Graduate Thesis Or Dissertation
 

Application of a Modified Microdosimetric-Kinetic Model to Analyze Cell Killing in Determination of the Optimal Particle for Light Ion Therapy

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  • Ion therapy has long been investigated as a potential modality to improve cancer treatments beyond what is currently feasible with photon irradiations. Ions offer both a physical and biological advantage over photons. The physical advantages are well understood, ions deposit their maximum dose at defined penetration depths, allowing for minimal deleterious effects on healthy tissues and maximal effects within a tumor volume. Biologically, the dense ionization tracks of ions have shown increased cell killing and mutation rates compared to equivalent photon doses. This biological enhancement is qualitatively accepted; however, quantitative assessment has proven difficult. Uncertainties in this biological effect could lead to significant errors in treatment prescription, planning, and execution. It is of pinnacle importance to advance our understanding of the biological response to ions for the further development of ion therapy. Presently 1H and 12C are the only ions utilized for clinical treatments. Historically, these ions have used a passive scattering technique to provide adequate tumor coverage. As a consequence, much of the biological data available for ion therapy is limited to 1H and 12C in a passive scattering system. As ion therapy becomes more common, it is possible that alternative ions will be selectively used for various treatment protocols. The biological responses to these alternative ions have only been sparsely investigated, if at all. Additionally, advancements in accelerator technology and delivery are allowing for systems that employ active scanning. These active methods require the implementation of a small diameter beam as opposed to the laterally spread fields used in passive techniques. It is not known to what degree these changes in beam geometry will have on the biological response of tissues. The purpose of this work is to computationally predict the biological response of various cells to irradiation from different ion species, delivered by a small diameter beam. The ion beams investigated will be 6 mm diameter 1H, 4He, 7Li, 10B, 12C, 14N, 16O, 20Ne beams. For each ion species, beams with an initial kinetic energy, that correspond to maximum dose deposition depths of 5, 10, 15, 20, 25, and 30 cm in water will be analyzed. The ions, beam size, and depths used are in accordance with suggestions from the 2013 joint NCI-DOE Workshop on Ion Beam Therapy, which was formed to discuss the required areas of research needed for the advancement of ion therapy in the United States. A modified microdosimetric kinetic model (MKM) will be used to evaluate biological response. Microdosimetic quantities, such as lineal energy, will be simulated using the PHITS Monte Carlo code and used in the modified MKM. Microscopic quantities, not the more commonly cited linear energy transferred (LET), are more appropriate for characterization of biological responses as they account for the uniqueness of dose deposition in regions the size of human cells and DNA strands, which are the targets of cancer therapy. According to the biological model and parameters used, 10B was found to be the optimal ion for therapy. Proximal to a tumor, 10B exhibited the lowest, or second lowest cell killing percentages for all beam energies investigated. For ions with a Bragg peaks at 50, 250, and 300 mm, 10B produced the lowest cell killing percentages, which were 2.41, 2.93, and 6.52% less than carbon. For ions with Bragg peaks at 100, 150, and 200 mm, 10B and 12C produced the lowest cell killing rates proximal to a tumor and were within ±0.35% of one another. For the lowest energy beams, 7Li has a cell killing percentage within 1% of 10B. At higher energies, fragmentation of 7Li greatly diminishes the usefulness of 7Li for treatments. Distal of the tumor volume, 10B and 12C reach cell survival rates of 90 and 95% at shorter depths than other ions for all but the lowest initial energy beams, these thresholds are achieved within 4 mm from the Bragg peak. If greater cell survival rates were desired, 4He attains 99% cell survival at the shortest distances, for all but the lowest energy beam. Radially away from the ion beam’s central axis, cell killing generally was lowest for ions of greater nuclear charge. However, for ions with charges greater than that of 7Li, radial cell killing rates where similar to one another for the majority of each ions range. As thus, ions with a charge greater than 12C did not demonstrate advantage over treatments with 10B or 12C. Various cell lines were simulated and human fibroblast (NB1RGB) cells were seen to the most sensitive to the lower charged hydrogen and helium ions, while a type of human submanbidular gland (HSG) cell was observed to be the most radiosensitive for irradiaions from ions of greater charge. For all ion types, human kidney (T1) cells were seen to be relatively radiorsistant. Use of ions with greater nuclear charge were seen to minimize variance in survival fractions between the five cell lines.
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  • 2018-05-04 to 2020-06-02

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