|
Stereotactic body radiotherapy (SBRT) shows promise for increasing local tumour control for many of the most lethal cancer types including pancreatic ductal carcinoma (PDA), compared to conventional radiotherapy. Yet SBRT radiation fractionation schedules may still be improved as its mechanism of action remains largely unknown. It has been suggested that this accelerated hypofractionated treatment benefits from vascular damage (in particular of blood capillaries ~10-30μm in diameter). We therefore hypothesize that monitoring radiation-induced microvascular changes will (1) yield insights into SBRT’s radiobiological effects, and (2) enable predictions of long-term tumour response. We addressed this hypothesis pre-clinically in PDA human xenografts grown in immunocompromised mice in a dorsal skinfold window chamber model. We monitored both micro- (via optical coherence tomography angiography (OCTA)) and macro- (via dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)) vascular responses to irradiation over time. We first studied responses to single fraction irradiation, and then to a full typical clinical SBRT regimen delivered via a small animal irradiator. Candidate predictive vascular biomarkers of radiobiological relevance were derived from 3D OCTA microvascular networks (micro-scale response) and correlated with the DCE-MRI functional metrics relating to the transport of an MRI contrast agent (macro-scale response). The longitudinal trajectories of both were measured before, during and following treatments. Herein we focus primarily on the DLF150 and λ metrics from OCTA which describe the microvascular heterogeneity and molecular transport efficiency. To assess the predictive power of the various metrics, their temporal trends were compared to the macroscopic tumour response (volume and viability). Efforts are ongoing to train neural networks for this time series analysis. The combined OCTA and DCE-MRI insights should yield a better understanding of tissue functional response to high doses of radiation employed in SBRT and help develop improved SBRT fractionation schedules (dose and time combinations) towards personalized and adaptive radiation therapy.
|
