Simulations on the efficacy of radiotherapy with different time schemes of antiangiogenic therapy

Abstract

The combination of radiotherapy and antiangiogenic agents has been suggested to be potent in tumor growth control compared to the application of antiangiogenic therapy or radiotherapy alone. Since radiotherapy is highly dependent on the oxygen level of the tumor area, antiangiogenic agents are utilized for the reoxygenation of tumor vasculature. We present a mathematical framework to investigate the efficacy of radiotherapy combined with antiangiogenic treatment. The framework consists of tumor cells, vasculature, and oxygenation levels evolving with time to mimic a tumor microenvironment. Non-linear partial differential equations (PDEs) are employed to simulate each component of the framework. Different treatment schemes are investigated to see the changes in tumor growth and oxygenation. To test combination schedules, radiation monotherapy, neoadjuvant, adjuvant, and concurrent cases are simulated. The efficiency of each therapy scheme on tumor growth control, the changes in tumor cell density, and oxygen levels shared by tumor cells are represented. The simulation results indicate that the application of radiotherapy after antiangiogenic treatment is more efficient in tumor growth control compared to other therapy schemes. The present study gives an insight into the possible interaction and timing of the combination of radiotherapy and antiangiogenic drug treatment.

Dynamics of a diffusive model for cancer stem cells with time delay in microRNA-differentiated cancer cell interactions and radiotherapy effects

“…Introducing R in the first equation of system (1), we obtain the following system: where is the cancer stem cells death rate by radiation therapy 66 . In linear quadratic model, R ( t ) can be defined as 67 , 68 : where and are the sensitivity parameters. corresponds to the cell that can not repair themselves after one radiation hit (important for hight LET radiation) and corresponds to cell that stop dividing after more then one radiation hit, but can repair the damage caused by radiation (important for low LET radiation), is the dose-rate at time t, is the repair rate constant defined as and is half-time for the repair of radiation-induced DNA damage.…”