The impact of radio-chemotherapy on tumour cells interaction with optimal control and sensitivity analysis

Abstract

Oncologists and applied mathematicians are interested in understanding the dynamics of cancer-immune interactions, mainly due to the unpredictable nature of tumour cell proliferation. In this regard, mathematical modelling offers a promising approach to comprehend this potentially harmful aspect of cancer biology. This paper presents a novel dynamical model that incorporates the interactions between tumour cells, healthy tissue cells, and immune-stimulated cells when subjected to simultaneous chemotherapy and radiotherapy for treatment. We analysed the equilibria and investigated their local stability behaviour. We also study transcritical, saddle–node, and Hopf bifurcations analytically and numerically. We derive the stability and direction conditions for periodic solutions. We identify conditions that lead to chaotic dynamics and rigorously demonstrate the existence of chaos. Furthermore, we formulated an optimal control problem that describes the dynamics of tumour-immune interactions, considering treatments such as radiotherapy and chemotherapy as control parameters. Our goal is to utilize optimal control theory to reduce the cost of radiotherapy and chemotherapy, minimize the harmful effects of medications on the body, and mitigate the burden of cancer cells by maintaining a sufficient population of healthy cells. Cost-effectiveness analysis is employed to identify the most economical strategy for reducing the disease burden. Additionally, we conduct a Latin hypercube sampling-based uncertainty analysis to observe the impact of parameter uncertainties on tumour growth, followed by a sensitivity analysis. Numerical simulations are presented to elucidate how dynamic behaviour of model is influenced by changes in system parameters. The numerical results validate the analytical findings and illustrate that a multi-therapeutic treatment plan can effectively reduce tumour burden within a given time frame of therapeutic intervention.