Tumour size: a factor influencing the isoeffect analysis of tumour response to combined modalities

Isoeffect analysis of complete dose response curves can be used to study the interaction of agents in combined modality protocols. When such an analysis is applied to data from in vivo tumour model systems, the effects of the agents on factors such as tumour vasculature, growth or reoxygenation pattern also need to be considered. In this study the change in tumour size, which can occur during a long time-interval between agents, was used as an example of a factor which may influence the position of data points on an isoeffect plot. Assays of in vivo tumour growth delay and in vitro clonogenic survival were performed to demonstrate that the radiation response curves of EMT-6/Ro tumours were size dependent. These curves were used to illustrate that data points obtained from a combined modality treatment may fall outside of the envelope of additivity of an isoeffect plot, as a direct consequence of tumour growth. This finding indicates that it may not be possible to interpret the results from isoeffect analyses of in vivo data on the basis of cellular interactions between agents, and suggests that instead isoeffect analyses be applied primarily to assess the overall response of the tumour system.