Review article
Update on the biology and management of canine osteosarcoma

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Ionizing radiation

Ionizing radiation, in both experimental and therapeutic settings, has long been known to cause OSA in dogs [1], [2], [3], [4], [5], [6]. One study described the development of OSA in the radiation therapy (RT) field 1.7 to 5 years after completing therapy in 3/87 dogs (3.4%) treated with megavoltage irradiation for soft tissue sarcomas [2]. The fractionation scheme described in this article was coarse, consisting of 10 fractions of 3.5 to 5 Gy over 3 weeks. Late responding tissues, such as

Canine appendicular osteosarcoma

Appendicular OSA is the most common form of OSA seen in dogs. This section will cover the typical incidence and signalment, history and physical examination, prognostic factors, and treatment options for dogs with appendicular OSA.

Incidence and signalment

Appendicular OSA is the most common of all primary bone tumors in dogs, accounting for up to 75% to 85% of these lesions [25]. OSA tends to occur in middle-aged to older dogs, with some reports showing another incidence peak at 2 years of age (bimodal distribution) [25]. Though male dogs are often reported to be over-represented, with a male to female ratio of 1.5:1, this finding is not consistent among all publications. [26], [27], [28], [29], [30], [31]. Large- and giant-breed dogs including

History and physical examination

Dogs with appendicular OSA most commonly are presented for acute to chronic onset of lameness and limb swelling. Owners often report some “traumatic incident” associated with the onset of lameness. Dogs are usually eating and drinking normally.

Weight-bearing or nonweight-bearing lameness may be observed, with limb swelling typically localized away from the elbow or toward the knee. Osteosarcoma occurs with equal frequency at the distal radius, proximal humerus, and proximal tibia. The mass is

Prognostic factors

Though breed and sex have not been recognized to have prognostic importance, young dogs with OSA appear to have shorter survival times and biologically more aggressive disease [31]. The presence of detectable metastatic lesions at the time of diagnosis is a recognized poor prognostic factor, standard chemotherapy being ineffective at improving survival in that setting [26], [32], [33]. A study found that, in addition to detectable metastasis at presentation, a telangiectatic (vascular) subtype,

Diagnosis

A minimum database consisting of a complete blood count, serum chemistry profile, and urinalysis is recommended to screen for concurrent disease, and to aid in establishing a prognosis by quantitating the serum alkaline phosphatase concentration. Certain therapeutic decisions might also be altered based on the results of such tests. For example, a patient with marginal renal function might not be an ideal candidate for cisplatin therapy, a known nephrotoxic agent, or could require a dose

Biologic behavior

Appendicular OSA is a locally invasive, highly metastatic disease. The pulmonary parenchyma is the most common metastatic site [29]. Lymph nodes appear to be an uncommon site of metastases, with a reported rate of 6.1% to 37% [26], [29], [31], [55]. With the now common use of adjuvant chemotherapy that provides excellent drug levels to pulmonary parenchyma, bones and soft tissues are increasingly the site of OSA metastasis [55].

Treatment

Standard of care, defined as the treatment option that results in the longest median survival times, is surgical resection of the primary tumor followed by 3 to 6 cycles of either a platinum- or doxorubicin-based chemotherapy protocol [27], [30], [36], [38], [45], [56], [57]. Surgery alone, in dogs with no evidence of metastatic disease, is associated with a median survival time of 19 weeks [31].

Surgical options for appendicular OSA include amputation or a limb-sparing procedure, in which the

Palliative therapy

Reported survival times for canine patients treated with palliative intent therapy range from 3 to 10 months [26], [31], [75], [76], [77], [78]. Amputation alone or administration of medications such as nonsteroidal anti-inflammatory drugs or opioids may significantly improve quality of life. Dogs treated with amputation alone are most often euthanized because of pulmonary metastatic disease, with a reported median survival time of 19 weeks [31].

The bisphosphonate drug alendronate has been

Signalment

Medium- to large-breed dogs are most commonly affected by axial OSA, with a reported range in weights of less than 5 kg to 55 kg [25]. Middle-aged dogs are most often reported to be affected, with the main exception being dogs with rib tumors. Dogs with rib OSA tend to be younger, although reported mean and median ages range from 5 to 9 years [91], [92], [93]. Female dogs are more commonly affected than males (2.1:1) [91]. Golden and Labrador retrievers, German Shepherds, Doberman Pinschers,

History and physical examination

The history varies depending on affected site. The tumor does not usually grow rapidly, and clinical signs may be insidious. One article cited a range in duration of signs before presentation extending from several days to 2 years [91].

The most common sites of axial OSA are the mandible and maxilla; less commonly affected sites include spine, ribs, nasal cavity, and cranium [84], [91]. One study reported that 4/37 primary spinal tumors were OSA, whereas another described vertebral OSA in 14/20

Diagnosis

Diagnostic evaluation of dogs with axial skeletal OSA is similar to that for dogs with appendicular OSA. A minimum database is advised to rule out concurrent disease; the significance of elevations of serum alkaline phosphatase in dogs with axial disease is unknown. Diagnostic imaging of the primary site and thorax is also recommended. Only 11% of axial skeletal OSA patients have visible pulmonary metastatic disease at the time of diagnosis (6/54); however, this metastatic incidence may be

Biologic behavior, prognosis, treatment

The biologic behavior of axial OSA has been postulated to be site-dependent, with mandibular OSA being less likely to metastasize than OSA originating in other sites [90]. Univariate analysis identified tumor location on the mandible, complete surgical excision, and lower body weight (<30 kg) as favorable prognostic factors in one study of 45 dogs [32]. In the same article, surgical margins and body weight were the most significant prognostic factors based on multivariate analysis. A large

Incidence and signalment

Canine extraskeletal osteosarcoma (ESOSA) is a rare tumor, accounting for 0.13% of biopsy submissions (169/130,754) and 12.6% of all OSA over a 10-year period in 1 study [103]. In this retrospective study, mammary gland OSA (MGOSA) was the most common site of ESOSA (108 of 169 cases) [103]. Of the remaining 61 cases, 10 were splenic, 13 originated within the GI tract, 7 were in the urogenital tract, 6 were hepatic, 6 were cutaneous, and 13 were in the subcutaneous tissues. In dogs, mixed

Risk factors and associations

Beagles and Rottweilers have a 3.8 and 3.6 odds ratio, respectively, for developing ESOSA [103]. Miniature Poodle and German Shepherd dogs have a 2.7 and 2.2 odds ratio, respectively, for developing MGOSA [103]. Rare cases of esophageal OSA have been associated with Spirocerca lupi infection [109]. Granulomas arise because of the migration and persistent presence of larvae and adults within the esophagus; malignant transformation of these lesions may then occur. Metastatic disease at the time

Diagnosis

Although no pathognomonic features will be revealed, a minimum database is recommended to assess overall health status before recommending and initiating treatment. Radiographs of the thorax are indicated to screen for metastatic disease. Thoracic radiographs made in 32/61 cases of ESOSA revealed lesions in 3/32 at the time of diagnosis; 38/108 cases of MGOSA had thoracic radiographs made, and 3/38 had lesions at diagnosis [103]. Abdominal radiographs and ultrasonography are indicated depending

Biologic behavior

Similar to the more common forms of OSA, ESOSA, and MGOSA are locally invasive and metastatic to lungs and other sites [103], [104], [105], [106], [108]. Lymph node involvement appears to be more common in ESOSA than in primary bone OSA, being identified in 5/11 dogs with ESOSA in a variety of locations and in 2/7 dogs with MGOSA [103], [104]. Liver metastases, diagnosed in 7/14 dogs with visceral or pulmonary primary sites of OSA, are also more commonly reported for ESOSA than for disease of

Treatment and prognosis

Only 83 of 169 cases had follow-up to death in 1 retrospective study [103]. A total of 72 out of 83 were euthanized or died because of the tumor. Dogs with ESOSA had a median survival of 26 days, with death from suspected local recurrence in 92%. Dogs with MGOSA had a median survival of 90 days with death from metastatic disease in 62.5% [103]. Because all of the reports of ESOSA and MGOSA are retrospective, patients received a variety of treatments. Based on the known biologic behavior of this

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