Clinically relevant nanodosimetric simulation of DNA damage complexity from photons and protons
Authors
Henthorn, NicholasWarmenhoven, 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
Affiliation
Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, UKIssue Date
2019
Metadata
Show full item recordAbstract
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 AdvancesDOI
10.1039/C8RA10168JAdditional Links
https://dx.doi.org/10.1039/C8RA10168JType
Meetings and ProceedingsLanguage
enae974a485f413a2113503eed53cd6c53
10.1039/C8RA10168J