ABSTRACT
The clinical evaluation and implementation of modified fractionation schedules based on biological rationales is an important focus of ‘translational research’ in radiation oncology. Throughout the history of radiotherapy, the optimal distribution of dose over time has been a major issue but important progress has been made in this area over the past two decades. The relationships uncovered between total dose and fraction number for late-responding normal tissues, early-responding normal tissues and tumours provide the basic information required to optimize the dose per fraction in radiotherapy. Work still needs to be done to determine the exact time of onset, the rate and the mechanisms of repopulation in 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 gain the full benefit from fractionation schedules employing multiple fractions per day.
