Lam Kwok Fai, Wong Kin Yau, Zhou Feifei
Department of Statistics and Actuarial Science, The University of Hong Kong, Pokfulam Road, Hong Kong.
Biom J. 2013 Sep;55(5):771-88. doi: 10.1002/bimj.201300004. Epub 2013 May 29.
There is a growing interest in the analysis of survival data with a cured proportion particularly in tumor recurrences studies. Biologically, it is reasonable to assume that the recurrence time is mainly affected by the overall health condition of the patient that depends on some covariates such as age, sex, or treatment type received. We propose a semiparametric frailty-Cox cure model to quantify the overall health condition of the patient by a covariate-dependent frailty that has a discrete mass at zero to characterize the cured patients, and a positive continuous part to characterize the heterogeneous health conditions among the uncured patients. A multiple imputation estimation method is proposed for the right-censored case, which is further extended to accommodate interval-censored data. Simulation studies show that the performance of the proposed method is highly satisfactory. For illustration, the model is fitted to a set of right-censored melanoma incidence data and a set of interval-censored breast cosmesis data. Our analysis suggests that patients receiving treatment of radiotherapy with adjuvant chemotherapy have a significantly higher probability of breast retraction, but also a lower hazard rate of breast retraction among those patients who will eventually experience the event with similar health conditions. The interpretation is very different to those based on models without a cure component that the treatment of radiotherapy with adjuvant chemotherapy significantly increases the risk of breast retraction.
尤其是在肿瘤复发研究中,对带有治愈比例的生存数据分析的兴趣日益浓厚。从生物学角度来看,合理的假设是复发时间主要受患者整体健康状况的影响,而整体健康状况取决于一些协变量,如年龄、性别或所接受的治疗类型。我们提出了一种半参数脆弱性 - Cox治愈模型,通过一个依赖协变量的脆弱性来量化患者的整体健康状况,该脆弱性在零处有离散质量以表征治愈患者,还有一个正的连续部分来表征未治愈患者之间的异质健康状况。针对右删失情况提出了一种多重填补估计方法,并进一步扩展以适应区间删失数据。模拟研究表明所提方法的性能非常令人满意。为作说明,该模型被应用于一组右删失的黑色素瘤发病数据和一组区间删失的乳房美容数据。我们的分析表明,接受辅助化疗放疗的患者乳房回缩的概率显著更高,但在最终会经历该事件且健康状况相似的患者中,乳房回缩的风险率也更低。这种解释与基于无治愈成分模型的解释非常不同,后者认为辅助化疗放疗会显著增加乳房回缩的风险。