A critical review of the analytical approaches for circulating tumor biomarker kinetics during treatment.

Changes in serum tumor biomarkers may indicate treatment efficacy. Traditional tumor markers may soon be replaced by novel serum biomarkers, such as circulating tumor cells (CTCs) or circulating tumor nucleic acids. Given their promising predictive values, studies of their kinetics are warranted. Many methodologies meant to assess kinetics of traditional marker kinetics during anticancer treatment have been reported. Here, we review the methodologies, the advantages and the limitations of the analytical approaches reported in the literature. Strategies based on a single time point were first used (baseline value, normalization, nadir, threshold at a time t), followed by approaches based on two or more time points [half-life (HL), percentage decrease, time-to-events…]. Heterogeneities in methodologies and lack of consideration of inter- and intra-individual variability may account for the inconsistencies and the poor utility in routine. More recently, strategies based on a population kinetics approach and mathematical modeling have been reported. The identification of equations describing individual kinetic profiles of biomarkers may be an alternative strategy despite its complexity and higher number of necessary measurements. Validation studies are required. Efforts should be made to standardize biomarker kinetic analysis methodologies to ensure the optimized development of novel serum biomarkers and avoid the pitfalls of traditional markers.