Model-based angiogenic inhibition of tumor growth using modern robust control method

Abstract

Cancer is one of the most destructive and lethal illnesses of the modern civilization. In the last decades, clinical cancer research shifted towards molecular targeted therapies which have limited side effects in comparison to conventional chemotherapy and radiation therapy. Anti-angiogenic therapy is one of the most promising cancer treatment methods. The dynamical model for tumor growth under angiogenic stimulator/inhibitor control was posed by Hahnfeldt et al. (1999), and it was investigated and partly modified many times. In this paper, a modified version of the originally published model is used in order to describe a continuous infusion therapy. To generalize individualized therapies a robust control method is proposed using H ∞ methodology. Uncertainty weighting functions are determined based on the real pathophysiological case and simulations are performed on different tumor volumes to demonstrate the robustness of the proposed method.

Potential Benefits of Discrete-Time Controller-based Treatments over Protocol-based Cancer Therapies

“…We investigated a well-known tumor growth model under antiangiogenic therapy [6] and designed several continuous-time controllers like an LQ control method and state observer [7][8][9], flat control [10][11][12], modern robust control method [13][14][15], feedback linearization method [16] and adaptive fuzzy techniques [17]. However, with the current scientific knowledge, there is no medical device which can handle continuous infusion cancer therapy [18]; hence we designed a discretetime control herein.…”

Critically Safe General Anaesthesia in Closed Loop: Availability and Challenges

“…TCI has relevance at other biomedical control fields as well. For example, diabetes control, where the control target is to hold the patient's blood glucose level in a narrow range through insulin infusion or anti-angiogenic targeted cancer control, where the target is to decrease the volume of cancer with anti-angiogenic drug (Szalay et al, (2014), Kovacs et al, (2014)). Whereas TCI presents an open-loop dosing strategy (the past output does not influence the future input), current research deals with the model based adaptive closed-loop administration of anaesthetics.…”

Physiological modeling and control at Obuda University

“…Our previous researches focused on development of control algorithms for antiangiogenic tumor therapy [5], [19] for the tumor growth model of [20]. However, based on our investigated inhibitors it turned out to identify a new tumor growth model.…”