Scott, J.G., Fletcher, A.G., Anderson, A.R. et al. (1 more author) (2016) Spatial Metrics of Tumour Vascular Organisation Predict Radiation Efficacy in a Computational Model. PLoS Computational Biology, 12 (1). e1004712. ISSN 1553-7358
Abstract
Intratumoural heterogeneity is known to contribute to poor therapeutic response. Variations in oxygen tension in particular have been correlated with changes in radiation response in vitro and at the clinical scale with overall survival. Heterogeneity at the microscopic scale in tumour blood vessel architecture has been described, and is one source of the underlying variations in oxygen tension. We seek to determine whether histologic scale measures of the erratic distribution of blood vessels within a tumour can be used to predict differing radiation response. Using a two-dimensional hybrid cellular automaton model of tumour growth, we evaluate the effect of vessel distribution on cell survival outcomes of simulated radiation therapy. Using the standard equations for the oxygen enhancement ratio for cell survival probability under differing oxygen tensions, we calculate average radiation effect over a range of different vessel densities and organisations. We go on to quantify the vessel distribution heterogeneity and measure spatial organization using Ripley's L function, a measure designed to detect deviations from complete spatial randomness. We find that under differing regimes of vessel density the correlation coefficient between the measure of spatial organization and radiation effect changes sign. This provides not only a useful way to understand the differences seen in radiation effect for tissues based on vessel architecture, but also an alternate explanation for the vessel normalization hypothesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Scott et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Mathematics and Statistics (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Feb 2016 14:12 |
Last Modified: | 15 Feb 2016 14:12 |
Published Version: | http://dx.doi.org/10.1371/journal.pcbi.1004712 |
Status: | Published |
Publisher: | Public Library of Science |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pcbi.1004712 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:94909 |