RT Journal Article
SR Electronic
T1 T2 heterogeneity provides a sensitive measure of early tumor response to radiotherapy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.21.053736
DO 10.1101/2020.04.21.053736
A1 Michal R. Tomaszewski
A1 William Dominguez-Viqueira
A1 Antonio Ortiz
A1 Yu Shi
A1 James R. Costello
A1 Heiko Enderling
A1 Stephen A. Rosenberg
A1 Robert J. Gillies
YR 2020
UL http://biorxiv.org/content/early/2020/04/23/2020.04.21.053736.abstract
AB Purpose External beam radiotherapy (XRT) is a widely used cancer treatment, yet responses vary dramatically between patients. These differences are not accounted for in clinical practice, in part due to a lack of sensitive biomarkers of early response. In this work, we test the hypothesis that quantification of intratumor heterogeneity is a sensitive and robust biomarker of early response to XRT. A novel Magnetic Resonance Imaging (MRI) approach is proposed, utilizing histogram analysis of clinically-used T2 relaxation measurements to assess early changes in the tumor heterogeneity following irradiation in murine models of pancreatic cancer, indicative of radiotherapy response.Methods and Materials Dynamic Magnetic Resonance T2 relaxation imaging was performed every 72h following 10 Gy dose XRT in two murine models of pancreatic cancer. Proposed biomarker of radiotherapy response was compared with tumor growth kinetics, and biological validation was performed through quantitative histology analysis.Results Quantification of tumor T2 interquartile range (IQR) as a measure of histogram width showed excellent sensitivity for detection of XRT-induced tumor changes as early as 72h after treatment, outperforming whole tumor T2 and Diffusion weighted MRI metrics. This response was observed both in quantitative T2 maps and in T2-weighted images that are routine in clinical practice. Histological comparison revealed the T2 IQR provides a measure of spatial heterogeneity in tumor cell density, related to radiation-induced necrosis. The early IQR changes were found to presage subsequent tumor volume changes in two distinct pancreatic models, suggesting promise for treatment response prediction. The metric showed excellent test-retest robustness.Conclusions Our preclinical findings indicate that spatial heterogeneity analysis of T2 MRI can provide a sensitive and readily translatable method for early radiotherapy response assessment in pancreatic cancer. We propose that this will be useful in adaptive radiotherapy, specifically in MRI-guided treatment paradigms.Competing Interest StatementDr Gillies is an investor and serves on an advisory board for HealthMyne Inc.