Canine appendicular osteosarcoma (OSCA) is an aggressive malignancy accounting for 85% of all canine bone tumors with a high metastatic rate and predilection for dogs of a larger stature. Standard of care is amputation followed by chemotherapy, definitive or palliative radiotherapy (RT) with or without chemotherapy, or limb-preserving surgery often followed by chemotherapy. Limb-salvage surgery is possible for smaller tumors located in specific anatomic locations (i.e., distal radius), but reconstruction via allografts or prosthetics are expensive and require a high degree of specialization, and dogs suffer a high-risk of infection, pathologic fracture, and distant metastasis. Non-surgical treatment options that extend the use of limbs, maintain excellent quality of life, delay progression of metastasis, and increase overall survival are needed.

We hypothesize that Spatially Fractionated Radiotherapy (SFRT) is an effective non-surgical treatment option for dogs with OSCA. Specific Aim 1 elucidates the radiobiological behavior of OSCA cells when subjected to SFRT +/- chemotherapy. This objective determines if SFRT dose regimens should be modified according to OSCA phenotypes. Specific Aim 2 explores the feasibility of high-precision SFRT treatments tailored for OSCAs in dogs when using standard radiation equipment. This objective assesses the feasibility of patient-specific SFRT deliveries for dogs that improve tumor control while minimizing toxicity. Specific Aim 3 examines the concept of modulating the spatial and temporal radiation dose in fractionated deliveries. This objective assesses whether there is a synergistic effect from the different mechanisms of cell killing from SFRT (cell signaling, inducing distant cell death) and conventional RT (local DNA damage).