Modeling late effects in hypofractionated stereotactic radiotherapy

Purpose: To investigate the effect of increasing fraction size on cell surv ival in late responding normal tissues, The hypothesis is that total dose c an be reduced for constant tumor cell kill and there will be consequent adv antage for some surrounding normal tissue cells. Also, the volume of normal tissue that can potentially be damaged by increasing fraction size is mini mized by a high degree of dose conformation achievable in stereotactic radi otherapy (SRT). Methods and Materials: The linear quadratic (LQ) model has been used to cal culate the allowed reduction in total dose with increased fraction size, us ing tumor alpha/beta ratios of 5 Gy and 10 Gy, Effect on normal tissue is c alculated 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 descr ibe 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 si ze is considered. Results: The decreasing total dose resulting from increasing the dose per f raction 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 fr action, when a larger volume of brainstem is covered by high isodose levels . Conclusion: 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 isodos e levels. (C) 1998 Elsevier Science Inc.