Reply to 'Comments on "Cellular response to modulated radiation fields"'

We have reported two new bystander effects derived from experimental data on the survival fraction following spatially modulated irradiation of a melanoma cell line, using a 6 MV therapeutic photon beam (Claridge Mackonis et al 2007 Phys. Med. Biol. 52 5469). The validity of survival fractions exceeding unity and statistical evidence for the new effects have been challenged (Ross and Klassen 2008). Survival fractions exceeding unity have been reported and are expected in the presence of conditions favouring colony formation. After a reanalysis using a comparison with a proportional hazards approach (Cox 1975 Biometrika 62 269) and separately modelling the different exposure types using a linear quadratic model, we are able to reconfirm our original conclusions for the melanoma cell line. We present new data for non-small cell lung cancer, which provide further support for the presence of new bystander effects. The usefulness of plots of average survival as a function of average dose to the cell culture is further discussed. From these plots we find significant evidence for a higher mean survival than would be expected in the absence of bystander effects. With the evidence provided by the additional data and further statistical analysis of all data, we conclude that there is strong evidence for bystander effects that promote cell survival.