Evaluating peripheral leukocyte ratios to predict disease status and outcome in dogs with appendicular osteosarcoma
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This study investigates the prognostic significance of peripheral leukocyte ratios and myeloid-derived suppressor cells (MDSCs) in dogs with appendicular osteosarcoma, a highly immunogenic and aggressive cancer. Osteosarcoma develops similarly in humans and dogs and is associated with high rates of tumor progression and metastasis. Immune cell ratios, such as the lymphocyte-monocyte ratio (LMR), neutrophillymphocyte ratio (NLR), and eosinophil-lymphocyte ratio (ELR) have been explored in human oncology as potential biomarkers for cancer prognosis, though these have been less studied in veterinary oncology. MDSCs, immature myeloid cells involved in immune suppression and tumor progression, accumulate in both the peripheral circulation and tumor microenvironment in osteosarcoma patients and may correlate with disease stage. This study aimed to assess the relationship between leukocyte ratios and clinical outcomes in dogs treated with amputation and carboplatin chemotherapy. A retrospective study was conducted evaluating 136 dogs diagnosed with appendicular osteosarcoma from 2016 to 2022 at two veterinary institutions. The study analyzed medical records to examine the prognostic significance of leukocyte ratios (LMR, NLR, ELR), absolute monocyte count, and alkaline phosphatase (ALP) levels in relation to progression-free interval (PFI) and overall survival time (OST). Survival analysis was performed, and receiver operating characteristic (ROC) curves were used to identify cutoff values for these biomarkers. Additionally, a prospective cohort of dogs diagnosed between October 2022 and December 2024 was monitored for trends in MDSC levels, monocyte counts, LMR, and ALP during treatment. The median age of dogs at diagnosis was 8 years, and the most common tumor locations were the distal radius and proximal humerus. Elevated ALP levels were significantly associated with shorter PFI and OST. Proximal humerus tumors were associated with worse survival outcomes. Lymphocyte and monocyte counts did not show prognostic significance, but the LMR at diagnosis correlated with both PFI and OST. Dogs with an LMR below 2.81 had significantly shorter PFI (127.5 days vs. 190 days, p = 0.0003) and OST (198 days vs. 295 days, p = 0.0011) compared to those with higher LMR values. The NLR also correlated with PFI, with an NLR greater than 2.99 associated with shorter progression-free survival. In contrast, the ELR did not provide significant prognostic differentiation. Changes in LMR and NLR during treatment suggested their potential as biomarkers for monitoring disease status, especially in relation to metastatic disease. In the prospective cohort, three dogs were monitored for trends in monocyte count, LMR, and MDSC levels during chemotherapy. There was an interesting but inconsistent correlation between LMR and MDSC at various stages of treatment, but no consistent relationship observed. The two dogs in this cohort that developed metastatic disease had a higher relative population of polymorphonuclear MDSCs (pMDSCs) at diagnosis compared to the dog that was 15-months disease free, who had a higher relative population of circulating mononuclear MDSCs (mMDSCs). Further studies are warranted to evaluate the relationship between absolute MDSCs and LMR, as well as the relative circulating levels of pMDSCs and mMDSCs for their influence on prognosis and disease burden. This study highlights the prognostic value of peripheral leukocyte ratios, especially LMR and NLR, in dogs with appendicular osteosarcoma. These biomarkers were associated with disease status and may provide a non-invasive, cost-effective means of assessing prognosis. Further research is needed to refine their clinical applicability and to better understand the role of MDSCs as potential biomarkers for osteosarcoma progression and treatment response.
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M.S.