Quantification of the tumour microvascular response to high dose-per-fraction radiotherapy

<i>Objective</i>. Microvascular ablation during high dose-per-fraction radiotherapy (HDFRT) is disparately reported in the literature. This study was conducted to quantify the tumour microvascular response to different HDFRT schedules.<i>Approach</i>. A high single-dose irradiation of 20 Gy and two multifraction schedules (three fractions of 10 Gy and 15 Gy each) were studied. Patient-derived BxPC-3 pancreatic tumours in a mouse dorsal skinfold window chamber were treated and their 3D microvascular networks were longitudinally imaged with speckle variance optical coherence tomography for up to 7 weeks post irradiation. The overall vascular volume density (VVD), VVD for small vessels (diameters between 15-25<i>μ</i>m and 25-35<i>μ</i>m), and the vascular convexity index<i>λ</i>(a measure of vessel organization and space filling at short distances) were quantified.<i>Main results</i>. There were no significant differences in overall VVD for treated vs. control tumours at all timepoints. Examination of small-diameter vessels revealed some transient reductions in VVD_{15-25<i>μ</i>m}and VVD_{25-35<i>μ</i>m}compared to controls at<i>t</i>∼ 3 weeks for larger dose-per-fraction regimens (3 × 15 Gy and 1 × 20 Gy); ablated vasculature regrew back to baseline values by 7 weeks. Convexity indices for these larger-dose-per-fraction tumours were ∼55% larger than unirradiated controls by the end of monitoring period; no such effects were seen in the 3 × 10 Gy cohort.<i>Significance</i>. The results of this study reveal the complex role of small vessels in microvascular ablation caused by HDFRT, with a dependence on the dose per fraction and total delivered dose. After small vessel ablation, regrown vessels had more uniform and regular spacing than non-ablated vessels as quantified by<i>λ</i>, potentially suggesting improved tumour response if subsequent retreatments are attempted.