William S. Dernell

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.

An initial investigation of photocurable three-dimensional lactic acid based scaffolds in a critical-sized cranial defect

Degradable polymer networks formed by the photoinitiated polymerization of multifunctional monomers have great potential as in situ forming materials, especially for bone tissue engineering. In this study, one specific chemistry was analyzed with respect to bone formation in a critical-sized defect model with and without adsorbed osteoinductive growth factors present. The scaffolds degraded in approximately 8 months and possessed an elastic modulus similar to that of trabecular bone. A porous scaffold fabricated with approximately 80% porosity and pore diameters ranging from 45 to 150 mm was implanted in a critical-sized cranial defect in rats. When implanted alone, the scaffolds were filled primarily with fibrous tissue after 9 weeks with only mild inflammation at the defect site. When the scaffolds released osteoinductive growth factors, statistically more bone filled the scaffold. For instance, 65.8+/-9.4% (n=5) of the defects were filled with radiopaque tissue in the osteoinductive releasing scaffolds, whereas only 24.2+/-7.4% (n=5) of the defects were filled in the untreated defects 9 weeks after implantation. These results illustrate not only the benefits of delivering osteoinductive factors when developing synthetic bone grafts, but the potential of these materials for supporting the infiltration and development of bone in large defects.

Use of single-agent carboplatin as adjuvant or neoadjuvant therapy in conjunction with amputation for appendicular osteosarcoma in dogs.

Survival following amputation and administration of single-agent carboplatin for treatment of appendicular osteosarcoma (OSA) in dogs was retrospectively examined. Records of 155 dogs with appendicular OSA treated with amputation and single-agent carboplatin were included from 14 centers. Any carboplatin dosage, number of doses, and protocol schedule were eligible for inclusion. The median disease-free interval (DFI) was 256 days. The median overall survival time was 307 days. Similar prognostic survival factors were identified in this study as reported in prior studies of canine appendicular OSA. Median DFI and survival were comparable to those reported in the original Bergman et al publication. Carboplatin treatment improves the survival probability in dogs with appendicular OSA compared to amputation alone and remains an acceptable alternative to adjuvant treatment with cisplatin.

Biodegradable Cisplatin Polymer in Limb-Sparing Surgery for Canine Osteosarcoma

Background: The rate of local recurrence of osteosarcoma after limb-sparing surgery in dogs and humans has been reported up to 28%. The primary purpose of this study was to determine whether a biodegradable cisplatin-containing implant (OPLA-Pt), inserted into the limb-sparing surgery site at the time of surgery, would decrease the rate of local recurrence. Secondary aims included evaluation of systemic toxicity associated with the release of cisplatin from the implant and identification of prognostic factors associated with limb-sparing surgery for osteosarcoma in dogs.Methods: Eighty dogs with spontaneously occurring osteosarcoma were treated with limb-sparing surgery. They were randomized to receive the biodegradable implant either without cisplatin (control group) or with cisplatin (OPLA-Pt group) and were targeted to receive four doses of an adjuvant cisplatin chemotherapy protocol.Results: Although this was not statistically significant (P = .071), dogs in the OPLA-Pt group were 53.5% less likely to develop local recurrence than dogs in the control group. There were no significant differences in systemic toxicity between treatment arms. Incomplete surgical resection, absence of infection, and fewer than four doses of adjuvant chemotherapy had a significant correlation with local recurrence and survival according to univariate analyses, although only incomplete surgical resection remained significant for local recurrence after multivariate analysis.Conclusions: Local tumor recurrence may be decreased after limb-sparing surgery by use of biodegradable implants impregnated with chemotherapeutic agents.

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.

Multilobular Osteochondrosarcoma in 39 Dogs: 1979-1993

Thirty-nine, older, large-breed dogs with multilobular osteochondrosarcoma (MLO) each presented primarily with a fixed mass involving the flat bones of the skull. Twenty-five dogs were treated with surgical resection alone, nine were treated with adjuvant therapy, and five were not treated. Forty-seven percent of dogs treated had local tumor recurrence, and 56% had metastasis. Median time to recurrence, median time to metastasis, and median survival time were 797, 542, and 797 days, respectively. Histological grade, surgical margins, and tumor location affected outcome. Long-term remission can be obtained with aggressive treatment of MLO, although it is locally invasive and moderately metastatic.

Extraskeletal osteosarcomas in dogs: 14 cases

Fourteen dogs (11 females, three males) with extraskeletal osteosarcomas (EsOSAs) were identified. The median age was 11.5 years. The median body weight was 18 kg. The primary sites of the EsOSAs were the spleen (n=6), mammary gland (n=3), lung (n=2), and one each in the skin, axilla, and mesenteric root. The overall median survival time was 74 days. The only factor which was found to be prognostic for survival was the use of chemotherapy (p of 0.02). Cases which did not have chemotherapy were 3.62 times as likely to die a tumor-related death than cases which had chemotherapy.

A review of sentinel lymph node evaluation and the need for its incorporation into veterinary oncology

Being the first lymph node or nodes to which many primary tumours reliably drain, the disease status of the sentinel lymph node/s (SLN) is important in the prediction of survival. SLN identification and biopsy are critical in the staging of human cancers. The status of the SLN helps determine prognosis and shape treatment plans. SLN evaluation is currently not routinely performed in veterinary oncology, not even at specialty oncology practices. Given the prognostic importance of lymph node involvement in tumours such as mammary gland carcinoma, osteosarcoma, synovial cell sarcoma and mast cell tumours, SLN evaluation should be incorporated into routine clinical practice so as to improve our clinical assessment of veterinary oncologic patients.

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.