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

• Published in: RSC advances Vol. 9; no. 12; pp. 6845 - 6858
• Main Authors: Henthorn, N T, Warmenhoven, J W, Sotiropoulos, M, Aitkenhead, A H, Smith, E A K, Ingram, S P, Kirkby, N F, Chadwick, A L, Burnet, N G, Mackay, R I, Kirkby, K J, Merchant, M J
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01-01-2019; The Royal Society of Chemistry
• Subjects: Biological effects; Cell death; Chemistry; Complexity; Computer simulation; Deoxyribonucleic acid; DNA; DNA damage; Linear energy transfer (LET); Mathematical models; Organic chemistry; Photons; Protons; Radiation damage; Radiation effects; Relative biological effectiveness (RBE); Therapy
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c8ra10168j

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.