Ntcp predictions for rat spinal cord tolerance following ion mixed-field irradiation: comparison with monochromatic exposure

Currently, treatment planning in hadrontherapy relies mainly on physical quantity constraints, in order to optimize the dose distribution within the patient body. However, one of the main challenges remains the prediction and mitigation of late normal tissue complications, through the incorporation of Normal Tissue Complication Probability (NTCP) models into the treatment planning process. This study aims to present a predictive model of NTCP and to quantify the impact of taking into account the mixed irradiation field, in contrast with the monochromatic approximation. NTCP was modelled using the mechanistic Critical Element model, which depends on four parameters. The two tissue-specific parameters were fixed from photon data fit, while the two radiation-dependent parameters were predicted using a dedicated interface combining Geant4 simulations of realistic irradiation conditions with the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model. Doses corresponding to 50% NTCP were calculated for both monoenergetic and mixed-field scenarios. In 38 out of 56 cases, the percentage difference was below 5%, while in the remaining 18 cases, mostly involving high-LET carbon ions, the difference remained under 20%. This Geant4-BIANCA–based approach enables NTCP prediction in hadrontherapy-like mixed-field scenarios, supporting the development of biologically driven and patient-personalized treatment plans.