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

Abstract

{\bf Purpose}: To develop a first principle and multi-scale 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 nano-scale radio-chemical to macro-scale cell biological pathways, spanning from initial DNA damage to tissue late effects. {\bf Methods}: The method is combination of analytical and multi-scale computational steps including (1) derivation of functional dependencies of NTCP on DNA driven cell lethality in nanometer and mapping to dose and LET in millimeter, and (2) 3D-surface fitting to Monte Carlo data set generated based on post radiation 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. {\bf Result}: Our model fits well the clinical data, generated for post radiation tissue toxicity and necrosis. The fitting procedure results in extraction of in-{\it vivo} radio-biological $\alpha$-$\beta$ indices and their numerical values. {\bf 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.

arXiv commentAccepted for publication in Medical Physics

References in corpus (4)

• Reactive Molecular Dynamics study on the first steps of DNA-damage by free hydroxyl radicals
• A molecular dynamics simulation of DNA damage induction by ionizing radiation
• A model for relative biological effectiveness of therapeutic proton beams based on a global fit of cell survival data
• Renormalization of radiobiological response functions by energy loss fluctuations and complexities in chromosome aberration induction: deactivation theory for proton therapy from cells to tumor control