Biologic treatment planning for high-dose-rate brachytherapy

Purpose: Interstitial brachytherapy treatment plans are conventionally opti mized with respect to total target dose and dose homogeneity, which does no t account for the biologic effects of dose rate. In an HDR implant, with a stepping source, the dose rate dramatically changes during the course of tr eatment, depending on location, as the source moves from dwell position to dwell position, These widely varying dose rates, together with the related sequencing of the dwell positions, may impart different biologic effects at points receiving the same total dose. This study applies radiobiologic pri nciples to account for the potential biologic impact of dose delivery at va rying dose rates within an HDR implant. Methods and Materials: The model under study uses a generalized version of the linear-quadratic (LQ) cell kill formula to calculate the surviving frac tion of cells subjected to HDR irradiation. Using a planar interstitial HDR implant with the dwell times optimized to produce a homogeneous dose distr ibution along a reference plane parallel to the implant plane, surviving fr actions were compared at selected reference points subjected to the same to tal dose. Biologic effect homogeneity was compared to dose homogeneity by p lotting the effects at the reference points. The effects were examined with LQ parameters alpha, beta, and sublethal repair time T-1 varied over a ran ge typical of human cells. Results: In a region in which dose is relatively uniform, surviving fractio n for some values of the model parameters are found to vary by as much as a n order of magnitude due to differences in the HDR irradiation profiles at different dose points. This effect is more pronounced for shorter repair ti mes and smaller alpha/beta ratios, and increases with increasing total irra diation time. Conclusion: Conventional HDR treatment planning currently considers dose di stribution as the primary indicator of clinical effect. Our results demonst rate that plans optimized to maximize homogeneity within a target volume ma y not reflect the effect of the sequential nature of HDR dose delivery on c ell kill. Biologic effect modeling may improve our understanding and abilit y to predict the adverse effects of our treatment, such as fat necrosis and fibrosis, Accounting for irradiation history and repair kinetics in the ev aluation of HDR brachytherapy plans may add an important new dimension to o ur planning capabilities. (C) 2001 Elsevier Science Inc.