Identifiability and model selection frameworks for models of high-grade glioma response to chemoradiation.

Abstract

We have developed a family of biology-based mathematical models of high-grade glioma (HGG), capturing the key features of tumour growth and response to chemoradiation. We now seek to quantify the accuracy of parameter estimation and determine, when given a virtual patient cohort, which model was used to generate the tumours. In this way, we systematically test both the parameter and model identifiability. Virtual patients are generated from unique growth parameters whose growth dynamics are determined by the model family. We then assessed the ability to recover model parameters and select the model used to generate the tumour. We then evaluated the accuracy of predictions using the selected model at four weeks post-chemoradiation. We observed median parameter errors from 0.04% to 72.96%. Our model selection framework selected the model that was used to generate the data in 82% of the cases. Finally, we predicted the growth of the virtual tumours using the selected model resulting in low error at the voxel-level (concordance correlation coefficient (CCC) ranged from 0.66 to 0.99) and global level (percentage error in total tumour cellularity ranged from -12.35% to 0.07%). These results demonstrate the reliability of our framework to identify the most appropriate model under noisy conditions expected in the clinical setting.This article is part of the theme issue 'Uncertainty quantification for healthcare and biological systems (Part 2)'.