Clinically relevant nanodosimetric simulation of DNA damage complexity from photons and protons

Nicholas Henthorn, John Warmenhoven, Marios Sotiropoulos, Adam Aitkenhead, Edward Smith, Samuel Ingram, Norman Kirkby, Amy Chadwick, Neil Burnet, Ranald Mackay, Karen Kirkby, Michael Merchant

Research output: Contribution to journalArticlepeer-review


Relative Biological Effectiveness (RBE), the ratio of doses between radiation modalities to produce the same biological endpoint, is a controversial and important topic in proton therapy. A number of phenomenological models incorporate variable RBE as a function of Linear Energy Transfer (LET), though a lack of mechanistic description limits their applicability. In this work we take a different approach, using a track structure model employing fundamental physics and chemistry to make predictions of proton and photon induced DNA damage, the first step in the mechanism of radiation-induced cell death. We apply this model to a proton therapy clinical case showing, for the first time, predictions of DNA damage on a patient treatment plan. Our model predictions are for an idealised cell and applied to an ependymoma case, at this stage without any cell specific parameters. By comparing to similar predictions for photons, we present a voxel-wise RBE of DNA damage complexity. This RBE of damage complexity shows similar trends to the expected RBE for cell kill, implying that damage complexity is an important factor in DNA repair and therefore biological effect.
Original languageEnglish
JournalRSC Advances
Early online date28 Feb 2019
Publication statusPublished - 2019

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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