The potential impact of relative biological effectiveness uncertainty on charged particle treatment prescriptions

There continues to be uncertainty regarding the relative biological effectiveness (RBE) values that should be used in charged particle radiotherapy (CPT) prescriptions using protons and heavier ions. This uncertainty could potentially offset the physical dose advantage gained by exploiting the Bragg peak effect and it needs to be clearly understood by clinicians and physicists. This paper introduces a combined radiobiological and physical sparing factor (S). This factor includes the ratio of the most relevant physical doses in tumour and normal tissues in combination with their respective RBE values and can be extended to contain the uncertainties in RBE. S factors can be used to study, in a simplified way for tentative modelling, those clinical situations in which high-linear energy transfer (LET) irradiations are likely to prove preferable over their low-LET counterparts for a matched tumour iso-effect. In cases where CPT achieves an excellent degree of normal tissue sparing, the radiobiological factors become less important and any uncertainties in the tumour and healthy tissue RBE values are correspondingly less problematic. When less normal tissue sparing can be achieved, however, the RBE uncertainties assume greater relevance and will affect the reliability of the dose-prescription methodology. More research is required to provide accurate RBE estimation, focusing attention on the associated statistical uncertainties and potential differences in RBE between different tissue types.