Cellular kinetics in rectal cancer

Abstract

Measurements of dynamic tumour cell kinetic parameters, particularly the potential doubling time (Tpot) may have potential as predictive assays for treatment outcome after radiotherapy. This paper details the distributions of Tpot and other kinetic and DNA content parameters measured in rectal cancers. Biopsies were taken from 119 patients approximately 6 h after infusion of 200 mg m-2 bromodeoxyuridine (BrdUrd). The samples were analysed by bivariate DNA/BrdUrd flow cytometry. The primary purpose of the study was to measure the kinetic parameters of labelling index (LI), duration of S-phase (TS) and Tpot. Secondarily, tumour DNA ploidy (DNA index) and S-phase fractions (SPFs) were also estimated from the univariate DNA histograms. The 101 evaluable patients were classified according to clinical stage as T2 (n = 12), T3 (n = 53), T4 (n = 28) or recurrent tumours (n = 8). Of the evaluable tumours, 73 were DNA aneuploid. The median LI, TS, and Tpot of the aneuploid tumours were 21%, 20 h and 3.3 days respectively. The calculated LI, TS, and Tpot of diploid tumours were subject to uncertainties because of the contribution of normal cells. The LI and SPF of all tumours were, however, significantly (P < 0.001) correlated, having a correlation coefficient of only 0.76. The wide distributions of values for LI (quartiles 13.5%, 26.9%) and Tpot (quartiles 2.4, 5.6 days) that were found are necessary baseline information if these parameters are to be useful in individual treatment selection or as predictors of treatment outcome.