Radiation carcinogenesis modelling for risk of treatment-related second tumours following radiotherapy.

Radiobiological modelling of the risk of radiation-induced tumours following high dose radiation implies a general form for the dose-response relationship. Generally, risk will rise with radiation dose at low doses, reach a maximum value and then decline with further increase in dose. The magnitude of risk and the dose at which this risk is maximum are strongly dependent on the kinetics of repopulation by surviving normal and mutant cells and on genetic factors likely to differ between tissues and between individuals. The most reliable way to reduce the risk of second tumours is to reduce radiation dose further at sites where the dose is already low. These sites are usually distant from the primary treatment volume. For illustrative purposes, we have compared the predicted relative risks of second tumours at "distant sites" for treatment plans giving similar dose distributions (dose volume histograms) at the primary site. We suggest that dose reduction to distant sites could be of significant benefit in reducing the risk of second tumours. Further improvement will require more detailed knowledge of the radiation sensitivities and mutagenicities, together with the repopulation kinetics of the various cell lineages within the treatment volume.