| Abstract: |
This paper investigates the problem of personalized chemotherapy scheduling using a system-modeling approach based on a nonlinear impulsive control technique. In particular, this work deals with the so-called Norton-Simon-Massagué (NSM) model, a minimal biologically grounded model for controlled tumor growth, which has been accepted in clinical oncology for breast cancer treatment. In this paper, we continue this line of research, to advance the concept of closed-loop control a step further towards widespread clinical use. In the present work, the problem of chemotherapy drug scheduling is approached using an impulsive control strategy combined with a state-space observer. The technical challenges of the nonlinearity of the controlled system and the impulsive nature of control input are handled via the utilization of a novel mapping that transforms the control problem into a “simplified” linear discrete-time control problem. Theoretical guarantees regarding the sign and invertibility of the proposed transformation are demonstrated. Then, an observer-based state feedback controller is proposed for chemotherapy drug scheduling as a proof-of-concept control strategy. Simulation results showing the performance of the designed closed-loop controlled chemotherapy schedules in reducing and eradicating tumor volume are provided using model's parameters derived using real tumor data and Doxirubicin drug. Copyright © 2023 The Authors. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
