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Joint model for left‐censored longitudinal data, recurrent events and terminal event: Predictive abilities of tumor burden for cancer evolution with application to the FFCD 2000–05 trial
Author(s) -
Król Agnieszka,
Ferrer Loïc,
Pig JeanPierre,
ProustLima Cécile,
Ducreux Michel,
Bouché Olivier,
Michiels Stefan,
Rondeau Virginie
Publication year - 2016
Publication title -
biometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.298
H-Index - 130
eISSN - 1541-0420
pISSN - 0006-341X
DOI - 10.1111/biom.12490
Subject(s) - event (particle physics) , event data , medicine , terminal (telecommunication) , cancer , computer science , oncology , machine learning , covariate , telecommunications , physics , quantum mechanics
Summary In oncology, the international WHO and RECIST criteria have allowed the standardization of tumor response evaluation in order to identify the time of disease progression. These semi‐quantitative measurements are often used as endpoints in phase II and phase III trials to study the efficacy of new therapies. However, through categorization of the continuous tumor size, information can be lost and they can be challenged by recently developed methods of modeling biomarkers in a longitudinal way. Thus, it is of interest to compare the predictive ability of cancer progressions based on categorical criteria and quantitative measures of tumor size (left‐censored due to detection limit problems) and/or appearance of new lesions on overall survival. We propose a joint model for a simultaneous analysis of three types of data: a longitudinal marker, recurrent events, and a terminal event. The model allows to determine in a randomized clinical trial on which particular component treatment acts mostly. A simulation study is performed and shows that the proposed trivariate model is appropriate for practical use. We propose statistical tools that evaluate predictive accuracy for joint models to compare our model to models based on categorical criteria and their components. We apply the model to a randomized phase III clinical trial of metastatic colorectal cancer, conducted by the Fédération Francophone de Cancérologie Digestive (FFCD 2000–05 trial), which assigned 410 patients to two therapeutic strategies with multiple successive chemotherapy regimens.