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

Autor: Smith EAK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. edward.smith-4@postgrad.manchester.ac.uk.; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK. edward.smith-4@postgrad.manchester.ac.uk., Henthorn NT; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Warmenhoven JW; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Ingram SP; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK., Aitkenhead AH; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK., Richardson JC; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK., Sitch P; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK., Chadwick AL; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Underwood TSA; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Merchant MJ; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Burnet NG; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Kirkby NF; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Kirkby KJ; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Mackay RI; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, UK.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Dec 27; Vol. 9 (1), pp. 19870. Date of Electronic Publication: 2019 Dec 27.
DOI: 10.1038/s41598-019-56258-5
Abstrakt: 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.
Databáze: MEDLINE
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