ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- Phase 2 trial (NCI-COTC030) of adjuvant inhaled recombinant human IL-15 combined with amputation and adjuvant chemotherapy in dogs with appendicular osteosarcoma.Frontiers in immunology · 2025Trial
- Integrated Multiomic Profiling Enhances Risk Stratification and Prognostication in Canine Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Article
- Percutaneous Cementoplasty as a Monotherapy in the Treatment of Appendicular Osteosarcoma in Ten Dogs.Animals : an open access journal from MDPI · 2026Article
- Engineering Osteoimmune Responses with Functionalized Orthopedic Implants for Post-Operative Osteosarcoma Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Comprehensive analysis of non-tumor lung, liver, and kidney transcriptomes in canine metastatic osteosarcoma.Communications biology · 2026Article
- Autoimmune lymphoproliferative syndrome in Boerboel dogs: treatment, clinical outcomes and prevention.Journal of veterinary internal medicine · 2026Article
- Characterization of canine metastatic pulmonary nodules onThe Canadian veterinary journal = La revue veterinaire canadienne · 2025Article
- The Immune Landscape of Canine Soft Tissue Sarcomas as a Model for Human Soft Tissue Sarcomas.Cancers · 2025Article
- Phosphatidylinositol 3-kinase and mechanistic target of rapamycin dualinhibitor, VDC597, as a therapeutic agent for canine osteosarcoma.The Journal of pharmacology and experimental therapeutics · 2025Article
- Spatial Transcriptomics Advances the Use of Canine Patients in Cancer Research: Analysis of Osteosarcoma-Bearing Pet Dogs Enrolled in a Clinical Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- Clinical Utility of Patient-Derived Cell-Based In Vitro Drug Sensitivity Testing for Optimizing Adjuvant Therapy in Dogs with Solid Tumors: A Retrospective Study (2019-2023).Animals : an open access journal from MDPI · 2025Article
- Immunological responses and clinical outcomes in dogs with osteosarcoma receiving standard therapy and a Listeria vaccine expressing HER2.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Large-Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Translational History and Hope of Immunotherapy of Canine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Comparative responses to demethylating therapy in animal models of osteosarcoma.Research square · 2024Article
- Single-cell T-cell receptor repertoire profiling in dogs.Communications biology · 2024Article
- Clinical, pathologic and molecular findings in 2 Rottweiler littermates with appendicular osteosarcoma.Research square · 2024Article
- Effects of neoadjuvant zoledronate and radiation therapy on cell survival, cell cycle distribution, and clinical status in canine osteosarcoma.Frontiers in veterinary science · 2024Article
Corrections and comments
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Authors and funding
44 authors at 20 institutions in 3 countries.
Funding
Abstract
purposeThe 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
methodsA 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.
resultsThere 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.
conclusionsIn 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.