Abstract
NanOx is a new biophysical model that aims at predicting the biological effect of ions in the context of hadron therapy. It integrates the fully-stochastic nature of ionizing radiation both at micrometric and nanometric scales and also takes into account the production and diffusion of reactive chemical species. In order to further characterize the new framework, we discuss the meaning and relevance of most of the NanOx parameters by evaluating their influence on the linear-quadratic coefficient and on the dose deposited to achieve 10% or 1% of cell survival, or , as a function of LET. We perform a theoretical study in which variations in the input parameters are propagated into the model predictions for HSG, V79 and CHO-K1 cells irradiated by monoenergetic protons and carbon ions. We conclude that, in the current version of NanOx, the modeling of a specific cell line relies on five parameters, which have to be adjusted to several experimental measurements: the average cellular nuclear radius, the linear-quadratic coefficients describing photon irradiations and the values associated with two carbon ions of intermediate and high-LET values. This may have interesting implications toward a clinical application of the new biophysical model.
Highlights
Hadron therapy is becoming an attractive modality for cancer treatment, as the exponential increase in the number of dedicated facilities built over the past decades shows
The latter present some shortcomings that may limit their improvement: in the modified microdosimetric kinetic model, the nanometric scale is disregarded, and the Poissonian distribution relating cell survival to the total number of lethal damages is corrected in a second instance, as it is not adapted for high-LET ions; in the local effect model, the stochastic nature of the dose deposition is not taken into account at the nanoscopic level, and the use of the amorphous track structure results in conceptual incongruities [8,9]
We stress again that in order to assess the effect induced by the variation of one single parameter at a time, we considered two different outcomes calculated by NanOx as a function of LET: on the one hand, the linear coefficient α, which is widely adopted both experimentally and theoretically to quantify the biological effect of ions; on the other, Dx%, the dose deposited to achieve x% of cell survival, which is more relevant to clinicians
Summary
Hadron therapy is becoming an attractive modality for cancer treatment, as the exponential increase in the number of dedicated facilities built over the past decades shows. The favorable depth-dose profile of protons is mostly exploited to eradicate localized tumors situated close to organs at risk, while the high biological effectiveness makes carbon ion beams more adequate than the conventional radiotherapy modalities to treat radioresistant cancers. Such an efficiency in cell killing is quantified through the RBE (relative biological effectiveness), which is a complex function of multiple parameters related to the incident particles, the irradiation conditions and the intrinsic properties of the biological system. NanOx is based on a solid mathematical architecture, comprised of fundamental
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