论文标题
生物标志物的修改风险检测方法通过脆弱的效果对多个时间到事件数据
A modified risk detection approach of biomarkers by frailty effect on multiple time to event data
论文作者
论文摘要
癌症患者在癌症患者中的多种迹象通过局部复发,遥远的转移和死亡发现。对这些适应症的早期识别对于改变治疗策略是必要的。生物标志物在这方面起着至关重要的作用。患者的生存机会取决于生物标志物,治疗策略也相应地不同,例如,被诊断为HER2阳性状态的乳腺癌患者的生存预测与HER2负面状态不同。这导致了不同的治疗策略。因此,在建模生存结果时,应考虑生物标志物状态或水平的异质性。这种异质性因子通常未观察到,称为脆弱。当同时存在多个指示时,场景就会变得更加复杂,因为其中只有一个可以发生,这将审查其他事件的发生。为每个原因纳入每个生物标志物状态的独立脆弱性不会描绘出异质性的完整情况。表明癌症进展的事件可能是相互关联的。因此,相关性应通过不同事件的脆弱性进行合并。在我们的研究中,我们考虑了具有异质性成分的多个事件或风险模型。根据脆弱的估计方差,将生物标志物的阈值水平用于疾病进展或死亡的早期检测工具。考虑到使用预期最大化算法进行不同脆弱组件之间的相关性和参数估计之间的相关性。随着R中广泛的算法,我们在多个事件方案中获得了生物标志物活性的阈值水平。
Multiple indications of disease progression found in a cancer patient by loco-regional relapse, distant metastasis and death. Early identification of these indications is necessary to change the treatment strategy. Biomarkers play an essential role in this aspect. The survival chance of a patient is dependent on the biomarker, and the treatment strategy also differs accordingly, e.g., the survival prediction of breast cancer patients diagnosed with HER2 positive status is different from the same with HER2 negative status. This results in a different treatment strategy. So, the heterogeneity of the biomarker statuses or levels should be taken into consideration while modelling the survival outcome. This heterogeneity factor which is often unobserved, is called frailty. When multiple indications are present simultaneously, the scenario becomes more complex as only one of them can occur, which will censor the occurrence of other events. Incorporating independent frailties of each biomarker status for every cause of indications will not depict the complete picture of heterogeneity. The events indicating cancer progression are likely to be inter-related. So, the correlation should be incorporated through the frailties of different events. In our study, we considered a multiple events or risks model with a heterogeneity component. Based on the estimated variance of the frailty, the threshold levels of a biomarker are utilised as early detection tool of the disease progression or death. Additive-gamma frailty model is considered to account the correlation between different frailty components and estimation of parameters are performed using Expectation-Maximization Algorithm. With the extensive algorithm in R, we have obtained the threshold levels of activity of a biomarker in a multiple events scenario.