Normal tissue radiosensitivity--how important is it?

The success of radiotherapy in eradicating tumours depends on the total radiation dose, but what limits this dose is the tolerance of the normal tissues within the treatment volume. Selection of the appropriate dose for all patients is based on a balance between minimising the incidence of severe normal tissue complications and maximizing the probability of local control. In patients treated to the same radical dose, a wide range of reactions is seen; in many clinical situations, radical doses are limited by the minority of patients whose normal tissues are particularly sensitive. Clinical studies of radiotherapy reactions have demonstrated that a large part of the spectrum of normal tissue reactions, perhaps as much as 80%, is due to differences in individual normal tissue sensitivity. This suggests that it might be possible to measure this sensitivity and to change treatment accordingly. The main objective of normal tissue sensitivity testing is to permit dose escalation without increased normal tissue complication rates in patients with more resistant normal tissues. Calculations suggest that the most "resistant' 40% of patients could be dose escalated by 17%-18%, which is likely to be associated with significant gains in local control, perhaps by as much as 34%-36%; this should translate into an increase in overall survival. It should also be possible to identify those relatively few patients who suffer serious normal tissue morbidity with conventional doses. Thus, if successful, predictive testing of normal tissue response should improve the therapeutic ratio of radiotherapy.