Optimization of temporal dose modulation: Comparison of theory and experiment

Abstract

To compare theoretical predictions and experimental measurements of cell survival after exposure to two different temporally modulated radiation dose patterns that deliver the same dose in the same overall time. The authors derived an analytic expression for the dose protraction factor G in the Lea-Catcheside formalism for cell survival for "triangle" and "V" temporal modulation of dose. These temporal dose patterns were used in experimental clonogenic studies of a melanoma cell line (MM576) and a nonsmall-cell lung cancer line (NCI-H460) that have different alpha, beta, and repair parameters. The overall treatment time and total dose were kept constant. The analytic expressions for G for the two temporal modulations are presented as a function of a single variable, the product of the exposure time, and the repair constant, enabling G to be evaluated for any exposure time and for any cell line. G for the triangle delivery pattern is always the larger. For the MM576 cell line, following a large dose of 6 Gy, a larger survival fraction was found for the V delivery pattern. No difference in survival was observed for lower doses or for the NCI-H460 cell line at any dose. These results are predicted by our theory, using published values of alpha, beta, and repair time within the limits of experimental uncertainty. The study provides evidence to confirm that cell lines having large beta values exhibit a response that is sensitive to the pattern of dose delivery when the delivery time is comparable with the repair time. It is recommended that the dose delivery pattern be considered in hypofractionated treatments.