A new formalism for modelling parameters α and β of the linear-quadratic model of cell survival for hadron therapy

We propose a new formalism for calculating parameters α and β of the linear-quadratic model of cell survival. This formalism, primarily intended for calculating relative biological effectiveness (RBE) for treatment planning in hadron therapy, is based on a recently proposed microdosimetric revision of the single-target multi-hit model. The main advantage of our formalism is that it reliably produces α and β that have correct general properties with respect to their dependence on physical properties of the beam, including the asymptotic behavior for very low and high linear energy transfer (LET) beams. For example, in the case of monoenergetic beams, our formalism predicts that, as a function of LET, (a) α has a maximum and (b) the α/β ratio increases monotonically with increasing LET. No prior models reviewed in this study predict both properties (a) and (b) correctly, and therefore, these prior models are valid only within a limited LET range. We first present our formalism in a general form, for polyenergetic beams. A significant new result in this general case is that parameter β is represented as an average over the joint distribution of energies E ₁ and E ₂ of two particles in the beam. This result is consistent with the role of the quadratic term in the linear-quadratic model. It accounts for the two-track mechanism of cell kill, in which two particles, one after another, damage the same site in the cell nucleus. We then present simplified versions of the formalism, and discuss predicted properties of α and β. Finally, to demonstrate consistency of our formalism with experimental data, we apply it to fit two sets of experimental data: (1) α for heavy ions, covering a broad range of LETs, and (2) β for protons. In both cases, good agreement is achieved.