Linear and Non-Linear Optimal Control Methods to Determine the Best Chemotherapy Schedule for Most Effectively...

Background/Objectives: Cancer is a dynamic and complex disease that remains largely untreated despite major advances in oncology and treatment. In this context, we aimed here to investigate optimal control techniques in the management of tumor growth inhibition, with a particular focus on cancer chemotherapy treatment strategies. Methods: Using both linear autoregressive with exogenous inputs (ARX) and advanced non-linear tumor growth inhibition (TGI) modeling approaches, we investigated various single-agent treatment protocols, including continuous, periodic, and intermittent chemotherapy schedules. By integrating advanced mathematical modeling with optimal control theory and methods, namely the Linear Quadratic Regulator (LQR) and the "pseudo-linear" state-space equivalent representation and suboptimal control of a non-linear dynamic system known as the State-Dependent Riccati Equation (SDRE) approach, this work explores and evaluates successfully, more effective chemotherapy treatment strategies at the computer simulation level, using real preclinical data which increases the expectation to be applied in the clinical practice of oncology. Results: The integration of these methods provides insights into how different drug administration schedules may affect tumor response at the preclinical level. This work uses mathematical modeling to evaluate the efficacy of various periodic and intermittent chemotherapy treatment strategies, with a focus on optimizing drug doses while minimizing the potential side effects of chemotherapy due to the administration of less effective chemotherapeutic doses. Conclusions: The treatment scenarios tested in this study could effectively stop tumor growth or even lead to tumor regression to a negligible or near-zero size. This approach highlights the importance of computational tools for more effective treatment strategies in chemotherapy and offers a promising direction for future research and more efficient clinical applications in oncology as part of a more individualized approach.