Development of a microdosimetry-based method to derive cell survival rates for evaluating the biological effects of BNCT

Boron neutron capture therapy (BNCT) dose calculation often relies on fixed relative biological effectiveness (RBE) and compound biological effectiveness (CBE) values, despite their dependence on beam quality and tumor biology. We developed a microdosimetry-driven framework that predicts cell survival and RBE for BNCT by coupling PHITS lineal energy (T-SED) calculations with the microdosimetric kinetic (MK) model. MK parameters (<i>α</i>₀,<i>β</i>,<i>r</i>_<i>d</i>,<i>y</i>₀) were derived for BNCT relevant cell lines (U87 glioblastoma, NB1RG skin fibroblasts, SAS human squamous carcinoma, and SCC7 murine squamous carcinoma) using low-LET reference datasets curated in the PIDE database and irradiation conditions reproduced in PHITS. The derived parameters successfully reproduced<i>in vitro</i>survival curves for various charged particles across different energies, and when applied to neutron fields representative of BNCT systems (Kyoto University Reactor thermal neutron beam, cyclotron-based epithermal neutron source using a beryllium target, and linear accelerator system using a lithium target), the framework also reproduced measured<i>in vitro</i>data. Predicted RBE at 10% survival (RBE₁₀) agreed with measurements across cell lines and beam qualities, with only a slight deviation for SCC7 under the CICS spectrum and moderate deviations for SAS due to limited and heterogeneous low-LET datasets in PIDE. This method enables spectrum and cell-line specific estimation of biological effect, supporting replacement of fixed RBE/CBE with spectrum aware quantities to improve BNCT dose prescription and safety. The framework can also guide neutron-beam design by providing preliminary RBE estimates prior to construction of the moderator and beam shaping assembly. Incorporating intracellular boron microdistribution in future work is expected to refine CBE estimates and enhance biological accuracy in BNCT treatment planning. This framework provides a physics-based alternative to fixed RBE/CBE values.