Oral mucositis is an inflammatory adverse event when treating head and neck cancer patients with radiation therapy (RT). The severity of its occurrence is believed to mainly depend on its site and the distribution of a cumulative radiation dose in the mouth area. The motivating study investigating differences in radiosensitivities (mucositis progression) at distinct sites where the severity of mucositis is assessed regularly at eight distinct sites on an ordinal scale results in multivariate longitudinal data and thus poses certain challenges. To deal with the multivariate longitudinal data in this particular setting, we take a time-to-event approach focusing on the first occurrence of severe mucositis at the distinct sites using the fact that the site-specific cumulative radiation dose thought to be the main driver of oral mucositis develops over time. Thereby, we may address multivariate longitudinal processes in a simpler and more compact fashion. In this article, to find out differences in mucositis progression at eight distinct sites we propose a shared frailty model for multivariate parallel processes within individuals. The shared frailty model directly incorporating ‘process indicators’ as covariates turns out to adequately explain the differences in the parallel processes (here, mucositis progressions at distinct sites) while taking individual effects into account. The parallel result with the one from the previous analysis based on the same data but conducted with an alternative statistical methodology shows adequacy of the proposed approach.

中文翻译：

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放射治疗不良事件多变量纵向数据的共享衰弱模型

口腔粘膜炎是用放射疗法 (RT) 治疗头颈癌患者时的炎症性不良事件。据信其发生的严重程度主要取决于其部位和口腔区域累积辐射剂量的分布。调查不同部位放射敏感性差异（粘膜炎进展）的激励性研究，其中在八个不同部位按顺序定期评估粘膜炎的严重程度，结果产生了多变量纵向数据从而带来了一定的挑战。为了处理这种特定环境中的多变量纵向数据，我们采用时间到事件方法，重点关注不同部位首次发生严重粘膜炎，利用被认为是主要驱动因素的部位特定累积辐射剂量这一事实口腔粘膜炎会随着时间的推移而发展。因此，我们可以以更简单和更紧凑的方式处理多变量纵向过程。在本文中，为了找出八个不同部位粘膜炎进展的差异，我们提出了一个共享的虚弱模型用于个体内部的多元并行过程。直接将“过程指标”作为协变量的共享虚弱模型证明可以充分解释平行过程（此处为不同部位的粘膜炎进展）的差异，同时考虑到个体效应。与基于相同数据但使用替代统计方法进行的先前分析的结果的平行结果表明所提出的方法是充分的。