Modeling of α/β for late rectal toxicity from a randomized phase II study: conventional versus hypofractionated scheme for localized prostate cancer

BACKGROUND: Recently, the use of hypo-fractionated treatment schemes for the prostate cancer has been encouraged due to the fact that α/β ratio for prostate cancer should be low. However a major concern on the use of hypofractionation is the late rectal toxicity, it is important to be able to predict the risk of toxicity for alternative treatment schemes, with the best accuracy. The main purpose of this study is to evaluate the response of rectum wall to changes in fractionation and to quantify the α/β ratio for late rectal toxicity METHODS: 162 patients with localized prostate cancer, treated with conformal radiotherapy, were enrolled in a phase II randomized trial. The patients were randomly assigned to 80 Gy in 40 fractions over 8 weeks (arm A) or 62 Gy in 20 fractions over 5 weeks (arm B). The median follow-up was 30 months. The late rectal toxicity was evaluated using the Radiation Therapy Oncology Group (RTOG) scale. It was assumed ≥ Grade 2 (G2) toxicity incidence as primary end point. Fit of toxicity incidence by the Lyman-Burman-Kutcher (LKB) model was performed. RESULTS: The crude incidence of late rectal toxicity ≥ G2 was 14% and 12% for the standard arm and the hypofractionated arm, respectively. The crude incidence of late rectal toxicity ≥ G2 was 14.0% and 12.3% for the arm A and B, respectively. For the arm A, volumes receiving ≥ 50 Gy (V50) and 70 Gy (V70) were 38.3 ± 7.5% and 23.4 ± 5.5%; for arm B, V38 and V54 were 40.9 ± 6.8% and 24.5 ± 4.4%. An α/β ratio for late rectal toxicity very close to 3 Gy was found. CONCLUSION: The ≥ G2 late toxicities in both arms were comparable, indicating the feasibility of hypofractionated regimes in prostate cancer. An α/β ratio for late rectal toxicity very close to 3 Gy was found.