Equivalent uniform RBE-weighted dose in eye plaque brachytherapy.

Background: Brachytherapy for ocular melanoma is based on the application of eye plaques with different spatial dose nonuniformity, time-dependent dose rates and relative biological effectiveness (RBE).

Purpose: We propose a parameter called the equivalent uniform RBE-weighted dose (EUD) that can be used for quantitative characterization of integrated cell survival in radiotherapy modalities with the variable RBE, dose nonuniformity and dose rate. The EUD is applied to brachytherapy with I eye plaques designed by the Collaborative Ocular Melanoma Study (COMS).

Methods: The EUD is defined as the uniform dose distribution with RBE = 1 that causes equal cell survival for a given nonuniform dose distribution with the variable RBE > 1. The EUD can be used for comparison of cell survival for nonuniform dose distributions with different RBE, because they are compared to the reference dose with RBE = 1. The EUD is applied to brachytherapy with I COMS eye plaques that are characterized by a steep dose gradient in tumor base-apex direction, protracted irradiation during time intervals of 3-8 days, and variable dose-rate dependent RBE with a maximum of about 1.4. The simulations are based on dose of 85 Gy prescribed to the farthest intraocular extent of the tumor (tumor apex). To compute the EUD in eye plaque brachytherapy and correct for protracted irradiation, the distributions of physical dose have been converted to non-uniform distributions of biologically effective dose (BED) to include the biological effects of sublethal cellular repair, Our radiobiological analysis considers the combined effects of different time-dependent dose rates, spatial dose non-uniformity, dose fractionation and different RBE and can be used to derive optimized dose regimens brachytherapy.

Results: Our simulations show that the EUD increases with the prescription depths and the maximum increase may achieve 6% for the tumor height of 12 mm. This effect stems from a steep dose gradient within the tumor that increases with the prescription depth. The simulations also show that the EUD increase may achieve 12% with increasing the dose rate when implant duration decreases. The combined effect of dose nonuniformity and dose rate may change the EUD up to 18% for the same dose prescription of 85 Gy to tumor apex. The absolute dose range of 48-61 Gy (RBE) for the EUD computed using 4 or 5 fractions is comparable to the dose prescriptions used in stereotactic body radiation therapy (SBRT) with megavoltage X-rays (RBE = 1) for different cancers. The tumor control probabilities in SBRT and eye plaque brachytherapy are very similar at the level of 80% or higher that support the hypothesis that the selected approximations for the EUD are valid.

Conclusions: The computed range of the EUD in I COMS eye plaque brachytherapy suggests that the selected models and hypotheses are acceptable. The EUD can be useful for analysis of treatment outcomes and comparison of different dose regimens in eye plaque brachytherapy.