Complete tumor staging warranted with osteosarcoma

Q. How does one manage dogs with diagnosed osteosarcoma?

A. Dr. Carolyn J. Henry, at the 2004 Western Veterinary Conference in Las Vegas, gave a lecture on treatment of canine osteosarcoma. Some relevant points in this lecture are provided in this article.

Of the primary bone tumors that occur in dogs, osteosarcoma (OSA) is by far the most common. Before choosing a treatment plan for canine OSA, complete tumor staging is warranted to determine which options are most reasonable. Approximately 90 percent of dogs with appendicular OSA are thought to have micrometastatic disease at the time of diagnosis and 10 percent to 15 percent may have other primary bone OSA sites.

Johnny D. Hoskins,DVM, Ph.D., Dipl. ACVIM

Accordingly, three-view thoracic radiography, a complete orthopedic examination to assess for other limb involvement, and radiography or bone scintigraphy to assess for other bone involvement or concurrent orthopedic diseases is warranted. Although veterinarians routinely perform thoracic radiography, they are less likely to suggest bone survey radiography or scintigraphy as part of the initial diagnostic workup.

Interestingly, a recent survey reported a greater likelihood of detecting other lesions on bone survey radiography than on thoracic radiography. The cost differential between a full set of appendicular and pelvic radiography and a nuclear bone scintigraphy is not great enough to warrant forgoing scintigraphy, especially when the propriety of surgery is in question.

Bone scintigraphy may detect early metastatic or second primary bone lesions that will become problematic, should amputation be pursued. If suspicious areas are noted on the bone scintigraphy, radiography of the site may be warranted to rule out non-neoplastic causes of osteoblastic activity and increased radionuclide uptake.

Other methods of assessment should include a complete physical examination with particular attention to orthopedic, cardiac and neurological evaluations. Perform a complete blood and urine evaluation to assess for underlying infectious/inflammatory disease plus to determine if surgery and chemotherapy are feasible. In addition to determining what treatment modalities may be appropriate, serum chemistry profile may provide an indication of prognosis.

Recent studies have shown that increased activity of serum alkaline phosphatase prior to treatment is associated with a poor prognosis for dogs with appendicular OSA.

Several treatment options are warranted for dogs with appendicular OSA. Treatment decisions should be tailored to the individual dog and take into consideration the dog's body weight, orthopedic and neurologic status, degree of lameness and bone lysis, cancer site(s) and other medical problems.

Treatment considerations

The goals and financial limitations of the owner should be considered too. The primary goals of therapy for OSA are to relieve pain and control or, at least, slow the progression of metastatic disease. In most cases, a combined modality approach is necessary to achieve both therapeutic goals.

Limb amputation will likely provide excellent pain relief - provided the dog has no other bone lesions and is free of other complicating orthopedic and neurological disease. Without adjuvant therapy, amputation should be considered a pain-palliative procedure. The one-year survival rate achieved with amputation alone is less than 10 percent and the mean survival time is four to five months.

Amputation and systemic chemotherapy is the standard of care for treatment of canine appendicular OSA. In addition to the contraindications mentioned for limb amputation alone, one should consider the toxicity of each chemotherapy agent in light of the dog's organ dysfunction and cardiovascular status.

Toxicities associated with the commonly used chemotherapy agents range from nephrotoxicity (cisplatin and, to a lesser degree, carboplatin) to cardiotoxicity (doxorubicin). The method of drug administration for each chemotherapy agent may also become a deciding factor when designing protocols suited to individual dogs. Cisplatin, for example, requires substantial fluid diuresis that may not be well tolerated by dogs with poor renal, cardiac or respiratory function.

Doxorubicin is a severe vesicant. Administration of doxorubicin to fractious dogs or those likely to move during infusion may necessitate sedation or placement of a venous access port. Cost is often a deciding factor as to which chemotherapy agent will be chosen. The cost of carboplatin may reach or exceed $1,000 per treatment, as compared to cisplatin ($300 to $500 per treatment) or doxorubicin ($50 to $100 per treatment). Reported survival times achieved with amputation and chemotherapy are summarized in Table 1.

Limb-sparing refers to surgery to remove diseased bone and replace it with a cortical allograft or may refer to any procedure that avoids complete limb amputation.

Amputation considerations

Examples may include scapulectomy, partial ulnectomy and digital amputation. Limb-sparing surgery to remove affected bone and replace it with allograft material may be a reasonable option when amputation is contraindicated and when owners fully understand the potential benefits and complications of the limb spare procedure.

For dogs that are good candidates for limb amputation, limb-sparing surgery may not be the best alternative. While improvement of limb function is achieved in most cases, post-operative complications such as osteomyelitis occur in roughly one-third of all dogs.

Initial reports that compared limb-sparing surgery and cisplatin chemotherapy to limb amputation and cisplatin chemotherapy indicated no difference in survival rates between groups.

More recent results suggest that dogs undergoing limb-sparing surgery followed with carboplatin-based chemotherapy enjoy longer overall survival times than those treated with limb amputation and carboplatin.

Factors that may contribute to this observation include infection of surgical sites in limb-sparing dogs leading to enhanced immune response, dog selection bias by tumor site, size and severity, and occult factors such as use of certain antibiotics and nonsteroidal anti-inflammatory agents that may affect tumor growth and angiogenesis.

It is interesting to note that dogs undergoing limb-sparing procedures and adjuvant chemotherapy fare better in terms of overall survival if their surgical sites become infected. Dogs treated with limb-sparing surgery had a median survival time of 529 days when surgical sites became infected, compared to 223 days for those that did not have infected limb-sparing procedure.

External beam radiation therapy may provide pain palliation for canine OSA. In this setting, radiation is typically delivered using a day 0-7-21 treatment plan or a day 0-7-14-21 treatment plan on an outpatient basis. Reported response rates (as determined by pain palliation) exceed 70 percent, with response duration of approximately 2 to 2.5 months. Studies are under way to evaluate new techniques of intra-operative radiation to the primary site of OSA. Another novel approach to radiation therapy is stereotactic radiosurgery. This technique involves one large dose of radiation therapy delivered using specialized equipment.

Radiation

The radiopharmaceutical, 153Sm-EDTMP [QuadrametTM, or "samarium"], is a bone-targeting radioisotope that shows promise in the treatment of primary bone tumors in dogs and other species. Currently marketed for treatment of human bone metastases, 153Sm-EDTMP is available for clinical use only in veterinary referral institutions that are licensed to handle the level of radioactivity associated with the radioisotope. The use of 153Sm-EDTMP is indicated only in dogs with bone lesions showing good uptake on nuclear scintigraphic material. Indications include dogs with multiple bone lesions, metastatic bone lesions or skull lesions that are not amenable to surgery.