Is there a future for cell kinetic measurements using IdUrd or BdUrd?

Purpose: The analysis of causes of radiation failure both in retrospective series of patients with head and neck cancer and in several randomized clin ical trials suggests a loss of local control as the overall treatment time increases for the same total dose. This is attributed to tumor cell prolife ration during fractionated radiotherapy. As longer treatment times lead to loss of local control, it has been suggested that shorter treatment times c ould lead to an increase in local control, For this reason accelerated trea tment regimens have been and are being designed, However, these treatments may cause severe acute reactions, Due to this, lower total doses are someti mes given, Slowly proliferating tumors, therefore, may do worse when treate d with accelerated schedules compared with conventional schedules, In addit ion, it is not desirable to subject all patients to the more intense acute reactions of accelerated schedules. It would thus be useful to predict whic h tumors will rapidly proliferate during treatment and are likely to benefi t from accelerated radiotherapy, The potential doubling time (Tpot) is defi ned as the time within which the cell population of a tumor would double if there were no cell loss, The hypothesis is that the median Tpot measured b efore treatment might correlate with the effective doubling time (Tp) durin g treatment. Conclusion: Tpot call be calculated knowing the labeling index (LI; proport ion of cells incorporating the DNA precursor IdUrd or BdUrd) and Ts (the DN A synthesis time) measured by flow cytometry, A recent multicenter analysis has shown that the only pretreatment kinetic parameter for which some evid ence is found for an association with local control is LI, not Tpot, Pitfal ls associated with cell kinetic measurements such as assay variability, int ratumor and intertumor variability, interlaboratory variability and the pro blem of an admixture of normal and malignant cells make Tpot not accurate a nd reproducible enough for a robust predictive assay. It therefore appears that pretreatment Tpot measurements using Row cytometry, provide only a rel atively weak predictor of outcome after radiotherapy in head and neck cance r. Immunohistochemistry allows a simple measure of LI and may give addition al independent information from labeling patterns, suggesting that this met hod is the (short term) future for clinical cell kinetic measurements using BdUrd or IdUrd, (C) 2001 Elsevier Science Inc.