Can dose-survival parameters be deduced from in situ assays?

The most readily quantifiable end-points of tumour response in situ are regrowth delay and cure, but neither of these permits straightforward estimation of dose-survival parameters for clonogenic cells. Regrowth delay, though often taken to reflect the magnitude of clonogenic survival, is usually the resultant of this component and of a component reflecting altered regrowth kinetics of surviving cells. Whilst altered kinetics of visible regrowth may be directly assessable, it is difficult to allow for altered kinetics of growth during the latent phase. Likewise, dose-cure studies, in principle, permit estimation of cellular parameters, but large-scale experiments are mandatory, and the analysis is beset by the existence of error-amplifying processes, requiring high levels of experimental accuracy to be attained. Recently attempts have been made to circumvent these difficulties by combining individual end-points and making use of the properties of tumours which transplant in accordance with Poisson statistics. Analyses based on these methods have yielded plausible estimates of the in situ parameters but the reliability of such procedures remains to be assessed.