Relation of growth delay to cure for experimental tumour systems conforming to Poisson cure statistics.

ABSTRACT

In tumour regrowth-delay experiments, the analysis of results in the higher dose ranges may be complicated by a dose-dependent proportion of non-recurrent (cured) tumours, whose inclusion in the analysis is not straightforward. A study of the relation of growth delay to cure has been carried out using a model of tumour response which assumes Poisson (single-cell) cure statistics and exponential regrowth kinetics of recurrent tumours, and which makes use of Monte Carlo simulation techniques to represent the effects of inter-tumour heterogeneity. This approach yields correction factors compensating for tumour cures in growth-delay experiments. For homogeneous tumour systems (all tumours and treatments identical) these corrections are small and not significantly different from corrections obtained using the "long delay" procedure suggested previously (Denekamp, 1980; Fowler et al., 1980). For heterogeneous systems, however, correction factors increase with the heterogeneity of the system, and may become quite large. It is concluded that the quantitative assessment of heterogeneity is required, and a possible approach to this is suggested. Should evaluation of heterogeneity prove feasible, it will allow more efficient use of tumour-response data, and may permit realistic estimates of clonogenic cell survival in situ.