The model assumes that a tumour is comprised of many small subsets (‘tumourlets’) that mathematically are considered homogeneous. That is, the variance inside a tumourlet was not considered.
The tumourlet might be identified with a given voxel at the treatment planning phase, based on pre-RT PET images. Here, each tumourlet was considered to be independent from each other and have a variable size over the course of therapy, with a constant number of tumourlets in a tumour. The initial number of cells in a tumourlet generally decreases during RT with volume shrinkage, although the volume might even increase if the treatment is not sufficient to counteract tumour growth. This is therefore not, strictly speaking, a ‘voxel’ simulation, except in the sense that a tumourlet could be identified with a given voxel at the treatment planning phase.
For purposes of modelling, we assume that each tumourlet has a constant blood (oxygen and nutrient) supply over a course of RT. This simplifies the model, and allows us to introduce the fundamental idea of the model, which is that every tumourlet has an inherent blood supply available and therefore, an inherent proliferative cell capacity. It seems likely there is some variation in blood flow during RT, the impact of variations in blood flow in our simulations (reported below) showed that this has only a modest impact. Given that the tumour vasculature (especially larger vessels) is relatively radioresistant and the damage to vascular endothelial cells in conventional RT is manifested in a relatively late phase of RT, the change of blood supply during RT might not be extensive (Park et al 2012 (link)). However, this would not be true for acute (or transient) hypoxia, in which the blood supply changes over a short period of time. It would not be difficult to include temporal changes in blood supply in the model. However, initially we focus on effects from non-transient (diffusion limited) hypoxia in this work.
The tumourlet might be identified with a given voxel at the treatment planning phase, based on pre-RT PET images. Here, each tumourlet was considered to be independent from each other and have a variable size over the course of therapy, with a constant number of tumourlets in a tumour. The initial number of cells in a tumourlet generally decreases during RT with volume shrinkage, although the volume might even increase if the treatment is not sufficient to counteract tumour growth. This is therefore not, strictly speaking, a ‘voxel’ simulation, except in the sense that a tumourlet could be identified with a given voxel at the treatment planning phase.
For purposes of modelling, we assume that each tumourlet has a constant blood (oxygen and nutrient) supply over a course of RT. This simplifies the model, and allows us to introduce the fundamental idea of the model, which is that every tumourlet has an inherent blood supply available and therefore, an inherent proliferative cell capacity. It seems likely there is some variation in blood flow during RT, the impact of variations in blood flow in our simulations (reported below) showed that this has only a modest impact. Given that the tumour vasculature (especially larger vessels) is relatively radioresistant and the damage to vascular endothelial cells in conventional RT is manifested in a relatively late phase of RT, the change of blood supply during RT might not be extensive (Park et al 2012 (link)). However, this would not be true for acute (or transient) hypoxia, in which the blood supply changes over a short period of time. It would not be difficult to include temporal changes in blood supply in the model. However, initially we focus on effects from non-transient (diffusion limited) hypoxia in this work.
