Abstract
Abstract INTRODUCTION: HCC is a highly vascular, rapidly fatal cancer and antiangiogenic drugs have shown clinical benefit despite lack of radiographic tumor shrinkage. We standardized imaging methods to assess HCC in the woodchuck animal model (Marmota monax). This is a large unique animal model of spontaneous HCC with several similarities to human Hepatitis b(HBV) related HCC and such studies would allow utilization of this model to assess the functional changes with currently used targeted therapies. METHODS: Fourteen woodchucks infected at birth with known titers of sera from a chronic infectious pool of chronic woodchuck hepatitis virus (WHV), which is similar in structure and replicative function to HBV. Serial measurement of WHV antigen titers was conducted. Chronic WHV infection occurred in greater than 60% of woodchucks by 12 months. The WHV carrier woodchucks were screened with serial ultrasound and ten animals which developed HCC at a median age of 24- 36 months were included. Mediports were placed in the femoral vein under aseptic precautions for intravenous (IV) contrast administration. DCE-MRI methods for assessment of woodchuck HCC blood flow and size were optimized in a 1.5T magnet human head coil and IV gadolinium injected at 5cc per second using a rapid injector. Four variables - the median Ktrans, median AUCBN90, necrotic volume (NV) and total volume (TV) were analyzed by Virtualscopics using published methods. A total of 44 images were obtained, 32 were included in the study. Death due to disease progression or missing paired data resulted in exclusion of 12 images. Statistical analysis: We performed a variability analysis by calculating the concordance correlation coefficient (CCC). This coefficient was calculated for all four variables and compared at different time points. RESULTS: The CCC calculated for images obtained on day 1 and day 8 images was 0.85 for Ktrans, 0.59 for AUCBN90, 0.93 for NV and 0.99 for TV. Strong concordance was seen in 3 of the 4 DCE-MRI variables recorded a week apart. This lack of change over an 8-day period is expected with this cancer. We also compared CCC for day 8 and day 14 with Ktrans 0.76, AUCBN 0.6, NV 0.76, TV 0.89 showing less agreement than day 1 and 8. When compared to day 14 and day 30 CCC for different variables were Ktrans 0.59, AUCBN90 0.38, NV 0.82, TV 0.85, suggesting a downward trend with increasing time. Our data using this technique is able to identify clinically relevant changes in tumor size with little variability in short interval scanning. CONCLUSION: This is the first study validating the accuracy of DCE-MRI in a translational animal model for HCC and has potential to aid development of newer antiangiogenic therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4546. doi:1538-7445.AM2012-4546
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