Deriving cell survival curves from the overall responses of irradiated tumours: analysis of published data for tumour spheroids

Curves of growth delay (GD) or 'cure' after graded doses of radiation were analysed for 16 lines of human and animal tumours grown as multicellular spheroids in vitro, and dose-survival curves derived for cellular units from which spheroids regrow after unsuccessful irradiation (spheroid-regenerating cellular units, SRU). For 10 sets of data from 6 spheroid lines, the Do's and extrapolation numbers of the SRU derived by GD could be compared with the response of clonogenic cells of the spheroids. For Do, a good correlation (r = 0.910) was found between the two also for Do derived from curves of spheroid 'cure' (7 sets of data from 6 spheroid lines) and clonogenic cells (r 0.986). Using GD, correlation of extrapolation numbers was less good (r 0.682), values for SRU commonly being higher than those for clonogenic cells. This may reflect features of the growth curves of spheroids after the lower range of doses of radiation. For human and animal tumour spheroids of 250 μm or less, derived Do ranged from 0.5 to 2.5 Gy. For spheroids of 350 μm or more, derived Do for animal lines ranged from 3.4 to 4.2 Gy, for human lines from 1.5 to 2.1 Gy. (author)