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

Autor:	Henthorn NT; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester UK nicholas.henthorn@manchester.ac.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 UK nicholas.henthorn@manchester.ac.uk.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre Manchester UK., Sotiropoulos M; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester UK nicholas.henthorn@manchester.ac.uk., Aitkenhead AH; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester UK nicholas.henthorn@manchester.ac.uk.; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust Manchester UK., Smith EAK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester UK nicholas.henthorn@manchester.ac.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 UK nicholas.henthorn@manchester.ac.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 UK nicholas.henthorn@manchester.ac.uk.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre Manchester UK., Chadwick AL; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester UK nicholas.henthorn@manchester.ac.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 UK nicholas.henthorn@manchester.ac.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 UK nicholas.henthorn@manchester.ac.uk.; Christie Medical Physics and Engineering, The Christie NHS Foundation Trust Manchester UK., Kirkby KJ; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester UK nicholas.henthorn@manchester.ac.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 UK nicholas.henthorn@manchester.ac.uk.; The Christie NHS Foundation Trust, Manchester Academic Health Science Centre Manchester UK.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2019 Feb 28; Vol. 9 (12), pp. 6845-6858. Date of Electronic Publication: 2019 Feb 28 (Print Publication: 2019).
DOI:	10.1039/c8ra10168j
Abstrakt:	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. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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