Canine Osteosarcoma - Jennifer McDaniel DVM (Practice Limited to Oncology)

Osteosarcoma (OSA) is the most common primary bone tumor of dogs. Unfortunately, it is a very common disease seen in veterinary medicine with greater than 10,000 dogs being affected every year in the United States alone. Although our canine patients are most commonly affected, osteosarcoma has been reported in horses, ferrets, rabbits, cats and human beings.  In Cats, OSA, as well as all other primary bone tumors, is less common.  Approximately 4.9 at risk cats per 100,000 develop primary bone tumors per year, with 80-90% of those tumors being osteosarcoma.  Although the disease is less common in humans than in dogs, osteosarcoma can be a devastating diagnosis in human beings affecting mainly children in their teenage years. Canine osteosarcoma has proven to be a very important comparative model in studying the disease and treatment options for children. There has been significant improvement in survival times of human beings with osteosarcoma. In 1980 there was a 20% 5 year-survival rate for human beings with OSA compared to a current long-term survival rate of 60%.  

Osteosarcoma most commonly affects large and giant breed dogs. Breeds found to be at the highest risk of developing OSA include the Great Dane, Saint Bernard, Irish Setter, Greyhound, Rottweiler, German Shepherd and Golden Retriever. Most commonly patients are middle aged to geriatric (median of 7 years), although there is a peak in incidence at 18 to 24 months.

Most commonly the disease occurs in the appendicular skeleton (~75% of cases) although it can also be seen in the axial skeleton as well as soft tissue sites. The forelimbs are affected much more commonly than the hindlimbs with the metaphyseal region of long bones being the most common primary site. The distal radius and the proximal humerus are frequently affected, as are the distal femur and proximal tibia leading to the saying “towards the elbow, away from the knee”.  In the axial skeleton the tumor can present in the mandible, maxilla, spine, cranium, ribs, nasal cavity and pelvis. Extraskeletal sites are much less common but sites reported include the mammary tissue, subcutaneous tissue, spleen, bowel, liver, kidney, eye, gastric ligament, synovium, meninges and adrenal gland. OSA of extraskeletal sites tends to be very aggressive and is often associated with a poor prognosis.

Patients with appendicular lesions most commonly present with lameness and swelling of the tumor site. Owners often associate a recent, minor trauma with the limping and present the patient for evaluation. If the patient has a pathologic fracture (not uncommon with OSA) they may present with severe pain and non-weight bearing lameness.

Radiographs of the affected limb (lateral and craniocaudal views of the lesion) should be pursued following a thorough history and physical exam. Radiographic abnormalities most commonly noted include cortical lysis and osseous proliferation, often with soft tissue extension and/or swelling.  A presumptive diagnosis if often made based on the radiographic appearance of the lesion, signalment, history and physical exam findings. However, differential diagnosis should include other primary bone tumors (chondrosarcoma, fibrosarcoma, hemangiosarcoma, etc.), metastatic lesions, multiple myeloma, solitary plasma cell tumor, lymphoma, systemic mycosis, bacterial osteomyelitis and a bone cyst.

               

If there is a strong suspicion of osteosarcoma based on the radiographs and case findings, three-view thoracic radiographs should be obtained as the next step. Osteosarcoma is aggressive both locally and systemically and metastatic disease is common. At the time of diagnosis only about 15% of patients will have gross metastatic disease; however, approximately 90% of patients will have micrometastatic disease. OSA spreads hematogenously and the most common metastatic site is the lungs, although spread to other bones or soft tissue structures is possible. Along with thoracic radiographs a minimum metabolic database is recommended including a complete blood cell count, serum chemistry and urinalysis. Several studies have reported that dogs with an elevated alkaline phosphatase have a poorer prognosis and may develop metastatic lesions earlier than patients with a normal alkaline phosphatase.

In order to confirm diagnosis a sample (either cytology or biopsy) needs to be obtained. Cytology can be difficult as samples are often poorly cellular and non-diagnostic. Biopsy is the preferred method and can be obtained as an open incisional biopsy or a closed needle biopsy. If biopsy is performed the sample should be collected from the center of the lesion and in a location that will allow removal of the incision and biopsy tract at the time of definitive surgery. Bone fracture is a concern with this tumor, especially when a biopsy is performed. Owners should be warned of this risk and care taken to avoid fracture. If a primary bone tumor is highly suspected, many owners will forego a definitive diagnosis prior to pursuing definitive therapy.

Although OSA is an aggressive disease with survival times of 2-4 months without therapy; there are multiple treatment options available to these patients. These treatments are aimed at treating the local disease and managing the associated pain while decreasing the potential for systemic spread.  Local therapies include amputation, limb sparing surgery, palliative radiation therapy and bisphosphonates.  All of these options are palliative in nature and do not extend survival times.

·         Amputation is a readily available option and the majority of orthopedically sound dogs (even giant breeds and dogs with mild to moderate arthritis) handle this option very well.

·         Limb sparing surgeries can be very beneficial in orthopedically unsound dogs when amputation is not possible.  Limb sparing surgeries are most beneficial for tumors of the distal radius or ulna with absence of a pathologic fracture. However, these surgeries need to be performed by experienced surgeons at specialized surgical centers.

·         Radiation therapy and bisphosphonates are surgical alternatives for pain control. Survival time is not extended by either of these therapies but can be very beneficial in managing discomfort. Radiation therapy typically consists of one treatment per week for 3-4 weeks.  Approximately 70-90% of patients experience 2-3 months of pain relief from this treatment. Side effects are minimal and the patients do not experience systemic side effects as a result of radiation.

·         Bisphosphonates, such as pamidronate, are another option for pain relief. They are administered intravenously along with a fluid diuresis. These drugs reduce bone pain by inhibiting formation of osteoclasts and decreasing their ability to resorb bone. Bisphosphonates can be administered every 4 weeks and pain relief may last weeks to months.

As a result of the high metastatic rate chemotherapy is used in conjunction with local therapy in an effort to slow or prevent disease spread.  The most common chemotheraputic drugs used to treat OSA include carboplatin, cisplatin and adriamycin.  Cisplatin is used much less commonly as a result of its potential for nephrotoxicity necessitating a 6-hour diuresis at the time of drug administration. Carboplatin and adriamycin are used more commonly either as single agents or as part of a multiagent protocol (alternating carboplatin and adriamycin). Both carboplatin and adriamycin are administered intravenously every 3 weeks. Carboplatin is given for 4-6 treatments and adriamycin is given 5 times.  The majority of patients  (approximately 85%) handle these treatments very well with few to no side effects. When side effects are noted, we most commonly see vomiting, diarrhea, decreased appetite, decreased energy level and bone marrow suppression. These side effects tend to be short lived and self-limiting and most patients recover with no intervention. A smaller percentage of patients will require oral anti-emetic or anti-diarrheal drugs and less than 1% of patients have side effects that necessitate hospitalization.

Currently there are studies looking at the benefit of using the oral tyrosine kinase inhibitor, Palladia, or oral metronomic chemotherapy in addition to conventional chemotherapy.  With the addition of these therapies we may see survival times of greater than one year. In addition, osteosarcomas have been shown to overexpress Cox-2 and thus the use of non-steroidal anti-inflammatory drugs may also be beneficial in slowing disease progression and are commonly used in chemotherapy protocols.

With local therapy alone (surgery, radiation therapy, bisphosphonates) average survival times are 3-4 months. With surgery and chemotherapy survival times increase to approximately 12 months with 25% of patients living two years.

The goal with treatment is not only to improve our patient’s length of life but also to ensure an excellent quality of life. With the treatments discussed, the majority of patients will maintain an excellent quality of life and enjoy a significant extension of life.

Dr. Jennifer McDaniel

References

·         London C, Mathie T, Stingle N, et al: Preliminary evidence for biologi activity of toceranib phosphate (Palladia) in solid tumors, Vet Comp Oncol  2011.

·         Withrow SJ, Powers BE, Straw RC, et al: Comparative Aspects of osteosarcoma: dog versus man, Clin Orthop Relat Res Sept(270): 159-168, 1991.

·         Withrow S, Vail D, Page R. (2013).  Small Animal Clinical Oncology.  St. Louis, MO: Elselvier