ABSTRACT
Throughout the history of radiotherapy, the optimal distribution of dose over time has been a major issue, but the most important progress has been made in this area since the early 1980s. The relationships uncovered between total dose and fraction number for late versus early responding normal tissues and tumours provide the basic information required to optimise the dose per fraction in radiotherapy. More work still needs to be done particularly in a clinical setting to determine the exact time of onset, the rate and the mechanisms of repopulation in all tumours and normal tissues during radiotherapy, but enough is now known about time factors to support the important conclusions that (1) the overall duration of fractionated radiotherapy should not be allowed to extend beyond the originally prescribed time, (2) a reduced overall treatment time should be considered in a number of clinical situations and (3) inter-fraction time intervals should be made as long as possible in order to maximise the available benefit from fractionation schedules employing multiple fractions per day if these are warranted.
