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Title: The use of joint modelling to analyze recurrent events: Appearance of new lesions in cancer. Authors:  Virginie Rondeau - Inserm (France) [presenting]
denis rustand - INSERM U1219 - Bordeaux Population health (France)
agnieszka Krol - INSERM U1219 - Bordeaux Population health (France)
Abstract: The Response Evaluation Criteria in Solid Tumors are used as standard guidelines for the clinical evaluation of cancer treatments. The assessment is based on the anatomical tumor burden: change in size of target lesions and evolution of nontarget lesions (NTL). Despite unquestionable advantages of this standard tool, Response Evaluation Criteria in Solid Tumors are subject to some limitations such as categorization of continuous tumor size or negligence of its longitudinal trajectory. In particular, it is of interest to capture its nonlinear shape and model it simultaneously with recurrent progressions of NTL and overall survival. We propose different multivariate nonlinear joint frailty models for recurrent events, and a terminal event with a longitudinal data. In the model, the tumor size trajectory accounts for the natural growth and treatment induced decline. The semicontinuous nature of the longitudinal biomarker is specified by a two-part model, which splits its distribution into a binary outcome represented by the positive versus zero values and a continuous outcome (second part) with the positive values only. On real data on colorectal cancers, we determine on which component, tumor size, NTL, or death the treatment acts mostly and perform dynamic predictions of death.