A DNA damage multi‐scale model for NTCP in proton and hadron therapy

PURPOSE: To develop a first principle and multiscale model for normal tissue complication probability (NTCP) as a function of dose and LET for proton and in general for particle therapy with a goal of incorporating nanoscale radio-chemical to macroscale cell biological pathways, spanning from initial DNA damage to tissue late effects. METHODS: The method is a combination of analytical and multiscale computational steps including (a) derivation of functional dependencies of NTCP on DNA-driven cell lethality in nanometer and mapping to dose and LET in millimeter, and (b) three-dimensional-surface fitting to Monte Carlo data set generated based on postradiation image change and gathered for a cohort of 14 pediatric patients treated by scanning beam of protons for ependymoma. We categorize voxel-based dose and LET associated with development of necrosis in NTCP. RESULT: Our model fits well the clinical data, generated for postradiation tissue toxicity and necrosis. The fitting procedure results in extraction of in vivo radio-biological alpha-beta indices and their numerical values. DISCUSSION AND CONCLUSION: The NTCP model, explored in this work, allows to correlate the tissue toxicities to DNA initial damage, cell lethality and the properties and qualities of radiation, dose, and LET.