title: Nonlinear system identification for prostate cancer and optimality of intermittent androgen suppression therapy.
abstract: These days prostate cancer is one of the most common types of malignant neoplasm in men. Androgen ablation therapy (hormone therapy) has been shown to be effective for advanced prostate cancer. However, continuous hormone therapy often causes recurrence. This results from the progression of androgen-dependent cancer cells to androgen-independent cancer cells during the continuous hormone therapy. One possible method to prevent the progression to the androgen-independent state is intermittent androgen suppression (IAS) therapy, which ceases dosing intermittently. In this paper, we propose two methods to estimate the dynamics of prostate cancer, and investigate the IAS therapy from the viewpoint of optimality. The two methods that we propose for dynamics estimation are a variational Bayesian method for a piecewise affine (PWA) system and a Gaussian process regression method. We apply the proposed methods to real clinical data and compare their predictive performances. Then, using the estimated dynamics of prostate cancer, we observe how prostate cancer behaves for various dosing schedules. It can be seen that the conventional IAS therapy is a way of imposing high cost for dosing while keeping the prostate cancer in a safe state. We would like to dedicate this paper to the memory of Professor Luigi M. Ricciardi.
authors: Department of Mathematical Informatics, Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors: Taiji
authors: T
authors: Suzuki
authors: Kazuyuki
authors: K
authors: Aihara
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage*; D001499:Bayes Theorem; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy; D017711:Nonlinear Dynamics; D016011:Normal Distribution; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen
keywords: Gaussian process; Hormone therapy; Intermittent androgen suppression; Piecewise affine system; Prostate cancer; System identification