Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model.
GRID directs alternating regions of high- and low-dose radiation at tumors. A large animal model mimicking the geometries of human treatments is needed to complement existing rodent systems (eg, microbeam) and clarify the physical and biological attributes of GRID. A pilot study was undertaken in pet dogs with spontaneous soft tissue sarcomas to characterize responses to GRID. Subjects were treated with either 20 Gy (3 dogs) or 25 Gy (3 dogs), delivered using 6 MV X-rays and a commercial GRID collimator. Acute toxicity and tumor responses were assessed 2, 4, and 6 weeks later. Acute Radiation Therapy Oncology Group grade I skin toxicity was observed in 3 of the 6 dogs; none experienced a measurable response, per Response Evaluation Criteria in Solid Tumors. Serum vascular endothelial growth factor, tumor necrosis factor α, and secretory sphingomyelinase were assayed at baseline, 1, 4, 24, and 48 hours after treatment. There was a trend toward platelet-corrected serum vascular endothelial growth factor concentration being lower 1 and 48 hours after GRID than at baseline. There was a significant decrease in secretory sphingomyelinase activity 48 hours after 25 Gy GRID ( P = .03). Serum tumor necrosis factor α was quantified measurable at baseline in 4 of the 6 dogs and decreased in each of those subjects at all post-GRID time points. The new information generated by this study includes the observation that high-dose, single fraction application of GRID does not induce measurable reduction in volume of canine soft tissue sarcomas. In contrast to previously published data, these data suggest that GRID may be associated with at least short-term reduction in serum concentration of vascular endothelial growth factor and serum activity of secretory sphingomyelinase. Because GRID can be applied safely, and these tumors can be subsequently surgically resected as part of routine veterinary care, pet dogs with sarcomas are an appealing model for studying the radiobiologic responses to spatially fractionated radiotherapy.
1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.|2 Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
Michael W
MW
Nolan
1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.|2 Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
Tracy L
TL
Gieger
3 Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA.
Alexander A
AA
Karakashian
3 Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA.
Mariana N
MN
Nikolova-Karakashian
4 Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
Lysa P
LP
Posner
5 Department of Radiation Oncology, Rex Cancer Center, Raleigh, NC, USA.
Donald M
DM
Roback
6 Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA.
Judith N
JN
Rivera
1 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.|6 Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA.|7 Department of Physics and Astronomy, University of North Carolina, Chapel Hill, NC, USA.|8 Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC, USA.
Sha
S
Chang
D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004285:Dogs; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011878:Radiotherapy / Q000379:methods* / Q000592:standards; D012509:Sarcoma / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
ablative; abscopal; canine; endothelial; microenvironment