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首页> 外文会议>IEEE International Conference on BioInformatics and BioEngineering >Multilevel Cancer Modeling in the Clinical Environment: Simulating the Behavior of Wilms Tumor in the Context of the SIOP 2001/GPOH Clinical Trial and the ACGT Project
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Multilevel Cancer Modeling in the Clinical Environment: Simulating the Behavior of Wilms Tumor in the Context of the SIOP 2001/GPOH Clinical Trial and the ACGT Project

机译：临床环境中的多级癌癌模拟：模拟威尔姆斯肿瘤在SIOP 2001 / GPOH临床试验和ACGT项目中的行为

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Mathematical and computational tumor dynamics models can provide considerable insight into the relative importance and interdependence of related biological mechanisms. They may also suggest the existence of optimal treatment windows in the generic setting. Nevertheless, they cannot be translated into clinical practice unless they undergo a strict and thorough clinical validation and adaptation. In this context one of the major actions of the EC funded project "Advancing Clinico-Genomic Trials on Cancer" (ACGT) is dedicated to the development of a patient specific four dimensional multiscale tumor model mimicking the nephroblastoma tumor response to chemotherapeutic agents according to the SIOP 2001/GPOH clinical trial. Combined administration of vincristine and dactinomycin is considered. The patient's pseudoanonymized imaging, histopathological, molecular and clinical data are carefully exploited. The paper briefly outlines the basics of the model developed by the In Silico Oncology Group and particularly stresses the effect of stem/clonogenic, progenitor and differentiated tumor cells on the overall tumor dynamics. The need for matching the cell category transition rates to the cell category relative populations of free tumor growth for an already large solid tumor at the start of simulation has been clarified. A technique has been suggested and succesfully applied in order to ensure satisfaction of this condition. The concept of a nomogram matching the cell category transition rates to the cell category relative populations at the treatment baseline is introduced. Convergence issues are addressed and indicative numerical results are presented. Qualitative agreement of the model's behavior with the corresponding clinical trial experience supports its potential to constitute the basis for an optimization system within the clinical environment following completion of its clinical validation and optimization. In silico treatment experimentation in the patient individualized context is expected to constitute the primary application of the model.
机译：数学和计算肿瘤动力学模型可以对相关生物机制的相对重要性和相互依赖提供相当大的洞察力。他们还可以建议在通用设置中存在最佳处理窗口。尽管如此，除非他们经历严格和彻底的临床验证和适应，否则它们不能翻译成临床实践。在这方面，EC资助项目的主要行动之一“推进癌症临床 - 基因组试验”（ACGT）致力于发展患者特异性四维多尺度肿瘤模型，其根据患者模仿肾细胞瘤肿瘤反应的患者对化学治疗剂的反应SIOP 2001 / GPOH临床试验。考虑了长春霉素和丁霉素的组合施用。仔细利用患者的假谐音成像，组织病理学，分子和临床数据。本文简要概述了在硅肿瘤组中开发的模型的基础知识，特别是茎/克隆因，祖细胞和分化肿瘤细胞对整个肿瘤动态的影响。已经阐明了在模拟开始时将细胞类别转变率与细胞类别的相对群体匹配到已经大的实体瘤的自由肿瘤生长的相对群体。已经提出了一种技术和成功应用，以确保对这种情况的满足感。介绍了将细胞类别转换率与治疗基线的细胞类别相对群体相匹配的NOM图的概念。收敛问题是解决的，并提出了指示性数值结果。该模型的定性协议具有相应的临床试验经验的行为，支持在完成其临床验证和优化后构成临床环境中优化系统的基础。在患者中的硅处理实验中，预计患者个性化背景下将构成模型的主要应用。

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