Cancer Detection and Clinical Staging

    Some cancers, however, may produce non-specific symptoms that make it extremely difficult to determine where in the body they may be developing. Such symptoms are referred to as paraneoplastic disorders, and they usually occur as a result of the tumor causing alterations in the patient's energy metabolism. Therefore, effects may be seen at sites distant from the actual location of the tumor. Symptoms of paraneoplastic disorders include weight loss, low-grade fever, muscle-weakness and/or seizures, lethargy, loss of appetite, diarrhea, skin rash, hair loss, and general arthritic-like symptoms. Usually, the "wait-and-see" method to diagnose such cancers is inappropriate since by the time these cancers actually become large enough to detect, they have already reached an advanced stage and are unlikely to respond favorably to treatment. Therefore, with these ellusive cancers, specialized diagnostic techniques such as laboratory screening tests and radiologic exams provide a means for earlier diagnosis and perhaps better long-term prognosis for treatment success.

    Survey radiography (x-ray) is probably the most common diagnostic imaging tool utilized in veterinary oncology. In many instances, radiographs are adequate for identifying the presence of a definite tumor mass or alterations in 1) position 2) size 3) shape or 4) density of bones, soft tissues, and organs that may indicate the presence of a cancerous growth. In human medicine, use of conventional radiography for identifying the presence of lung metastases is equally effective as imaging with computed tomography (CT).

    CT imaging equipment is not as widely available in veterinary medicine, but is found at many large veterinary hospitals and universities that cater to specialized medicine. CT provides a three-dimensional view with section-by-section images; a process that is more sensitive to changes in the examined tissues and capable of imaging areas that may be hidden behind other tissues. CT imaging is particularly valuable over survey radiography when assessing tumors of the brain and central nervous system.

    Magnetic resonance imaging (MRI), like CT imaging, has limited availability in veterinary medicine. Unlike survey radiography and CT imaging that use a radiation source, MRI uses magnetic fields and radiofrequency waves to create images of the body without the need of ionizing radiation. MRI provides some advantages over these former imaging techniques in that it allows better contrast between different types of soft tissue as in the case of identifying tumor beside soft tissue. Additionally, MRI does not require the use of injectable contrast material to distinguish bloodvessels, since it can directly detect blood flow. There are, however, some disadvantages to MRI compared to CT and survery radiography including the inability of MRI to detect small deposits of calcium in tissues that often signifies cancer processes. Additionally, MRI requires longer interludes to acquire images that may increase the chances of poor imaging due to movement.

    Many veterinary clinics currently use ultrasound imaging on a regular basis. Ultrasound provides a safe and non-invasive method for imaging solid organs. Additionally, ultrasound may be used for guiding fine-needle aspirations for the purpose of biopsy. Some disadvantages to imaging with ultrasound include the necessity to shave the fur in the area undergoing examination and the frequent difficulty in making a distinction between lesions and possible artifacts.

    Positron emission tomography (PET) imaging has been evaluated recently for its diagnostic value in canine medicine. This imaging technique is based on the rationale that short-lived positron-emitting radionuclides can serve as tags on cellular metabolites. These metabolites are injected intravenously into the dog and within a short time become concentrated within tumor cells causing these areas to "light-up" on external radiation detectors. In early investigations, this imaging strategy appears to have some benefit over other imaging techniques for successfully locating early sites of metastases.

    Cancer cells often produce molecules that are not produced by normal cells or may express molecules on their surface that are not present on normal cells. Detection of these molecules within the body is, therefore, often indicative of the presence of cancer. For this reason, such molecules are called tumor markers. The following are some tumor markers that have demonstrated an association with some canine cancers:

Skin Cancer

• Ki67

Mammary Cancer

• c-kit proto-oncogene
• MAb 1A10 (mammary cancer antibody)
• MAb SB2 (mammary cancer antibody)
• Type IX collagen

Lymphoma

• AgNOR
• Plasma thymidine kinase
• CCI-103F (nitroimidazole hypoxia marker)
• CD3 (T-cell lymphoma antibody)
• CD79a (B-cell lymphoma antibody)

Oropharyngeal Cancer (Mouth Cancer)

• BrdU labeling index

Pancreatic Cancer

• Chromogranin A plasma concentration

Bladder Cancer

• basic fibroblast growth factor urine concentration

Other Solid Tumors

• CCI-103F (nitromidazole hypoxia marker)

    In addition to detection and diagnosis of malignant tumors, tumor markers may provide information on: prognosis (some markers indicate the degree of invasiveness of the cancer); staging (some markers provide an indication of how much the disease has spread); and monitoring (some markers indicate treatment efficacy or recurrence of disease following treatment).

    Once cancer is detected, the next step in the clinical management of the dog is to determine the extent of the disease throughout the body. This procedure is referred to as staging and is necessary to assess the prognosis and to select a course of therapy that will provide the best outcome in terms of disease remission and quality-of-life.

Together with mammary cancers (see next section), cancers of the skin comprise 58% of the total cancers occurring in the dog, and thus, account for the majority of canine cancers. The most common skin neoplasm of the dog is the mastocytoma (mast cell tumor), which accounts for as many as 20% of all possible skin tumors. Mast cells are a connective tissue cell that secrete heparin (an anti-coagulant) and histamine (an agent that controls permeability of blood vessels and which is responsible for swelling) and hence, are involved in inflammatory responses. Mastocytomas occur more frequently in Boxers, Boston Terriers, and Labrador Retrievers. These tumors occur in both sexes with equal frequency.

AVERAGE AGE OF ONSET: Mastocytomas usually present in middle-aged or older dogs.

CAUSE: Both chromosomal and proto-oncogene abnormalities have been discovered in cancer cells originating from mast cells. Mast cell activation is associated with allergic reactions in which antibodies produced against a particular allergen bind to the mast cells and cause release of its biologically reactive agents. Chronic activation of mast cells that have been genetically compromised by hereditary or environmental factors may lead to transformation of these cells to a cancerous state.

SYMPTOMS: Mast cell tumors may appear anywhere in the skin, but occur most frequently on the posterior half of the body particularly on the limbs or on the scrotum of males. There are predominantly two forms of mastocytomas. The more common type appears as a quickly growing and ulcerated mass that may occur as either a single- or multi-nodular tumor. The tumor is firm, white, but often has areas of bluish-purple attributed to broken blood vessels. The second type grows slowly without ulceration, appears yellowish in color and is soft and flabby.

DIAGNOSIS: Clinical diagnosis is made by biopsy of the lesion. In cases of ulcerated lesions, a rapid biopsy may be obtained by touching a microscope slide to the surface of the ulceration to obtain a cell sample for analysis.

TREATMENT: The treatment of choice is surgery involving radical excision of the tumor and some surrounding tissue and removal of regional lymph nodes, which are often the first sites of metastasis. Following healing at the surgical site, radiation therapy is administered to provide control against local recurrence of the tumor. Inoperable tumors may be treated with radiation and chemotherapy. Partial surgery of inoperable tumors followed by injections of deionized water at the site of the tumor, has been found to control recurrence of tumors, as well. These injections are continued at 10-21 day intervals. Use of corticosteroids, like Prednisone, may also help to control inoperable, wide-spread mast cell tumors.

PROGNOSIS: Dogs diagnosed with poorly-differentiated mast cell tumors by biopsy experience only short-term survival (~18 weeks) compared to dogs with well-differentiated tumors (~51 weeks) following surgery. In cases of incomplete surgical excision followed by radiation therapy, approximately 77% of treated dogs were still alive at 2 years following treatment. Mast cell tumors of the extremities respond better to radiation therapy than those tumors invading the trunk of the body. Tumor deaths are usually associated with metastasis to the regional lymph nodes, spleen, liver, kidneys, lungs, and heart that impair organ function.

AVERAGE AGE OF ONSET: Cancerous lesions usually present with the highest frequency between the ages of 6-10 years and rarely prior to 2 years of age.

CAUSE: Both mutations for activation of oncogenes and inactivation of tumor suppressor genes have been identified in canine mammary tumors. Additionally, strong evidence links hormones associated with the estrus cycle ("heat" or "season") of the female to play a major in-direct role in development of this disease.

SYMPTOMS: Malignant tumors may present as a single lump, a mass, or multiple swellings in the tissues comprising the mammary glands. Most frequently these tumors occur in the glands situated closer to the rear legs. Compared to benign growths, malignant growths may grow rapidly, have irregular shape, feel "fixed" to the skin or underlying tissue, and/or become ulcerated. Malignant tumors may occur simultaneously with mastitis in lactating females and become apparent when symptoms of mastitis are resolved with antibiotic treatment. Inflammatory carcinoma, an extremely aggressive form of mammary cancer, is similar to mastitis in appearance but should be immediately suspected when its symptoms occur in a non-lactating female. This cancer presents as a mass that may involve several or a chain of the mammary glands. The effected area appears red, swollen, and warm to the touch. In fact, touching the area results in obvious discomfort to the female.

DIAGNOSIS: Physical examination alone is not sufficient to distinguish between a benign and malignant mammary tumor. Fine-needle aspiration biopsies have been found to be very accurate for determining the presence of malignant cells within mammary tumors. However, in instances where a fine-needle biopsy is negative for cancer, but the mammary tumor is behaving as a malignant lesion (as described under symptoms above), complete surgical resection of the tumor may be advisable for accurate diagnosis. This course of action is further substantiated by evidence that many benign tumors in the dog progress to malignant lesions over a period of time.

TREATMENT: In early stage, localized mammary cancers, surgery is the first choice of treatment if the dog is in otherwise good health and can endure stress of the procedure. In such instances, radical surgery for removal of the entire effected mammary chain and regional lymph nodes (usually the superficial inguinal node located in the groin which holds the highest risk for harboring metastatic cells from the adjacent mammary chain) provide 100% cure. Spaying the dog may circumvent the need to remove the second mammary chain to prevent new benign growths. Additionally, spaying will allow easy detection of any new tumors that may arise in the second chain since following surgery the mammary tissue will shrink (atrophy). In advanced mammary cancers where metastasis has occurred or in which the tumor is fixed to the underlying tissues, surgery will not be curative but may be considered an option to reduce local tumor-burden and improve quality of life (palliative therapy). Additionally, radiation therapy may provide local control of inoperable mammary cancers. Use of chemotherapeutic drugs has produced complete and partial remissions of disease in only some isolated cases. Clinical studies examining the efficacy of the systemic chemotherapeutic agent Tamoxifen for advanced mammary cancer in dogs has shown no measurable therapeutic gain in any of the dogs within the study. Another report, however, indicates that administering the drug Adriamycin, either alone or in combination with other drugs, may decrease risk of cancer recurrence following surgery in dogs.

PROGNOSIS: It is estimated that at the time of presentation at least 50-70% of dogs with malignant mammary tumors will already have distant metastasis and thus, be in an advanced stage of disease. Despite surgical intervention, 40-60% of dogs with mammary cancer will experience tumor-related death within the first two years.

• Immunoreactivity of canine mammary neoplasms with monoclonal antibody CC49. R. Shahar et al., Zentralbl Veterinarmed A., 44:317-23, 1997.

• Imaging of spontaneous canine mammary tumors using fluorescent contrast agents. J.S. Reynolds et al., Photochem. Photobiol., 70:87-94, 1999.

• In vitro cytotoxicity of recombinant human TNF-alpha and actinomycin D on canine normal and tumor cells. M. Aoki et al., J. Vet. Med. Sci., 60:1087-91, 1998.

AVERAGE AGE OF ONSET: Lymphoma may occur in dogs of any age but is seen more frequently in dogs over 5 years of age.

CAUSE: Malignancies originating from lymphatic cells have been shown to be of viral origin in a number of animals, however, no virus has yet been identified in association with this disease in the dog. However, recent findings have identified the presence of a virus, which reportedly has similarities to the feline leukemia virus, in the lymph nodes of a dog with an immunodeficiency disorder. In a separate report, researchers identified germ-line (hereditary) abnormalities of a gene encoding a specific tumor suppressor protein as being present in the cells of dogs with lymphoma.  In light of these findings, it is suspected that transformation of lymphatic cells is dependent upon the initial presence of compromised lymphoid tissue due to genetic defects, radiation exposure, immunosuppressive agents, or immune system abnormalities that predisposes the dog to environmental carcinogens.

SYMPTOMS: There are four forms of lymphoma that may develop in the dog. General symptoms of all forms of lymphoma include fever, weight loss and anorexia (loss of appetite). Specific symptoms are dependent upon which form the dog develops. 1) Multicentric lymphoma is a diffuse form with wide-spread involvement of lymph nodes and lymphatic organs. Dogs will present with enlarged, painless lymph nodes in the neck (cervical nodes), under the front legs (axillary nodes) and in the groin (inguinal nodes). It is not unusual for these nodes to enlarge to the size of golf balls or even baseballs virtually overnight in the case of this disease. Enlargement of the tonsils may obstruct swallowing and obstruction of lymphatic drainage by the tumor may cause fluid build-up and swelling of the face and legs. The spleen is often enlarged. 2)Alimentary lymphoma occurs in the digestive tract. Growing tumors may cause obstruction of the processing and passage and present symptoms of vomiting and diarrhea. These symptoms may be intermittent in the early course of the disease and progress in severity with the disease. Often, these dogs also become emaciated (abnormally thin) because the diseased gastrointestinal tract is unable to absorb protein and nutrients during digestion. 3) Mediastinal lymphoma (developing in the center of the chest usually associated with the thymus gland) is a rare form of lymphoma in the dog. Dogs with this form of lymphoma show signs of easily being fatigued and have respiratory symptoms such as difficulty breathing. 4) Cutaneous lymphoma effects the skin but may also involve superficial lymph nodes. This form of the disease appears as a number of raised lesions or pale plaques that invade the skin.

DIAGNOSIS: Biopsy and microscopic examination of the lymphoid tissue are required for accurate diagnosis of lymphoma in early stages. Fine-needle aspiration for the purpose of biopsy is often not sufficient for diagnosing this form of cancer. Additionally, during the early stage, laboratory blood work may be within normal values and provide little help in patient evaluation. In more advanced stages of the disease, white blood cell count may be elevated and cancerous lymphocytes may be detected in the blood. In many advanced cases, radiographic evidence of chest and/or abdominal masses in the presence of wide-spread lymph node enlargement may preclude the necessity of biopsy.

TREATMENT: Combination chemotherapy for lymphoma, which is a treatment regimen where the dog is administered two or more drugs on a particular schedule, is the standard therapy. Clinically, the most effective treatment regimen, called UW-M, has resulted in response rates (tumor regression) as high as 91% for periods of 6 months or more. This regimen uses a combination of 5 drugs (Vincristine, L-Asparaginase, Prednisone, Cyclophosphomide and Doxorubicin), administered over a nine week period. If this initial treatment schedule is successful in producing remission of the disease, then this treatment is followed by a maintenance drug schedule, which ideally continues for up to 2 years. Single-agent therapy with Doxorubicin alone or Prednisone alone also produces remissions, albeit with shorter durations, in some dogs and provides a more convenient treatment schedule for pet owners. Immunotherapy with a monoclonal antibody (Mab 231) that specifically recognizes some canine lymphomas has been used successfully following chemotherapy for the purpose of prolonging disease remission. Conventional radiation therapy has been found to be ineffective against lymphoma. However, clinical studies exploring radiation therapy with bone-marrow transplant in dogs indicates a possible therapeutic gain may be achieved by combining these two methods.

PROGNOSIS: Without therapy, dogs diagnosed with lymphoma succumb to the disease within 4-6 weeks following diagnosis. There is strong evidence to suggest that lymphomas developed from T-lymphocytes are more aggressive and bear a poorer prognosis than those developed from B-lymphocytes. Treatment produces tumor remission in approximately 90% of cases, with duration of remission and survival dependent upon the treatment regimen used. Use of Prednisone alone helps to improve quality of life, however, remissions are brief, lasting only about 30 days. Combining Cyclophosphamide with Prednisone may provide a slightly longer duration of remission (30-60 days). Treatment with Doxorubin alone has produced remissions for up to 18-29 weeks. A recent study indicates that monitoring plasma glutathione-S-transferase may be helpful in evaluating therapeutic response to doxorubicin treatment. The UW-M protocol (described above) has demonstrated the longest durations of remissions lasting 44-69 weeks for early stage lymphomas and 36-51 weeks for more advanced lymphomas.

Orophayngeal tumors account for about 6% of all tumors occurring in the dog. There are a number of different types of tumors that may develop in the oral cavity of the body. Among them, the most common is melanoma followed by fibrosarcoma, squamous cell carcinoma and adenocarcinoma. Melanoma involves tissues of the gums most frequently, followed by the tongue, lip and palate. Soft tissue tumors will sometimes invade the jawbones. This is particularly the case of osteosarcomas. Cocker Spaniels have an increased incidence for melanoma compared to other breeds, and there may be a slight predominance for this tumor-type to occur in males.

AVERAGE AGE OF ONSET: Cancerous lesions of the oral cavity may present at any age with the highest frequency occurring between the ages of 7-11 years.

CAUSE: A tumor virus, called papillomavirus, is suspected of playing a role in oncogene activation associated with the development of carcinomas and sarcomas of the oral cavity. Dogs with oral and ocular papillomas (benign tumors) reportedly are at increased risk to developing malignant tumors. Dogs living in the city are at higher risk to developing malignancies associated with the tonsils. One study found a significant increase of risk for sinonasal tumors in pet dogs in homes using indoor coal or kerosene heaters suggesting strong evidence for environmental carcinogens in the development of oropharyngeal cancers.

SYMPTOMS: Unfortunately, malignancies of the oral cavity are not often found until the disease is in an advanced stage. Increased salivation, difficulty chewing, loss of appetite, weight loss, difficulty swallowing, bad breath, and bloody saliva are all symptoms of oropharyngeal cancers. Tumors involving the tonsils or the base of the tongue may also cause difficulty breathing. Loose teeth in an otherwise healthy mouth may also signal the presence of bone lesions. Sarcomas may present as ulcerating mass lesions, however, carcinomas may be less obvious in terms of detection.

DIAGNOSIS: Dogs presenting with tumors of the oral cavity must undergo biopsy of the lesion for identification of tumor-type. Additionally, x-rays of the local and surrounding area of the tumor as well as films of the chest are usually required to determine extent of the spread of the disease. Many melanomas and some carcinomas will have already metastasized to the lungs by the time the dog is identified as having an oral tumor. Additionally, it is not uncommon for tumors of the soft tissues of the mouth to invade underlying bone. Regional lymph nodes should be examined for possible involvement, and suspicious nodes should be biopsied by fine-needle aspiration for evidence of malignant cells. Computed tomography (CT) may be valuable for determining the extent to which the nasal cavity may be involved.

TREATMENT: Surgery involving the removal of portions of the effected upper (maxillectomy) or lower (mandibulectomy) jaw results in average survival times of 8 or 11 months, respectively. The best outcomes are reported for radical excision in which an average of at least 2-cm of surrounding normal tissue is removed with the diseased tissue. In the cases of incomplete excision or inoperable tumors due to wide spread invasion, radiation therapy may provide palliative control of some radiation-responsive tumors. Radiation therapy may be combined with chemotherapy, however, no significant advantage of providing longer survival has been observed for this combination compared to radiation therapy alone. For chemotherapy alone, squamous cell carcinomas are moderately responsive to Cisplatin or Carboplatin, and sarcomas demonstrate a 30-50% response rate to Doxorubicin treatment.

PROGNOSIS: Early detection, when oropharyngeal tumors are less than 2 cm in diameter, provides a better outlook for therapeutic response and long-term prognosis since likelihood of metastasis increases with the size of the primary tumor.

    Melanomas of the oral cavity are usually resistant to radiation therapy and carry a poor prognosis due to the high incidence of metastases associated with this tumor-type. Average survival following therapy for melanoma is about 8 months.

    Fibrosarcomas present more problems associated with local invasion than with distant metastases. Additionally, this tumor-type appears to be extremely resistant to local control when it occurs in dogs under the age of 2 years. In general, however, fibrosarcomas are responsive to radiation therapy with control of tumors lasting an average of 12 months. Greater tumor control has been observed in dogs treated with a combination of radiation therapy and local hyperthermia (heat therapy). Most successful treatment regimens combine surgery with radiation therapy (before or after surgical excision) and chemotherapy.

    Squamous cell carcinomas are locally invasive with preponderance toward invading underlying bones, however, metastases associated with this tumor-type are rare in the dog. Average survival of dogs treated with surgery and radiation therapy is a little over 1 year. An exception to this occurs when this tumor-type develops in the tonsils. Average survival decreases dramatically (to about 4 months) even with surgery and radiation therapy, and is associated with the increased tendency of the tumor to metastasize from this location. Addition of Cisplatin or Doxorubicin to the standard treatment regimen may assist to prolong survival.

    Osteosarcomas of the oral cavity bear a particularly dismal prognosis due to both local invasiveness and high incidence of metastases. Average survival of dogs undergoing treatment with surgery and radiation is about 4-5 months. Addition of chemotherapy to the treatment regimen may further increase anticipated survival of dogs with this tumor-type (see next section).

PREVENTION: The increased incidence for dogs with papillomas to develop oropharyngeal tumors combined with the decreased incidence of these tumors in dogs immunized against papillomavirus provides strong evidence that predisposition to oral cavity tumors is virally induced. Additionally, it has been found that dogs who are immunosuppressed due to therapy with glucocorticoids show increased risk to infection with the papillomavirus. Therefore, factors such as viral infection and immunosuppression combined with environmental carcinogens may be the most common events leading to development of oropharyngeal tumors.

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• Systemic immunization with papillomavirus L1 protein completely prevents the development of viral mucosal papillomas. J.A. Suzich et al., Proc. Natl. Acad. Sci. USA, 92:11553-7, 1995.

Though osteosarcoma was presented in the prior section as an oropharyngeal tumor, it is also the most common primary bone tumor occurring in dogs. These tumors develop most frequently in the long bones of limbs and less commonly in the bones of the spinal column or skull. These tumors are locally invasive, destroying normal bone as they progress, and frequently metastasize to the lungs thereby complicating therapeutic management of the disease. Giant breeds have a greater risk for developing osteosarcomas, and males have a slightly higher risk than females for this form of cancer.

AVERAGE AGE OF ONSET: Cancerous lesions of the bone present most commonly between 2-8 years of age, with 7 years being the average age for presentation.

CAUSE: Mutations in the gene encoding a tumor suppressor protein reportedly occur in close association with and are probably predisposing factors for development of osteosarcoma in dogs. Other risk factors are associated with increasing age and increasing height. Neutered dogs appear to have an approximate two-fold increase in risk to developing osteosarcoma. Additionally, one report has found evidence linking bone infarction (loss of blood supply resulting in dead tissue) occurring after surgery for total hip replacement in dogs with subsequent development of osteosarcoma at the site of the infarction.

SYMPTOMS: Progressive lameness often leads to the finding of a painful swelling at the site of the bone tumor. Occasionally, a sudden fracture of the effected bone may be the presenting condition, but this occurs less frequently. Dogs are usually free of other symptoms. Only when the tumor has progressed to a metastatic stage may other symptoms like weight loss, enlarged lymph nodes, or difficulty breathing become evident.

DIAGNOSIS: Many conditions may cause lameness and swelling also associated with osteosarcoma. Additionally, the possibility of other primary bone tumors or metastasis of other tumor-types to the bone must be ruled out prior to making a diagnosis of primary osteosarcoma. Biopsy of bone tumors by surgical sampling is often difficult because of complications that may arise following surgery. The use of a bone marrow biopsy needle to resection a small portion of the tumor site has proven minimally invasive while providing sufficient cellular material to provide accurate diagnosis. Once a diagnosis of osteosarcoma is determined, presence of metastasis to the lungs is confirmed by chest x-ray. Bone scans (nuclear scintigraphy) may be helpful for locating sites of other bone lesions caused by metastases, however, fewer than 10% of dogs usually show detectable evidence of secondary bone metastases by either of these methods. Recent evidence suggests that dogs with osteogenic tumors that are more vascularized, as determined during microscopic examination, have a greater likelihood of having lung metastases than those having tumors with fewer blood vessels. This observation may serve as a prognostic indicator for using more aggressive therapies despite the absence of detectable secondary metastases.

TREATMENT: Up until recently, amputation of the tumor-bearing limb followed by Cisplatin chemotherapy was the most effective therapy. It has been found, however, that limb sparing surgery (in which the tumor is removed and the bone is reconstructed at the site of excision) followed by Cisplatin treatment is just as effective in selected cases while providing excellent cosmetic and functional results. Radiation therapy may be used before or after surgery or in cases of inoperable or incompletely removed bone tumors, and is often used to provide pain relief from secondary bone tumors associated with metastases. Surgical removal of lobes of the lungs harboring metastatic lesions has been indicated as increasing survival in some dogs in which the primary bone tumor has been successfully treated by surgery.

PROGNOSIS: Without treatment, dogs diagnosed with osteosarcoma will succumb to their cancer in about 1-2 months. Worsening pain at the site of the bone tumor usually results in the dog being euthanized prior to this period of time, however. Amputation alone provides short-term benefit with anticipated average survival of about 5 months and about 10% of dogs surviving up to one year. This procedure also increases quality-of-life for the dog by alleviating the primary source of the pain. Because metastasis is the main limitation to effective long-term survival for osteosarcoma, combining Cisplatin therapy with amputation has been found to increase 1 year survival to 50%. Similarly, treatment with Doxorubicin or Carboplatin increases average duration of survival though to a lesser extent than Cisplatin therapy. Limb sparing surgery in which the area at the site of the tumor is removed and reconstructed is most successful in dogs that have tumors involving less than 50% of the effected bone. In such instances, limb sparing surgery combined with Cisplatin therapy is just as effective in terms of survival rates as complete amputation combined with Cisplatin therapy. Radiation therapy combined with Cisplatin therapy to treat inoperable or incompletely resected tumors provides pain relief for an average of about 2-3 months and in some cases up to 6 months or longer.

PREVENTION: Size, in regard to height more so than weight, appears to be one of the predisposing factors for development of osteosarcoma. Additionally, evidence suggests that bone trauma may be another factor. It is possible that stimulation of genetically (either inherited or acquired) abnormal bone cells during rapid growth or incidences of bone repair may induce the development of osteosarcomas.

NEW OR UPCOMING TREATMENTS AND TECHNIQUES: (use the "Back" command of your internet browser to return to this page after viewing the abstracts of these following journal articles)

• In vitro and in vivo cytotoxicity of an anti-osteosarcoma immunotoxin containing pokeweed antiviral component. P.M. Anderson et al., Cancer Res., 55:1321-7, 1995.