Each year, about 6 million of the 65 million pet dogs in the United States will be diagnosed with spontaneous, naturally occurring cancer. Of the 32 million pet cats, 6 million will be diagnosed with cancer. Pet animals with naturally occurring cancers are traditionally treated by veterinary oncologists in private practices or at teaching hospitals, using therapies similar to those used in humans, including surgery, chemotherapy, radiation therapy, and biotherapy. The inclusion of this large number of animals suffering from cancer in the study of human cancer is referred to as comparative oncology. Comparative oncology brings together the work of veterinary clinical oncologists with medical oncologists, the pharmaceutical industry, and academic centers involved in cancer research. The product of this effort is an improved understanding of the biology of cancer and improved treatment options for both animals and humans afflicted with cancer.
Information on individual canine cancers
Osteosarcoma is the most common primary bone tumor in dogs (85 – 98% of all primary bone tumors). Large breed dogs are most commonly affected, including Scottish Deerhound, Rottweiler, Irish Wolfhound, Saint Bernard, Great Dane, Doberman, German Shepherd, and Golden Retriever. Age distribution of the disease in dogs is biphasic, with a peak at 1-2 years and another peak at 8-10 years. Primary tumors are most commonly found in the appendicular skeleton (fore and hind limbs). Most common sites include the distal radius (forearm), proximal humerus, distal femur, and the proximal or distal tibia. A diagnosis is made based on radiographic (x-ray) findings of the affected bone, and fine needle aspirate or biopsy of the boney lesion. Appendicular OSA is a highly malignant tumor as 75-90% of dogs will develop distant metastases. The most common site for metastasis is the lungs, however, with aggressive treatment (surgery and chemotherapy) it is more common to see boney metastasis. Treatment options include palliative care (pain management) and more definitive therapies that involve combinations of either surgery or radiation and chemotherapy. Median survival times for palliative pain management, either via oral analgesics or radiation therapy, are 107 days and 122-313 days respectively. Surgery alone (typically amputation) has a median survival time of 101-175 days, while surgery with adjunctive chemotherapy extends survival time to roughly one year.
OSA in people is typically seen in children and teens, although it can occur at any age. It accounts for about 2% of childhood cancers. Similar to dogs, OSA in people often occurs in long bones and is more often seen in taller individuals. Treatment involves surgery, chemotherapy and/or radiation. With current treatment options, the average 5-year survival rate is roughly 70%.
Lymphoma in dogs is characterized by a malignant overgrowth of immune cells called lymphocytes. There are two basic types of lymphocytes, called T- and B- cells, which can be found all over the body. For this reason, lymphoma can appear in any organ in the body. The most common form of lymphoma is multicentric which is characterized by overgrowth of cancerous lymphocytes initially in the lymph nodes. This is often noted as a generalized enlargement of multiple lymph nodes which are non-painful. Other common lymphomas include cutaneous (or skin), gastrointestinal, and mediastinal (involving the thymus of lymph nodes in the chest). A diagnosis is often made by aspirating cells from the affected lymph nodes. Imaging studies are often performed to help stage the disease, and other tests may be performed to further characterize the subtype of lymphoma. Significant tumor burdens can cause dogs to become lethargic and weak, anorexic, dehydrated, and even cause a fever. The disease is often in multiple areas within the body once diagnosed, and so chemotherapy is the most common form of treatment. This is often achieved with multimodal therapeutic protocols, but single agent protocols are available as well. If an initial remission is achieved with treatment, dogs will often live at least a year before the disease returns. Sequential remissions are often shorter and the lymphoma is more resistant to further treatment.
People can be affected by lymphoma as well, which is typically subtyped into Hodgkin’s and non-Hodgkin lymphoma (NHL). The majority of canine patients with lymphoma have a very similar disease to non-Hodgkin lymphoma in people, as Hodgkin’s lymphoma is rare in dogs. In people this disease is treated with immunotherapy, chemotherapy, targeted therapy or radiation therapy. The five year and ten year survival rates for people are 69% and 59%, respectively, however these are highly dependent on various factors and tumor type.
Canine mast cell tumors are aberrant overgrowths of a type of resident granulocyte in tissues called mast cells. Mast cell tumors are very common in dogs, accounting for anywhere between 11-20% of all skin tumors. Predisposed breeds include Boxers, Staffordshire Bull Terriers, Boston Terriers, Bulldogs, Labrador Retriever, Golden Retrievers, Beagles, Scottish Terriers, Weimaraners, Rhodesian Ridgeback, German Short-Haired Pointer, Chinese Shar-Pei, and Schnauzer. Of the predisposed breeds, Boxers appear to have the highest incidence of disease. Tumors typically develop in older dogs (mean age 8-9 years) and may appear in any internal organ, including circulating in the blood. Skin tumors are most commonly found on the limbs, especially the posterior upper thigh, ventral abdomen and thorax. Most often times the tumors are solitary raised masses or lumps in or just underneath the skin. Tumors may be soft or solid on palpation, and potentially may ulcerate. In roughly 10% of cases multiple skin masses are found. Mast cell tumors are often locally invasive with microscopic extensions spreading from the mass. Mast cells produce many different vasoactive substances that are part of the body’s normal allergic response. These substances include histamine, prostaglandins, and heparin. Mast cell tumors may spontaneously degranulate causing massive inflammation leading to acute changes in the size of the mass, gastric ulceration (histamine increases gastric acid secretion), and hypotension. Diagnosis is made either with fine needle aspiration or biopsy of the tumor. Further diagnostic tests that may be recommended include abdominal ultrasound, regional lymph node aspiration and bone marrow aspiration. A biopsy is required to determine grade which can be used to predict biological behavior. This is vital for determining the appropriate treatment. Low grade tumors with no metastases often may be treated with surgery alone and have an excellent prognosis. Prognosis is poor for higher grade tumors as these are more likely to metastasize and recur locally post-surgical removal. If evidence of metastasis is noted then chemotherapy may be used to help slow progression of disease. Radiation therapy may also be used either in conjunction with surgery or alone to control local disease. Targeted therapies are available that target a receptor, called KIT, which is commonly mutated in mast cell tumors. Similar mutations are found in several human cancers including systemic mastocytosis, gastrointestinal stromal tumors, and small cell lung cancer.
Hemangiosarcoma is a malignant cancer of cells that line blood vessels called vascular endothelial cells. These cancerous cells tend to make tortuous and abnormal vessels, and so are commonly associated with sporadic bleeding events. Hemangiosarcoma is most commonly seen in middle aged to older large breed dogs, specifically German Shepherds, Golden and Labrador Retrievers. Tumors typically form in the spleen, skin, and heart. Cutaneous (skin) hemangiosarcoma has a guarded prognosis, but may potentially be cured by surgically removing the tumor. If local invasion is noted on the surgical biopsy, then chemotherapy will typically be recommended to follow surgery. Hemangiosarcoma that affects internal organs (spleen and heart) are often slow growing and show no clinical signs until acute collapse occurs due to severe internal hemorrhage. Dogs may wax and wane with signs of unexplained weakness, tiring more easily, and depression. Due to the slow growing nature of this disease, it is difficult to detect early, and so often dogs already have distant metastasis at time of diagnosis. Treatment involves surgery to remove the primary tumor, if possible, and chemotherapy. A Chinese herbal medicine, called Yunnan baiyao, is becoming more popular in palliative care for canine hemangiosarcoma for its pro-coagulant (helps control small bleeds) attributes. More studies are required to appropriately assess the efficacy of this drug. Prognosis for hemangiosarcoma is guarded. Median survival time (MST) for surgery alone (reduce risk of bleeding from primary tumor) is 19-86 days. Surgery and chemotherapy together provide an MST of 172-202 days, depending on clinical stage of the disease, and the 12-month survival rate is increased from 6.25% to 20%. A new potential immunotherapy may prolong survival times more when combined with surgery and standard chemotherapy.
Angiosarcoma in people is a very rare soft tissue sarcoma of blood vessel endothelial cells. It typically appears in the head and neck region, but may appear anywhere in the skin. It has been associated with radiation therapy, ultraviolet ray exposure, chronic lymphedema and exposure to toxins such as vinyl chloride and polychlorinated biphenyls. These tumors are highly aggressive and even with appropriate surgical technique the literature reports local recurrence of disease in 26-54% of cases. Distant metastatic rate is high as well, and 5 year survival times are reported to be between 12-61%. A potential benefit of following surgical removal with chemotherapy may reduce risk of local recurrence.
Malignant histiocytosis, also known as disseminated histiocytic sarcoma, is a cancer of immune cells that are involved in identifying foreign material and presenting antigens to the rest of the immune system. There are several different forms of histiocytosis in dogs: histiocytoma, reactive histiocytosis and localized and disseminated histiocytic sarcomas. Histiocytomas are benign, raised lesions that form in the skin of young (typically < 3 years), predisposed dog breeds (boxers, dachshunds, cocker spaniels, Great Danes, Shetland sheepdogs). These will resolve on their own without any treatment. Reactive histiocytosis is an overabundance of histiocytic cells that may form localized skin lesions, or also be found as lesions in various internal organs. These disease differs from the sarcoma form because lesions may wax and wane with time. Malignant histiocytosis is a truly malignant disease characterized by dysplastic, immature histiocytes that invade multiple organs. Most common organs involved are the liver and spleen, however, bone marrow, lungs, lymph nodes and other organs can be involved. Cutaneous lesions around the joints are typical for localized histiocytic sarcoma, with rapid progression of metastases in distant locations. Breeds that are at highest risk for this disease are Bernese Mountain dogs, Rottweilers, and Flat-coated, Golden and Labrador retrievers. A diagnosis can be made off of fine needle aspiration of lesions within internal organs or cutaneous lesions. Often times the cells appear as indiscernible round cells, and so further characterization through special staining (i.e. immunohistochemistry) may be required to get a definitive diagnosis. Further diagnostic tests, including blood tests, radiographs and ultrasound imaging, are essential for predicting prognosis. Treatment involves chemotherapy, or combinations of radiation and chemotherapy. One small study has shown potential benefit for immunotherapy, but more studies are required to validate the efficacy of this therapeutic option. Prognosis is poor for both the disseminated and localized forms of histiocytic sarcoma with reported median survival times between 106 days - 5 months depending on treatments pursued and several other factors.
Malignant histiocytosis is a rare disease in people. Similar to dogs the disease is rapidly progressive. Treatment involves combinations of chemotherapeutics with very little efficacy. People also develop benign forms similar to canine histiocytomas, which are self-limiting.
Soft tissue sarcomas are a group of tumors that originate from mesenchymal cells, or cells that give rise to connective tissues and structural tissues. These tumors include fibrosarcomas, peripheral nerve sheath tumors, and hemangiopericytomas, leiomyosarcomas, and liposarcomas. These tumors tend to be locally invasive and send out small finger-like projections that extend into surrounding tissues. Risk of metastasis is dependent on tumor grade. Low grade tumors have a low risk (10%) while high-grade tumors have a moderate risk (40%). These tumors typically appear on the trunk, limbs or head and neck region, and tend to grow slowly. Diagnosis is made with a biopsy of the mass, as fine needle aspiration does not tend to yield diagnostic quality samples. However, aspiration can be used to rule out benign lipomas and other causes of skin growths. Further testing may include biopsy or aspiration of local lymph nodes, chest radiographs (x-rays), and CT scan of the mass to evaluate extent of invasion. CT scan is very helpful when planning for surgery, which is typically the first option for treatment. Wide margins of at least 3 cm around and 1-2 fascial planes deep to the tumor are taken to minimize the risk of tumor regrowth. Surgery may be repeated if regrowth occurs or when margins are incomplete. Other treatment options include radiation therapy following surgery for incompletely excised tumors. If metastasis is noted then chemotherapy or other systemic therapies may be recommended. Amputation may be used to control local disease when located on the limbs, but it does not affect metastasis or survival time. For grade I and II tumors treated with surgery followed by radiation therapy a median survival time (MST) of over 4 years is reported, while an MST of roughly 3 years is reported for grade III. Prognosis is much worse when metastasis is noted with a reported MST of 250 days. In general, prognosis determined by local disease control and not distant metastasis.
Canine melanomas are tumors comprised of pigmented cells called melanocytes. Unlike in people, melanomas in the skin of dogs are typically benign. Malignant melanomas in dogs arise in the mouth (oral melanoma), along mucocutaneous junctions, or in the toes/nail beds. These tumors are highly aggressive, and tend to readily invade local soft tissue and bone, and also metastasize readily to lymph nodes then the lungs and potentially other organs. Oral melanoma is often seen in older, black-coated dogs. These dogs often have halitosis (bad breath) and may have difficulties eating or pain when chewing. Tumors are diagnosed based on fine needle aspiration or biopsy of the mass. Chest radiographs should be taken as well, and local lymph nodes aspirated to monitor for spread of the disease. Treatment involves controlling the local tumor via surgery and/or radiation therapy. If local lymph nodes are already invaded by the cancer, then they may be removed at the time of surgery. Local control of the primary tumor should be followed by systemic therapy. Traditionally chemotherapy was used but the efficacy of these treatments were poor. Now a vaccine containing Human DNA that encodes a protein expressed on melanocytes is used to treat/slow progression of metastatic lesions. Clinical staging of oral melanoma is based on tumor size and degree of metastasis. Prognosis is guarded for oral melanoma with median survival times of 5-7 months depending on stage at presentation.
Human melanoma is a malignant disease often found on the skin as asymmetrical, multicolor, nodules that change over time. Melanomas in people are staged in a similar fashion to canines, with tumor size and distant spread influencing the prognosis. Treatment for humans involves surgery, chemotherapy, immunotherapy and targeted therapies. Several different forms of immunotherapies are being tested in melanoma patients, including vaccines similar to the canine melanoma vaccine.
Primary lung tumors are uncommon in dogs accounting for about 1% of all tumors. A much more common finding are metastatic cancers in the lungs of dogs. Primary lung tumors are most often seen in older dogs (10-12 years old), but there are no gender or breed predispositions. They tend to be indolent, slow growing tumors and so often clinical signs do not develop until the cancer has spread, or the tumor has become severe enough to cause pleural effusion or other related problems that will make breathing more difficult. These tumors may also cause an abnormal proliferation of bone in the distal limbs, called hypertrophic osteopathy, which is painful and may result in lameness. A diagnosis is often made with chest radiographs (x-rays), and may even be made while looking at the chest for other reasons given the indolent nature of this disease. Advanced imaging such as a CT scan may be recommended because this imaging modality is much more sensitive than standard x-rays for looking for metastases to other parts of the lung. The abdomen should also be examined to look for distant spread. Biopsies may be taken either by fine needle aspiration if the tumor is located in the peripheral lung, or surgically. Treatment involves surgery to remove the tumor if possible. Chemotherapy is only used if metastases are detected, or if surgery is not an option. The prognosis for primary lung tumors in dogs is highly variable and depends on multiple factors such as tumor size, location, type, grade, and whether or not there is evidence of metastasis. A solitary, small tumor (< 5 cm) located at the periphery of the lung carries the best prognosis, and with surgery alone median survival time is reported to be around 20 months. A high grade tumor with spread to local lymph nodes or other lung lobes carries a much poorer prognosis.
Primary lung cancer is much more common in people and is currently the number one cause of cancer related death in people. Although smoking is associated with most lung cancer in people, it most likely is not the predominant cause of primary lung tumors in dogs. That being said, second hand smoke has been associated with development of tumors in pet animals, and can contribute to development of primary lung tumors especially in brachycephalic breeds (short nosed dogs).