Variations in tumor growth, intra-individual biological variability, and the interpretation of changes

The identification of changes in tumor markers (TMs) in cancer patients that indicate response to treatment, stabilization or disease progression is a challenge for laboratory medicine. Several approaches have been proposed: assessing percentage increases, applying discriminant values, and estimating half-life (t_1/2) or doubling time (DT). In all of them it is assumed that the TM is a surrogate of the variation in tumor size. In general this variation is time-dependent, but this is not the case of intraindividual biological variability (CVi), which can range from 6 % in CA15-3 to 22 % in CA125. When decisions are made on the basis of DT or t_1/2, these values can be affected by the CVi; if it is very large, the growth rate very slow and the period of time between determinations very short, the result obtained for DT may be due mainly to the CVi. The aim of this study is to establish the relationship between the CVi and temporal variables.

We related equations for calculating DT and t_1/2 to the reference change values in tumor markers.

The application of the formula obtained allows the calculation of the optimal time between measurements to ensure that the influence of the CVi is minimal in different types of tumors and different scenarios.

Intraindividual variation affects the calculation of DT and t_1/2. It is necessary to establish the minimum time between two measurements to ensure that the CVi does not affect their calculation or lead to misinterpretation.