Page 571 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

CHAPTER 25 Tumors of the Skeletal System 549

TABLE 25.3 A Comparison of Canine and Human Osteosarcoma Characteristics
Variable Dog Human
VetBooks.ir Incidence in United States >8000/year 1000/year

Mean age
14 years
7 years
Race/breed Large or giant purebreds None
Body weight 90% >20 kg Heavy
Site 77% long bones 90% long bones
Metaphyseal Metaphyseal
Distal radius > proximal humerus Proximal humerus
Distal femur > tibia Distal femur > proximal tibia
Etiology Generally unknown Generally unknown
Percentage clinically confined to the limb at presentation 80%–90% 80%–90%
Percentage histologically high grade 95% 85%–90%
DNA index 75% aneuploid 75% aneuploid
Genetic and molecular alterations See Etiology Section See Etiology Section
Prognostic indicators 178,179 Alkaline phosphatase Alkaline phosphatase
Metastatic rate without chemotherapy 90% before 1 year 80% before 2 years
Metastatic sites Lung > bone > soft tissue Lung > bone > soft tissue
Improved survival with chemotherapy Yes Yes
Regional lymph node metastasis <5%, negative prognostically Poor prognosis

Modified with permission from Withrow SJ, Powers BE, Straw RC, et al. Clin Orthop Relat Res. 1991; 270:159–167. 7

bone pain have been evaluated in dogs with skeletal tumors. Zole- biologic behavior, and metastatic progression and has been shown
dronate (ZOL) has a 100-fold greater antiresorptive potency than through many studies to be a valuable comparative model for
PAM and has the advantage of being safely administered over a study (Table 25.3). 7,341 OSA is more common in dogs than in
shorter period of time than other NBPs. In one case report, IV humans, and therefore case accrual is more rapid. Because disease
ZOL administered every 28 days was effective for the long-term progression is more rapid in dogs than in humans, results of novel
pain management of a dog with a distal radial OSA. 337 The bone treatment protocols can be reported earlier than in similar trials in
biologic effects of IV ZOL were evaluated in 10 dogs with primary humans. Research costs for clinical trials in dogs are less compared
and secondary skeletal tumors. 338 ZOL was administered at a dose with those in human clinical trials, and, from an animal welfare
of 0.25 mg/kg as a 15-minute CRI every 28 days. This was well standpoint, no disease is induced and dogs with cancer can poten-
tolerated with no overt biochemical evidence of renal toxicity in tially be helped through the course of the research.
patients receiving multiple monthly infusions. Pain was alleviated OSA is an uncommon cancer in humans, affecting mainly
in 50% of the 10 dogs with appendicular OSA for more than 4 adolescents in their second decade of life, and it remains a very
months. These dogs demonstrated significant increases in rBMD, serious, aggressive tumor. Fortunately, there has been an improve-
which suggests that ZOL inhibits local malignant osteolysis and ment in survival rates with the use of established multidrug adju-
the generation of pain within the immediate bone tumor micro- vant protocols incorporating high-dose methotrexate, DOX, and
environment. Although studies evaluating the safety of long-term cisplatin. The long-term survival rate for human OSA is presently
PAM or ZOL in dogs with primary and secondary bone tumors 60% to 70% at 5 years, which contrasts with the 20% 5-year sur-
have not been thoroughly evaluated, infrequent and severe bone vival rate of the early 1980s. A recent retrospective study of 251
metabolic changes, such as osteonecrosis of the jaw, have been patients showed that the 5-year survival rate increased from 36%
reported in one dog treated with monthly ZOL (0.1 mg/kg IV, in the 1980s to 67% in the early 2000s. During the same period,
15-minute CRI) for 43 consecutive months. 339 LSS for local disease control increased from 53% to 97%, and
the need for amputation due to failure of the LSSs concurrently
Comparative Aspects decreased, indicating that the increased adoption of LSSs did not
negatively affect outcome. 343
Animal models for the study of human diseases are important to Poor prognostic factors include older age, advanced local or
better understand the mechanisms and etiology of diseases and to systemic stage, axial location, larger size, and percentage TN. 344
develop and refine therapeutic strategies. Spontaneously develop- Tumor necrosis of more than 90% after neoadjuvant chemo-
ing diseases in animal populations are particularly useful for trans- therapy is highly prognostic for improved patient outcome with
lational purposes. 340–342 Canine OSA has many similarities to 5-year survival rates of 75% to 80% compared with 45% to
human OSA in terms of genetic similarities, clinical presentation, 50% for those with less than 90% necrosis. A recent phase III