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.     

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.     

Evaluation of survival times after limb amputation, with and without subsequent administration of cisplatin, for treatment of appendicular osteosarcoma in dogs: 30 cases (1979-1990).

Appendicular osteosarcoma was diagnosed in 30 dogs. Fifteen dogs were treated by limb amputation alone, and 15 dogs were treated by limb amputation followed by 2 doses of cisplatin given IV approximately 2 and 7 weeks after limb removal. Mean survival time after limb amputation alone +/- SD was 190 +/- 138 days (median, 168 days); 7 dogs survived longer than 6 months, and 3 dogs survived more than 1 year. Fourteen of 15 dogs treated by amputation and administration of cisplatin survived a mean of 315 +/- 158 days (median, 290 days) after amputation, and 1 dog was still alive at 1,095 days; 13 dogs survived longer than 6 months and 5 dogs survived more than 1 year. Survival time was significantly (P less than 0.05) greater in dogs given cisplatin.     

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.     

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.     

Cohort study examining long‐term respiratory health,career duration and racing performance in racehorses that undergo left‐sided prosthetic laryngoplasty and ventriculocordectomy surgery for treatment of left‐sided laryngeal hemiplegia

Reasons for performing study: The risk of respiratory conditions, such as inflammatory airway disease (IAD) and exercise‐induced pulmonary haemorrhage (EIPH), are thought to be higher in racehorses that undergo prosthetic laryngoplasty with ventriculocordectomy (PLVC) surgery to treat left‐sided laryngeal hemiplegia (LLH) than in racehorses with normal laryngeal function. However, this has not been investigated formally owing to the difficulty of obtaining reliable follow‐up data. Objectives: To determine the incidence of respiratory conditions (IAD and EIPH), duration of racing career, number of starts and number of starts for which stakes money was earned in racehorses that had undergone PLVC surgery to treat LLH, compared with racehorses that did not have LLH or undergo any laryngeal surgery. Methods: A retrospective cohort study design was used, with surgical, clinical and race data of Thoroughbred racehorses obtained from the time of importation until retirement. The surgical cohort consisted of racehorses that had undergone PLVC for LLH and met specific inclusion criteria. Every surgical case was matched, according to trainer, year of import into Hong Kong and pre‐import international handicap rating, to 2 unexposed racehorses. Results: Respiratory conditions, such as excessive tracheal mucus and epistaxis due to severe EIPH, were significantly increased in the surgical cohort, compared with the matched unexposed cohort (P values <0.001 and <0.004, respectively). Racing career duration in the surgical cohort was significantly shorter than in the unexposed cohort, which was primarily due to retirement because of epistaxis. The number of race starts was fewer in the surgical than in the unexposed cohort after surgery/matching, but the number of starts for which stakes money was earned was not significantly different. Conclusions and potential relevance: Owners and trainers should be advised that racehorses with LLH that undergo PLVC surgery are at an increased risk of respiratory conditions (IAD and severe EIPH), which is likely to shorten their racing career compared to racehorses with normal laryngeal function. Racing performance in terms of race starts was significantly less in racehorses that had undergone PLVC surgery; however, the number of starts for which stakes money was earned was similar to those racehorses that were unexposed.     

Use of routine histopathology and factor VIII‐related antigen/von Willebrand factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from telangiectatic osteosarcoma in 54 dogs

Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear similar histologically, but differ in histogenesis (malignant endothelial cells versus osteoblasts), and may warrant different treatments. Immunohistochemistry (IHC) for endothelial cell marker factor VIII‐related antigen/von Willebrand factor (FVIII‐RAg/vWF) is a well‐documented ancillary test to confirm HSA diagnoses in soft tissues, but its use in osseous HSA is rarely described. Archived samples of 54 primary appendicular bone tumours previously diagnosed as HSA or tOSA were evaluated using combination routine histopathology (RHP) and IHC. Approximately 20% of tumours were reclassified on the basis of FVIII‐RAg/vWF immunoreactivity, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was immunopositive for FVIII‐RAg/vWF. RHP alone was specific but not sensitive for diagnosis of HSA, compared with combination RHP and IHC. Routine histopathological evaluation in combination with FVIII‐RAg/vWF IHC can help differentiate canine primary appendicular HSA from tOSA.     

Stereotactic body radiation therapy as an alternative to adrenalectomy for the treatment of pheochromocytomas in 8 dogs

The objective of this report is to describe the use and outcome of stereotactic body radiation therapy (SBRT) for treatment of pheochromocytomas in 8 dogs. Pheochromocytomas are an uncommon but challenging tumour to manage. Adrenalectomy is the standard of care for treatment of pheochromocytomas in both animals and humans; however, unpredictable catecholamine secretion from the tumour and vascular and local invasion of the tumour and thrombi can pose life-threatening perioperative and anaesthetic risks. SBRT has been investigated as an alternative to adrenalectomy in human patients with pheochromocytomas. Eight dogs with clinical signs, an adrenal mass, and cytology and/or urine normetanephrine/creatinine ratios consistent with pheochromocytoma were treated with SBRT in lieu of adrenalectomy. Three dogs presented with acute hemoabdomen. Seven dogs had caval tumour invasion, 3 with extension into the right atrium. Following SBRT, all dogs had complete resolution of clinical signs and reduced urine normetanephrine/creatinine ratio and/or tumour size. No significant anaesthetic complications were encountered. Acute radiation toxicity was limited to grade I gastrointestinal signs in 3 dogs and resolved within 1–2 days of symptomatic therapy. Five of 8 dogs were alive at the time of follow up, with a median follow up time of 25.8 months. SBRT resulted in a favourable outcome and mitigated the life-threatening risks of adrenalectomy in these 8 dogs. SBRT may be a safe and effective alternative to adrenalectomy for pheochromocytomas in dogs with non-resectable tumours, or for owners averse to the risks of surgery.