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    In silico models of DNA damage and repair in proton treatment planning: a proof of concept

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    Authors
    Smith, Edward AK
    Henthorn, Nicholas
    Warmenhoven, John
    Ingram, Samuel
    Aitkenhead, Adam H
    Richardson, JC
    Sitch, Peter
    Chadwick, Amy
    Underwood, Tracy
    Merchant, Michael J
    Burnet, Neil G
    Kirkby, Norman
    Kirkby, Karen J
    Mackay, Ranald I
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    Affiliation
    Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
    Issue Date
    2019
    
    Metadata
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    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.
    Citation
    Smith EAK, Henthorn NT, Warmenhoven JW, Ingram SP, Aitkenhead AH, Richardson JC, et al. In Silico Models of DNA Damage and Repair in Proton Treatment Planning: A Proof of Concept. Sci Rep. 2019;9(1):19870.
    Journal
    Scientific Reports
    URI
    http://hdl.handle.net/10541/622685
    DOI
    10.1038/s41598-019-56258-5
    PubMed ID
    31882690
    Additional Links
    https://dx.doi.org/10.1038/s41598-019-56258-5
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-019-56258-5
    Scopus Count
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