Degree Name

Master of Science – Research


Centre for Medical Radiation Physics


The surviving fraction of cells following irradiation is affected by the temporal pattern of dose delivery. Modern technology for external beam radiation therapy allows complex manipulation of both the spatial and temporal pattern of dose delivery during a single treatment fraction. The aim of this thesis was to investigate the influence of temporal dose effects in external beam radiotherapy, and predict the potential for biological optimisation when the pattern of dose delivery is manipulated to achieve maximum effect in the target.

A radiobiological model, based on the linear quadratic formalism and including the pattern of dose delivery of individual voxels, was used to calculate the cell surviving fraction across the target volume. Dose patterns were manipulated to optimise cell kill and predict the potential for biological optimisation. Prostate external beam treatments were chosen as the clinical site to investigate due to the sensitivity of prostate carcinoma to temporal dose effects.

For clinical treatment plans, the biological effect due to the original dose prescription was found to vary across the target volume when temporal dose effects are incorporated. The percentage difference in cell surviving fraction between the prescribed treatment and that with temporal effects included was found to be on average 27% for 3DCRT and 87.6% for IMRT treatments. Over the whole target volume this corresponded to a decrease in treatment effectiveness [assessed using equivalent uniform dose (EUD)] of 1.3% and 3% for 3DCRT and IMRT respectively. The distribution of biological effect was visualised on the original treatment plans. This gave insight into the areas of the prostate which are most likely to be affected by the temporal dose pattern. Generally, the middle of the prostate was found to exhibit a biological ‘under dosing’ due to this region receiving sub-optimal dose arrangements.

For the theoretical scenario of optimising the temporal dose pattern to every voxel in the target volume the impact on treatment effectiveness was found to be modest – on average a 0.8% increase in EUD for a 2 Gy per fraction IMRT treatment plan. Larger effects were observed for larger dose per fraction treatments. A 1.4% increase in EUD was calculated for an 8 Gy per fraction treatment.

The final stages of this thesis investigated if simply altering the order of treatment beam delivery could provide biological optimisation over the whole target area due to the change in temporal dose arrangements. Generally, the treatment beam order that delivered the fastest treatment was found to be biologically optimal due to the minimisation of sublethal damage repair.

This investigation has shown that the temporal pattern of dose delivery is an important component when determining the biological effect of external beam treatments. It is recommended that temporal dose effects can and should be considered when planning modulated and/or hypofractionated treatments where the treatment time is of the same order as the half-time for repair of sublethal damage of the tissue. Where appropriate, it would be advantageous to irradiate target volumes as rapidly as possible.