arXiv 2410.160052024-10q-bio.QMnlin.AOphysics.bio-ph

前列腺癌的适应性高级严格控制：从终末期疾病到慢性病的路径

Adaptive High-Level Tight Control of Prostate Cancer: A Path from From Terminal Disease to Chronic Condition

Scripps and Pitzer Colleges, Claremont Colleges Consortium（斯克里普斯学院和皮策学院，克莱蒙特学院联盟）；Princeton University（普林斯顿大学）；Scripps College（斯克里普斯学院）；Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine（约翰霍普金斯医学院布雷泌尿研究所癌症生态学中心）；Moffitt Cancer Center（莫菲特癌症中心）；Johns Hopkins University（约翰霍普金斯大学）；Bloomberg School of Public Health, Johns Hopkins University（约翰霍普金斯大学布隆伯格公共卫生学院）；Department of Chemical and Biomolecular Engineering, John Hopkins University（约翰霍普金斯大学生物化学工程系）

Trung V. Phan, Shengkai Li, Luciana Sarabia, Caroline N. Cappetto, Benjamin Howe, Sarah R. Amend, Kenneth J. Pienta, Joel S. Brown, Robert A. Gatenby, Constanti… 展开作者

Trung V. Phan, Shengkai Li, Luciana Sarabia, Caroline N. Cappetto, Benjamin Howe, Sarah R. Amend, Kenneth J. Pienta, Joel S. Brown, Robert A. Gatenby, Constantine Frangakis, Robert H. Austin, Ioannis G. Keverkidis

DOI：: 10.1016/j.physa.2026.131836

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AI总结：

研究探索临床肿瘤学家用Stackelberg博弈论框架延长转移性前列腺癌生存期，通过贝叶斯优化确定阿比特龙最佳化疗策略，经精确药物递送优化可延长癌症抑制期，高级严格控制治疗或能改善激素敏感性癌症化疗。

摘要：

转移性前列腺癌是全球癌症相关发病和死亡的主要原因之一，死亡率高且预后差。本文探索临床肿瘤学家如何应用Stackelberg博弈论框架延长转移性前列腺癌患者生存期甚至使其转为慢性病。利用贝叶斯优化方法确定单药（阿比特龙）的最佳适应性化疗策略以最大化患者出现症状前的时间。研究表明，精确的药物递送适应性优化可显著延长癌症抑制期，多数患者的转移性前列腺癌可能从终末期疾病转为慢性病，临床和分析证据支持此结论。通过计算和理论分析证明，实施高级严格控制（HLTC）治疗，即给药和停药的触发信号（生物标志物水平）都高且接近，通常能产生最佳结果，这可为改善其他激素敏感性癌症的当前适应性化疗提供有价值的指导。

英文摘要：

Metastatic prostate cancer is one of the leading causes of cancer-related morbidity and mortality worldwide. It is characterized by a high mortality rate and a poor prognosis. In this work, we explore how a clinical oncologist can apply a Stackelberg game-theoretic framework to prolong metastatic prostate cancer survival, or even make it chronic in duration. We utilize a Bayesian optimization approach to identify the optimal adaptive chemotherapeutic treatment policy for a single drug (Abiraterone) to maximize the time before the patient begins to show symptoms. We show that, with precise adaptive optimization of drug delivery, it is possible to significantly prolong the cancer suppression period, potentially converting metastatic prostate cancer from a terminal disease to a chronic disease for most patients, as supported by clinical and analytical evidence. We suggest that clinicians might explore the possibility of implementing a high-level tight control (HLTC) treatment, in which the trigger signals (i.e. biomarker levels) for drug administration and cessation are both high and close together, typically yield the best outcomes, as demonstrated through both computation and theoretical analysis. This simple insight could serve as a valuable guide for improving current adaptive chemotherapy treatments in other hormone-sensitive cancers.

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