title: 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.
abstract: 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.
authors.affiliation: University of Bordeaux, INSERM U1219, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. agnieszka.krol@isped.u-bordeaux2.fr.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Król
authors.affiliation: University of Bordeaux, INSERM U1219, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Ferrer
authors.affiliation: INSERM U1018 CESP, Service de Biostatistique et d'Épidémiologie Gustave Roussy, U. Paris-Sud, 114 rue Édouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pignon
authors.affiliation: University of Bordeaux, INSERM U1219, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Proust-Lima
authors.affiliation: Medical Oncology, Gustave Roussy, U. Paris-Sud, 114 rue Édouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.affiliation: University Hospital, Hôpital Robert Debré, Avenue du Général Koenig, 51092 Reims Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.affiliation: INSERM U1018 CESP, Service de Biostatistique et d'Épidémiologie Gustave Roussy, U. Paris-Sud, 114 rue Édouard-Vaillant, 94805 Villejuif Cedex, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.affiliation: University of Bordeaux, INSERM U1219, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Rondeau
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D003198:Computer Simulation; D003643:Death; D018450:Disease Progression; D006801:Humans; D008137:Longitudinal Studies; D015233:Models, Statistical; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents
keywords: Colorectal cancer; Joint model; Longitudinal data; Predictive accuracy; Recurrent events; Tumor measurement