Studies with bromodeoxyuridine in head and neck cancer and accelerated radiotherapy

Using bromodeoxyuridine (BrdUrd), tumour cell proliferation was assessed, by flow cytometric (FCM) and immunohistochemical methods, in patients treated by the CHART regime of radiotherapy. Of 115 cases studied, data were complete in 90 using both methods. No cell kinetic-related parameter predicted the outcome of patients treated by CHART, in keeping with the view that, with this regime, cellular proliferation had been minimised as a cause of failure. Histological evaluation of the labelling index (LI) revealed a trend for higher LI is in diploid tumours (16.2%) than in aneuploid (13.8%), contrasting to that found by FCM (5.0 and 9.3% respectively). When the Tpot was calculated using a combination of histology LI and FCM TS, diploid tumours showed more rapid proliferation (Tpot 1.8 days) than aneuploid tumours (Tpot 3.2 days); this finding was significant (p < 0.02). A novel parameter, termed proliferation pattern, unique to these studies with BrdUrd in vivo, was assessed. Both proliferation pattern and histological grading had predictive power to discriminate the outcome in univariate analysis (p = < 0.031 and 0.037, respectively). In a Cox multivariate analysis, proliferation pattern was the more important predictor. The studies reported highlight the extra information that can be gained from combining immunohistochemistry with flow cytometry to study the cellular proliferation of human tumours.