RT Journal Article
SR Electronic
T1 Spatial metrics of tumour vascular organisation predict radiation efficacy in a computational model
JF bioRxiv
FD Cold Spring Harbor Laboratory Press
DO 10.1101/029595
A1 Scott, Jacob G
A1 Fletcher, Alexander George
A1 Anderson, Alexander RA
A1 Maini, Philip K
YR 2015
UL http://biorxiv.org/content/early/2015/10/26/029595.abstract
AB Intratumoural heterogeneity is known to contribute to heterogeneity in 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 endeavour 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 in simulated, random, vessel organizations. 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 spatial homogeneity. 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.