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Canine Appendicular Osteosarcoma

Talbott_gray_cat-web - USEJessica Lee Talbott, DVM, DACVIM (Medical Oncology)
www.angell.org/oncology
617-541-5136
oncology@angell.org

Osteosarcoma (OSA) is the most common primary bone tumor in dogs, accounting for approximately 85% of all malignancies originating in the skeleton.1 Approximately 75% of OSA affects the appendicular skeleton with the remaining 25% affecting the axial skeleton. OSA commonly affects large to giant breed dogs, with a bimodal age distribution of 2 and 9-10 years of age with a median age of 7 years at presentation. Great Danes, Saint Bernards, Irish Setters, Dobermans, Rottweilers, German Shepherds and Golden Retrievers have an increased risk of developing OSA. The forelimbs are affected twice as often as the hind limbs, with the distal radius and proximal humerus being the most frequently affected sites, specifically within the metaphyseal region.2

Left lateral radiograph of the distal femur of a dog with osteosarcoma. Radiographic features include osteolysis of the metaphyseal region of the femur, Codman’s triangle, and mild cortical lysis of the caudal cortex.

Left lateral radiograph of the distal femur of a dog with osteosarcoma. Radiographic features include osteolysis of the metaphyseal region of the femur, Codman’s triangle, and mild cortical lysis of the caudal cortex.

Appendicular OSA is an aggressive and invasive cancer that destroys bone locally and has a high rate of metastasis. Metastasis occurs predominantly to the lungs with lower frequency to distant bones and regional lymph nodes. While less than 15% of dogs have radiographically detectable pulmonary metastasis at the time of initial diagnosis, 85-90% of patients will develop gross metastasis despite effective control of the primary bone tumor, indicating that subclinical micrometastases arise early in the course of disease.1

Dogs with appendicular OSA often present with a history of progressive limb lameness that is minimally responsive to oral pain medications, with or without associated soft tissue swelling of the limb. Alternatively, dogs may present with an acute non-weight bearing lameness that is often associated with a pathologic fracture. It is important to consider other causes of lameness in these patients and obtain a thorough patient history including travel history and recent trauma.

A presumptive diagnosis of osteosarcoma is often made based on signalment, history, clinical presentation and radiographic findings. Diagnostic imaging plays an important role in the diagnosis and staging of dogs with OSA. Two view (lateral and craniocaudal) radiographs of the primary lesion, including the joint above and below the affected bone, are required. The radiographic appearance of appendicular OSA is most commonly a combination of osteoproliferative and osteolytic changes. However, there is an entire spectrum of changes that can be seen, making the appearance quite variable.

A definitive diagnosis can be attempted using a fine needle aspiration (using an 18 gauge needle) and cytology of the lesion using heavy sedation or general anesthesia. In one study, OSA was accurately diagnosed in 85% of fine needle aspirates.3 In many cases a presumptive diagnosis of sarcoma is reached and therefore facilitates a discussion of treatment options. If unsuccessful, bone biopsy via closed (Jamshidi needle or Michelle’s trephine) or open techniques could be considered. Owners should be advised of the risk of pathologic fracture associated with a bone biopsy. If the owners are considering limb spare treatment options (see below), it is recommended to consult with a surgical or medical oncologist prior to performing a biopsy.

Staging dogs with osteosarcoma is performed with the goal of evaluating the lungs and remainder of the skeleton, based on known local and metastatic behavior. Three-view thoracic radiographs are performed to evaluate for the presence of pulmonary metastasis. CT is becoming more widely used for thoracic staging as it has been shown to be more sensitive than thoracic radiographs, in detecting smaller lung lesions.4 Evaluation for the presence of bone metastasis varies based on institution but can include radiography or nuclear scintigraphy. With scintigraphy the incidence of occult bone metastasis at the time of diagnosis of the primary tumor, is 8%.5 Many factors are considered when deciding which diagnostic tests to perform, including the presence of a pathologic fracture, physical exam findings, finances, and/or owner preference.

Multiple factors have been associated with prognosis and survival in canine appendicular OSA including: large tumor size, location (humerus), elevated ALP, young age (<5 years) at diagnosis, use of adjuvant chemotherapy, stage, and post-operative infection at limb-sparing surgical sites.6 A recent meta-analysis found that elevated serum ALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.7 Patients that present with preoperative elevations in ALP are expected to have a shorter disease free interval and survival time.8 Active research is underway to further characterize the biology of OSA as well as identification of tumor- and host-associated molecular, genetic, and immunologic events as important factors that influence prognosis.

 

TREATMENT

The most effective management of canine appendicular OSA involves the incorporation of multimodal therapy to address the primary tumor and metastatic disease.

Primary Tumor

Limb amputation remains the standard of care for local tumor management. All dogs should be considered candidates for amputation with each case being evaluated individually. Each patient should be assessed for possible contraindications including severe obesity or concurrent debilitating orthopedic or neurologic disease. Treatment with amputation eliminates pain and the risk for pathologic fracture. It is a well-tolerated procedure with minimal complications and a short recovery period. Most dogs (including large and giant breeds) usually function well after limb amputation and most owners are pleased with their pet’s mobility and quality of life after surgery.9 Complete forequarter amputation is recommended for forelimb lesions, and a coxofemoral disarticulation is recommended for hind limb lesions. This level of amputation ensures complete local disease removal as well as cosmetic and functional outcome.

Limb-spare (surgery or radiation) treatment options may be considered for those patients where amputation isn’t permitted due to owner preference, or severe neurologic or orthopedic disease. Limb-sparing is a complicated and expensive process that requires an organized team approach between surgical and medical oncologists, radiologists, and pathologists. Therefore consultation with a surgical oncologist should be performed for those clients that are interested in limb spare procedures, in order to determine eligibility and discuss available techniques. Colorado State University and the University of Florida are the two facilities that offer surgical oncology fellowship training programs and are most likely to consider patients on a case-by-case basis for limb spare procedures.

Metastasis

Adjuvant chemotherapy improves survival of dogs with appendicular OSA when combined with surgery and/or radiation therapy. Currently platinum based (carboplatin) single agent chemotherapy is the most commonly utilized treatment as it has been demonstrated to improve survival after amputation. The survival times are similar for patients treated with single agent platinum compounds vs treatment with combined protocols (including doxorubicin). The median survival time for patients treated with amputation and chemotherapy increases to approximately 10-12 months, from 4-6 months with amputation alone. The 1- and 2-year survival rates with chemotherapy range from 31-48% to 10-26%, respectively.10

Palliative Treatment Options

The goal of palliative-intent treatment is to alleviate pain and improve quality of life in situations where the standard of care is declined. Radiation therapy can be utilized for palliation of bone pain associated with OSA and has been shown to be a very effective in management of osteolytic bone pain in humans and dogs.10 Consultation with a Radiation Oncologist is recommended to discuss available radiation treatment options and which is best for the patient.

Bisphosphonates are synthetic analogs of inorganic pyrophosphate that were originally used for diagnostic purposes in bone scanning, however they possess bone protective effects exerted through induction of osteoclast apoptosis. This results in inhibition of pathologic bone resorption without inhibiting bone mineralization. Zoledronate (IV over 15 minutes) and pamidronate (IV over 2 hours) are the most commonly used bisphosphonate medications and each has demonstrated pain palliation in 30-50% of treated dogs.11

Adequate pain medication is required for any patient being treated with palliative-intent treatment alone. In patients where appropriate, it is important to balance the use of non-steroidal anti-inflammatory drugs (NSAIDs), opioid medications, NMDA antagonists (amantadine), and anticonvulsants (gabapentin). In addition to pharmacologic manipulation and directed treatments, complementary therapies including acupuncture, laser therapy, hydrotherapy, and massage should be considered.

Immunotherapy on the Horizon

Currently under investigation at the University of Pennsylvania, the Mason Lab is evaluating a vaccine that aims to stimulate the body’s immune system to recognize and kill osteosarcoma cancer cells. This is an attenuated bacterial (Listeria monocytogenes) vaccine which is genetically modified to express a certain tumor-protein (HER-2/neu) found to be expressed in osteosarcoma cancer cells. The goal is to stimulate the immune system to recognize primary and metastatic cancer cells and eliminate them. This is promising research based on preliminary data. Currently there are no open trials in osteosarcoma for Dr. Mason’s Lab.

For more information, please contact Dr. Lee Talbott at the Angell Oncology Service (617-541-5136 or oncology@angell.org).

 

References:

  1. Ehrhart N, Ryan SD, Fan TM. Tumors of the Skeletal System. In: Small Animal Clinical Oncology. 5th ed. Elsevier; 2013. p. 463–94.
  2. Dernell WS, Ehrhart NP, Straw RC, Vail DM. Tumors of the Skeletal System. In: Withrow, S.J., Vail, D.M. (Eds.), Withrow and MacEwen’s Small Animal Clinical Oncology. Saunders, Elsevier; 2007. p. 540-582.
  3. Neihaus SA, Locke JE, Barger AM, Borst LB, Goring RL. A novel method of core aspirate cytology compared to fine-needle aspiration for diagnosing canine osteosarcoma. J Am Anim Hosp Assoc Sept-Oct; 47 (5): 317-23, 2011.
  4. Nemanic S, London CA, Wisner ER. Comparison of thoracic radiographs and single breath-hold helical CT for detection of pulmonary nodules in dogs with metastatic neoplasia. J Vet Intern Med Jun; 20(3):508–15, 2006.
  5. Jankowski MK, Steyn PF, Lana SE, Dernell WS, Blom CM, Uhrig JL, et al. Nuclear scanning with 99mTc-HDP for the initial evaluation of osseous metastasis in canine osteosarcoma. Vet Comp Oncol. Sep;1(3):152–8, 2003.
  6. Fenger JM, London CA, Kisseberth WC. Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology. ILAR J Natl Res Counc Inst Lab Anim Resour. 55(1):69–85, 2014.
  7. Boerman I, Selvarajah GT, Nielen M, Kirpensteijn J. Prognostic factors in canine appendicular osteosarcoma – a meta-analysis. BMC Vet Res. 8:56, 2012.
  8. Ehrhart N, Dernell WS, Hoffman WE, et al: Prognostic importance of alkaline serum phosphatase activity in serum from dogs with appendicular osteosarcoma: 75 cases (1990-1996), J Am Vet Med Assoc 213: 1002-1006, 1998.
  9. Carberry CA, Harvey HJ. Owner satisfaction with limb amputation in dogs and cats. J Am Vet Med Assoc 23:227-232, 1987.
  10. Morello E, Martano M, Buracco P. Biology, diagnosis, and treatment of canine appendicular osteosarcoma: Similarities and differences with human osteosarcoma. The Vet Journal 189: 268-277, 2011.
  11. Fan, Timothy M. Pain Management in Veterinary Patients with Cancer. Vet Clin Small Anim 44: 989-1001, 2014.
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