Modeling late effects in hypofractionated stereotactic radiotherapy

To investigate the effect of increasing fraction size on cell survival in late responding normal tissues. The hypothesis is that total dose can be reduced for constant tumor cell kill and there will be consequent advantage for some surrounding normal tissue cells. Also, the volume of normal tissue that can potentially be damaged by increasing fraction size is minimized by a high degree of dose conformation achievable in stereotactic radiotherapy (SRT).

The linear quadratic (LQ) model has been used to calculate the allowed reduction in total dose with increased fraction size, using tumor alpha/beta ratios of 5 Gy and 10 Gy. Effect on normal tissue is calculated using an alpha/beta ratio of 3 Gy. Maximum dose is normalized to 100% and the effect on normal tissue at different isodose levels assessed. A new quantity, the standard percentage dose, is proposed in order to describe a dose distribution in terms of an isodose distribution for a standard fraction size. Integral biologically effective dose (IBED) in the brainstem is calculated, where the variation with isocenter position and fraction size is considered.

The decreasing total dose resulting from increasing the dose per fraction is found to reduce late normal tissue effect for low isodose levels. The threshold isodose level at which there is an advantage corresponds to the ratio of normal tissue to tumor alpha/beta ratios. Brainstem IBED for a higher dose per fraction increases relative to that for a low dose per fraction, when a larger volume of brainstem is covered by high isodose levels.

Hypofractionation may be biologically sound when a small volume of normal tissue is covered by high isodose levels. There is a calculated advantage in using larger fractions in terms of cell survival at low isodose levels.