Biological dose representation for carbon-ion radiotherapy of unconventional fractionation

In carbon-ion radiotherapy, single-beam delivery each day in alternate directions has been commonly practiced for operational efficiency, taking advantage of the Bragg peak and the relative biological effectiveness (RBE) for uniform dose conformation to a tumor. The treatment plans are usually evaluated with total RBE-weighted dose, which is however deficient in relevance to the biological effect in the linear-quadratic model due to its quadratic-dose term, or the dose-fractionation effect. In this study, we reformulate the extrapolated response dose (ERD), or synonymously BED, which normalizes the dose-fractionation and cell-repopulation effects as well as the RBE of treating radiation, based on inactivation of a single model cell system and a typical treating radiation in carbon-ion RT. The ERD distribution virtually represents the biological effect of the treatment regardless of radiation modality or fractionation scheme. We applied the ERD formulation to simplistic model treatments and to a preclinical survey for hypofractionation based on an actual prostate-cancer treatment of carbon-ion radiotherapy. The proposed formulation was demonstrated to be practical and to offer theoretical implications. In the prostate-cancer case, the ERD distribution was very similar to the RBE-weighted-dose distribution of the actual treatment in 12 fractions. With hypofractionation, while the RBE-weighted-dose distribution varied significantly, the ERD distribution was nearly invariant, implying that the carbon-ion radiotherapy would be insensitive to fractionation. However, treatment evaluation with simplistic biological dose is intrinsically limited and must be complemented in practice somehow by clinical experiences and biology experiments.