Nonlinear multilevel joint model for individual lesion kinetics and survival to characterize intra-individual heterogeneity in patients with advanced cancer - Université de Tours Access content directly
Preprints, Working Papers, ... Year : 2023

Nonlinear multilevel joint model for individual lesion kinetics and survival to characterize intra-individual heterogeneity in patients with advanced cancer

Abstract

In advanced cancer patients, tumor burden assessment relies on the Sum of the Longest Diameters (SLD) of the target lesions, a marker that lumps all lesions together and ignores intra-patient heterogeneity. Here, we relied on a rich dataset of 342 metastatic bladder cancer patients treated with a novel immunotherapy agent to develop a Bayesian multilevel joint model that can quantify the heterogeneity in lesion dynamics and measure their impact on survival. Using a nonlinear model of tumor growth inhibition, we estimated that dynamics differed greatly among lesions, and inter-lesion variability accounted for about 35% of the total variance of both tumor shrinkage and treatment effect duration. Next, we investigated the impact of individual lesion dynamics on survival. Lesions located in the liver and in the bladder had twice as much impact on the instantaneous risk of death as compared to those located in the lung or the lymph nodes. Finally we evaluated the gain of individual lesion follow-up for dynamic predictions. Consistent with results at the population levels, the individual lesion model outperformed a model relying only on SLD, especially at early landmark times and in patients having liver or bladder target lesions. Our results show that the use of SLD leads to a loss of information and our model can be used to characterize tumor dynamics and survival of advanced cancer patients.
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Dates and versions

hal-03695061 , version 1 (15-06-2022)
hal-03695061 , version 2 (05-07-2024)

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Marion Kerioui, Maxime Beaulieu, Solène Desmée, Julie Bertrand, François Mercier, et al.. Nonlinear multilevel joint model for individual lesion kinetics and survival to characterize intra-individual heterogeneity in patients with advanced cancer. 2024. ⟨hal-03695061v2⟩
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