrast to dogs with tumors bigger than 2 cm and metastases, who usually succumb to the disease within five months (approximately 25% of dogs will be alive one year after diagnosis if treated).

The addition of the melanoma vaccine to treatment protocols has been shown to significantly extend patient survival times.  While the specific result varies from one patient to another, most patients experience a doubling or tripling of expected survival times. 

Mast Cell Tumors in Dogs

Dr. Gail Mason, DVM, MA, DACVIM
Kathi L. Smith, RVT
 

Mast cell tumors (MCTs) are fairly common tumors in dogs. They are most frequently found in the superficial layers of the skin, on any part of the body. Frequently, there will be ulceration over the area of the tumor, and the dog may scratch or bite at the affected area. The appearance of the tumor does not reveal its potential for spread or recurrence with any certainty. The tumors are usually singular, but dogs may present with multiple nodules, or recurrent ones. Some nodules occasionally enlarge and then regress in size on their own, due to swelling within the tumor itself. This should always raise the suspicion of the presence of an MCT.

Diagnosis of Mast Cell Tumors

Mast cell tumors do not have a specific appearance. However, they are fairly easily detected by a "needle aspirate and cytology." Insertion of a small needle into the tumor (virtually painless) area is followed by examination of the cells under a microscope. Mast cells are large, round cells that usually have dark granules in them. The granules contain substances which, when released, cause swelling, itching, and redness. Infrequently, when a large number of granules spontaneously discharge their chemical contents into the bloodstream, vomiting, stomach ulcers, shock and even death may result.

Mast Cell Tumor Staging

Mast cell tumors can be somewhat unpredictable in their behavior, relative to other types of tumors in dogs. Because of this, care is taken to "grade" the tumors that are discovered. The grade reflects the degree to which the malignant mast cells differ from normal, non-malignant mast cells. The stage can generally be correlated with tumor behavior, tumor recurrence, and survival of the patient. Mast cell tumors affecting the limbs, head, or neck tend to correlate with a more favorable prognosis than those found on the trunk or groin. Multiple mast cell tumors or those exhibiting rapid growth tend to have a more guarded prognosis. A pathologist determines the tissue grade of the tumor after the tumor is biopsied or removed.

*Grade I: well-differentiated-25% recurrence rate post-surgery

*Grade II: moderately differentiated-44% recurrence rate post-surgery

*Grade III: poorly differentiated-76% recurrence rate post-surgery

 

Treatment for Mast Cell Tumors

Treatment for mast cell tumors may involve surgery (the mainstay), chemotherapy, and/or radiation therapy. Recommendations for treatment are based on the type and grade of the tumor, surgical feasibility, and the presence or absence of spread (dissemination) of malignant mast cells throughout the body. Your veterinarian will usually submit blood tests and request abdominal ultrasound or radiographs (x-rays) to determine the likelihood of malignant mast cells elsewhere in the dog's body. Bone marrow biopsies are no longer routinely done, as they have not shown to have high predictive value for tumor staging.

 

Surgery
For single mast cell tumors, a surgical procedure known as a "wide resection" by an experienced surgeon is performed. This means aggressively excavating the tumor and surrounding tissues so that at least 2-3 cm of normal tissue in all directions is removed. This must include a "deep margin" which involves removing tissue below the tumor. The margins of the removed tissue are marked and examined by a pathologist to determine the presence of any lingering malignant cells. If negative, we refer to it as "clean margins". If the pathologist suspects the presence of mast cells in the remaining tissues of the surgery site, we refer to it as "dirty margins". If the remaining, malignant cells are less than 2 cm from the edge of the biopsy specimen, it is referred to as "close margins".

An aggressive surgery early in the course of mast cell tumor disease is associated with the best overall prognosis. A grade I or II tumor that has been completely removed usually requires no other immediate therapy. A grade III tumor, multiple tumors, recurrent tumors, or tumors with dirty margins (those which for anatomical reasons could not be subjected to further surgery) often require follow-up or "adjunct" therapy.

Radiation Therapy
Radiation therapy is an option for dogs whose mast cells tumors are localized, but too large for a clean resection or in an area difficult to resect such as tissues of the facial region, or as follow-up therapy for tumors with dirty margins. Dogs tolerate radiation therapy well, and it can offer long-term control for these tumors. Radiation therapy would not be appropriate for dogs with multiple tumors or those with evidence of disease throughout the body since the radiation beam treats only a single focus of disease. Radiation treatment can be accessed at New England Veterinary Oncology Group (NEVOG) in Waltham MA., Angell Memorial Animal Hospital in Boston, MA. and Tufts University School of Veterinary Medicine in Grafton, MA. This is a highly specialized form of therapy and we are pleased to refer your pet to these centers if need arises.

Chemotherapy
Chemotherapy denotes the administration of certain anti-cancer drugs in order to delay/prevent tumor growth or spread. It may be used before or after surgery, or alone.

Prednisone (a cortisone) is the most commonly used drug for therapy of mast cell tumors. It is well tolerated by dogs and is usually employed for a minimum of six months. If no new tumors appear within that time, your doctor may wean your dog off the prednisone completely. The side effects of prednisone include weight gain, increased appetite and thirst, bladder or skin infections, and panting. Occasionally, stomach irritation or ulcers can occur, or inflammation of the pancreas. Most of the time, the drug dose can be titrated to the patient to minimize any overt symptoms. If the tumor type is determined to be aggressive, additional drugs such as stomach protectants may be prescribed to guard against untoward tumor effects. By itself, prednisone is considered to have only mild anti-cancer effects on MCTS.

Chlorambucil Protocol
If your pet is deemed to have an increased risk of tumor recurrence, we may recommend combination oral therapy with prednisone and chlorambucil (Leukeran¨). Chlorambucil is a chemotherapy drug that is extremely well tolerated in most patients and yet offers more tumor protection than prednisone alone. This drug is usually administered twice weekly and requires that your pet be monitored at least every 6-8 weeks. The minimum treatment period is 6 months.

Vinblastine Protocol
For recurrent or multiple tumors, and for those tumors that cannot be surgically removed, combination chemotherapy can be effective in controlling tumor growth and spread for weeks to months or more. A cure per se is generally not realistic, but many dogs tolerate therapy extremely well. The six-month protocol involves:

Prednisone: high dose at first, then taper over 4 months
Vinblastine: an outpatient injection, given once every 21 days
Cyclophosphamide (Cytoxan¨): an oral chemotherapy drug, given by the owners on days 8,9,10, and 11 of a 21-day cycle.

This protocol has produced a 1 and 2 year survival rate for grade 2 tumors of 91%. For patients with grade 3 tumors, the 1-year survival rate is 66%.

Side Effects
The side effects of prednisone are discussed above. Vinblastine and Cytoxan have the ability to cause nausea and or vomiting, though this is not usual. The most important possible side effects are lowering the body's defenses so that infections occurs, or (rarely) causing many mast cells to release their contents at once. Both situations can be life threatening. However, these are NOT common, and the risk of these is significantly lower than the risk of untreated mast cell disease. You will be given instructions on what to do if any side effects occur, so do not hesitate to contact us.

Lomustine (CeeNu¨) 
CeeNu is a potent oral chemotherapy drug that can be used once every three weeks in patients who MCTs have become resistant to other treatments. It is very well tolerated in general. However, because it can increase the risk of infection (especially seven days after it is given), any noted fever, depression, weakness, or refusal to eat should be reported to us or your veterinarian, or an emergency hospital immediately. Infection is almost always completely reversible. This drug is more potent than Cytoxan¨ and maybe substituted for it if indicated. Occasionally, this drug may decrease patient blood cell counts, which requires a dose reduction or discontinuance.

Prognosis
The factors that are known to influence patient outcome are grade of tumor (I is best, III is most dangerous), completeness of surgical removal (clean margins), and tumor location. Dogs with high-grade tumors, multiple or recurrent tumors, or evidence of spread to the bloodstream or other organs have a much more guarded prognosis for a lengthy survival.

Patient Monitoring
Close patient monitoring is essential in dogs with a history of mast cell tumors. As with many tumors, early detection and treatment increases the chances of successful treatment. You may be asked to have your dog examined and monitored every 6-8 weeks following surgery, or every 21 days during chemotherapy. Blood tests and/or needle aspirates are often requested to assess tumor control. Any time you suspect a new or recurrent tumor, or that your dog is physically ill, contact us immediately. We welcome the opportunity to help you and your dog in any manner we can.

 

Reference: Mast cell tumors in dogs; In: Managing The Veterinary Cancer Patient; Ogilvie, OK and Moore, As. © 1995 Veterinary Learning Systems. Trenton, NJ. *Based on protocol published by Elmslie, Robin; published in the Veterinary Cancer Newsletter.

 

Mammary Gland Tumors

       Carcinomas are the most common type of mammary gland cancer in both dogs and cats, and approximately 50% of all canine mammary tumors are malignant. Most tumors appear in dogs between 8-10 years of age (similar to cats). The exact etiology of mammary cancer is unknown. It is known that spaying a cat or dog before her first estrus (heat) cycle dramatically decreases the risk of mammary tumors (0-5% risk vs. 26%).

        It is general consensus among veterinary oncologists that no mammary lump should ever be left in place and "observed." Needle biopsies are frequently inconclusive and misleading in this case. Biopsy with wide excision is the primary recommendation. These results help determine the best treatment plan for the patient.

        Mammary tumors can develop either as a single mass or as multiple masses within the mammary gland.  Dogs and cats have multiple mammary glands, all of which can develop one or more benign or malignant tumors.  Benign tumors are typically well defined and firm upon examination whereas the clinical symptoms of malignant tumors include rapid growth, ill-defined boundaries, ulceration and/or inflammation.  Inflammatory carcinomas are typically rapidly growing, affect multiple mammary glands and are characterized by firmness, warmth, observable swelling, redness/rash on the skin, thickening and signs of pain.  Extensive swelling (lympedema) of a limb next to the affected gland(s) can also be observed.  
        Tumor size in both dogs and cats has been found to be prognostic. Dogs with tumors less than 5 cm in diameter (cats less than 2 cm) have significantly longer survival times than animals with larger tumors.


Disease Staging
As with other cancers, it is important to assess the extent of cancer in a particular patient. Complete staging usually requires: 
1. Complete blood count
2. Serum chemistry panel
3. Urinalysis
4. Chest radiographs (x-rays) 
5. Abdominal radiographs
6. +/- Ultrasonography
7. Cytology of regional lymph nodes
8. Review and assessment of biopsy results. This includes complete vs. incomplete resection borders as well as cell types and degree of tumor invasiveness.


Treatment
The traditional method of treatment for mammary tumors in dogs and cats is surgery. Treatment by local excision with wide and deep (at least 2 cm) margins is advised. This means that the surgeon needs to take some healthy tissue from around the tumor to ensure the best chance for complete removal. Remember, even though the incision may be quite large, it heals in the same amount of time as a "short one." There appears to be no advantage of a bilateral chain masectomy (over local excision) unless multiple mammary glands are involved. Local and wide excision for tumors that are less than 5 cm (2 cm for cats) may be curative.

As in human medicine, chemotherapy can be considered for patients that have a high risk for recurrent or metastatic disease. These patients would include: 
1. those in which complete tumor resection is not possible
2. those having sarcomas vs. carcinomas
3. those having large and/or multiple tumors
4. those whose biopsy results indicate aggressive disease
5. those with local or distant metstasis

        Chemotherapeutic agents that have been used as adjunct therapy include doxorubicin, cyclophosphamide, mitoxantrone and carboplatin. Most dogs can be treated without serious side effects and owner acceptance of costs and potential for complications is generally good. Overall, anti-estrogen drugs (e.g. Tamoxifen) have failed to show clinical benefit in veterinary patients. Radiation therapy has not yet been evaluated as a treatment modality in animals but may hold promise as it does in humans.

        Survival times for patients with invasive carcinomas are difficult to predict. Published medical reports generally state ranges of 6.5-30 months for patients on adjuvant chemotherapy.


Good Prognostic Factors

Poor Prognostic Factors

Indifferent Prognostic Factors

Tumor is less than 3 cm in diameter

Tumor is greater than 3 cm in diameter

Age

Well defined tumor boundaries

Poorly defined tumor boundaries, ulceration

Breed

Negative lymph nodes

Positive lymph nodes

Weight

Carcinoma-well differentiated, complex, tubular/papillary

Carcinoma-poorly differentiated, simple, solid, anaplastic, inflammatory carcinom, sarcoma

Type of surgery (simple or radical)

Tumor grade I

Tumor grade III

Number of tumors

Positive estrogen and progesterone receptors

Negative estrogen receptors

Glands involved

Index of proliferation

Low AgNOR

Low Ki-67

Low PCNA

Index of proliferation

High AgNOR

High Ki-67

High PCNA

P53 gene mutation

 

Cancer and Chemotherapy in Companion Animals

Dr. Gail Mason, DVM, MA, DACVIM
Kathi Smith, RVT, VTS Oncology 

A cancer is a tissue mass characterized by persistent, excessive, and disorganized cell growth that is unresponsive to normal control mechanisms. Cancer is a leading cause of death in dogs and cats. Why this happens, in most cases, is not yet known. As a result of improved owner and veterinary care, pets are living much longer and thus are more susceptible to diseases of old age, such as tumors. Compared to people, dogs develop tumors twice as frequently, but cats only half as frequently. If your pet is thought or known to have cancer, a consultation with a veterinarian experienced in oncology can provide you with valuable information regarding treatment options and expectations.

Terms Used in Cancer Medicine:

Tumor: simply means a "swelling," which may or may not represent cancer.

Benign Tumors: have many normal growth characteristics. They do not "spread" or invade other organs. They, may however, compress body organs or tissues by virtue of their size. Surgical removal is usually curative.

Malignant Tumors: often have rapid, irregular growth characteristics. These tumors can invade normal, local tissues, as well as spread to other tissues (especially the liver and lungs). New tumors can grow at these secondary sites, eventually causing the demise of the patient.

Metastasis: the process whereby a tumor spreads to secondary sites. These new tumors are referred to as "metastatic"," or "metastases."

Oncology: refers to the study of tumors, including their biological behavior and treatment.

Remission: denotes a decrease in tumor size (often called "tumor burden") over time. Remission time is the length of time in which the tumor is under control.

Currently, treatment of cancer in animals can often result in fairly lengthy, good quality remission times. That still means that for many types of cancers, their return is inevitable. This fact must be contemplated and discussed before the client and the veterinarian decide to treat an animal for cancer. Having reasonable and accurate expectations will provide a more positive experience for all those involved.

Types of Cancer Treatments

Surgery: surgical removal of tumors is a very common and valuable approach for solid tissue tumors. It can be used for soft tissue as well as for bone tumors. It can sometimes be curative on its own, if the disease process is localized and detected very early.

Radiotherapy: or "radiation" therapy is available at large veterinary institutions such as New England Veterinary Oncology Group (Waltham, Massachusetts), Tufts University School of Veterinary Medicine (North Grafton, Massachusetts) and Angell Memorial Animal Hospital (Boston, Massachusetts). It consists of the use of a radioactive beam to damage and/or kill malignant cells in a localized area. It can offer good quality remission times for many types of tumors, but usually not cure. Animals are surprisingly tolerant of radiation therapy.

Chemotherapy: is the use of certain drugs alone, or in combination to control tumor growth. All of the drugs currently given to animals are human anti-cancer drugs. Fortunately, many of the negative consequences of their use in human medicine are not experienced in veterinary medicine. Chemotherapy and/or surgery are the two most important treatment modalities in veterinary cancer medicine. A combination of therapies may also be indicated in certain cancers. Some cancers require a specific, brief number of treatments, while others requiring ongoing treatment to maintain remission.

Specific Cancers
Type of Tumor Type of Treatment
Lymphoma Chemotherapy (several types available). Surgery usually not advantageous.
Mast Cell Tumors Surgery +/- chemotherapy, radiation
Fibrosarcomas Surgical +/-chemotherapy, radiation
Oral Cancers Surgical, with reconstruction, +/- canine melanoma vaccine for dogs
Mammary Tumors Surgical (+/-chemotherapy)
Osteosarcomas (bone) Surgical + chemotherapy
Hemangiosarcomas Surgical + chemotherapy
Skin Tumors Surgical +/- chemotherapy, radiation
Transitional Cell Carcinomas Surgical + chemotherapy
Undifferentiated Sarcomas Surgical +/-chemotherapy, radiation

CANINE AND FELINE LYMPHOMA

Lymphoma is a malignancy (cancer) arising from the lymphoid tissues involving the immune system as well as any organ. When the malignant cells are present in the patient's bone marrow, causing blood disorders, it is referred to as leukemia. Some patients have multiple sites where the malignant lymphocytes can be found. The patient can be staged (assessed for disease) as follows:

Stage 1: Malignancy involves a single lymph node or single site.

Stage 2: Involvement of a cluster of lymph nodes in a regional area (including a single tumor of the intestinal tract).

Stage 3: Involvement of all peripheral lymph nodes.

Stage 4: Involvement of liver and/or spleen; associated with shorter remissional/survival times.

Stage 5: Involvement of the bone marrow and peripheral blood stream; associated with shorter remissional/survival times. Substages: Lymphoma patients can be subdivided into:

Substage A: Without systemic signs (ie. not ill).
Substage B: With systemic signs (ie. physically ill).

Staging the cancer patient is vital in determining the best treatment and preparing prognostic information.

 

T-Cell vs. B-Cell Lymphomas
You may see mention of lymphomas and leukemias as being either of a "B-cell" or "T-cell" origin. A patient's biopsy tissue can be further tested by a technique called immunohistochemistry. This determines the type of cell of the immune system that the malignant clone arose from. The treatment options are the same for both types of lymphoma but over large numbers of patients, it has been shown that the T-cell lymphomas are generally more aggressive. Overall, patients with T-cell lymphomas achieve remission as often B-cell lymphoma patients but their remission times can be significantly shorter (though not always).


Why Chemotherapy?
The word "chemotherapy" usually evokes unpleasant thoughts in most people's minds. We prefer to think of it as "therapy" for a disease, in the same way people take medications for certain illnesses. The ultimate goal of therapy would be to cure the patient of cancer. In most instances at this point in time in veterinary medicine, this goal is not realistic. The goal we do strive for is to control a rapidly progressive disease, prevent spread of the tumor, restore deteriorated function, and provide a good quality of life during the time of remission. The term ÒremissionÓ means a time interval during which there are no outward signs that the patient has cancer. In the case of lymphoma, if the maximum combination protocol is used, it is expected that 80% or more of patients will go into full remission. The average duration of remission is longer than 12 months. Unfortunately, it is impossible to predict which animals will achieve a full remission or for how long. We do know, however, that if no therapy is used, most pets will die from their disease in a few days to a few weeks. 
 

Protocols for Lymphoma
There are many "protocols" or treatment schedules available for canine and feline lymphoma. Unfortunately, there is not one "key" formula as yet that has been proven superior to all others. Most published protocols contain the same or similar class chemotherapy agents, with minor variations on combination agents and timing of treatments. Most veterinary internists and oncologists use the protocols that they are the most familiar with, and that best fit the particular lifestyle and expectations of the client, and well being of the patient. A brief synopsis of treatment categories for feline/canine lymphoma is as follows: These are continually updated as the field of veterinary oncology advances.

Oral Drug Protocols

Regimen Relative Risk of
Side Effects
Average
Remission Time
Costs
Prednisone (cortisone) low About 2 months very low
Prednisone + Cyclophosphamide low About 2-4 months low
Prednisone + Lomustine low to moderate About 2-6 months low to moderate

Oral Plus Injectable Protocol

Regimen Relative Risk of
Side Effects
Average
Remission Time
Costs
COP (cyclophosphamide, prednisone and vincristine or vinblastine low to moderate Average 6-12 months moderate
ACOPA (asparaginase, cyclophosphamide, vincristine or vinblastine and adriamycin (doxorubicin) Moderate to high,
but very individual
About 1-3 years high
*NOTE: No guarantee of remission times can be made. These are average lengths. The stage of the disease, protocol selected, general health of the animal, and several other factors are only some of the determinants of remission time. The patient may live longer than the actual remission time.

Selecting a Protocol
As a general rule, combination chemotherapy is superior to single agent chemotherapy. There are several areas of consideration when determining a chemotherapy protocol for an individual patient. These include:

Stage of the patientÕs disease
Willingness/availability of the owner to endure treatment schedule
Client expectations/desires
Financial issues
Response of the patient to the treatment

Care of the cancer patient requires unique skills, expertise, drugs, procedures, philosophies and supportive care. Each area can be discussed in depth to assist you in determining what path will be best for your particular circumstances.

Please recognize that veterinary patients usually have a dynamic course to their disease and treatment. Estimates for treatment costs do not include unexpected illness, diagnostics, treatment, or hospitalization. Our health team will strive to provide you and your pet with compassionate care as you take this journey with us.


What is Life Like for Chemotherapy Patients?
Chances are that you, or someone you know, have experienced chemotherapy for the treatment of cancer. Veterinarians who treat animals for cancer use many of the same chemotherapy agents that human oncologists use. Yet, in many ways the experience for pets seems very different. Why? For one thing, dosages of chemotherapy agents used in animals tend to be much lower than those used in people. Humans are given the highest doses possible, the consequences of which may require bone marrow transplantation, extended hospitalization, and numerous costly medications-all with good cause. However, for veterinary patients, this process would be unacceptable and cost prohibitive for most owners. The general quality of life for many veterinary cancer treatment patients can be surprisingly good and very close to normal. Most of the time they can maintain their normal activities, travel, and have fun with the families that love and care for them.

Most currently used anti-cancer agents do not specifically target cancer cells. Rather, they target and damage or kill rapidly growing cells. For the patient, this means cells lining the stomach and intestine (high turnover rate), cells of the bone marrow that make up the immune system (white blood cells, in particular), and cancer cells. It then is little surprise that the most common side effects of chemotherapy agents include mild to moderate nausea, vomiting, diarrhea, and increased risk of infection. Hair loss, in contrast to humans, is uncommon in dogs and cats on chemotherapy. In most animals, hair does not grow continually throughout their lives like it does in people. Some breeds, however, are susceptible to at least some hair loss (especially poodles, sheepdogs, Scotties and schnauzers). If your pet requires a groomer to trim its hair coat Ð then some hair loss can be anticipated. Pets, however, are not bothered much by this Ð and they seem to enjoy stylish polar-tec jackets as gifts. The good news is that the normal cell lines can almost always regenerate themselves, while the less well organized malignant cells suffer great damage. However, even at higher dosages, microscopic malignant cell clones remain alive, albeit dormant in the body. Eventually these give rise to drug-resistant cell lines. This is the biological basis of recurrent or metastatic cancers.

It is not a "given" that untoward side-effects will occur in any one patient. In fact, the majority of our patients complete their therapies without major complications. If they do occur, however, you should be prepared to recognize them and take appropriate action. Over time, the tendency is to have less frequent side effects, as the individual animalÕs sensitivity to the drug agents become known, the treatments are less frequent, and the cancer is in remission.

Risks to People Living with Chemotherapy-treated Pets
The anti-cancer drugs are excreted from the animal's body via urine and feces. This usually happens in the 48 hours following treatment, but can be as long as 5 days for Adriamycin. If it is possible, you should try to have the animal eliminate in an area away from the immediate yard or play area. Cat boxes should be changed regularly, and waste material handled with a scoop. If urine or feces must be handled, use heavy rubber or latex gloves and disposable wipes/towels. Place all waste/towels in a plastic bag and seal it, before disposal. Smooth surfaces may be washed with a dilute bleach solution (1/4 c. to 1 gallon of water). Humans and other household pets living with treated pets are generally thought not to be at any health risk, just as in the case with humans. Pregnant women should not handle ANY animal waste or anti-cancer medications. If any family member living with the pet has a condition that would suppress his/her immune system, it would be prudent to let the veterinarian know.
 

POST-CHEMOTHERAPY INSTRUCTIONS

Gastrointestinal Side Effects

Nausea (and refusal to eat) can occur in veterinary patients, and seems to occur more frequently in cats than in dogs. If this happens 1-3 days post-treatment, it is usually transient and requires no specific treatment. Tempting the pet with favorite foods, and warming the foods slightly will often increase palatability. For dogs, adding cooked eggs, pasta, lean chicken, or hamburger can be helpful. If this condition persists, medication to reduce nausea and promote appetite can be used; metoclopramide is most commonly used in dogs; cyproheptadine for cats.

Vomiting can also occur at any time during treatment. When it occurs 1-2 days post-treatment, and the pet is otherwise bright, active, and alert you can use Pepto Bismol¬ using the label "adult dose" for dogs over 40 lbs.; "childrenÕs dose" for dogs under 40 lbs., and 1/4 tsp. for cats (dosed up to twice daily). Remove food for 12-24 hours, and replace it with a pile of ice in a dish. This will help to maintain hydration without stimulating further vomiting. If the vomiting is repetitive (greater than 4X), contains blood, or the pet seems weak and depressed, assume your pet requires immediate veterinary attention.

Diarrhea may occur, but is often mild and transient. Several over-the-counter treatments may be given safely to pets and may reduce intestinal discomfort. Imodium A-D ¬ or "Kaopectate" is dosed at "adult dose" for dogs 40 lbs. and over; "children's dose" for dogs less than 40 lbs.; and 1/4 tsp. for cats up to 2-3X daily. If the diarrhea is severe, persistent, contains blood, or the animal seems weak or depressed, veterinary attention is required.

Fever/Sepsis As previously mentioned, virtually all chemotherapeutic drugs have the ability to at least temporarily suppress the bodies own immune system. The normal range of white blood cell counts in animals is about 6,000-17,000/cmm. If the white blood cell count (neutrophils or "wbcs") are below about 2,000, then the pet runs the risk of systemic infection. The pet will usually manifest fever (but not always). If the bacteria travel through the bloodstream, it is known as "sepsis." In rare cases, shock can occur (septic shock), and without rapid treatment, the risk of death is high. Though this period of susceptibility is brief, and occurs at a fairly predictable time, its consequences can be life-threatening. Below is a list of the most commonly used drugs and the expected low point in cell counts (the "nadir"), given in days post-treatment:

Drug

High Risk Period

Doxorubicin (Adriamycin®) 7-10 days
Vinblastine 5 - 7 days
Cyclophosphamide ( Cytoxan®) 7 - 10 days
Lomustine (CeeNu®) 7 days, then again at 21 days
Mitoxantrone 7 - 10 days
Cisplatin 10 - 14 days
Carboplatin 10 -13 days
Vincristine 7 - 10 days


Signs of Fever or Sepsis

fever > 103F (temperature taken by rectal thermometer should be between 100 and 102.8 F.
extreme lethargy (refusal to get up off of dog bed, etc.)
complete disinterest in food
extreme weakness
pale and somewhat "sticky" gums
severe vomiting/diarrhea
 

WHAT DO YOU DO IF YOU SUSPECT INFECTION

immediate action is necessary
start the antibiotics you have been given; double the first dose, then continue as label directs
track the temperature at hourly intervals
if pet is not significantly better in 1-2 hours, call your local veterinarian or a local emergency clinic. DO NOT WAIT OVERNIGHT! This situation can be treated rapidly and almost always successfully. However, an extended delay before initiation of treatment may result in health complications or even death. Your local veterinarian has been given treatment protocols for this situation and in most cases this will be more convenient for you.


Drug Dosages
Chemotherapy treads a narrow path between effectiveness and toxicity. In fact, chemotherapeutic protocols are most often limited not by the ability of drugs to kill tumor cells, but by their toxicity to the patient. The goal is to destroy as many malignant cells as possible while leaving enough normal, "organized" cells to recover organ function. It is important, therefore, that we use the highest dosages that we think the patient can tolerate. The more cancer cells surviving any one time, the sooner the patient will become resistant to the beneficial effects of the drugs.

Visits and Costs
It is important to make an appointment for each chemotherapy administration. At each visit, a doctor or an oncology nurse will examine and treat your dog or cat. We work as a team to minimize the time you and your dog or cat will spend at the hospital. The team approach maximizes quality care and extends the time, which we are available to you. This may mean you might not see the same veterinarian or nurse each time you visit but rest assured that our intent is to provide the most comprehensive and compassionate care possible.

For a cancer such as lymphoma, therapy involves a significant time commitment on the part of the owner/family. Outpatient visits are generally once weekly for 4 weeks, then every 3 weeks for up to 18 months. Other types of cancer require less treatment time. However, we make every effort to accommodate the owner's schedule, and most visits require 20 to 30 minutes. Many clients like to leave their pet with us temporarily while they go do errands, and you are welcome to do this. You may halt therapy at any time, but we like to have the owner commit to at least 4 weeks, so you will have the benefit of seeing how well a pet can do. Due to the new OSHA hazard laws, and the fact that the animal must make no movement during the intravenous injections, we regret that it is not feasible to have the owner present during the few minutes of chemotherapy injections. Rest assured that your pet will be gently and expertly restrained by the oncology technician and the doctor. Relative to most other treatments in veterinary medicine, chemotherapy is a costly service to provide. The costs reflect the professional time and expertise required, the high costs of chemotherapy agents (the same used by humans), the special equipment and personnel protection required, and the removal of biomedical hazard waste. Realize however, that this therapy is unique in that it can successfully prolong an animal 's life!

Is It Worth It?
This is a difficult question for us to answer. Every situation and client-pet relationship is different and must be dealt with individually. If it were ever obvious that therapy was not working, or that the pet was indeed experiencing pain or discomfort, we are ethically obligated to inform you. What we can say is that most pets do indeed appear to enjoy their extended life period and do not even realize that they are "ill." However, the owner(s) must believe that they are doing the right thing for their pet and for their situation.

Specific Drugs

Prednisone is the least toxic of all the chemotherapy agents. It is not a specific chemotherapy drug, and has many different uses in medicine. It is usually well tolerated by pets. It commonly causes increased thirst, urinations, and appetite which are dose related. It can have irritating effects on the stomach lining. Please notify us if you detect a problem.

Asparaginase ( Elspar®) is also well tolerated. In rare instances, it can cause vomiting due to pancreatitis. Since it is a protein, there is a (rare) possibility that an animal can have an allergic reaction to it. We would ask that your pet remain in the lobby for about 15 minutes after this injection.

Vincristine® has little tendency to make an animal ill. Occasionally, there will be 1 or 2 episodes of "innocuous" vomiting 24 hours after the injection, which disappears without treatment. More commonly in people and cats than in dogs, Vincristine can cause intestinal cramps or constipation. The pet may seem "restless" 24-48 hours after administration. We have found that over-the-counter Imodium A-D works well in dogs ("adult dose" for dogs >40lbs; "childrens dose" if <40lbs). For cats, use any standard hairball laxative or add _ tsp of Metamucil to daily feedings. It is very irritating to the surrounding tissues if it leaks from the vein at the injection site. If you notice any inflammation where the injection was given, notify the doctor.

Cyclophosphamide (Cytoxan®) is a potent chemotherapeutic agent and can lower the white blood cell count about 7 days after it is given. Mild to moderate nausea can occur. The tablets should be given in the morning (all at once with food), and the pet should be given ample opportunity to empty his bladder throughout the day. Occasionally, bloody urine can occur due to direct bladder effects. This drug is often given with a diuretic (lasix or furosemide) to speed its excretion from the body. If your pet should get sick about 1 week post treatment, follow the instructions on the ownerÕs sheet given at the start of treatment. The caregiver should wear disposable gloves while handling the tablets.

Doxorubicin (Adriamycin®) is the most potent of the agents, and like Cytoxan®, can lower the white blood cell count and nausea and vomiting, and or diarrhea can occur. If the signs are mild, use "adult dose" Pepto Bismol for dogs >40lbs and "childrens dose" for dogs <40lbs. Moderate to severe illness requires veterinary intervention. If there is irritation at the injection sites, notify the doctor. Long-term effects can involve the heart, but our protocols have been calculated to lower this risk. If your pet gets ill about 1 week after therapy, follow the instructions on the owner's sheet.

Vinblastine (Velban®) is an injectable vinca alkaloid drug that is closely chemically related to Vincristine. They have similar effects but Vinblastine has fewer tendencies to cause intestinal side effects, though it can lower the white blood cell and platelet count.

Chlorambucil (Leukeran¨) is an oral alkylating agent which is very well tolerated. Mild decreases in appetite and white blood cell/platelet counts can occur.

Lomustine (Ceenu¨) is also an oral alkylating agent related to Cytoxan and Leukeran. While most pets tolerate this versatile drug, significant decreases in cell counts can occur and the CBC must be monitored closely.

Lymphoma and Lymphoma Vaccine in Dogs

Lymphoma, one of the most common neoplasms in the dog, can arise in any
tissue in the body but tends to appear in lymphoid tissues, such as lymph
nodes, spleen and bone marrow.  It primarily occurs in middle-aged dogs (6-9
years of age).  Lymphoma is classified by where it is located, the
histologic criteria, and the immunophenotypic characteristics of the
lymphocytes, of which the two most common phenotypes are B-cell and T-cell,
with 75-80% of those reported as B-cell. These classifications are
important in determining prognosis and treatment options. The oncologist
will explain all of this at your oncology consultation.

Prognosis depends on many different factors.  Untreated lymphoma typically
progresses rapidly, going from presentation to terminal stages within 1 to 2
months.  Lymphoma is rarely curable (less than 10% of cases), however
considerable improvement in duration and quality of life can be seen in dogs
treated with chemotherapy. A common chemotherapeutic protocol for treating
canine B-cell lymphoma, CHOP or modified CHOP, typically results in an
80-90% remission rate with a median survival time of 12 months.  However,
only approximately 25% of dogs that respond to this protocol will be
long-term survivors (>2 years).  Therefore, a majority of dogs require
repeated chemotherapeutic intervention, with highly variable response rates
to maintain remission state.

The development of an exogenous antibody vaccine that targets native surface
antigens on B-cells has sparked a revolution in the treatment of B-cell
lymphoma in humans.  The antibody is directed against an antigen found on
the surface of B cells, and has been shown to be an excellent target for
passive immunotherapy.  Thus, a vaccine to induce antibodies that target the
same antigen has been produced for canine patients.  DNA cancer vaccines
offer a safe adjunct to existing therapies with the potential to induce
longer term remissions.

Canine Lymphoma Vaccine, DNA, is indicated for the therapeutic immunization
of dogs diagnosed with Large B-cell Lymphoma upon achieving remission
through chemotherapy.  The challenge with many cancers is that the host does
not recognize the neoplastic cells as "foreign", so the immune system is not
elicited to defend the body against the neoplastic cells.  Upon vaccination
with the lymphoma vaccine, the antigen is taken up by the host cells and is
then transcribed in the host and actively presented to the immune system.
The immune system recognizes the form as foreign and procedures an immune
response thus leading to destruction of the neoplastic B-cells.  Studies of
the vaccine have shown significantly improved survival times (>734 days)
over dogs treated with chemotherapy alone (approximately one year).

Initial treatment with the canine lymphoma vaccine is four doses of vaccine
at two-week intervals, followed by a booster dose at six-month intervals.

Hemangiosarcomas

Dr. Gail Mason, DVM, MA, DACVIM
Kathi Smith, RVT, VTS (Oncology)

Hemangiosarcomas (HSA) are highly aggressive malignancies arising from the lining of blood vessels. These tumors can arise anywhere in the body but most frequently involve the spleen, heart, liver and skin. About 25% of dogs with HSA have both the spleen and heart involved. Tumor spread occurs most often to the liver, mesentery, lungs, and brain.

Symptoms of HSA in animals are usually attributable to the tendency for HSAs to hemorrhage. If internal organs are involved, the patient may be weak/collapsing, have pale gums, a rapid and shallow respiratory rate and perhaps abdominal enlargement. Emergency intervention (surgery and supportive care) is critical to patient survival.

Patient Evaluation
The first step in treating veterinary patients for HSA is to evaluate general patient health and to assess the extent of the cancer (clinical staging.) This step helps the clinician formulate a treatment plan and allows more precise determination of the prognosis. Evaluation may include the following diagnostics: 
• Complete blood count (CBC)
• Serum chemistry panel (assess organ function) 
• Urinalysis
• Coagulation profile
• Chest radiographs (x-rays) - (assess evidence of a mass or metastasis) 
• Ultrasonography - (assess extent or spread of HSA)

Staging of HSA
The prognosis for dogs with HSA is known to be affected by the clinical stage of the disease. In general, this refers to: 
Stage I: Localized tumor; no other tumors seen at the time of surgery
Stage II: A ruptured tumor which is confined to the primary site, such as an HSA of the heart or spleen. There may or may not be metastasis present near the site of the primary tumor. 
Stage III: A ruptured primary tumor with invasion into adjacent structures plus local or distant metastasis.

Teatment of HSA
Hemangiosarcomas are, unfortunately, highly aggressive tumors and virtually all patients will eventually die from the disease. Currently, these tumors defy cure in veterinary patients. However, a systemic thrapeutic approach which involves, 1) surgical resection of the primary tumor and 2) the addition of chemotherapy, can provide a remission from the cancer.

Drugs used for HSA (post surgery)include: 
1. Doxorubicin (intravenous administration) 
2. Vincristine (intravenous administration) 
3. Cyclophosphamide or Lomustine (oral administration)
 4. Non-steroidal anti-inflammatories (oral administration)
5. Tyrosine kinase inhibitors (oral administration)
6. Low-dose daily oral metronomic therapy (oral administration)

The combination of drugs used may differ but the most common treatment interval is about every 21 days. Most often, treatment is continued for at least 6 months.

Prognosis
An exact prognosis for a particular patient with HSA is impossible to predict. However, over fairly large numbers of treated animals published, the following statistics are offered as guides:

 


Stages
Median Survival (days)
Range (days)
I
257-273
14-890
II
156-210
35-476
III
73-87
5-760

 

Surgery Alone:
Stages
Median Survival (days)
Range (days)
I
30
35-91
II
40

HSA Patients in Therapy
The quality of life for patients being treated for HSA is generally good to excellent. The chemotherapy drugs are given as to minimize toxicity to the patient while still damaging the malignant cells. The disease, even its late stages, does not appear to cause a pain response in animals. Instead, as the metastatic disease progresses, original symptoms (such as bleeding/anemia/weakness) recur.

Relative to many other animal cancers HSA remains a formidable enemy. The one year survival rate for patients with surgery alone is 6.25%.  For those undergoing surgery plus chemotherapy, the one year survival rate is 20%. Newer therapies are close at hand which should greatly enhance control of this illness. Currently, though patient remissions are generally months (vs. years), treatment can be rewarding for both the pet and the family.

Handling Chemotherapy

Portland Veterinary Specialists


Whenever handling chemotherapy medications or caring for patients that have received chemotherapy, there are some general precautions that should be taken to minimize the potential for human exposure to the drugs.  

1)    When handling the drugs, you should wear protective gloves and wash your hands well after handling them.  We will provide you with gloves for those drugs that are to be given only once or over several days.  For those medications that are to be administered on an ongoing basis, you should purchase exam gloves at your local drugstore to use.  

2)    Tablets should not be split, crushed or dissolved as this may disrupt the protective film coating that many of the drugs have.

3)    Capsules should be administered whole, and not opened when given.  

4)    Many of the drugs can be given with food or in food.  It is important, if it is given in food, to make sure your pet eats the entire dose.  

5)    If a tablet or capsule becomes moistened, crushed or broken while giving it to your pet, you should wear gloves when re-administering the drug.  

6)    Drugs should not be handled by children or by women that are pregnant, planning to become pregnant or who are nursing.

7)    Keep the drugs in the prescription vial or original packaging, outside of the reach of children and pets.

8)    Any remaining drug that is not to be used should be brought back to your veterinarian for proper disposal. 

9)    Chemotherapy can be eliminated in the urine and feces following treatment, particularly for the first 48 hours.  In order to avoid any possible exposure, we recommend that you wear gloves and wash your hands well after cleaning up after your pet.  This includes when cleaning a litter box.  You should also take care that your pet does not eliminate in the areas where children may play.  

10)     If the bedding becomes soiled during the first 48 hours, you should wear gloves  
      while handling the bedding and wash it separately in hot water.  

11)     If your pet has received oral chemotherapy within the past 6-12 hours and      
vomits, we also recommend that you wear gloves while cleaning up after your 
pet, and wash your hands well.