RBE, reference RBE and clinical RBE: Applications of these concepts in hadron therapy

Introduction of heavy particles (hadrons) into radiation therapy aims at im proving the physical selectivity of the irradiation (e.g. proton beams), or the radiobiological differential effect (e.g. fast neutrons), or both (e.g . heavy-ion beams). Each of these new therapy modalities requires several t ypes of information before prescribing safely the doses to patients, as wel l as for recording and reporting the treatments. (i) absorbed dose measured in a homogeneous phantom in reference conditions; (ii) dose distribution c omputed at the level of the target volume(s) and the normal tissues at risk ; (iii) radiation quality from which a RBE evaluation could be predicted an d (iv) RBE measured on biological systems or derived from clinical observat ion. In hadron therapy, the RBE of the different beams raises specific prob lems. For fast neutrons, the RBE varies within wide limits (about 2 to 5) d epending on the neutron energy spectrum, dose, and biological system. For p rotons, the RBE values range between smaller limits (about 1.0 to 1.2). A c linical benefit can thus not be expected from RBE differences. However, the proton RBE problem cannot be ignored since dose differences of about 5% ca n be detected clinically in some cases. The situation is most complex with heavy ions since RBE variations are at least as large as for fast neutrons, as a function of particle type and energy, dose and biological system. In addition, RBE varies with depth. Radiation quality thus has to be taken int o account when prescribing and reporting a treatment. This can be done in d ifferent ways: (a) description of the method of beam production; (b) comput ed LET spectra and/or measured microdosimetric spectra at the points clinic ally relevant; (c) RBE determination. The most relevant RBE data are those obtained for late tolerance of normal tissues at 2 Gy per fraction ("refere nce RBE"). The "clinical RBE" selected by the radiation oncologist when pre scribing the treatment will be close to the reference RBE, but other factor s (such as heterogeneity in dose distribution) may influence the selection of the clinical RBE. Combination of microdosimetric data and experimental R BE values improves the confidence in both sets of data.