Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism

Abstract

Cite this article as: Akudugu J, Serafin A. Estimation of transition doses for human glioblastoma, neuroblastoma and prostate cell lines using the linear-quadratic formalism. Int J Cancer Ther Oncol 2015; 3(3):3311. Original ArticleAbstract Purpose: 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 D* below which the LQ model retains its predictive strength has been proposed. Estimates of D* which depends on the , β, and D0 parameters are much lower than fractional doses typically encountered in stereotactic radiotherapy. D0, often referred to as the final slope of the cell survival curve, is thought to be constant. In vitro cell survival curves generally extend over the first few logs of cell killing, where D0-values derived from the multi-target formalism may be overestimated and can lead to low transition doses. Methods: D0-values were calculated from first principles for each decade of cell killing, using experimentally-determined  and β parameters for 17 human glioblastoma, neuroblastoma, and prostate cell lines, and corresponding transition doses were derived. Results:D0 was found to decrease exponentially with cell killing. Using D0-values at cell surviving fractions of the order of 10 -10 yielded transition doses~3-fold higher than those obtained from D0-values obtained from conventional approaches. D* 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. Conclusion: 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.D0-values derived from the multi-target formalism. FIG. 5: Plot of D0, derived from LQ parameters, against the decade of cell killing in which D0 is derived for human glioblastoma, neuroblastoma, and prostate cell lines. Symbols representing pooled data from Figures 2-4 are superimposed on fitted curves from historical data for glioblastoma (dotted line) 41 , neuroblastoma (dashed line) 31, 43 and prostate (solid line) 44 cell lines. Large symbols represent D0-values derived from the multi-target formalism from cell survival data for each group of cell lines. 36-38 Error bars represent the standard error of the mean for each set of pooled data.Similarly, D0 declined from 1.85 ± 0.38 to 0.68 ± 0.04 Gy in the neuroblastoma cell lines (Figure 3). For the prostate cell lines, D0 decreased from 2.28 ± 0.23 Gy at high levels of cell survival to 0.81 ± 0.08 Gy at high levels of cell killing (Figure 4). In all cases, D0-values derived from the multi-target formalism were significantly higher than those obtained from the LQ model at a cell survival level of 10 -10 (P  0.0023).The resulting transition doses obtained from D0-values derived from the LQ model were f...

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“…Hypofractionated and stereotactic radiotherapy can be given as fractional doses ranging from 5 to 30 Gy [4][5][6][7][8][9]. Evidence suggests that even at such large fractional doses, the linear-quadratic formalism can be used for estimating the effect of treatment in tumours and normal tissue to the same degree of certainty as in conventional fractionated radiotherapy [10][11][12].…”