Data-driven ion-independent relative biological effectiveness modeling using the beam quality Q

Beam quality Q = Z2/E (Z = ion charge, E = energy), an alternative to the conventionally used linear energy transfer (LET), enables ion-independent modeling of the relative biological effectiveness (RBE) of ions. Therefore, the Q concept, i.e. different ions with similar Q have similar RBE values, could help to transfer clinical RBE knowledge from better-studied ion types (e.g. carbon) to other ions. However, the validity of the Q concept has so far only been demonstrated for low LET values. In this work, the Q concept was explored in a broad LET range, including the so-called overkilling region. The particle irradiation data ensemble (PIDE) was used as experimental in vitro dataset. Data-driven models, i.e. neural network (NN) models with low complexity, were built to predict RBE values for H, He, C and Ne ions at different in vitro endpoints taking different combinations of clinically available candidate inputs: LET, Q and linear-quadratic photon parameter α x/β x. Models were compared in terms of prediction power and ion dependence. The optimal model was compared to published model data using the local effect model (LEM IV). The NN models performed best for the prediction of RBE at reference photon doses between 2 and 4 Gy or RBE near 10% cell survival, using only α x/β x and Q instead of LET as input. The Q model was not significantly ion dependent (p > 0.5) and its prediction power was comparable to that of LEM IV. In conclusion, the validity of the Q concept was demonstrated in a clinically relevant LET range including overkilling. A data-driven Q model was proposed and observed to have an RBE prediction power comparable to a mechanistic model regardless of particle type. The Q concept provides the possibility of reducing RBE uncertainty in treatment planning for protons and ions in the future by transferring clinical RBE knowledge between ions.