Hypofractionation: what does it mean for prostate cancer treatment?

Abstract

Using current radiobiologic models and biologic parameters, we performed an exploratory study of the clinical consequences of hypofractionation in prostate cancer radiotherapy. Four hypofractionated treatment regimens were compared with standard fractionation of 2 Gy x 39 for prostate carcinoma using a representative set of anatomical structures. The linear-quadratic model and generalized equivalent uniform dose formalism were used to calculate normalized equivalent uniform dose (gEUD(2)), from which tumor control probability and normal tissue complication probability were calculated, as well as "complication-free tumor control probability" (P+). The robustness of the results was tested for various tumor alpha/beta values and broad interval of biologic parameters such as surviving fraction after a dose of 2 Gy (SF2). A 2.5% and 5.8% decrease in NTCP for rectum and bladder, respectively, was predicted for the 6.5 Gy/fraction regimen compared with the 2 Gy/fraction. Conversely, TCP for hypofractionated regimens decreased significantly with increasing SF2 and alpha/beta. For tumor cells with SF2 = 0.4-0.5, P+ was superior for nearly all hypofractionated regimens even for alpha/beta values up to 6.5 Gy. For less responsive tumor cells (SF2 = 0.6), hypofractionation regimens were inferior to standard fractionation at much lower alpha/beta. For a sample set of anatomical structures, existing radiobiologic data and models predict improved clinical results from hypofractionation over standard fractionation not only for prostate carcinoma with low alpha/beta but also for high alpha/beta (up to 6.5 Gy) when SF2 < 0.5. Predicted results for specific patients may vary with individual anatomy, and large-scale clinical conclusions can be drawn only after performing similar analysis on an appropriate population of patients.