Pasteurized tumoral autograft as a novel procedure for limb sparing in the dog: A clinical report

OBJECTIVE: To evaluate use of a pasteurized tumoral autograft prepared from the resected primary bone neoplasm for limb sparing in a dog with distal radial osteosarcoma (OSA). STUDY DESIGN: Clinical case report. ANIMALS: A 9-year-old male Maremma shepherd dog. METHODS: After right distal radial OSA removal, the tumoral autograft was pasteurized. The excised bone segment was placed in a sterile watertight box containing sterile saline solution preheated to 65 degrees C in a water bath. The box was kept immersed in the water bath at 65 degrees C for 40 minutes to kill the tumor cells. The autograft was then fixed in the host with a plate and screws based on standard AO/ASIF technique for carpal arthrodesis. Three doses of cisplatin (70 mg/m(2) intravenously) were administered, 3 weeks apart; the initial dose was administered the day after surgery. RESULTS: The autograft was incorporated in a manner comparable to an allograft, and after 708 days, the metallic implants were removed. A 1-month activity restriction as well as spoon splint to protect the leg from a full loading were used thereafter. Limb function was fair to good, and the dog remains disease free after 56 months. CONCLUSIONS: A pasteurized autograft consisting of the resected primary bone neoplasm is a valid alternative to a cortical bone allograft for limb sparing in dogs with appendicular OSA in terms of feasibility and pattern of healing. CLINICAL RELEVANCE: This procedure can be an alternative method of limb sparing when difficulties are encountered in establishing and maintaining a canine bone allograft bank.     

Vascularized ulnar bone grafts for limb-sparing surgery for the treatment of distal radial osteosarcoma

The objective of this retrospective study was to compare vascularized free or roll-in ulnar bone grafts for limb-sparing surgery in dogs with radial osteosarcoma with the cortical allograft, metal endoprosthesis, or distraction osteogenesis techniques. Overall, the ulnar graft techniques used in this study demonstrated excellent healing properties. Complications included recurrence of the tumor in 25% (2/8) of the dogs, metastasis in 50% (4/8) of the dogs, implant loosening in 37.5% (3/8) of the dogs, implant failure in 12.5% (1/8) of the dogs, and infection in 62.5% (5/8) of the dogs. Mean survival time was 29.3 mo (range, 9 to 61 mo). The mean metastasis-free interval was 33.67 mo (range, 8 to 54 mo). Tumors recurred locally in two dogs at 10 mo and 20 mo postoperatively. This study yielded similar long-term complications as other limb-sparing options (such as cortical allografts and metal endoprostheses) and allowed dogs to bear weight on the operated limb with acceptable limb function. More research is needed regarding specific healing times for ulnar vascularized grafts, time until implant removal, and the extent of radial bone that could ultimately be replaced by the ulna.     

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).     

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.     

Toxicity and efficacy of cisplatin and doxorubicin combination chemotherapy for the treatment of canine osteosarcoma

Thirty-five dogs with appendicular osteosarcoma underwent amputation and chemotherapy with cisplatin and doxorubicin every 21 days for up to four cycles. Sixteen dogs completed all four cycles. Two dogs had therapy discontinued because of metastases. The remaining 17 dogs experienced toxicities necessitating protocol alteration or discontinuation. The median survival time of 300 days was not improved over previously reported single-agent protocols, but the 10 dogs that survived to a year lived a median of 510 days.     

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized,phase III trial

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease‐free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin.     

Transverse ulnar bone transport osteogenesis: a new technique for limb salvage for the treatment of distal radial osteosarcoma in dogs

Objective— To develop instrumentation and a technique for transverse ulnar bone transport osteogenesis in dogs.
Study Design— Cadaveric study and in vivo validation (1 dog).
Sample Population— Paired cadaveric antebrachii (n=10 dogs) and 1 live dog.
Methods— Circular fixator constructs were applied and fitted with reeling or linear motors designed to transport an ulnar segment transversely into a defect created by excising the distal 50% of the ipsilateral radius. A longitudinal osteotomy of the adjacent ulna was created and the segment was transported across the radial defect. Pre- and post-distraction CT scans were used to compare the efficacy of each construct. The procedure was performed unilaterally in a live dog using the reeling motor (RM) construct.
Results— Both constructs effectively transported the ulnar segment into the defect. Subjectively, the RMs were easier to apply and operate. No significant differences were observed in the objective measures of efficacy between the 2 construct types. The live dog produced viable regenerate bone after transverse ulnar bone transport.
Conclusions— Transverse ulnar bone transport should be considered a potential method for limb salvage in dogs with osteosarcoma (OSA) of the distal radius. The RMs were effective and clinically applicable.
Clinical Relevance— Transverse ulnar bone transport osteogenesis affords the benefits of longitudinal radial bone transport osteogenesis, allowing resolution of large longitudinal radial defects in a substantially less time as a result of shortening the transport distance. This would be beneficial when treating conditions such as OSA where minimizing convalescence and maximizing quality of life is a priority.     

Outcome and prognostic factors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumour: 61 cases

The medical records of 61 dogs with MCT at high risk for metastasis that were treated with prednisone and VBL following excision+/-radiation therapy were reviewed, and median disease-free interval (DFI), median overall survival time (OS) and prognostic factors assessed. Adverse effects, mostly mild, were noted in 26% of patients, usually after the first VBL dose. 6.5% experienced severe neutropenia. The DFI was 1305 days, and the OS was not reached, with 65% alive at 3 years. 100% of dogs with "high-risk" grade II MCT were alive at 3 years. The OS for dogs with grade III MCT was 1374 days. Histologic grade, location (mucous membrane vs. skin) and use of prophylactic nodal irradiation predicted outcome. Prednisone and VBL chemotherapy is well tolerated, and results in good outcomes following surgery in dogs with MCT at high risk for metastasis. High-grade and mucocutaneous tumors had a worse outcome, and the use of prophylactic nodal irradiation appeared to improve outcome in this group of dogs.     

Ipsilateral vascularised ulnar transposition autograft for limb-sparing surgery of the distal radius in 2 dogs with osteosarcoma

Canine osteosarcoma is the most commonly diagnosed primary bone tumour in the dog, affecting mainly large and giant breed dogs with the predilection site being the metaphysis of long bones, specifically the distal radius, proximal humerus, distal femur and proximal tibia and fibula. Treatment options are either palliative or curative intent therapy, the latter limb amputation or limb-sparing surgery together with chemotherapy. This article describes the use of an ipsilateral vascularised ulnar transposition autograft as well as chemotherapy in 2 dogs with osteosarcoma of the distal radius. Both dogs showed minimal complications with the technique and both survived over 381 days following the surgery. Complications seen were loosening of the screws and osteomyelitis. The procedure was well tolerated with excellent limb use. This technique is indicated for use in cases with small tumour size that have not broken through the bone cortex.     

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.     

Biology, diagnosis and treatment of canine appendicular osteosarcoma: similarities and differences with human osteosarcoma

Osteosarcoma (OSA) is the most common primary bone tumour in dogs. The appendicular locations are most frequently involved and large to giant breed dogs are commonly affected, with a median age of 7–8 years. OSA is a locally invasive neoplasm with a high rate of metastasis, mostly to the lungs. Due to similarities in biology and treatment of OSA in dogs and humans, canine OSA represents a valid and important tumour model. Differences between canine and human OSAs include the age of occurrence (OSA is most commonly an adolescent disease in humans), localisation (the stifle is the most common site of localisation in humans) and limited use of neoadjuvant chemotherapy in canine OSA.     

Evaluation of a single subcutaneous infusion of carboplatin as adjuvant chemotherapy for dogs with osteosarcoma: 17 cases (2006-2010)

Objective-To evaluate adverse effects and survival times in dogs with osteosarcoma that received a single SC infusion of carboplatin as adjunctive chemotherapeutic treatment following limb amputation or limb-sparing surgery. Design-Retrospective case series. Animals-17 client-owned dogs with spontaneously occurring osteosarcoma. Procedures-Medical records of dogs that underwent limb amputation or limb-sparing surgery followed by a single continuous SC infusion of carboplatin (total dose, 300 mg/m(2) infused over 3, 5, or 7 days) were evaluated. Signalment, tumor location, type of surgery (amputation or limb-sparing), duration of carboplatin infusion, results of hematologic and serum biochemical analyses, and adverse effects were recorded. Kaplan-Meier survival analysis was performed. Results-Median survival time for all dogs was 365 days. Nine dogs had adverse bone marrow-related (hematologic) effects, 1 had adverse gastrointestinal effects, and 7 had infections at the surgical site. No significant differences were detected in survival times of dogs grouped according to tumor location, type of surgery, duration of carboplatin infusion, or development of postoperative infection. Conclusions and Clinical Relevance-Median survival time and adverse effects in dogs with osteosarcoma that received a single SC infusion of carboplatin over a 3-, 5-, or 7-day period as adjunctive treatment following limb amputation or limb-sparing surgery were comparable to those of previously reported chemotherapy protocols requiring IV drug administration over several weeks. Further investigation is needed to evaluate the efficacy of this protocol as adjunctive treatment for osteosarcoma and other tumors in dogs.     

Combination CCNU and vinblastine chemotherapy for canine mast cell tumours: 57 cases

The purpose of this study was to evaluate the efficacy and toxicity of a CCNU and vinblastine chemotherapy protocol for canine mast cell tumours. Fifty-seven tumours in 56 dogs were evaluated, 37 had macroscopic disease and 20 had microscopic disease. A 57% response rate was seen in dogs with macroscopic disease for a median duration of 52 weeks. Dogs with macroscopic disease had a median progression free survival time (PFST) of 30 weeks and a median overall survival time (OST) of 35 weeks. Dogs with microscopic disease had a median PFST of 35 weeks and a median OST of 48 weeks. Toxicity was recorded in 54% of the dogs treated, with the majority of events being mild. This chemotherapy protocol appears to be well tolerated and should be considered for canine mast cell tumours.     

CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma

Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01).     

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.     

Mitoxantrone and cyclophosphamide combination chemotherapy for the treatment of various canine malignancies.

Thirteen dogs with histopathologically confirmed malignancies were treated with mitoxantrone and cyclophosphamide combination therapy. One to four doses were administered at 21-day intervals. Recombinant human granulocyte colony-stimulating factor was administered to ameliorate myelosuppression in dogs with neutrophil nadirs less than 1,000/microl. While the protocol appears to be safe for use in tumor-bearing dogs, an advantage over mitoxantrone single-agent protocols in terms of tumor response was not demonstrated in this initial pilot study.     

Evolution of the treatment of canine radial and tibial fractures with external fixators

OBJECTIVES: To determine if indications for external fixator treatment of radial and tibial fractures, management of the fractures, or outcomes have changed over three decades. METHODS: Three groups of dogs were identified from discrete time spans within three decades and the medical records and radiographs were evaluated. The groups were compared in order to determine whether indications (signalment, etiology, fracture type and configuration), reduction method, equipment and implants, frame types and pin numbers, numbers of radiographic reevaluations, use of destabilization, frequency of pin track osteolysis, frame removal times and percentage of complications remained the same over the decades. RESULTS: The indications for external fixator treatment of radial and tibial fractures remained consistent over three decades. The equipment and implants changed over the decades. Frame construction changed from the predominately Type II frames constructed in the 1980's and 1990's to a variety of modified Type II, Type Ia, Type Ib and hybrid frames constructed in the 2000's. The frequency of pin track osteolysis decreased significantly over the decades. Frame removal times have not changed significantly over the past three decades. Complications (nonunion, delayed union, osteomyelitis, implant failure and premature frame loss) have decreased over this time. CLINICAL SIGNIFICANCE: Improvements in techniques and equipment have led to decreased complications with external fixators.     

Cortical allograft and endoprosthesis for limb-sparing surgery in dogs with distal radial osteosarcoma: a prospective clinical comparison of two different limb-sparing techniques

OBJECTIVE: To compare surgical and oncologic outcome in dogs with osteosarcoma (OSA) of the distal aspect of the radius treated with limb-sparing surgery, using either a cortical allograft or endoprosthesis, and postoperative chemotherapy; and to evaluate predictive factors for outcome. STUDY DESIGN: Prospective cohort study. ANIMALS: Dogs (n = 20) with spontaneous, non-metastatic OSA of the distal aspect of the radius. METHODS: Dogs were prospectively randomized for limb-sparing surgery with either a cortical allograft (n = 10) or endoprosthesis (10) and full-course adjuvant chemotherapy using single or dual agent protocols of cisplatin, carboplatin, and/or doxorubicin. Surgical (intraoperative findings, postoperative infection, construct failure) and oncologic (local tumor recurrence, metastasis, survival) outcomes were compared. The influence of intraoperative and postoperative variables on surgical and oncologic outcome were evaluated. RESULTS: No clinically significant differences in surgical and oncologic outcome were detected between groups. The percentage of radius replaced by the implant was significantly greater in the endoprosthesis group (60.9% compared with 48.6%, P = .008). Median survival time (MST) for dogs with construct failure, regardless of implant type, was 685 days and significantly greater than MST of dogs without construct failure (322 days, P = .042; hazard ratio [HR] 16.82). Median metastasis-free interval and MST (685 days versus 289 days; P = .034, HR 24.58) were significantly greater in dogs with postoperative infection. Disease-free and overall limb-salvage rates were 70% and 85%, respectively. Overall MST was 430 days. CONCLUSIONS: For dogs with OSA of the distal aspect of the radius, a cortical allograft or endoprosthesis can be used for limb-sparing surgery. Construct failure and postoperative infection significantly improve survival time regardless of implant type. CLINICAL RELEVANCE: An endoprosthesis is an attractive alternative to cortical allografts for limb-salvage of the distal aspect of the radius in dogs because surgical and oncologic outcomes are similar, but the endoprosthesis is an immediately available off-the-shelf implant which is not complicated by the bone harvesting and banking requirements associated with cortical allografts. Mechanisms whereby postoperative infection improves survival time requires further investigation and, if elucidated, may provide the opportunity to improve the outcome of dogs and humans with OSA.