Comparison of examination of thoracic radiographs and thoracic computed tomography in dogs with appendicular osteosarcoma

Appendicular osteosarcoma (OSA) is a highly metastatic tumour in dogs. The aim of the study was to compare thoracic radiographs with thoracic computed tomography (CT) in the staging of canine appendicular OSA. In all, 39 canine patients histologically diagnosed with OSA were reviewed in the retrospective study. All dogs underwent radiographic examination as well as CT examination of the thoracic cavity. Pulmonary nodules were detected radiographically in two cases (5%), whereas the CT imaging showed that pulmonary nodules were evident in 11 cases (28%, P = 0.024). There was an improved detection of small pulmonary nodules in the lung parenchyma with CT (P = 0.021). The number of nodules in CT examination had a significant negative influence on survival time (P = 0.005). However, whether nodules were present in CT or not did not influence overall survival (P = 0.368). CT examination was superior to thoracic radiography in the screening and detection of pulmonary nodules in dogs with OSA.     

Vertebral telangiectatic osteosarcoma in a dog

Telangiectatic osteosarcoma (TOS) affecting the seventh cervical vertebra (C7) was diagnosed in a 4-year-old male dog with signs of locomotor dysfunction. Bone lysis and an extradural-extramedullary mass were observed in radiographs and occipital myelograms. The diagnosis was confirmed by histopathologic and immunohistochemical examination of the mass. The tumor was composed of large blood-filled cavities lined by anaplastic stromal cells (malignant osteoblasts). Around the cavities were characteristic tumor giant cells ("bizarre cells"). Immunohistochemically the tumor cells were positive for proliferating cell nuclear antigen. The lining cells of the cysts were negative for von Willebrand factor. The histologic findings in this case of TOS involving C7 were similar to those seen in other cases of TOS in dogs and in people. Immunohistochemistry was a useful tool for assessing malignancy and for ruling out other differential diagnoses.     

Cutaneous metastasis of primary appendicular osteosarcoma in a dog

A 6-year-old, neutered male Rottweiler was presented to the University of Illinois Veterinary Teaching Hospital because of a lytic bone lesion involving the distal portion of the right radius and possible pulmonary metastases on thoracic radiographs. Results of serum biochemical analysis were unremarkable. Aspiration and cytologic examination of the bone lesion indicated likely sarcoma with reactive bone. Cutaneous masses were found on the left thigh, interscapular region, and dorsal lumbar region, 4 weeks after initial presentation. Neoplastic spindle cells were found in aspirates from 2 of the masses. The neoplastic cells stained positive for alkaline phosphatase activity using cytochemistry. Re-evaluation of serum biochemical values at this time revealed a marked increase in alkaline phosphatase activity (413 U/L, reference interval 12-110 U/L) compared with the initial value (26 U/L). Due to progressive disease, the dog was euthanized and a necropsy was performed. Histologic findings included primary osteosarcoma of the distal portion of the right radius, with metastases in the lungs, spleen, left fourth and fifth ribs, soft tissue of the right medial thigh, and T1-T3/interscapular region. Cutaneous metastasis of primary appendicular osteosarcoma has been reported rarely in animals and humans. Increased serum alkaline phosphatase activity may be a potential indicator of poor prognosis for this neoplasm.     

Right ventricular rupture after lateral thoracotomy for removal of rib-associated telangiectatic osteosarcoma in a dog

Objective – To describe a case of a focal right ventricular rupture following removal of a rib-associated telangiectatic osteosarcoma (TOS) in a dog.
Case Summary – A 2-year-old spayed female mixed-breed dog, weighing 20 kg, was presented in compensated hypovolemic shock due to active bleeding into the thoracic cavity. The dog was stabilized with appropriate fluid administration. Subsequent computed tomographic examination revealed a large mineralized mass originating from the body of a rib and displacing the heart. Two days after surgical removal of this mass, focal right ventricular rupture occurred and the dog died. The mass was later identified as a TOS.
New or Unique Information Provided – Although hemothorax secondary to TOS has been described previously, this report describes for the first time, spontaneous focal right ventricular rupture as a rare complication of thoracotomy and rib resection for the removal of a rib-associated, intrathoracic TOS.     

Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine osteosarcoma cells

The development of metastasis is the most significant cause of death for both canine and human patients with osteosarcoma (OS). Ezrin has been associated with tumour progression and metastasis in human, canine and murine OS. Ezrin activation is dynamically regulated by protein kinase C (PKC) during metastatic progression in human and murine OS. To include the dog in the development of therapeutics that target ezrin biology, we characterized four new canine OS cell lines and confirmed the relationship between PKC and ezrin in these cells. Three of four cell lines formed tumours in mice that were histologically consistent with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC. Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC inhibitor. These data suggest that an association between PKC-mediated activation of ezrin and the metastatic phenotype in canine OS cells.     

Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma

Efficacious therapies for measurable metastatic canine osteosarcoma (OSA) are generally lacking. Preliminary retrospective studies suggested that approximately 50% of dogs with measurable metastatic OSA experienced clinical benefit (objective response or clinically meaningful disease stabilisation) following toceranib (TOC) treatment. The purpose of this clinical trial was to prospectively evaluate the clinical outcome following TOC treatment in dogs with measurable pulmonary metastatic OSA. A secondary goal was to identify potential biomarkers of clinical benefit by measuring changes in plasma vascular endothelial growth factor (VEGF) and circulating regulatory T‐cell (Treg) percentage. Twenty‐two dogs with pulmonary metastasis from appendicular OSA having undergone previous amputation were treated prospectively with TOC. Adverse events (AEs) were common but predominantly low grade. Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable AEs. Of the patients evaluable for disease progression at week 8 (or earlier), 3/17 (17.6 %) had stable disease with the remainder having PD. The median progression‐free survival time for all patients was 57 days (range 7‐176 days) with a median overall survival time of 89 days (range 7‐574 days). Plasma VEGF concentrations were significantly elevated in patients after 4 weeks of TOC treatment, but no changes were observed in percentage of Treg in peripheral blood. Overall, the results of this clinical trial do not support the use of TOC as single agent therapy for canine metastatic OSA.     

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.     

A novel small molecule Met inhibitor, PF2362376, exhibits biological activity against osteosarcoma

The receptor tyrosine kinase Met is dysregulated in several human cancers including osteosarcoma (OSA) in which overexpression is a negative prognostic indicator and enforced Met expression in normal osteoblasts leads to genomic instability and malignant transformation. Met is also known to be inappropriately expressed in canine OSA tumour samples and cell lines. The purpose of this study was to evaluate the potential utility of an orally bioavailable small molecule Met inhibitor, PF2362376, against canine OSA cell lines as a prelude to future clinical work. PF2362376 inhibited phosphorylation of Met, Gab‐1, Erk and Akt, but not of Src or STAT3. Furthermore, PF2362376 inhibited proliferation of canine OSA cell lines and induced cell death at biologically achievable concentrations. Last, activities associated with Met signalling including migration, invasion, branching morphogenesis and colony formation in soft agar were blocked by PF2362376. These studies support the notion that Met is a relevant target for therapeutic intervention in OSA.     

Limb-sparing surgery in a dog with osteosarcoma of the proximal femur

OBJECTIVE: To report successful limb-sparing surgery in a dog with a proximal femoral osteosarcoma (OSA) using a composite allograft-prosthetic technique. STUDY DESIGN: Case report. ANIMAL: Client-owned dog. METHODS: A stage IIB OSA of the proximal aspect of the femur was resected in accordance with oncologic and limb-sparing principles. The osseous defect was reconstructed with a proximal femoral allograft and cemented, long-stemmed femoral prosthesis. Soft tissue reconstruction was achieved by suturing host tendons to their respective allogeneic tendons on the allograft. Coxofemoral joint function was preserved using standard total hip arthroplasty techniques. RESULTS: Limb-sparing surgery of the proximal aspect of the femur using a composite allograft-prosthetic technique resulted in excellent limb function. Postoperative complications included aseptic loosening of the femoral composite graft and allograft nonunion, which required revision, traumatic implant luxation, and local tumor recurrence. Limb function was excellent after surgical stabilization of the allograft nonunion but deteriorated after implant luxation 270 days postlimb-sparing surgery. Pulmonary and skeletal metastases were diagnosed and local tumor recurrence suspected 596 and 650 days postoperatively, respectively. The dog was euthanatized 688 days after limb-sparing surgery as a result of progressive local and metastatic disease. CONCLUSIONS AND CLINICAL RELEVANCE: Limb-sparing surgery for dogs with primary bone tumors of the proximal aspect of the femur is feasible with good functional results.     

Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcome

The purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed with OSA that had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty‐seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P = 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P = 0.071). However, the identification of lesions in either the liver (P = 0.021) or the kidney (P = 0.003) was statistically associated with shorter survival.     

Longitudinal bone transport for treatment of primary bone tumors in dogs: technique description and outcome in 9 dogs

OBJECTIVE: To describe a surgical technique for bone transport osteogenesis (BTO) limb salvage and report outcome in 9 dogs with primary bone tumors. ANIMALS: Nine dogs with spontaneously occurring primary bone tumors. RESULTS: BTO surgery was performed as a primary means of limb salvage in 7 dogs and as a salvage procedure after catastrophic allograft infection and failure in 2 dogs. Mean defect size was 9.5 cm with a mean of 123 days distraction until docking. Mean time from surgery to fixator removal was 205 days. Minimum follow-up was 9 months. There were 2 histologically confirmed local recurrences where although limb function was excellent, eventually resulted in limb amputation. Limb function was good to excellent in all but 2 dogs; 1 was chronically non-weight bearing before BTO surgery because of complications associated with an allograft limb salvage that had been performed previously on the same limb. The cause of lameness in the other dog was undetermined. CONCLUSIONS: BTO limb salvage can be successful in dogs with primary bone tumors. Whereas allograft limb salvage may be simpler from an initial management perspective, BTO has some unique advantages when compared with the allograft technique. CLINICAL RELEVANCE:BTO has an emerging role in limb salvage surgery for dogs with primary bone tumors. BTO provides excellent long-term outcomes in some dogs with primary bone tumors and will likely become increasingly more attractive as technique modifications allow the duration of the treatment to be shortened.     

Accuracy of computed tomography in determining lesion size in canine appendicular osteosarcoma

Multidetector contrast enhanced computed tomography with acquisition of 0.625-mm thick transverse images was used to measure the extent of appendicular osteosarcoma in 10 dogs. The measured length of tumor based on CT was compared to the true length of tumor using histopathology. There was a statistically significant association with good correlation between the true length of osteosarcoma compared to the length of intramedullary/endosteal abnormalities on CT with a mean overestimation of 1.8% (SD = 15%). There was not a statistically significant association between the true tumor length and the length of periosteal proliferation on CT with a mean overestimation of 9.7% (SD = 30.3%). There was a statistically significant association, but with poor correlation, between the true tumor length compared to the length of abnormal contrast enhancement with a mean overestimation of 9.6% (SD = 34.8%). The extent of intramedullary/endosteal CT abnormalities assessed from submillimeter transverse images may be of value in assessing patient candidacy and surgical margins for limb-sparing surgery.     

Primary ocular osteosarcoma in a dog

An adult male Rottweiler presented to the veterinary medical teaching hospital at Purdue University with a 1-month history of hyphema. On physical examination conjunctivitis, episcleral hyperemia, corneal edema, hyphema, mild glaucoma and loss of vision were observed in the left eye. No other abnormalities were found. The left globe was surgically removed because of the high likelihood of neoplasia and it was fixed in 10% buffered formalin and submitted for pathology. A histologic diagnosis of primary osteosarcoma of the eye was made. Radiographic evaluation did not reveal any evidence of other tumors or pulmonary metastasis. This is the fourth canine case of primary intraocular osteosarcoma to be documented.     

Configuration of pathologic fractures in dogs with osteosarcoma following stereotactic body radiation therapy: A retrospective analysis

For some cases of canine appendicular osteosarcoma (OSA), limb-sparing treatment options are often desired, one of which is stereotactic body radiation therapy (SBRT). A major complication of SBRT is fracture of the irradiated bone at the site of treatment. The present study evaluated 127 appendicular OSA sites in 122 dogs treated with SBRT to identify the most common pathologic fracture locations and configurations. A total of 50 tumours experienced a pathologic fracture, and 38 had imaging sufficient to identify fracture configuration. The distal tibia was more likely to develop a fracture than other sites. Multiple types of fracture configuration (transverse, oblique, spiral and comminuted) were observed. The distal radius was significantly more likely to develop a transverse fracture than other sites. Documentation of fracture location and configuration leads to the identification of the forces contributing to fracture occurrence, since each configuration is a result of different forces acting on each affected bone. Such knowledge is imperative for the development of new approaches to diminish the occurrence of pathologic fractures.     

Intraoperative extracorporeal irradiation for limb sparing in 13 dogs

OBJECTIVE: To evaluate extracorporeal intraoperative radiation therapy (IORT) as a treatment method for limb and joint sparing in dogs with appendicular sarcomas in sites other than the distal aspect of the radius. STUDY DESIGN: Retrospective study. ANIMALS: Thirteen client-owned dogs. METHODS: The bone tumor database and medical records (1998-2002) were reviewed for dogs with primary appendicular bone tumors treated with IORT limb-sparing surgery and adjuvant chemotherapy. The segment of bone containing the tumor was isolated from adjacent soft tissue and an osteotomy performed distant to the tumor. The bone segment was exteriorized, irradiated (70 Gy single fraction), and then stabilized with internal fixation. Adjuvant chemotherapy was administered. Lameness was graded and local and distant tumor control was determined. Associations between intra- and postoperative variables with complications and Kaplan-Meier survival analysis for median disease-free interval and survival time were calculated. RESULTS: Limb function was good or excellent in 10 dogs (77%). Postoperative complications (9 dogs, 69%) included deep infection, fracture of the irradiated bone, and implant failure. Surgical failure was more likely if a single implant was used to stabilize the osteotomized bone and if deep infection developed postoperatively. In 3 dogs, tumors recurred locally within bone in the radiation field. The disease-free and overall success rates of extracorporeal IORT for limb and joint preservation were 46% and 54%, respectively. CONCLUSIONS: Extracorporeal IORT provides a novel alternative to traditional techniques for preservation of joint and limb function in dogs with primary appendicular sarcomas. A minimum of 2 implants and intramedullary bone cement should be used to stabilize the osteotomized bone to minimize postoperative complications. Extracorporeal IORT should be used with caution in dogs with tumors of the distal tibia because of a high complication rate. Dogs with tumors in areas of good soft-tissue coverage, such as the humerus and femur, may be good candidates for limb and joint-sparing surgery using extracorporeal IORT. CLINICAL RELEVANCE: Extracorporeal IORT is a surgical technique that can be used for limb and joint salvage in dogs with primary appendicular sarcomas in sites usually not amenable to traditional limb-sparing techniques.     

Surgical decompression,with or without adjunctive therapy,for palliative treatment of primary vertebral osteosarcoma in dogs

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client‐owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3‐1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56‐305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223‐653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.