Mary H. Lafferty

Improved survival associated with postoperative wound infection in dogs treated with limb-salvage surgery for osteosarcoma.

BackgroundLimb-salvage surgery and adjuvant chemotherapy are performed as a treatment of appendicular osteosarcoma in dogs. Approximately 50% of dogs that undergo limb-salvage surgery develop postoperative surgical wound infections. Postoperative surgical infections may affect survival in cancer patients. The purposes of this study were to examine the effect of surgical wound infection on survival, local recurrence, and metastasis in relation to other prognostic factors for dogs with spontaneous osteosarcoma treated with limb-salvage surgery.MethodsForty-seven client-owned dogs with osteosarcoma of the distal radius were treated with limb-salvage surgery and adjuvant chemotherapy—either carboplatin or carboplatin and doxorubicin. Hazard ratios were estimated by using the Cox proportional hazard model, and survival functions were estimated by using the Kaplan-Meier product-limit life-table method.ResultsOf the 47 dogs in this study, 32 (68%) developed a postoperative wound infection. Infection, dog weight, and extent of the primary tumor (percentage of length) significantly affected survival, and infection and percentage of length significantly affected time to metastasis. None of the variables considered in this study affected local recurrence. Dogs that were diagnosed with an infection were less likely to die (hazard ratio, .446), and dogs with greater body weight and greater percentage length involvement were more likely to die (hazard ratios of 3.37 and 3.66, respectively).ConclusionsIn dogs with osteosarcoma treated with limb-salvage surgery, infection has a positive influence on survival, as does a smaller initial length of radius involved and lower body weight.

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.

Curative-intent radiation therapy as a treatment modality for appendicular and axial osteosarcoma: a preliminary retrospective evaluation of 14 dogs with the disease.

Canine osteosarcoma is a common bone malignancy associated with aggressive local disease and rapid metastasis. Current local therapeutic modalities do not provide curative-intent options for dogs with significant orthopaedic or neurologic disease, dogs which are denied amputation or dogs with non-resectable lesions. The goals of this retrospective study included the evaluation of local control, survival, and time to the development of metastases in 14 dogs treated with curative-intent radiation therapy and chemotherapy. Median local disease control was 202 days (79-777). Median survival was 209 days (79-781). Median time to metastasis was 314 days (7-645). No significant correlation was found between the outcome and pre-treatment alkaline phosphatase levels, radiographic appearance, tumour site, radiation dose or chemotherapeutics administered. In these dogs, full-course radiation therapy in conjunction with chemotherapy was not found to yield equivalent results to the standard of care options.

Combined dorsolateral and intraoral approach for the resection of tumors of the maxilla in the dog

This paper describes in detail a combined dorsal and intraoral approach for maxillectomy for tumors involving tissues more caudal to the third premolar. The only intraoperative complication was that of blood loss, with six out of 20 dogs requiring a single unit of blood. Histopathologically clean margins were obtained in 14 of the 20 cases, with a recurrence rate of 50% in these dogs and a median time to recurrence of 24 months. This represents an improvement in outcome over previously reported studies, and the authors postulate this is due to the better exposure and access to the area afforded by the combined approach over the standard intraoral approach.

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.

Survival analysis of one versus two treatments of local delivery cisplatin in a biodegradable polymer for canine osteosarcoma

The purpose of this study was to evaluate one versus two doses of local delivery cisplatin in a biodegradable polymer (OPLA-Pt) for the treatment of osteosarcoma (OSA) after amputation in dogs. Medical records were reviewed retrospectively, and 105 dogs were included in the study; 39% of dogs received one treatment (surgical implantation) of OPLA-Pt and 61% of dogs received two treatments of OPLA-Pt after amputation. Administration of two doses of OPLA-Pt did not have a significant effect on disease-free interval or survival time compared to one dose. The anatomic site of the tumour was identified as a prognostic factor, and dogs with proximal humeral OSA had the shortest disease-free interval and survival times. There was no advantage to giving a second dose of local delivery cisplatin following amputation for the treatment of OSA in dogs.

Evaluation of outcome and prognostic factors for dogs living greater than one year after diagnosis of osteosarcoma: 90 cases (1997–2008)

OBJECTIVE To evaluate clinical characteristics, outcome, and prognostic variables in a cohort of dogs surviving > 1 year after an initial diagnosis of osteosarcoma. DESIGN Retrospective case series. ANIMALS 90 client-owned dogs. PROCEDURES Medical records for an 11-year period from 1997 through 2008 were reviewed, and patients with appendicular osteosarcoma that lived > 1 year after initial histopathologic diagnosis were studied. Variables including signalment, weight, serum alkaline phosphatase activity, tumor location, surgery, and adjuvant therapies were recorded. Median survival times were calculated by means of a Kaplan-Meier survival function. Univariate analysis was conducted to compare the survival function for categorical variables, and the Cox proportional hazard model was used to evaluate the likelihood of death > 1 year after diagnosis on the basis of the selected risk factors. RESULTS 90 dogs met the inclusion criteria; clinical laboratory information was not available in all cases. Median age was 8.2 years (range, 2.7 to 13.3 years), and median weight was 38 kg (83.6 lb; range, 21 to 80 kg [46.2 to 176 lb]). Serum alkaline phosphatase activity was high in 29 of 60 (48%) dogs. The most common tumor location was the distal portion of the radius (54/90 [60%]). Eighty-nine of 90 (99%) dogs underwent surgery, and 78 (87%) received chemotherapy. Overall, 49 of 90 (54%) dogs developed metastatic disease. The median survival time beyond 1 year was 243 days (range, 1 to 1,899 days). Dogs that developed a surgical-site infection after limb-sparing surgery had a significantly improved prognosis > 1 year after osteosarcoma diagnosis, compared with dogs that did not develop infections. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study indicated that dogs with an initial diagnosis of osteosarcoma that lived > 1 year had a median survival time beyond the initial year of approximately 8 months. As reported previously, the development of a surgical-site infection in dogs undergoing a limb-sparing surgery significantly affected prognosis and warrants further study.

Outcome and prognostic factors for osteosarcoma of the maxilla, mandible, or calvarium in dogs: 183 cases (1986-2012)

OBJECTIVE To describe the biological behavior, clinical outcome, and prognostic factors of osteosarcoma of the maxilla, mandible, or calvarium in dogs. DESIGN Retrospective case series. ANIMALS 183 client-owned dogs with osteosarcoma of the maxilla, mandible, or calvarium. PROCEDURES Medical records for dogs treated for osteosarcoma of the maxilla, mandible, or calvarium from 1986 through 2012 were reviewed. Dogs with a histopathologic diagnosis of osteosarcoma and treated for a primary tumor arising from these bones of the head were included. RESULTS Mean age was 9.3 years, and body weight was 31.8 kg (70.0 lb). Most dogs (124/183 [67.8%]) were purebred, and the most common primary tumor site was the maxilla (80 [43.7%]). Treatments included palliative medical treatment only (11/183 [6.0%]), coarsely fractionated radiation therapy (RT; 12 [6.6%]), fractionated or stereotactic RT (18 [9.8%]), surgery (135 [73.8%]), and both surgery and fractionated RT (7 [3.8%]). Eighty-three (45.4%) dogs received adjuvant chemotherapy. Local recurrence or progression occurred in 80 of 156 (51.3%) dogs, and 60 of 156 (38.5%) dogs developed distant metastases. Median survival time for all dogs was 239 days. Dogs that underwent surgery had a median survival time of 329 days. Histologically tumor-free surgical margins were associated with significantly decreased hazards of progression or recurrence (hazard ratio [HR], 0.4) and death (HR, 0.5). Dogs with osteosarcoma of the calvarium had a significantly greater hazard of local recurrence or progression (HR, 2.0). CONCLUSIONS AND CLINICAL RELEVANCE In this study, tumor excision in dogs with histologically tumor-free margins resulted in better local control and longer survival time than did other treatment types.

Evaluation of Cisplatin in Combination with a Biologic Response Modifier in a Murine Mammary Carcinoma Model

The purpose of this study was to determine the efficacy of intracavitary cisplatin against local regrowth and metastasis after resection of a murine mammary carcinoma and the ability of a biologic response modifier (Virulizin®) to enhance chemotherapy. C3H-HeJ mice were injected with Gollin-B tumor cells. Once growth reached 8 mm, tumors underwent marginal resection and the mice were assigned randomly to intraperitoneal (IP) cisplatin, Virulizin, a controlled release cisplatin-impregnated sponge (OPLA–Pt), a combination of treatments or no treatment and were evaluated for local regrowth, metastasis, and toxicity at 14 or 60 days after surgery. A possible beneficial interaction was seen between OPLA–Pt and Virulizin at 14 days. All cisplatin groups had significant advantages over controls in all variables measured with OPLA–Pt displaying significant advantages over IP cisplatin in local recurrence rate, tumor score, survival time, and delay in regrowth at 60 days. No toxicity related to either cisplatin or Virulizin was observed.

Prognosis for dogs with stage III osteosarcoma following treatment with amputation and chemotherapy with and without metastasectomy

OBJECTIVE To determine survival times of selected dogs with metastatic (stage III) osteosarcoma, whether disease-free interval (DFI) was associated with survival time after diagnosis of stage III disease (ie, stage III survival time), and whether a survival benefit of metastasectomy existed. DESIGN Retrospective case series with nested cohort study. ANIMALS 194 client-owned dogs treated for histologically confirmed appendicular osteosarcoma from 1997 through 2009. PROCEDURES Dogs were included if they had stage I or II osteosarcoma at the time of initial evaluation, had amputation of the affected appendage and ≥ 1 dose of chemotherapy afterward, and developed metastasis within the follow-up period or prior to death. Data collected from the medical records included signalment, primary tumor location, clinical and laboratory findings, whether metastasectomy was performed, and outcome. Various factors were examined for associations with outcome. RESULTS Dogs that received no treatment for the metastasis had a median survival time between 49 and 57 days after diagnosis of stage III osteosarcoma. Duration of the preceding DFI had no association with this period. Metastasectomy alone was associated with a longer median stage III survival time (232 days) than no metastasectomy (49 days). Among all dogs identified as qualifying for pulmonary metastasectomy on the basis of < 3 pulmonary nodules visible on thoracic radiographs and a DFI > 275 days (n = 21), a survival advantage was also identified for those that actually received pulmonary metastasectomy (6). CONCLUSIONS AND CLINICAL RELEVANCE Preceding DFI had no influence on survival time of dogs with stage III osteosarcoma. Metastasectomy was associated with an increase in survival time for selected dogs.