System identification and parameter estimation in mathematical medicine: examples demonstrated for prostate cancer

Hirata, Yoshito; Morino, Kazuhide; Suzuki, Taiji; Guo, Qian; Fukuhara, Hiroshi; Aihara, Kazuyuki

doi:10.1007/s40484-016-0059-0

Cited by 3 publications

(1 citation statement)

References 30 publications

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“…This makes sense because existing mathematical models often contain a large number of parameters, so having more data gives a better chance of estimating the parameters. A study of model identification methods by Hirata et al [86] shows that 1.5 cycles, where a cycle refers to an onand off-treatment period in IAS, of data is the minimum requirement for model identification in most cases. Yet in clinical settings, a model should be useful even when a limited amount of information is available; however, this is often not the case.…”

Section: Real-time Estimabilitymentioning

confidence: 99%

Review: Mathematical Modeling of Prostate Cancer and Clinical Application

et al. 2020

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We review and synthesize key findings and limitations of mathematical models for prostate cancer, both from theoretical work and data-validated approaches, especially concerning clinical applications. Our focus is on models of prostate cancer dynamics under treatment, particularly with a view toward optimizing hormone-based treatment schedules and estimating the onset of treatment resistance under various assumptions. Population models suggest that intermittent or adaptive therapy is more beneficial to delay cancer relapse as compared to the standard continuous therapy if treatment resistance comes at a competitive cost for cancer cells. Another consensus among existing work is that the standard biomarker for cancer growth, prostate-specific antigen, may not always correlate well with cancer progression. Instead, its doubling rate appears to be a better indicator of tumor growth. Much of the existing work utilizes simple ordinary differential equations due to difficulty in collecting spatial data and due to the early success of using prostate-specific antigen in mathematical modeling. However, a shift toward more complex and realistic models is taking place, which leaves many of the theoretical and mathematical questions unexplored. Furthermore, as adaptive therapy displays better potential than existing treatment protocols, an increasing number of studies incorporate this treatment into modeling efforts. Although existing modeling work has explored and yielded useful insights on the treatment of prostate cancer, the road to clinical application is still elusive. Among the pertinent issues needed to be addressed to bridge the gap from modeling work to clinical application are (1) real-time data validation and model identification, (2) sensitivity analysis and uncertainty quantification for model prediction, and (3) optimal treatment/schedule while considering drug properties, interactions, and toxicity. To address these issues, we suggest in-depth studies on various aspects of the parameters in dynamical models such as the evolution of parameters over time. We hope this review will assist future attempts at studying prostate cancer.Prostate cancer (PCa) is the leading cause of cancer in US men (behind non-melanoma skin cancers), as well as the second leading cause of cancer-related mortality in men. The American Cancer Society estimates that in 2020, 191,930 Americans will be diagnosed with prostate cancer, with approximately 21.5% of all new cancer cases in men. The average five-year survival rate for all cases of prostate cancer is about 99%, which is a 31% point higher than in the 1970s [1]. However, once cancer metastasizes, the five-year survival rate drops to 30%, an increase of 10 percentage-point compared to the 1970s [2]. While the incidence of prostate cancer in the US is decreasing (see Figure 1), one possible cause is doctors' discouragement of early PCa diagnosis due to the fear of overtreating cancer. Globally, the incidence of prostate cancer is increasing, especially among developing nations [3].

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Section: Real-time Estimabilitymentioning

confidence: 99%