Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. Patients and Methods: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. Results: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively. Conclusions: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

NSAIDs are the cornerstone of medical management of canine osteoarthritis (OA). Meloxicam is a daily‐administered NSAID widely available in a liquid formulation and manufacturer's summary of product characteristics (SPC) advise that it is given at the lowest effective dose. Mavacoxib is a long‐acting NSAID given as a monthly tablet. This study compares these drugs in the management of canine OA. In all, 111 dogs with OA of the elbow, hip or stifle were randomly assigned to receive one of these NSAIDs for a 12‐week period, and to administer them as per the manufacturer's SPC. Outcomes, including ground reaction forces and three validated clinical metrology instruments, were measured at baseline, 6 and 12 weeks. Improvements were seen in all outcome measures for both groups to a similar degree, and adverse events occurred at a similar rate. There were significant improvements in outcome measures from week 6 to week 12, as well as from baseline. Long‐term meloxicam dose was more important than recent dose. Clinical efficacy and adverse event rates are similar for meloxicam and mavacoxib when administered as per their UK SPC. This is relevant information for veterinary surgeons when prescribing NSAID treatment for canine OA.

Local recurrence after surgical excision of canine massive hepatocellular carcinoma (HCC) has been poorly studied in veterinary medicine with scant information published regarding risk factors for and outcome following recurrence. The aim of this case–control study was to describe the time to recurrence, evaluate potential risk factors for recurrence, and report the outcome in dogs with massive HCC. Medical records for 75 dogs who developed recurrence and 113 dogs who did not develop recurrence were reviewed. Statistical analyses were performed to determine risk factors for recurrence as well as the median time to develop recurrence and overall survival time (OS). None of the risk factors evaluated were significant for the development of recurrence. The median time to develop recurrence was 367 days (range 32–2096 days). There was no significant difference in median OS for dogs who developed recurrence vs. those who did not (851 vs. 970 days). For dogs with recurrent HCC, treatment at recurrence trended toward prolonged OS but was not significantly different from dogs not undergoing treatment at recurrence. There was no significant difference in median OS for dogs with histologically complete vs. incomplete tumour excision (990 vs. 903 days). Although specific risk factors for recurrence were not identified, elevations in liver values were noted in patients with recurrent disease and could act as a noninvasive surveillance tool. Recurrence was noted earlier in dogs who had routine post‐operative surveillance (228 vs. 367 days). Routine surveillance for recurrence is recommended especially in dogs where further intervention is possible and should extend beyond 1 year. Patients with massive HCC have a good long‐term prognosis regardless of incomplete excision, pulmonary metastasis, or recurrent local disease.