Report of the AAPM TG-256 on the relative biological effectiveness of proton beams in radiation therapy

Abstract

The biological effectiveness of proton beams relative to photon beams in radiation therapy has been taken to be 1.1 throughout the history of proton therapy. While potentially appropriate as an average value, actual relative biological effectiveness (RBE) values may differ. This Task Group report outlines the basic concepts of RBE as well as the biophysical interpretation and mathematical concepts. The current knowledge on RBE variations is reviewed and discussed in the context of the current clinical use of RBE and the clinical relevance of RBE variations (with respect to physical as well as biological parameters). The following task group aims were designed to guide the current clinical practice: Assess whether the current clinical practice of using a constant RBE for protons should be revised or maintained. Identifying sites and treatment strategies where variable RBE might be utilized for a clinical benefit. Assess the potential clinical consequences of delivering biologically weighted proton doses based on variable RBE and/or LET models implemented in treatment planning systems. Recommend experiments needed to improve our current understanding of the relationships among in vitro, in vivo, and clinical RBE, and the research required to develop models. Develop recommendations to minimize the effects of uncertainties associated with proton RBE for well-defined tumor types and critical structures.

Keywords: RBE; proton therapy; relative biological effectiveness.

Figure 1

Increase in RBE for 2 Gy (relative to 6‐MV photons) across various SOBPs created by a passive scattering system. (a) Range/SOBP widths: 15 cm/5 cm; (b) 20 cm/10 cm; (c) 25 cm/10 cm. The RBE values are based on a linear fit of experimental data on RBE vs LET _d in the range of LET _d < 15 keV/μm independent of α/β for all published in vitro cell survival data. Only the region >95% of the SOBP dose is included.

Figure 2

Distribution of all possible RMF parameters that fit measured data for three proton energies equally well (within few % in terms of the surviving fraction). The large dots with error bars represent the mean values (Robert Stewart; unpublished).

Figure 3

Uncertainty weighted experimental RBE data for clonogenic cell survival measured in vitro at 2 Gy for LET _d <25 keV/μm relative to ⁶⁰Co. Note that the vertical line is drawn through RBE = 1.1. All data are shown irrespective of α/β. (adopted from69).

Figure 4

Uncertainty weighted RBE for clonogenic cell survival as a function of LET _d for different ranges of α/β and LET _d <25 keV/μm relative to ⁶⁰Co (adapted from69). Note that the vertical lines are drawn through RBE = 1.1.

Figure 5

Clinically equivalent dose distributions for two IMPT plans (chordoma; dose in % of prescribed dose; GTV in blue). The right column shows the LET _d distributions in keV/μm differ significantly.