A cell-type resolved proton RBE model for potential clinical application

Despite decades of effort, researchers have failed to develop a clinically implementable Relative Biological Effectiveness (RBE) model that can improve dose accuracy in proton therapy. A key challenge is that RBE's dependence on cell-type is not well understood. This study aimed to overcome this challenge.

A total of 139 eligible experimental datasets covering 33 cell lines from the Particle Irradiation Data Ensemble (PIDE) database were used in this study. A Poisson-based cell survival model, which has two new parameters α and β conceptually different from that in the conventional LQ model, was used to derive a proton RBE model by globally fitting the proton experimental data. The two parameters' fitting values for a cell's photon data, α_X and β_X, were used to characterize the cell type. RBE's dependence on cell type was investigated by studying RBE variation on α_X and β_X.

The Poisson-based model showed better global fitting than the LQ model (RMSE_w = 6.4% vs. 7.8%, p = 0.00003). A comprehensive RBE model expressed as RBE (LET, D_P, α_X, β_X) was consequently derived. Interestingly, RBE appears to vary minimally within 95% CI of α_X variation, while vary greatly for β_X variation. Cells were divided into two groups according to β_X, and the comprehensive model was simplified into a cell-type resolved model by establishing two cell-type-independent models for the two groups, respectively. This cell-type resolved model shows better agreement with experimental data than the comprehensive model derived from the LQ model.

The variation of β_X, which represents a cell's repair capability for critical damages, mainly contributes to RBE's cell-type dependence. A cell-type resolved model agreeing well with experimental data has been established.