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A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing Neoadjuvant Therapies
Published on: July 28, 2020
Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model
Michael W Nolan1,2, Tracy L Gieger1,2, Alexander A Karakashian3
11 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
This study found that high-dose GRID radiation therapy did not shrink canine soft tissue sarcomas. However, it showed potential for short-term reduction in certain serum markers, making dogs a viable model for radiotherapy research.
Area of Science:
- Radiation Oncology
- Veterinary Medicine
- Radiobiology
Background:
- Spatially fractionated radiotherapy, like GRID, requires large animal models for human treatment simulation.
- Pet dogs with spontaneous tumors offer a translational model for studying radiotherapy effects.
Purpose of the Study:
- To assess the safety and efficacy of GRID therapy in dogs with soft tissue sarcomas.
- To characterize the biological response to GRID, including serum marker changes.
Main Methods:
- Pilot study involving 6 pet dogs with soft tissue sarcomas treated with 20 Gy or 25 Gy GRID therapy.
- Tumor response and acute toxicity were evaluated over 6 weeks.
- Serum levels of vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were measured at various time points.
Main Results:
- No measurable tumor volume reduction was observed following GRID therapy.
- Grade I skin toxicity occurred in 3 dogs; no significant acute toxicity was noted.
- Trends showed decreased vascular endothelial growth factor and tumor necrosis factor α, with a significant decrease in secretory sphingomyelinase at 48 hours post-25 Gy GRID.
Conclusions:
- GRID therapy at high doses is safe in canine soft tissue sarcomas but does not induce tumor shrinkage.
- GRID therapy may transiently alter serum biomarkers, suggesting its potential as a preclinical model.
- Pet dogs with sarcomas provide a valuable platform for investigating spatially fractionated radiotherapy radiobiology.
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