Individual prediction of thrombocytopenia at next chemotherapy cycle: Evaluation of dynamic model performances

Abstract

Thrombocytopenia is a common major side-effect of cytotoxic cancer therapies. A clinically relevant problem is to predict an individual's thrombotoxicity in the next planned chemotherapy cycle in order to decide on treatment adaptation. To support this task, 2 dynamic mathematical models of thrombopoiesis under chemotherapy were proposed, a simple semimechanistic model and a comprehensive mechanistic model. In this study, we assess the performance of these models with respect to existing thrombocytopenia grading schemes. We consider close-meshed individual time series data of 135 non-Hodgkin's lymphoma patients treated with 6 cycles of CHOP/CHOEP chemotherapies. Individual parameter estimates were derived on the basis of these data considering a varying number of cycles per patient. Parsimony assumptions were applied to optimize parameter identifiability. Models' predictability are assessed by determining deviations of predicted and observed degrees of thrombocytopenia in the next cycles. The mechanistic model results in better agreement of model prediction and individual time series data. Prediction accuracy of future cycle toxicities by the mechanistic model is higher even if the semimechanistic model is provided with data of more cycles for calibration. We successfully established a quantitative and clinically relevant method for assessing prediction performances of biomathematical models of thrombopoiesis under chemotherapy. We showed that the more comprehensive mechanistic model outperforms the semimechanistic model. We aim at implementing the mechanistic model into clinical practice to assess its utility in real life clinical decision-making.