Jelveh S.,Ontario Cancer Institute |
Kaspler P.,Ontario Cancer Institute |
Bhogal N.,Radiation Medicine Program |
Mahmood J.,Ontario Cancer Institute |
And 8 more authors.
International Journal of Radiation Biology | Year: 2013
Purpose: Radioprotection and mitigation effects of the antioxidants, Eukarion (EUK)-207, curcumin, and the curcumin analogs D12 and D68, on radiation-induced DNA damage or lipid peroxidation in murine skin were investigated. These antioxidants were studied because they have been previously reported to protect or mitigate against radiation-induced skin reactions. Methods: DNA damage was assessed using two different assays. A cytokinesis-blocked micronucleus (MN) assay was performed on primary skin fibroblasts harvested from the skin of C3H/HeJ male mice 1 day, 1 week and 4 weeks after 5 Gy or 10 Gy irradiation. Local skin or whole body irradiation (100 kVp X-rays or caesium (Cs)-137 γ-rays respectively) was performed. DNA damage was further quantified in keratinocytes by immunofluorescence staining of γ-histone 2AX (γ-H2AX) foci in formalin-fixed skin harvested 1 hour or 1 day post-whole body irradiation. Radiation-induced lipid peroxidation in the skin was investigated at the same time points as the MN assay by measuring malondialdehyde (MDA) with a Thiobarbituric acid reactive substances (TBARS) assay. Results: None of the studied antioxidants showed significant mitigation of skin DNA damage induced by local irradiation. However, when EUK-207 or curcumin were delivered before irradiation they provided some protection against DNA damage. In contrast, all the studied antioxidants demonstrated significant mitigating and protecting effects on radiation-induced lipid peroxidation at one or more of the three time points after local skin irradiation. Conclusion: Our results show no evidence for mitigation of DNA damage by the antioxidants studied in contrast to mitigation of lipid peroxidation. Since these agents have been reported to mitigate skin reactions following irradiation, the data suggest that changes in lipid peroxidation levels in skin may reflect developing skin reactions better than residual post-irradiation DNA damage in skin cells. Further direct comparison studies are required to confirm this inference from the data. © 2013 Informa UK, Ltd.
Van Prooijen M.,Radiation Medicine Program
Journal of applied clinical medical physics / American College of Medical Physics | Year: 2010
The impact of the treatment couch on a radiotherapy plan is rarely fully assessed during the treatment planning process. Incorporating a couch model into the treatment planning system (TPS) enables the planner to avoid or dosimetrically evaluate beam-couch intersections. In this work, we demonstrate how existing TPS tools can be used to establish this capability and assess the accuracy and effectiveness of the system through dose measurements and planning studies. Such capabilities may be particularly relevant for the planning of arc therapies.Treatment couch top models were introduced into a TPS by fusing their CT image sets with the patient CT dataset. Regions of interest characterizing couch elements were then imported and assigned appropriate densities in the TPS. Measurements in phantom agreed with TPS calculations to within 2% dose and 1 degrees gantry rotation. To clinically validate the model, a retrospective study was performed on patient plans that posed difficulties in beam-couch intersection during setup. Beam-couch intersection caused up to a 3% reduction in PTV coverage, defined by the 95% of the prescribed dose, and up to a 1% reduction in mean CTV coverage. Dose compensation strategies for IMRT treatments with beams passing through couch elements were investigated using a four-field IMRT plan with three beams passing through couch elements. In this study, ignoring couch effects resulted in point dose reductions of 8 +/- 3%.A methodology for incorporating detailed couch characteristics into a TPS has been established and explored. The method can be used to predict beam-couch intersections during planning, potentially eliminating the need for pretreatment appointments. Alternatively, if a beam-couch intersection problem arises, the impact of the couch can be assessed on a case-by-case basis and a clinical decision made based on full dosimetric information.