Lattice Radiation Therapy Delays Progression and Extends Survival for Dogs with Macroscopic Soft Tissue Sarcoma.

Abstract

Soft tissue sarcomas are common tumors in dogs with many pathologic and molecular cross-species similarities existing between dogs and humans. Spatially fractionated radiotherapy, utilizing an intensity-modulated technique known as Lattice radiation therapy, enables the safe delivery of hypofractionated, dose-escalated treatment to large tumors and has been associated with increased response rates and the induction of immune responses. Seven dogs were prospectively randomized to receive either palliative (n = 3, 20 Gy in 5 consecutive daily fractions) or lattice (n = 4, 20 Gy to 95% of the PTV with a simultaneous integrated boost of 66.7 Gy delivered every other day) radiation therapy. Tumor biopsies were performed before the first dose of radiation, and at the end of the final dose of radiation. Peripheral blood mononuclear cells were collected before the first dose of radiation, and at the end of the final dose of radiation, as well as 2 weeks after completion of treatment. Analysis of immune response within the tumor microenvironment was analyzed using the Nanostring Canine IO panel. An overall response rate of 50% was noted in the Lattice group. While no local tumor progression was observed in the lattice group, all 3 (100%) dogs in the palliative radiation cohort had evidence of local tumor progression at 21, 35 and 150 days postirradiation. Median overall survival was 436 days in dogs receiving lattice radiation therapy compared with 194 days in the palliative cohort. These results suggest that lattice radiation therapy can be safely administered to dogs with large macroscopic sarcomas and may confer improved local control and survival outcomes compared with conventional palliative radiotherapy. These findings also suggest that dogs with naturally occurring tumors can serve as valuable translational models to bridge current gaps in our understanding and help accelerate clinical translation of spatial fractionation approaches.