ABSTRACT
The response of normal tissues to therapeutic radiation exposure must be considered over a wide range of overall treatment durations from minutes, e.g. in stereotactic single-dose treatment, to many months to years such as in re-irradiation scenarios. Several distinct processes define the time factor for treatment-induced morbidity, differently in different (groups of) tissues. First, on a short scale of minutes to hours, incomplete recovery of sublethal damage may reduce the radiation tolerance of a tissue, particularly with regard to late radiation sequelae. Second, over a range of days to weeks, i.e. during a regular course of fractionated radiotherapy with varying overall treatment times, radiation-induced tissue regeneration (repopulation) may modulate the radiation tolerance. This radiation-induced compensatory response is seen in early responding tissues. Third, over a range of months to years, long-term restoration can occur in some tissues, which renders them more resistant to re-irradiation. In contrast, also long-term progression of the damage can occur – even at subclinical levels – in other tissues, which causes decreased re-irradiation tolerance with increasing time after the first treatment.
