Variability of HCC Tumor Diameter and Density Measurements on Dynamic Contrast-Enhanced Computed Tomography

Purpose: In cancers imaged using contrast-enhanced protocols, such as hepatocellular carcinoma (HCC), formal guidelines rely on measurements of lesion size (in mm) and radiographic density (in Hounsfield units [HU]) to evaluate response to treatment. However, the variability of these measurements across different contrast enhancement phases remains poorly understood. This limits the ability of clinicians to discern whether measurement changes are accurate. Methods: In this study, we investigated the variability of maximal lesion diameter and mean lesion density of HCC lesions on CT scans across four different contrast enhancement phases: non-contrast-enhanced phase (NCE), early arterial phase (E-AP), late arterial phase (L-AP), and portal venous phase (PVP). HCC lesions were independently segmented by two expert radiologists. For each pair of a lesion's scan timepoints, one was selected randomly as the baseline measurement and the other as the repeat measurement. Both absolute and relative differences in measurements were calculated, as were the coefficients of variance (CVs). Analysis was further stratified by both contrast enhancement phase and lesion diameter. Results: Lesion diameter was found to have a CV of 5.11% (95% CI: 4.20-6.01%). About a fifth of the measurement's relative changes were greater than 10%. Although there was no significant difference in diameter measurements across different phases, there was a significant negative correlation (R = -0.303, p-value = 0.030) between lesion diameter and percent difference in diameter measurement. Lesion density measurements varied significantly across all phases, with the greatest relative difference of 47% in the late arterial phase and a CV of 22.84% (21.48-24.20%). The overall CV for lesion density measurements was 26.19% (24.66-27.72%). Conclusions: Changes in tumor diameter measurements within 10% may simply be due to variability, and lesion density is highly sensitive to contrast timing. This highlights the importance of paying attention to these two variables when evaluating tumor response in both clinical trials and practice.