Relating the proton relative biological effectiveness to tumor control and normal tissue complication probabilities assuming interpatient variability in α/β

Abstract

Background: Proton therapy uses a constant relative biological effectiveness (RBE) of 1.1. The use of variable RBE values has been suggested but is currently not feasible due to uncertainties. The impact of variable RBE has solely been studied using dosimetric indices. This work elucidates the impact of RBE variations on tumor control and normal tissue complication probabilities (TCP/NTCP). Methods: Models to estimate TCP and NTCP were used in combination with an empirical proton RBE model. Variations in outcome as a function of linear-quadratic model parameters for cellular radiosensitivity were determined for TCP in prostate and ependymoma. In addition, NTCP analysis was done for brainstem necrosis. Results: Considering a variable proton RBE as a dose-modifying factor for prescription doses and dose constraints is misleading, as TCP/NTCP do not simply scale with RBE. The dependency of RBE on α/β cannot be interpreted independent of TCP/NTCP because variations in radiosensitivity affect both photon and proton treatments. Assuming interpatient variability in radiosensitivity results in lower TCP for patients with low α/β. In proton therapy, the magnitude of TCP variations is reduced due to an RBE increase as α/β decreases. The TCP in proton therapy is less affected by interpatient variability in α/β. On the other hand, patients with a lower α/β would have a lower complication probability, which is counteracted by an increase in RBE as α/β decreases. Toxicities in proton therapy would be more affected by α/β variations compared to photon therapy. Conclusions: Assessment of variable RBE in proton therapy should be based on TCP and NTCP. Potential interpatient variability in radiosensitivity causes a smaller variance in TCP but a larger variance in NTCP for proton patients. The relative TCP as a function of α/β was found to be higher than the RBE, whereas the relative NTCP was lower than a calculated RBE.