Lattice Radiation Therapy (LRT) for macroscopic soft tissue sarcomas in dogs
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Soft tissue sarcomas (STS) are common tumors in dogs with many cross-species similarities existing between canine and human STS including pathologic and molecular features. Spatially fractionated radiotherapy, utilizing an intensity-modulated technique known as Lattice Radiation Therapy (LRT), enables the safe delivery of hypofractionated, dose-escalated treatment to large tumors and has been associated with the induction of immune responses. Seven dogs were prospectively randomized to receive either palliative radiation (n=3, 20 Gy in 5 daily fractions) or LRT (n=4, 20 Gy to 95% of the PTV with a simultaneous integrated boost of 66.7 Gy delivered every other day). Tumor biopsy was performed before the first dose of radiation therapy, and at the end of the final dose of radiation. The peripheral blood mononuclear cell was collected before the first dose of radiation therapy, and at the end of the final dose of radiation as well as 2-weeks post completion of treatment. Analysis of immune response within the tumor microenvironment will be analyzed using the Nanostring Canine IO panel. An overall response rate of 50% was noted in the LRT group. While no local tumor progression was observed in the LRT group, all 3 (100%) patients in the palliative RT had evidence of local tumor progression at 21-, 35- and 150-days post radiation. Median overall survival was 436 days in patients receiving LRT versus 194 days in the pRT cohort. These results suggest that LRT can be safely administered to canine patients with large macroscopic sarcomas and may confer improved local control and survival outcomes. Findings in gene expression in patients receiving LRT can be potentially correlated with important signaling pathways. Collectively these findings suggest dogs with naturally occurring tumors can serve as valuable translational models to bridge current gaps in our understanding and help accelerate clinical translation of Lattice approaches.
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M.S.