Abstract

Osteosarcoma is the most common primary bone tumor in dogs. While its diagnosis is often not difficult, staging and treatment options vary depending on the goals of treatment. Known causes of this tumor will be reviewed. This lecture will also cover the various diagnostic tests that are done to stage the tumor including bone biopsy and aspirates, the use of radiographs, CT and MRI imaging, bone scintigraphy and lymph node aspirates. Surgical options to treat the primary tumor will be discussed. Adjuvant therapy including the use of bisphosphonates as well as chemotherapy options and outcomes will also be reviewed. As pain control is an important aspect of managing this cancer, especially for clients who do not choose amputation or limb-sparing surgery for treatment, palliative measures will also be covered.

Introduction

It has been estimated that there are up to 10,000 cases of canine appendicular osteosarcoma in the United States each year, making osteosarcoma the most common primary bone tumor in dogs. It is important to rule out other diseases that can present with similar clinical signs and radiographic appearance. Other primary bone tumors include chondrosarcoma, histiocytic sarcoma, fibrosarcoma and hemangiosarcoma. Tumors from the soft tissues can also metastasize to bone; most commonly transitional cell carcinoma, mammary tumors and prostatic tumors, although these tumors are often located in the diaphysis. Infectious causes of boney lesions are also possible including fungal disease and bacterial osteomyelitis. Generally dogs with osteosarcoma present with a history of lameness and/or a mass. The cause of most cases of osteosarcoma remains unknown, with a hereditary component likely. There are reports however of tumors forming at the sites of previous trauma, fracture sites, TPLO sites and at sites of bone cysts.

Diagnosis

Definitive diagnosis of bone tumor requires histopathology but this can sometimes be difficult to get. As the pieces of tissue that are submitted to the pathologist are generally small, a non-representative sample may be obtained causing the diagnosis to be different. For example a chondrosarcoma may be diagnosed initially and then when the entire bone is submitted after a definitive treatment that diagnosis might be changed to osteosarcoma. This is one reason that the diagnosis should be confirmed after the bone is removed. It is also possible to obtain a non-diagnostic sample of reactive bone. Bone biopsies do have the risk of causing a pathologic fracture in a severely compromised bone.

Ultrasound guided bone aspirates have the advantage of being less invasive and do not carry the risk of pathologic fracture that biopsy procedures can. On the other hand an aspirate does not provide tissue architecture and may only be able to confirm or suggest a sarcoma but not provide a more definitive diagnosis.

Staging

Staging of dogs diagnosed with osteosarcoma is important in determining prognosis and also in helping decide the proper course of therapy. Staging includes a thorough physical examination, including a complete orthopedic exam to look for possible sites of metastasis and concurrent orthopedic disease. A CBC, chemistry panel and urinalysis should be done to assess the dog's general health. Three view thoracic radiographs are done to assess for pulmonary metastasis as about 10% of dogs will have gross evidence metastasis. A CT scan of the thorax is an even more sensitive method to look for pulmonary metastasis. A bone scan using technetium di-phosphate can be used to look for additional sites of metastasis. In one study 7.8% of dogs had evidence of boney metastasis of a primary osteosarcoma lesion at presentation.

Treatment of the Primary Tumor

Amputation remains the standard of care for appendicular osteosarcoma. More recently limb sparing surgery has allowed the preservation of the limb with removal of the primary tumor. For the most part these procedures are limited to tumors located in the distal radius and tibia. Amputation or limb sparing alone can treat the primary tumor effectively, however >90% of dogs will have microscopic metastasis at diagnosis and the median survival without adjuvant therapy will be about 3 months.

Chemotherapy

The agents most commonly used to treat osteosarcoma are carboplatin, cisplatin and doxorubicin used either alone or in combination. Most protocol will give a median survival of about one year, with the 1 and 2-year survival rates varying depending on the protocol (Table 1).

Table 1. Outcomes of dogs treated with chemotherapy for osteosarcoma.

Palliative Care

Several studies have looked at the effectiveness of hypofractionated courses of radiation therapy with the goal of palliation of clinical signs. Heidner et al. Looked at 12 dogs diagnosed with osteosarcoma. Dogs were treated with 24-40Gy of cobalt megavoltage irradiation. They also received intraarterial cisplatin on the first and last day of therapy. Median survival was 4.9 months. If the two dogs with evidence of gross pulmonary metastasis at the start of therapy were removed from analysis median survival was 6.7 months and three dogs were still alive at one year. Four dogs developed pathologic fractures.

McEntee et al. examined 15 dogs treated with three once weekly fractions of 10Gy per fraction. Twelve dogs experience some improvement in lameness between 7 and 22 days after starting therapy with a duration of response between 17 and 288 days.

Ramirez et al. looked at 95 dogs who underwent palliative radiotherapy for an osteosarcoma lesion. 47 of the 95 dogs received either carboplatin or cisplatin chemotherapy. Dogs received either 3 fractions of 10Gy (n=58) each or 2 fractions of 8Gy (n=37). Median survival was 122 days (range of 7-2035 days). Dogs that received chemotherapy concurrently with radiotherapy were 3.5 times more likely to respond to treatment. 74% of dogs had a clinical response to treatment. This was seen at anywhere from 1-60 days after starting treatment with a median time to response of 11 days. Median duration of response for the 63 dogs for which this information was available was 73 days. 14 dogs developed pathologic fractures.

The most commonly used drugs to treat cancer pain include non-steroidal anti-inflammatories, tramadol, gabapentin, amantadine and opioids (see Table 2). Often an NSAID is used in combination with drugs from other classes. There are multiple NSAIDs available for the use in dogs. Some dogs will respond better to different drugs within the class, so if there is not adequate pain control with one drug then the dog can be tried on a different one.

Table 2. Analgesics.

Bisphosphonates

Bisphosphonates are a class of drugs that inhibit bone resorption through the inhibition of osteoclasts. They also have been shown to have some anti-tumor properties including induction of tumor cell apoptosis in vitro, inhibition of angiogenesis, and inhibition of matrix metalloproteinase. There have been 3 bisphosphonates that have been evaluated in veterinary medicine: alendronate, pamidronate and zoledronate. Alendronate is an oral bisphosphonate, which unfortunately is not readily bioavailable in the dog. It has also been associated with gastrointestinal and esophageal toxicity. Both of these things combined limit its use in veterinary medicine. Pamidronate is given as an IV infusion. It is dosed at 1-2mg/kg diluted in 250 mls of NaCl given as an IV infusion over 2 hours every 21-28 days. Renal function should be monitored as renal toxicity has been reported. Zoledronate is another bisphosphonate that is dosed at 0.25 mg/kg IV in 50ml saline over 15 minutes every 28 days. This drug is more expensive than pamidronate.

These drugs can be used alone or more effectively with other pain medications. Fan et al reported on 43 dogs with appendicular osteosarcoma treated with pamidronate and deracoxib. 12 (28%) had some pain alleviation of at least 4 months for a median duration 231 days.

Failure and Salvage

Most dogs with osteosarcoma will eventually die of their disease. For dogs who have definitive treatment of their primary tumor the most common site of metastasis is the lungs. Other sites include bone, skin, kidneys and liver. No chemotherapy agents have been shown to be effective once gross metastatic disease has been diagnosed. Surgery to remove pulmonary metastases can be effective for palliation of disease, although most dogs will have recurrence. A CT scan of the lungs should be done to assess if a candidate is an appropriate candidate. In one study evaluating outcome for dogs that underwent metastasectomy for osteosarcoma pulmonary metastasis, patients with a disease free interval > 300 days and fewer than 3 pulmonary nodules did better than those patients who had evidence of metastasis early or who had larger number of tumors.

References

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