Amputation and Cisplatin for Treatment of Canine Osteosarcoma

Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventeen dogs were treated with amputation and two postoperative [corrected] doses of IV cisplatin given 21 days apart (group 1). Nineteen dogs were treated with IV cisplatin 21 days before amputation, with a second dose given immediately after amputation (group 2). Thirty-five dogs were treated by amputation of the affected limb with no chemotherapy (group 3). The median disease-free interval for group 1 was 226 days, and 177 days for group 2. This was not significantly different. The median survival time was 262 days for group 1, 282 days for group 2 and 119 days for group 3. Group 1 and 2 dogs had survival times that were significantly longer than for dogs in group 3. Two IV courses of cisplatin given before or after amputation appears to improve the survival of dogs with osteosarcoma.     

Proximal radial and distal humeral osteosarcoma in 12 dogs

Twelve dogs were diagnosed with osteosarcoma of the proximal radius or distal humerus from 1990 to 2002, representing 1.0% of all dogs diagnosed with appendicular osteosarcoma. The median body weight (29.8 kg) was significantly less than that of dogs with appendicular osteosarcoma at other sites. Ten dogs were treated with amputation and chemotherapy. These dogs had a metastatic rate of 60%, a median metastasis-free interval of 356 days, and a median survival time of 824 days. There were no significant differences in metastasis-free interval or survival time between dogs with osteosarcoma of the proximal radius or distal humerus and dogs with appendicular osteosarcoma at other sites.     

Amputation and Carboplatin for Treatment of Dogs With Osteosarcoma: 48 Cases (1991 to 1993)

Forty-eight dogs with histologically confirmed appendicular osteosarcoma (OSA) entered a prospective clinical trial evaluating treatment with amputation and up to 4 doses of carboplatin given every 21 days. The median disease-free interval (DFI) was 257 days, with 31.2% of the dogs disease-free at 1 year. The median survival time was 321 days, with 35.4% of the dogs alive at 1 year. Dogs with proximal humeral OSA had shorter DFI (P = .016) and survival (P = .037) times than dogs with OSA at other locations. Dogs with lower body weights (40 kg) had longer DFI (P = .0056) and survival (P = .007) times than larger dogs. Survival times for dogs that received carboplatin were statistically longer than those previously reported for amputation alone (P < .001). DFI and survival times are similar to those previously reported for 2 to 4 doses of cisplatin. Carboplatin appears to be a well-tolerated chemotherapeutic drug that can be given safely every 21 days at a dose of 300 mg/m². Neutropenia was the dose-limiting toxicity in this study. J Vet Intern Med 1996_;10:76–81. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

Bone allografts and adjuvant cisplatin for the treatment of canine appendicular osteosarcoma in 18 dogs

The results achieved in 18 dogs following the use of frozen bone cortical allografts for limb-sparing resection of non-metastatic canine appendicular osteosarcoma are presented. Three to five cisplatin doses (70 mg/m2) were administered, starting the day after surgery. The mean and median survival times were 478 and 266 days (range 80 to 2,611 days), respectively. The survival rate was 94 per cent at three months, 78 per cent at six months, 35 per cent at 12 months, 23 per cent at 18 months and 19 per cent at 24 months; the disease-free interval was 80 to 1,246 days (mean 365 days, median 266 days). Lung metastasis developed in 55 per cent of the dogs within one year. Complications were observed in 14/18 dogs (78 per cent), comprising local recurrence (28 per cent), allograft infection (39 per cent) and implant failure (11 per cent). Despite complications, limb sparing is a useful alternative to amputation in selected cases of appendicular osteosarcoma.     

Use of alternating administration of carboplatin and doxorubicin in dogs with microscopic metastases after amputation for appendicular osteosarcoma: 50 cases (1999-2006)

OBJECTIVE:To evaluate the efficacy and toxicity of an alternating carboplatin and doxorubicin chemotherapy protocol in dogs with putative microscopic metastases after amputation for appendicular osteosarcoma and assess patient-, tumor-, and treatment-related factors for associations with prognosis. DESIGN: Retrospective case series. ANIMALS: 50 client-owned dogs. PROCEDURES: Records of dogs that underwent amputation for appendicular osteosarcoma and received an alternating carboplatin and doxorubicin chemotherapy protocol were reviewed. Dogs had full staging and were free of detectable metastases prior to chemotherapy. Data on disease-free interval (DFI), survival time, and toxicoses were retrieved from medical records and owner or referring veterinarian communications. RESULTS: Median DFI was 202 days. Median survival time was 258 days. Twenty-nine (58%) dogs completed the protocol as planned, and the rest were withdrawn typically because of metastases or toxicoses. Grade 3 or 4 myelosuppression was reported in 9 of 50 (18%) dogs and grade 3 or 4 gastrointestinal toxicosis in 6 of 50 (12%) dogs. There were no chemotherapy-related fatalities. Univariate factors associated with significant improvement in DFI included tumor location (radius), receiving doxorubicin as the first drug, starting chemotherapy more than 14 days after amputation, and no rib lesions on preamputation bone scans. Multivariate factors associated with a significant improvement in survival time were tumor location (radius) and completing chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Alternating administration of carboplatin and doxorubicin resulted in DFI and survival time similar to those reported for single-agent protocols. Clients should be counseled regarding the likelihood of toxicoses. Relevance of sequence and timing of starting chemotherapy should be further evaluated.     

Canine Osteosarcoma

Osteosarcoma was diagnosed in 38 dogs. Thirty-six tumors originated from the appendicular skeleton and two from the axial skeleton. Nineteen of the dogs were treated with amputation alone, and 19 were treated with amputation and adjuvant chemotherapy consisting of doxorubicin and cisplatin. The 36 dogs with appendicular osteosarcoma had complete amputation of the affected limb, whereas the two dogs with osteosarcoma of the axial skeleton had an en bloc resection. The mean survival of the 19 dogs treated with amputation alone was 218 days (median, 175 days). Ten dogs were alive at 6 months and four survived 1 year. None of the dogs survived longer than 16 months. Radiographic lesions consistent with metastatic osteosarcoma were seen after surgery in the nine dogs in which radiographs were taken. The mean survival of the 19 dogs treated with amputation and chemotherapy was 415 days (median, 300 days). Drug toxicity was not observed. Fifteen dogs were alive at 6 months, seven dogs were alive at 1 year, 5 dogs were alive at 2 years, and two dogs were alive at 3 years or longer. One dog is alive and well at 25 months. Radiographic lesions suggestive of metastatic osteosarcoma developed in the other 18 dogs. The 19 dogs treated with amputation and chemotherapy had significantly longer survival times than the dogs treated with amputation alone.     

Use of cisplatin for treatment of appendicular osteosarcoma in dogs

Nineteen dogs were treated for osteosarcoma of the appendicular skeleton. Eleven dogs treated by amputation and adjunctive cisplatin chemotherapy had a significantly longer (P less than 0.003) median survival time of 43 weeks (range, 20 to 108 weeks) than did 8 dogs whose median survival time was 14.5 weeks (range, 8 to 46 weeks) after amputation alone. All 11 dogs given cisplatin were evaluated for signs of drug toxicosis. Transient episodes of vomiting were recorded in 9 of 11 dogs. Additional toxic effects included gradual decreases in endogenous creatinine clearance in 3 dogs and thrombocytopenia in 1 dog. On the basis of prolonged survival times and minimal adverse effects, we concluded that cisplatin has promise as an effective and relatively nontoxic agent, when combined with amputation, for treatment of dogs with osteosarcoma of the appendicular skeleton.     

Treatment of Canine Appendicular Osteosarcoma Using Cobalt 60 Radiation and Intraarterial Cisplatin

Twelve dogs with appendicular osteosarcoma were treated with 24–40 Gy of cobalt 60 radiation and two doses of intraarterial cisplatin. Improvement in limb function occurred in four dogs, and three dogs, which had only mild initial lameness, had no worsening of their lameness post-treatment. In nine dogs in which local control was evaluable, eight had local failure, with the median (95% CI) duration of local control being 5.9 (4.6, 6.7) months. Two dogs had metastatic disease before therapy, and an additional nine dogs had metastatic disease at a median time of 6.4 months. Pathologic fracture was present in four dogs; two fractures occurred before treatment and two were documented at the time of tumor recurrence. Median (95% CI) survival time for all 12 dogs was 4.9 (3.4, 6.8) months. Excluding the two dogs with preexisting metastatic disease, median survival time was 6.7 months. Three dogs survived longer than 1 year. This mode of therapy was well tolerated and may be considered an alternative to amputation or limb-sparing surgical procedures in selected dogs with appendicular osteosarcoma.     

Cisplatin and doxorubicin combination chemotherapy for the treatment of canine osteosarcoma: a pilot study

Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2 intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was given on a 21-day cycle for 4 cycles. No dose delays were required, but dose reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic radiography was performed every 2 months after completion of therapy to monitor for metastatic disease. Two dogs were still alive and free from disease at the time of last contact (24 and 75 months, respectively). Postmortem examinations were performed on 13 of the 14 dogs that died. Eight of these dogs were euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs, euthanasia was performed because of complications of idiopathic megaesophagus (n = 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free interval and survival times were 15.7 and 18 months, respectively. When compared to a historical group of 36 dogs with appendicular osteosarcoma treated with surgery and 4 doses of cisplatin. both disease-free interval and overall survival were significantly longer in the study population (P < .015 and P < .007, respectively).     

Treatment of canine appendicular osteosarcoma using cobalt 60 radiation and intraarterial cisplatin.

Twelve dogs with appendicular osteosarcoma were treated with 24-40 Gy of cobalt 60 radiation and two doses of intraarterial cisplatin. Improvement in limb function occurred in four dogs, and three dogs, which had only mild initial lameness, had no worsening of their lameness post-treatment. In nine dogs in which local control was evaluable, eight had local failure, with the median (95% CI) duration of local control being 5.9 (4.6, 6.7) months. Two dogs had metastatic disease before therapy, and an additional nine dogs had metastatic disease at a median time of 6.4 months. Pathologic fracture was present in four dogs; two fractures occurred before treatment and two were documented at the time of tumor recurrence. Median (95% CI) survival time for all 12 dogs was 4.9 (3.4, 6.8) months. Excluding the two dogs with preexisting metastatic disease, median survival time was 6.7 months. Three dogs survived longer than 1 year. This mode of therapy was well tolerated and may be considered an alternative to amputation or limb-sparing surgical procedures in selected dogs with appendicular osteosarcoma.     

Aggressive local therapy combined with systemic chemotherapy provides long‐term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012)

This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188–2340). Median disease‐free interval was 2120 days (149–2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188–2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300–2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco‐regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local‐regional therapy can provide a median survival in excess of 40 months.     

Retropective Evaluation of Survival Time of Dogs with Stage III Osteosarcoma that Undergo Treatment

Introduction:  Stage III osteosarcoma generally carries a grave prognosis. Despite this, some owners elect to treat using palliative or curative intent protocols. The purpose of this study was to determine the survival times for dogs with stage III osteosarcoma that undergo treatment and to evaluate the variables that affect survival time.
Methods:  Retrospective study using the CSU Animal Cancer Center osteosarcoma data base. Search criteria included dogs diagnosed with osteosarcoma 1985–2004 with metastasis at the time of presentation. Dogs were excluded if they were euthanized at the time of diagnosis (13 dogs) or lost to follow‐up (10 dogs). There were 90 cases for analysis. The survival times were compared based on the primary tumor site, site of metastasis, treatment given, age, sex and breed.
Results:  Survival times in days ranged from 0 to 1583 days. The overall median survival time was 76 days. The one‐year, two‐year and three‐year percent survival were 7%, 4.7% and 3.5%, respectively. Treatment included various combinations of chemotherapy, surgery, radiation therapy, bisphosphonates and NSAIDs. Findings included an increased survival time with surgery and adjuvant therapy compared with surgery alone and a decreased survival time with metastasis to the lung or lymph node.
Conclusions:  Treatment of dogs with stage III osteosarcoma can result in variable survival times. Multimodality therapy appears to result in longer survival times. Metastasis to the lung or lymph node correlated with a decreased survival time.     

Carboplatin and doxorubicin combination chemotherapy for the treatment of appendicular osteosarcoma in the dog

Twenty-four client-owned dogs with histologically diagnosed appendicular osteosarcoma (OSA) and no evidence of gross metastatic disease were treated with amputation or limb salvage followed by combination chemotherapy consisting of carboplatin (175mg/ m2 IV, day 1) and doxorubicin (15 mg/m2 IV, day 2) given on a 21-day cycle for a maximum of 4 cycles. Hematologic and gastrointestinal adverse effects were graded according to National Cancer Institute guidelines. Thoracic radiographs were obtained before the 3rd chemotherapy cycle and then every 2 months. Median disease-free interval was 195 days (95% confidence interval 111-228 days) and median survival was 235 days (95% confidence interval 150-283 days). Two patients required dose reductions: 1 for grade 3 thrombocytopenia and 1 for grade 3 adverse gastrointestinal effects. Patients with a longer duration of clinical signs before definitive diagnosis and surgery (greater than 30 days) were more likely to develop progressive disease and to die or be euthanized because of progressive disease on any day; hazard ratios were 3.0 (P = .02) and 3.7 (P .02), respectively. In conclusion, although this combination chemotherapy protocol was well tolerated, it did not provide any improvement over historical single-agent protocols.     

Treatment of dogs with osteosarcoma by administration of cisplatin after amputation or limb-sparing surgery: 22 cases (1987-1990).

Twenty-two dogs with appendicular osteosarcoma were treated by amputation (n = 17) or limb-sparing surgery (n = 5). All dogs were given cisplatin (60 mg/m2 of body surface, IV) at 3-week intervals, beginning 1 week after surgery. Number of cisplatin treatments ranged from 1 to 6. Survival data for the 22 dogs were compared with survival data from a historical control group consisting of 162 dogs with appendicular osteosarcoma treated by amputation alone. Median survival time for the 22 dogs given cisplatin was estimated to be 46.4 weeks, and 1- and 2-year survival rates were estimated to be 45.5 and 20.9%, respectively. Survival time was significantly (P less than 0.0001) longer for treated dogs than for control dogs. Statistically significant relation was not found between survival time and number of cisplatin treatments. Three dogs were alive with no evidence of disease at the time of reporting. Of the remaining 19 dogs, 14 (73.4%) were euthanatized for problems documented to be related to metastases. Nine (47.4%) dogs were euthanatized because of bone metastases, and 5 (26.3%) were euthanatized because of pulmonary metastases. The proportion of dogs euthanatized because of bone metastases was significantly (P less than 0.0001) higher for treated than for control dogs. Median survival times for dogs developing bone and lung metastases were estimated to be 51.2 weeks and 21.2 weeks, respectively; however, this difference was not statistically significant. One local tumor recurrence was observed among dogs that had limb-sparing surgery. Significant difference in survival time was not observed between dogs that had limb-sparing surgery and dogs that underwent amputation.     

Resection of Pulmonary Metastases in Canine Osteosarcoma: 36 Cases (1983–1992)

Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both.
Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma.     

Samarium Sm 153 lexidronam for the palliative treatment of dogs with primary bone tumors: 35 cases (1999-2005)

OBJECTIVE: To evaluate survival times and palliative effects associated with the use of samarium Sm 153 lexidronam in dogs with primary bone tumors. DESIGN: Retrospective case series. ANIMALS: 35 dogs with primary appendicular (n = 32) or axial (3) bone tumors. PROCEDURES: 1 to 4 doses of samarium Sm 153 lexidronam were administered at a rate of 37 MBq/kg (16.8 MBq/lb), IV. Response to treatment, measured by lameness improvement, and survival time were determined. RESULTS: Of the 32 dogs with appendicular tumors, 20 (63%) had an improvement in the severity of lameness 2 weeks after administration of the first dose of radioactive samarium, 8 (25%) had no change in the severity of lameness, and 4 (12%) had a worsening. Overall median survival time was 100 days, with 3 dogs (8.6%) alive after 1 year. Median survival time for the 32 dogs with appendicular tumors was 93 days, with 3 (9.4%) alive after 1 year. This was not significantly different from the median survival time of 134 days for a historical cohort of 162 dogs with appendicular osteosarcoma that underwent amputation as the only treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that samarium Sm 153 lexidronam may be useful in the palliation of pain in dogs with primary bone tumors that are not candidates for curative-intent treatment.     

Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004)

OBJECTIVE: To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment. DESIGN: Retrospective case series. ANIMALS: 54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data. PROCEDURE: Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment. RESULTS: Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.     

Biologic Behavior and Clinical Outcome of 25 Dogs with Canine Appendicular Chondrosarcoma Treated by Amputation: A Veterinary Society of Surgical Oncology Retrospective Study

Objective— To characterize biologic behavior, clinical outcome, and effect of histologic grade on prognosis for dogs with appendicular chondrosarcoma treated by amputation alone. Study Design— Case series. Animals— Dogs (n=25) with appendicular chondrosarcoma. Methods— Medical records were searched to identify dogs with appendicular chondrosarcoma treated by limb amputation alone. Information recorded included signalment, anatomic location, radiographic appearance, and development of metastasis. Histopathologic diagnosis was confirmed and graded (1, 2, or 3). Survival curves were generated by the Kaplan–Meier method and the association between covariates (gender, age, weight, and tumor grade) and survival were evaluated using the univariate proportional hazards model. Results— Histopathology slides were available for 25 dogs. Rates of pulmonary metastasis were as follows: grade 1–0%, grade 2–31%, and grade 3–50%. Overall median survival time (MST) was 979 days. Age, weight, and sex were not significantly associated with survival (P=.16; .33; and .31, respectively). Survival was significantly associated with tumor grade (P=.008), with dogs with tumor grade of 1, 2, and 3 having MSTs of 6, 2.7, and 0.9 years, respectively. Conclusion— Canine appendicular chondrosarcoma can be treated effectively with amputation alone. Low to intermediate grade chondrosarcoma has a good prognosis, whereas high‐grade tumors appear to behave aggressively. Clinical Relevance— The overall prognosis for appendicular chondrosarcoma is better than that of appendicular osteosarcoma treated by amputation alone or in combination with chemotherapy.     

Toxicity and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of canine appendicular osteosarcoma following limb amputation

Objective To evaluate the safety and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of dogs with appendicular osteosarcoma following limb amputation. Design Retrospective study. Procedure Dogs diagnosed with appendicular osteosarcoma, with no evidence of metastatic disease, treated with amputation and adjuvant chemotherapy consisting of two doses of doxorubicin given 14 days apart, followed by four doses of carboplatin at 3‐weekly intervals between September 2003 and December 2009 were identified from the medical records of Perth Veterinary Oncology. Haematological and gastrointestinal toxicities were assessed based on information in the medical records and recorded complete blood count results. The efficacy of the protocol was assessed by determining the median disease‐free interval (DFI) and overall survival time (OST) using the Kaplan‐Meier product‐limit method. Results In total, 33 dogs met the inclusion criteria. The median DFI was 231.5 days and the median OST was 247 days. With regard to haematological toxicity, 56% of dogs had a grade 1–2 neutropenia recorded as their highest marrow toxicity and 9% of dogs experienced a grade 3–4 neutropenia, all subsequent to doxorubicin administration. The highest gastrointestinal toxicity was grade 1–2 in 15 dogs (47%) and 5 dogs (16%) experienced grade 3–4 gastrointestinal toxicity. Conclusion This chemotherapy protocol did not result in a longer time to disease recurrence or OST in this population of dogs. Dual‐agent protocols have failed to improve survival times and therefore we conclude that a single‐agent protocol using carboplatin may be equally effective with less toxicity.     

Alternating carboplatin and doxorubicin as adjunctive chemotherapy to amputation or limb-sparing surgery in the treatment of appendicular osteosarcoma in dogs

Thirty-two dogs with appendicular osteosarcoma treated by amputation or limb sparing had adjuvant chemotherapy of alternating doses of carboplatin (300 mg/m2 IV) and doxorubicin (30 mg/m2 IV) every 21 days for a total of 3 cycles. Efficacy, toxicity, and previously identified prognostic factors for osteosarcoma were evaluated. The median progression free survival was 227 days (range 180-274), and the median overall survival was 320 days (range 153-487). The 1-year survival rate was 48%, and the 2-year survival rate was 18%. Age, sex, surgical procedure, and alkaline phosphatase activity above the reference ranges were not prognostic for survival. There was minimal toxicity associated with the chemotherapy. This protocol could be useful for the adjuvant treatment of appendicular osteosarcoma of dogs.