In Silico Models of DNA Damage and Repair in Proton Treatment Planning: A Proof of Concept

Sci Rep. 2019 Dec 27;9(1):19870. doi: 10.1038/s41598-019-56258-5.

Abstract

There is strong in vitro cell survival evidence that the relative biological effectiveness (RBE) of protons is variable, with dependence on factors such as linear energy transfer (LET) and dose. This is coupled with the growing in vivo evidence, from post-treatment image change analysis, of a variable RBE. Despite this, a constant RBE of 1.1 is still applied as a standard in proton therapy. However, there is a building clinical interest in incorporating a variable RBE. Recently, correlations summarising Monte Carlo-based mechanistic models of DNA damage and repair with absorbed dose and LET have been published as the Manchester mechanistic (MM) model. These correlations offer an alternative path to variable RBE compared to the more standard phenomenological models. In this proof of concept work, these correlations have been extended to acquire RBE-weighted dose distributions and calculated, along with other RBE models, on a treatment plan. The phenomenological and mechanistic models for RBE have been shown to produce comparable results with some differences in magnitude and relative distribution. The mechanistic model found a large RBE for misrepair, which phenomenological models are unable to do. The potential of the MM model to predict multiple endpoints presents a clear advantage over phenomenological models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • DNA Damage / genetics*
  • DNA Damage / physiology
  • DNA Repair / genetics*
  • DNA Repair / physiology
  • Female
  • Humans
  • Linear Energy Transfer / genetics
  • Linear Energy Transfer / physiology
  • Monte Carlo Method
  • Young Adult