New insights into prognostic and therapeutic aspects of canine appendicular osteosarcoma

The present thesis investigates prognostic and therapeutic aspects of canine appendicular osteosarcoma, with particular focus on prognostic factors and innovative immunomodulatory strategies. Canine osteosarcoma is the most common primary bone tumor in dogs and is characterized by aggressive local behavior and high metastatic potential. Despite multimodal treatment, typically consisting of limb amputation followed by adjuvant chemotherapy, prognosis remains poor, highlighting the need for improved prognostic tools and novel therapeutic approaches. Due to its biological similarities to human osteosarcoma, it also represents a valuable model in comparative oncology. The thesis provides a critical review of currently described prognostic factors, emphasizing the inconsistency of evidence, particularly regarding histopathological parameters, and the need for reliable biomarkers. Serum lactate dehydrogenase (LDH), a marker of tumor metabolic activity, was prospectively evaluated as a prognostic biomarker in dogs with appendicular osteosarcoma. Elevated LDH levels were highly sensitive for detecting metastases at diagnosis and were significantly associated with shorter survival in dogs receiving standardized multimodal treatment, supporting its role as an accessible and cost-effective prognostic indicator. The prognostic relevance of tumor grade and histologic subtype was retrospectively assessed in a large, uniformly treated population. Neither parameter was significantly associated with stage at diagnosis or overall survival, possibly due to histologic heterogeneity and grading variability. These findings support the integration of biochemical markers, such as ALP and LDH, and therapeutic variables, particularly immunotherapy, into prognostic assessment. Finally, the potential role of postbiotics as immunomodulatory adjuvants was explored in a prospective single-arm study. Postbiotic supplementation was well tolerated and showed preliminary signals of survival benefit, warranting further investigation.