[The in vivo use of bromodeoxyuridine for the study of cell kinetics in squamous tumors of the neck and head. Implications for the radiotherapist]

Abstract

Cell kinetics in 22 human epidermoid head and neck tumors were studied in vivo using bromodeoxyuridine (BUrD). Patients were infused with 250 mg/m2 of intravenous BUrD in a variety of sites (oral cavity, pharynx, larynx and lip) four/five hours prior to biopsy. BUrD incorporating cells were detected by flow-cytometry using anti-BUrD monoclonal antibodies. Ploidy (DNA index) labelling index (LI%), duration of S-phase (Ts) and potential doubling time (Tpot) could be measured within 12-24 hours from sampling in 77%, 72%, 63 and 63% of cases, respectively. Six failures (few viable cells in biopsy specimen and difficulties in BUrD cell analysis and DNA staining) were recorded. Labelling index values in this study ranged from 2.2% to 28% with a median value of 11%. The median total LI% of diploid tumor (n = 7) was 5% compared to 13% in aneuploid tumors (n = 7). Ts measurement ranged from 6.5 hours to 12 hours, median value being 10.5 hours (euploid tumors: 6.5, aneuploid 12). The calculated potential doubling time ranged from 2.6 to 15 days and the median Tpot was shorter at 5.0 days (euploid tumors: 7 days, aneuploid 4 days). 70% of the tumors had potential doubling time of 5 days or less. Potential doubling time did not correlate with ploidy and tumor or neck nodes status while shorter Tpots were observed in moderate or poorly differentiated tumors. Our data strongly suggest BUrD technique as a useful tool for studying the proliferative behavior of human tumors: the pre-treatment knowledge of individualized potential doubling times for the tumors scheduled for irradiation could help the radiotherapist to choose the more effective fractionation regimen (i.e.: accelerated fractionation for tumors with Tpot less than or equal to 6 days and standard fractionation for tumors with higher values.