Comparison of carboplatin and doxorubicin-based chemotherapy protocols in 470 dogs after amputation for treatment of appendicular osteosarcoma.

BackgroundMany chemotherapy protocols have been reported for treatment of canine appendicular osteosarcoma (OSA), but outcome comparisons in a single population are lacking.ObjectiveTo evaluate the effects of protocol and dose intensity (DI) on treatment outcomes for carboplatin and doxorubicin-based chemotherapy protocols.AnimalsFour hundred and seventy dogs with appendicular OSA.MethodsA retrospective cohort study was performed comprising consecutive dogs treated (1997-2012) with amputation followed by 1 of 5 chemotherapy protocols: carboplatin 300 mg/m(2) IV q21d for 4 or 6 cycles (CARBO6), doxorubicin 30 mg/m(2) IV q14d or q21d for 5 cycles, and alternating carboplatin 300 mg/m(2) IV and doxorubicin 30 mg/m(2) IV q21d for 3 cycles. Adverse events (AE) and DI were evaluated. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare disease-free interval (DFI) and survival time (ST) among protocols.ResultsThe overall median DFI and ST were 291 days and 284 days, respectively. A lower proportion of dogs prescribed CARBO6 experienced AEs compared to other protocols (48.4% versus 60.8-75.8%; P = .001). DI was not associated with development of metastases or death. After adjustment for baseline characteristics and prognostic factors, none of the protocols provided a significant reduction in risk of development of metastases or death.Conclusions and clinical importanceAlthough choice of protocol did not result in significant differences in DFI or ST, the CARBO6 protocol resulted in a lower proportion of dogs experiencing AEs, which could be advantageous in maintaining high quality of life during treatment. DI was not a prognostic indicator in this study

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified

Association of tibial plateau leveling osteotomy with proximal tibial osteosarcoma in dogs

OBJECTIVE To assess for any association between a history of tibial plateau leveling osteotomy (TPLO) and subsequent development of proximal tibial osteosarcoma in dogs. DESIGN Matched case-control study. ANIMALS 34 client-owned dogs in which proximal tibial osteosarcoma was diagnosed between January 2005 and December 2012 (cases) and 79 dogs without osteosarcoma, matched 3:1 to cases (when possible) by age, breed, and initial examination date (controls). PROCEDURES Information on each case and control was collected from the medical records and other sources regarding date of birth, sex and neuter status, body weight, breed, and whether TPLO had been performed ≥ 1 year ago. A multivariable conditional logistic regression model was constructed to evaluate associations of body weight and history of TPLO with the outcome of proximal tibial osteosarcoma in dogs. RESULTS After adjusting for body weight in the multivariable model, dogs with a history of TPLO were 40 times as likely to develop proximal tibial osteosarcoma as were dogs with no history of TPLO. In addition, each 1-kg (2.2-lb) increase in body weight was associated with an 11% increase in the odds of proximal tibial osteosarcoma. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that dogs with a history of TPLO were at increased risk of developing osteosarcoma of the proximal region of the tibia relative to dogs with no such history. Therefore, it is important for proximal tibial osteosarcoma to be included among the differential diagnoses for new or worsening hind limb lameness in dogs that underwent TPLO ≥ 1 year previously

Evaluation of P16 expression in canine appendicular osteosarcoma

Abstract Background Osteosarcoma (OSA) is a common malignant bone tumor of large breed dogs that occurs at predictable anatomic sites. At the time of initial diagnosis, most affected dogs have occult pulmonary metastases. Even with aggressive surgical treatment combined with chemotherapy, the majority of dogs diagnosed with OSA live less than 1 year from the time of diagnosis. The ability to identify canine OSA cases most responsive to treatment is needed. In humans, OSA is also an aggressive tumor that is histologically and molecularly similar to canine OSA. The expression of the tumor suppressor gene product P16 by human OSA tissue has been linked to a favorable response to chemotherapy. Results We identified an antibody that binds canine P16 and developed a canine OSA tissue microarray in order to test the hypothesis that P16 expression by canine OSA tissue is predictive of clinical outcome following amputation and chemotherapy. Although statistical significance was not reached, a trend was identified between the lack of canine OSA P16 expression and a shorter disease free interval. Conclusions The identification of a molecular marker for canine OSA is an important goal and the results reported here justify a larger study

BMI1 Is Expressed in Canine Osteosarcoma and Contributes to Cell Growth and Chemotherapy Resistance

BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy