Tumour cells are less responsive to radiotherapy in low oxygen environments. Oxygen availability depends on the structure of the supplying microvessel network. Previous studies have used mathematical modelling to predict tumour response to radiotherapy for different network morphologies, but have used a range of simplified and artificial networks. The goal of this study was to simulate radiotherapy in a real tumour microvessel network and compare the predicted response to those from typical artificial networks. Three-dimensional images of well vascularized tumours were obtained by multiphoton imaging of MC38 derived tumours in mice. A hybrid multiscale model, that couples a cellular automaton model of tumour growth with a model for oxygen transport from blood vessels, was used to predict the viable fraction of cells following one week of simulated radiotherapy. This was done in both the real network and a collection of artificial networks.
We predicted that there was little difference in cell viable fraction when three-dimensional network representations of biological or artificial vessel networks were employed. Different two-dimensional representations were shown to either over- or under-estimate viable fractions relative to the three-dimensional cases, with predictions based on point-wise descriptions shown to have greater sensitivity to vessel network morphology. We showed that real and artificial network descriptions and assumptions of spatially uniform oxygen distributions lead to similar radiotherapy response predictions in small tissue volumes. This suggests that either a more detailed description of oxygen transport in the microvasculature is required or that the oxygen enhancement ratio used in the well known linear-quadratic radiotherapy response model is relatively insensitive to microvascular structure. Simulations were performed using the open source Microvessel Chaste library, with further details here: https://jmsgrogan.github.io/MicrovesselChaste/.
Keywords: Multiscale modelling, oxygen transport, vascular tumour growth, radiotherapy.
Web: https://jmsgrogan.github.io/MicrovesselChaste/ (open source after the study).