A Predictive Simulation Chain for DNA Damage and Cell Death Induced By Ionizing Radiation
Loading...
Date
2023
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Proton therapy is an effective form of cancer treatment that uses proton beams in the MeV range to destroy cancer cells. However, the protons' efficiency at killing cells varies as the beam penetrates tissue, thus, their biologically effective range presents a significant challenge in predicting the effects of proton irradiation. In this work, the development of a novel methodology in the determination the biological effect of protons through Monte Carlo (MC) beam transport and DNA damage simulations in combination with mechanistic cellular survival modeling is presented. The simulations show that the DNA damage generation and subsequent cell killing is affected by the evolution of the proton beam as it penetrates tissue without recurring to a definition of relative biological effectiveness (RBE). This also shows that a fixed RBE of 1.1 such as the one used in the clinics today may not be enough to predict the biological effect. Furthermore, the proton killing probability shift with respect to their deposited dose, i.e., the biological penumbrae, is estimated employing this framework. The methodology is also tested in various conditions, i.e., different mechanistic model parametrizations, considering proton beam fragmentation, and accounting for changes related to the cell cycle. Results suggest that this framework can provide insight into the biological effects of proton therapy and improve the accuracy of treatment planning. This study contributes to the field of radiobiology by providing a method to reliably simulate the biological response of living tissues to proton radiation, making us able to potentially answer important questions such as the proton biological range uncertainty, the effects of cell phase upon its survival probability, the contribution of heavier ion fragmentation to the DNA damage, among many others presented in this thesis.
Description
Tesis (Master in Medical Physics)--Pontificia Universidad Católica de Chile, 2023