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

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    Authors
    Henthorn, Nicholas
    Warmenhoven, J
    Sotiropoulos, M
    Aitkenhead, Adam H
    Smith, E
    Ingram, S
    Kirkby, Norman
    Chadwick, A
    Burnet, Neil G
    Mackay, Ranald I
    Kirkby, Karen J
    Merchant, Michael J
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    Affiliation
    Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UK
    Issue Date
    2019
    
    Metadata
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    Abstract
    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 are 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.
    Citation
    Henthorn NT, Warmenhoven JW, Sotiropoulos M, Aitkenhead AH, Smith EAK, Ingram SP, et al. Clinically relevant nanodosimetric simulation of DNA damage complexity from photons and protons. RSC Adv. 2019;9(12):6845-58.
    Journal
    RSC Advances
    URI
    http://hdl.handle.net/10541/621755
    DOI
    10.1039/C8RA10168J
    Additional Links
    https://dx.doi.org/10.1039/C8RA10168J
    Type
    Meetings and Proceedings
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1039/C8RA10168J
    Scopus Count
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    All Christie Publications

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