Glioblastoma multiforme treated by the chemotherapeutic agent temozolomide in vivo:: a 4D simulation model of the tumor response

A novel four dimensional, patient specific simulation model of solid tumor response to chemotherapeutic treatment in vivo is presented. The special case of glioblastoma multiforme treated by temozolomide is addressed as a simulation paradigm. The model is based on the patient's imaging, histopathologic and genetic data. For a given drug administration schedule lying within acceptable toxicity boundaries, the concentration of the prodrug and its metabolites within the tumor is calculated as a function of time based on the drug pharamacokinetics. A discretization mesh is superimposed upon the anatomical region of interest and within each geometrical cell of the mesh the most prominent biological "laws" are applied. The biological cell fates are predicted based on the drug pharmacodynamics. The outcome of the simulation is a prediction of the spatiotemporal activity of the entire tumor and is virtual reality visualized. A good qualitative agreement of the model's predictions with clinical experience has strengthened the applicability of the approach. Long term clinical and quantitative adaptation and validation as well as modeling the normal tissue reactions are in progress. The proposed model primarily aims at providing a reliable platform for performing patient individualized in silico experiments as a means of chemotherapeutic treatment optimization.