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

Objective. 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.Approach. 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 15-25μm and 25-35μm), and the vascular convexity indexλ(a measure of vessel organization and space filling at short distances) were quantified.Main results. 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_15-25μmand VVD_25-35μmcompared to controls att∼ 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.Significance. 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 byλ, potentially suggesting improved tumour response if subsequent retreatments are attempted.