Clinical estimation of α/ß values for prostate cancer from isoeffective phase III randomized trials with moderately hypofractionated radiotherapy.

ABSTRACT

BACKGROUND: The α/ß values for prostate cancer (PCa) are usually assumed to be low (1.0-1.8 Gy). This study estimated the α/ß values of PCa from phase III randomized trials of conventional (CRT) versus hypofractionated (HRT) external beam radiotherapy (RT), reported as isoeffective in terms of their 5-year biochemical (BF) or biochemical and/or clinical failure (BCF) rates. MATERIAL AND METHODS: The α/ß for each trial was estimated from the equivalent biological effective doses using the linear-quadratic model for each of their HRT and CRT schedules. The cumulative outcomes of these trials were evaluated by meta-analysis for odds ratio (OR), risk ratio (RR) and risk difference (RD). RESULTS: Eight trials from seven studies, randomized 6993 patients between CRT (n = 2941) and HRT (n = 4052). RT treatment varied between the two treatment groups in terms of dose/fraction, total dose, overall treatment time and %patients on androgen deprivation therapy (ADT). Differences in OR, RR, and RD for both BF and BCF were nonsignificant. The computed α/ß ranged from 1.3 to 11.1 Gy (4.9 ± 3.9 Gy; 95% CI 1.6-8.2). On multivariate regression, %ADT was the sole determinant of computed α/ß (model R2 0.98, p < .001). CONCLUSIONS: Clinically estimated α/ß for PCa from isoeffective randomized trials using known variables in the linear-quadratic expression ranged between 1.3 and 11.1 Gy. The estimated α/ß values were inversely related to %ADT usage, which should be considered when planning future RT dose-fractionation schedules.