The predictive role of flow cytometry-derived tumor potential doubling time (Tpot) in radiotherapy: open questions and future perspectives.

Measurement of tumor-cell kinetic parameters, following in vivo administration of thymidine analogues and bivariate flow cytometry, allows quantitative cell kinetic determinations in a clinically relevant time-scale, potentially useful for selection of individual radiotherapy schedules. Among the dynamic cell kinetic parameters that can be measured using the in vivo method, the tumor potential doubling time (Tpot), defined as the time to double the number of proliferating tumor cells in the absence of cell loss, has been postulated to be a predictor of a tumor's proliferative capability, thus representing a potential predictive factor of local control after irradiation. So far, published data have shown the safety and feasibility of the technique, even in multicenter studies, and demonstrated a wide range of parameter values in many tumor sites. With only a few exceptions the hypothesis that Tpot is an independent prognostic indicator cannot be considered proven yet. We review the major controversial issues and open questions, mainly in the area of data production and analysis, that must be resolved before the predictive role of Tpot is unequivocally defined. The future of radiotherapy predictive assays lies in the development of multiparametric studies, accounting for multiple factors of radiation response, which may prove of greater prognostic significance than any single parameter approach based only on cell kinetics.