Radiobiological meta-analysis of the response of prostate cancer to high dose rate brachytherapy

Background and purposeClinical studies have shown a marked reduction in tumor control in prostate cancer treated with radically hypofractionated high-dose-rate brachytherapy (HDR-BT). The purpose of this study was to analyze the dose-response of prostate cancer treated with HDR-BT, specifically aiming at investigating the potential failure of the linear-quadratic (LQ) model to describe the response at large dosesper-fraction. Materials and methodsWe collated a dataset of dose-response to HDR-BT (3258 patients). The analysis was conducted separately for low and intermediate risk, resulting in 21 schedules (1643 patients) and 22 schedules (1615 patients), respectively. Data were fitted to tumor control probability models based on the LQ model, the linear-quadratic-linear (LQL), and a modification of the LQ model to include the effect of reoxygenation during treatment. ResultsThe LQ cannot fit the data unless the /{beta} is allowed to be very high ([~][20-100] Gy, 95% confidence interval). If the /{beta} is constrained to be low (< 8 Gy) the LQ model cannot reproduce the clinical results, and the LQL model, which includes a moderation of radiation damage with increasing dose, significantly improves the fitting. On the other hand, the reoxygenation model does not match the results obtained with the LQL. ConclusionThe clinically observed reduction in tumor control in prostate cancer treated with radical HDR-BT is better described by the LQL model. Using the best-fitting parameters, the BED for a 20 Gy x 1 treatment (95 Gy) is far less than that of a conventional 2 Gy x 37 fractionation (184 Gy). These results may assist in the design of radical HDR-BT treatment.