Combined Stochastic Models for the Evaluation of Cancer Progression and Patient Trajectories

Abstract

Cancer is a major burden of disease around the globe and one of the leading causes of premature death. The key to improve patient outcomes in modern clinical cancer research is to gain insights into dynamics underlying cancer evolution in order to facilitate the search for effective therapies. However, most cancer data analysis tools are designed for controlled trials and cannot leverage routine clinical data, which are available in far greater quantities. In addition, many cancer models focus on single disease processes in isolation, disregarding interaction This work proposes a unified stochastic modelling framework for cancer progression that combines (stochastic) processes for tumour growth, metastatic seeding, and patient survival to provide a comprehensive understanding of cancer progression. In addition, our models aim to use non-equidistantly sampled data collected in clinical routine to analyse the whole patient trajectory over the course of the disease. The model formulation features closed-form expressions of the likelihood functions for parameter inference from clinical data. The efficacy of our model approach is demonstrated through a simulation study involving four exemplary models, which utilise both analytic and numerical likelihoods. The results of the simulation studies demonstrate the accuracy and computational efficiency of the analytic likelihood formulations. We found that estimation can retrieve the correct model parameters and reveal the underlying data dynamics, and that this modelling framework is flexible in choosing the precise parameterisation. This work can serve as a foundation for the development of combined stochastic models for guiding personalized therapies in oncology.