Clinical evidence for tumor clonogen regeneration: interpretations of the data

A therapeutic gain is expected from accelerated fractionation in radiotherapy because of reduced times for proliferation of tumor clonogens and the likelihood that the late effects of radiation are unaffected by changes in overall time. While there can be no dispute over the existence of the phenomenon, there are questions about the ways clinical data have been interpreted to adduce the influence of proliferation. Moreover, recent clinical and experimental evidence throw some doubt on the assumption that late effects are independent of overall treatment time. It is concluded that some of the issues remain in doubt, and that rather large-sized phase-III trials may be required to show any benefit from reductions in the overall time, especially if this is accompanied by substantial reductions in the total dose.