The effect of setup uncertainties on the radiobiological advantage of fractionation in stereotaxic radiotherapy

Purpose: There may be radiobiological advantages in administering stereotaxic radiation treatment in multiple fractions instead of by a single irradiation. However, a larger planning target volume may be required for fractionated stereotaxic radiotherapy than for a single session treatment, if decreased geometrical precision and increased setup uncertainty are associated with multiple-fraction treatments. This factor may partially offset the radiobiological gain. The purpose of this study is to estimate the potential therapeutic gain of fractionated treatments for brain tumors, and to assess the effect of increased setup uncertainty on the potential gain. Methods and Materials: The concept of biologically effective dose (BED), based on the linear quadratic (LQ) model, was used to quantify the therapeutic efficacy of the respective treatment schema. Therapeutic gain (TG) was defined as the ratio of tumor BEDs, for multiple fractions and single treatment, respectively, for the same normal brain BED: To include the effect of increased planning volume in fractionated treatment, a power-law relationship was assumed for the volume dependence of prescription dose, and the TG was recalculated using the ''volume-adjusted'' doses. Results: The therapeutic gain for fractionated treatment increases with fraction number, and is smaller for larger single treatment doses. For example, in going from 1 to 10 fractions, the TG is 1.40, 1.32, or 1.27 for single treatment dose of 20, 30, or 40 Gy, respectively. Also, the TG is more significant for the initial few fractions. The benefit of fractionation is diminished if larger planning volume is needed for multiple fraction treatments. For example, the above TG are reduced to 1.19, 1.11, or 1.06, if a 2 cm planning target volume in single fraction treatment is enlarged to 2.3 cm in fractionated treatment. Conclusion: Consideration of the therapeutic gain with fractionation should include estimates of setup uncertainty for multiple-fraction treatments, relative to that of single fraction radiosurgery.