Outcomes of Spatially Fractionated Radiotherapy (GRID) for Bulky Soft Tissue Sarcomas in a Large Animal Model
| Autor: | Lysa P. Posner, Mariana Nikolova-Karakashian, Alexander A. Karakashian, Sha Chang, Michael W. Nolan, Donald M. Roback, Tracy L. Gieger, Judith N. Rivera |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty medicine.medical_treatment canine Pilot Projects abscopal 030218 nuclear medicine & medical imaging 03 medical and health sciences chemistry.chemical_compound Dogs 0302 clinical medicine endothelial medicine Animals Humans Radiotherapy business.industry Dose fractionation Soft tissue Sarcoma Articles medicine.disease microenvironment Combined Modality Therapy Acute toxicity Vascular endothelial growth factor Radiation therapy Disease Models Animal Oncology chemistry Response Evaluation Criteria in Solid Tumors 030220 oncology & carcinogenesis Female Tumor necrosis factor alpha Dose Fractionation Radiation business ablative |
| Zdroj: | Technology in Cancer Research & Treatment |
| ISSN: | 1533-0338 1533-0346 |
| DOI: | 10.1177/1533034617690980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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