Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas
Computational design of improved standardized chemotherapy protocols for grade II oligodendrogliomas
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II 级少突胶质细胞瘤标准化化疗方案改进的计算设计
DOI：
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
J. Sepúlveda
中科院分区：
文献类型：
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作者：
V. Pérez;L. E. Ayala;J. Belmonte;P. Schucht;M. Murek;A. Raabe;J. Sepúlveda
将数学模型用于癌症治疗的个人化，并提出潜在临床影响的假说，是数学与肿瘤学之间的一个新兴课题。在这里，我们提出了一个描述低级别(WHO II级)少突胶质瘤(LGO)对替莫唑胺(TMZ)反应的数学模型。该模型描述了11名接受TMZ治疗的LGO患者的肿瘤对TMZ反应的纵向体积动力学。在找到患者特定的参数后，对这些患者的“硅胶双胞胎”进行了不同的治疗策略的计算试验。连续周期之间休息时间大于标准的化疗方案与标准的28天周期相比，具有相同或更好的长期疗效。这一结果在一项包括2000名患者的大型虚拟临床试验中得到了证实。这些长周期方案还将降低毒性并推迟耐药性的出现。在这些结果的基础上，由每月给予5个诱导TMZ周期加上每3个月给予12个维持周期组成的组合方案被发现在包括2000名患者的大型虚拟试验中为11名LGO患者的硅胶双胞胎提供了显著的生存益处(中位数为5.69岁，范围为0.67至68.45岁)。这一方案可能有助于为LGO患者定义标准化的TMZ治疗，并提高患者的存活率。作者摘要一个数学模型描述了II级少突胶质瘤患者的纵向体积增长数据以及他们对替莫唑胺的反应。该模型被用来探索患者的硅胶双胞胎的替代治疗方案，并用于虚拟临床试验。模拟表明，延长化疗周期之间的时间间隔将保持治疗效果，同时限制毒性和延缓耐药性的产生。这可能会通过在更长的治疗期内实施更多的周期来改善药物暴露。基于这一想法的方案包括诱导期(5个连续周期，每月1个)和维持阶段(12个周期，每隔3个月)，导致了显著的生存益处。
The use of mathematical models for personalization of cancer therapies and raising hypothesis of potential clinical impact is an emerging topic in the interface between mathematics and oncology. Here we put forward a mathematical model describing the response of low-grade (WHO grade II) oligodendrogliomas (LGO) to temozolomide (TMZ). The model described the longitudinal volumetric dynamics of tumor response to TMZ of a cohort of 11 LGO patients treated with TMZ. After finding patient-specific parameters, different therapeutical strategies were tried computationally on the ‘in-silico twins’ of those patients. Chemotherapy schedules with larger-than-standard rest periods between consecutive cycles had either the same or better long-term efficacy than the standard 28-day cycles. The results were confirmed in a large virtual clinical trial including 2000 patients. These long-cycle schemes would also have reduced toxicity and defer the appearance of resistances. On the basis of those results, a combination scheme consisting of five induction TMZ cycles given monthly plus 12 maintenance cycles given every three months was found to provide substantial survival benefits for the in-silico twins of the 11 LGO patients (median 5.69 years, range: 0.67 to 68.45 years) and in a large virtual trial including 2000 patients. This scheme could be useful for defining a standardized TMZ treatment for LGO patients with survival benefits. Author summary A mathematical model described the longitudinal volumetric growth data of grade II oligodendrogliomas patients and their response to temozolomide. The model was used to explore alternative therapeutical protocols for the in-silico twins of the patients and in virtual clinical trials. The simulations show that enlarging the time interval between chemotherapy cycles would maintain the therapeutical efficacy, while limiting toxicity and defering the development of resistances. This may allow for improved drug-exposure by administering a larger number of cycles for longer treatment periods. A scheme based on this idea consisting of an induction phase (5 consecutive cycles, 1 per month) and a maintenance phase (12 cycles given in three-months intervals) led to substantial survival benefits in-silico.
影响因子：
16.6
作者：
Ramirez M;Rajaram S;Steininger RJ;Osipchuk D;Roth MA;Morinishi LS;Evans L;Ji W;Hsu CH;Thurley K;Wei S;Zhou A;Koduru PR;Posner BA;Wu LF;Altschuler SJ
通讯作者：
Altschuler SJ
DOI：
10.1016/j.ijrobp.2014.11.012
发表时间：
2015-03-01
影响因子：
7
作者：
Fisher, Barbara J.;Hu, Chen;Macdonald, David R.;Lesser, Glenn J.;Coons, Stephen W.;Brachman, David G.;Ryu, Samuel;Werner-Wasik, Maria;Bahary, Jean-Paul;Liu, Junfeng;Chakravarti, Arnab;Mehta, Minesh
通讯作者：
Mehta, Minesh