<p><strong>Purpose:</strong> The introduction of stereotactic radiotherapy has raised concerns regarding the use of the linear-quadratic (LQ) model for predicting radiation response for large fractional doses. To partly address this issue, a transition dose <em>D</em>* below which the LQ model retains its predictive strength has been proposed. Estimates of <em>D</em>* which depends on the a, β, and <em>D</em><sub>0</sub> parameters are much lower than fractional doses typically encountered in stereotactic radiotherapy. <em>D</em><sub>0</sub>, often referred to as the final slope of the cell survival curve, is thought to be constant. <em>In vitro</em> cell survival curves generally extend over the first few logs of cell killing, where <em>D</em><sub>0</sub>-values derived from the multi-target formalism may be overestimated<em> </em>and can lead to low transition doses. <strong></strong></p><p><strong>Methods:</strong> <em>D</em><sub>0</sub>-values were calculated from first principles for each decade of cell killing, using experimentally-determined a and β parameters for 17 human glioblastoma, neuroblastoma, and prostate cell lines, and corresponding transition doses were derived.</p><p><strong>Results:</strong> <em>D</em><sub>0</sub> was found to decrease exponentially with cell killing. Using <em>D</em><sub>0</sub>-values at cell surviving fractions of the order of 10<sup>-10 </sup>yielded transition doses ~3-fold higher than those obtained from <em>D</em><sub>0</sub>-values obtained from conventional approaches. <em>D</em>* was found to increase from 7.84 ± 0.56, 8.91 ± 1.20, and 6.55 ± 0.91 Gy to 26.84 ± 2.83, 23.95 ± 2.03, and 22.49 ± 2.31 Gy for the glioblastoma, neuroblastoma, and prostate cell lines, respectively. <strong></strong></p><p><strong>Conclusion:</strong> These findings suggest that the linear-quadratic formalism might be valid for estimating the effect of stereotactic radiotherapy with fractional doses in excess of 20 Gy.</p
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