External beam
radiotherapy (XRT) is a widely used
cancer treatment, yet responses vary dramatically among patients. These differences are not accounted for in clinical practice, partly due to a lack of sensitive early response
biomarkers. We hypothesize that quantitative magnetic resonance imaging (MRI) measures reflecting
tumor heterogeneity can provide a sensitive and robust
biomarker of early XRT response. MRI T2 mapping was performed every 72 hours following 10 Gy dose XRT in two models of
pancreatic cancer propagated in the hind limb of mice. Interquartile range (IQR) of
tumor T2 was presented as a potential
biomarker of
radiotherapy response compared with
tumor growth kinetics, and biological validation was performed through quantitative histology analysis. Quantification of
tumor T2 IQR showed sensitivity for detection of XRT-induced
tumor changes 72 hours
after treatment, outperforming T2-weighted and diffusion-weighted MRI, with very good robustness. Histological comparison revealed that T2 IQR provides a measure of spatial heterogeneity in
tumor cell density, related to radiation-induced
necrosis. Early IQR changes were found to correlate to subsequent
tumor volume changes, indicating promise for treatment response prediction. Our preclinical findings indicate that spatial heterogeneity analysis of T2 MRI can provide a translatable method for early
radiotherapy response assessment. We propose that the method may in future be applied for personalization of
radiotherapy through adaptive treatment paradigms.