Clinical Consequences of Relative Biological Effectiveness (RBE) Variations in Proton Radiotherapy of the Prostate, Brain, and Liver

Abstract

The large range of (α/β)x-rays values reported for prostate (1.2Gy-5.0Gy), brain (10Gy-15Gy) and liver (13Gy-17Gy) imply that the proton RBE for these tissues could differ from the commonly used value of 1.1. Our aim was to evaluate the impact of this uncertainty on the RBE-weighted total dose (RWTD) to normal and tumor tissues when proton doses are delivered using standard or hypofractionated isoeffective regimes. RWTD distributions for five prostate, brain and liver patients were calculated using an in-house developed RBE model as a function of dose, Linear Energy Transfer (LET) and (α/β)x-rays. Variation on the DVH for the GTV and the organs-at-risk due to changes of (α/β)x-rays or fractionation regime were calculated and the RWTD received by 10% and 90% of the organ volume reported. The goodness of the plan, bearing the uncertainties, was then evaluated compared to the delivered plan with assumed RBE = 1.1. Table 1 summaries values of RWTD10 and RWTD90 when RBE is assumed to be equal to 1.1 and when RBE changes with the specified values of (α/β)x-rays. Standard fractionated regimes assuming an RBE varying with (α/β)x-rays provide RWTD10 values in organs-at-risk always smaller than those obtained in the case RBE = 1.1 except for the case of the chiasm, brainstem and the optical nerves. However, in hypofractionated regimes, the total doses received by normal tissues when RBE = 1.1 are in all cases larger than in the case of a variable RBE. The results show that, except for the case of prostate, large variations of (α/β)x-rays are not accompanied by large variations of RBE and, in standard fractionation regimes, the RWTD values derived from RBE = 1.1 or a variable RBE do not differ substantially. However, this difference increases in hypofractionated regimes, with a clear advantage for the case of a flexible RBE as in this case the RWTD delivered to the normal tissues is substantially smaller than in the case of RBE = 1.1. The results show that the use of a variable RBE with dose, LET and (α/β) x-rays would help to optimize the dose delivered to the target. The consideration of RBE variations could also influence the comparison of proton and photon treatments in clinical trials.Tabled 1GTV (1.2Gy< α/β <5.0Gy) Prescribed Dose (Standard Fractionation): 78.3GyANT RECTUM (2.5Gy< α/β <5.0Gy)BLADDER (3.0Gy< α/β <7.0Gy)GTV (10Gy< α/β <15Gy) Prescribed Dose (Standard Fractionation): 52.1GyCHIASM (1.5Gy< α/β <3.9Gy)BRAINSTEM (1.5Gy< α/β <3.9Gy)LT OPTICAL NERVE (1.5Gy< α/β <3.9Gy)RT OPTICAL NERVE (1.5Gy< α/β <3.9Gy)GTV (13Gy< α/β <17Gy) Prescribed Dose (Standard Fractionation): 60.2GyLUNG (1.6Gy< α/β <6.9Gy)HEALTHY LIVER (1.5Gy< α/β <3.0Gy)n = 3RWTD10RBE≠1.136 - 4931 - 3229.6 - 29.831.8 - 32.530.9 - 31.530.1 - 30.823.7 - 24.522.7 - 23.530.9 - 31.314.6 - 14.811.6 - 11.8RBE = 1.135.533.932.433.733.632.525.5824.532.415.812.3RWTD90RBE≠1.135 - 478 - 90.129.9 - 30.630 - 30.60.040.090.0929.2 - 29.60.010RBE = 1.134.59.10.1232.332.60.030.080.0830.60.010n = 10RWTD10RBE≠1.157 - 8049 - 5046 - 4752 - 5451 - 5350 - 5239 - 4137.7 - 39.848.6 - 49.423.1 - 23.518.6 - 19.8RBE = 1.155.552.950.555.154.853.041.839.950.524.619.2RWTD90RBE≠1.156 - 7713 - 140.2049 - 5149 - 510.050.160.1945.8 - 46.70.010.01RBE = 1.153.814.10.2052.853.20.050.150.1747.60.010.01Standard FractionationRWTD10RBE≠1.194 - 13979 - 8274.9 - 77.256 - 5955 - 5954 - 5843 - 4841 - 4665 - 6631.1 - 31.625 - 26.7RBE = 1.188.2684.280.457.957.755.843.94267.532.925.6RWTD90RBE≠1.191 - 13322 - 240.31 - 0.3454 - 5753.5 - 57.50.160.160.1661 - 620.010.01RBE = 1.185.720.70.3255.555.90.070.150.1663.70.010.01PROSTATE RWTD [Gy(RBE)]BRAIN RWTD [Gy(RBE)]LIVER RWTD [Gy(RBE)] Open table in a new tab