Positive Impulsive Control of Tumor Therapy - A Cyber-Medical Approach

Chemotherapy optimization based on mathematical models is a promising direction of personalized medicine. Personalizing, thus optimizing treatments, may have multiple advantages, from fewer side effects to lower costs. However, personalization is a complicated process in practice. We discuss a mathematical model of tumor growth and therapy optimization algorithms that can be used to personalize therapies. The therapy generation is based on the concept of keeping the drug level over a specified value. A mixed-effect model is used for parametric identification, and the doses are calculated using a two-compartment model for drug pharmacokinetics, and a nonlinear pharmacodynamics and tumor dynamics model. We propose personalized therapy generation algorithms for having a maximal effect and minimal effective doses. We handle inter-and intra-patient variability for the minimal effective dose therapy. Results from mouse experiments for the personalized therapy are discussed and the algorithms are compared to a generic protocol based on overall survival. The experimental results show that the introduced algorithms significantly increased the overall survival of the mice, demonstrating that by control engineering methods an efficient modality of cancer therapy may be possible.