Quantifying the effect of dose inhomogeneity in brachytherapy: application to permanent prostatic implant with 125I...

To quantitate the influence of dose inhomogeneity on brachytherapy efficacy.

A computed tomography-based system of planning, implementation and evaluation was used to generate tumor-specific dose-volume histograms of eight permanent 125I implants of prostate cancers. The radiobiological effect was then assessed, voxel by voxel, in terms of the biologically effective dose and the associated cell inactivation. The overall cell survival of the entire target volume was then computed. To evaluate the influence of inhomogeneity, the dose-volume histogram was modified in an iterative fashion, with the corresponding surviving fraction calculated after each step. Specifically, the volume in the highest dose bin was combined with that in the next bin to give a new frequency distribution from which cell survival was generated. Tumor control probability (TCP) was also used as an endpoint, using the same iterative procedure.

Doses 20-30% higher than D99 (the dose that covered 99% of the target volume) contributed to additional cell inactivation, but still higher doses did not further increase cell kill. With homogeneous irradiation at D99 as a reference, we defined the inhomogeneity enhancement factor as the ratio of the biologic effective dose of the actual implant to that of the reference dose distribution. The calculated enhancement factors were inversely dependent on tumor potential doubling time (Tp), about 1.2-1.3 for a Tp of 30 days, and between 1.3 and 1.7 if Tp = 10 days, with higher values for implants with low D99. Dose inhomogeneity enhanced TCP. For implants with high control probabilities does significantly higher (> 20%) than the D99 value did not further enhance the tumor control probabilities. In contrast, for implants with relatively low tumor control and D99 values, the control probability continued to increase with doses significantly higher than D99, up to a dose of 2 x D99. The underlying reasons were the incorporation of patient "population averaging" in the calculation and the saturation of tumor control dose response at about 120 Gy.

Dose heterogeneity in implants increased tumor cell kill and local control probability, although doses > 20% higher than the prescription dose is wasted. The increase the beneficial effect of dose inhomogeneity may be greatest when most needed.