Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial

Abstract

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Graphical abstract

Figure 1:

Participant enrollment flowchart. CE = contrast enhanced, HCC = hepatocellular carcinoma, TACE = transarterial chemoembolization.

Figure 2:

Example of two-dimensional (2D) contrast-enhanced (CE) US and CE MRI concordance. (A) Transverse 2D dual B-mode (left) and CE US (right) images obtained 1–2 weeks after transarterial chemoembolization (TACE). (B) Transverse 2D dual B-mode (left) and CE US (right) images obtained 4–6 weeks after TACE. (C) Axial CE MRI scan obtained 4–6 weeks after TACE. All images were obtained in a 67-year-old male participant with a 2.8-cm hepatocellular carcinoma in segment VI of the liver that was incompletely treated with TACE and that was confirmed when residual viability was present on the 4–8-month follow-up CE MRI scan (reference standard). Peripheral enhancement visible on C suggests residual tumor after TACE, which parallels the enhancement within the tumor on the CE US scan. This example shows 2D CE US and CE MRI diagnostic concordance, where readers for both modalities deemed this lesion incompletely treated based on arterial phase hyperenhancement (arrows). Here, CE US was used effectively to determine post-TACE viability earlier than with CE MRI, which ultimately yielded the same result.

Figure 3:

Example of two-dimensional (2D) contrast-enhanced (CE) US and CE MRI discordance. (A) Transverse 2D dual B-mode (left) and CE US (right) images obtained 1–2 weeks after transarterial chemoembolization (TACE). (B) Transverse 2D dual B-mode (left) and CE US (right) images obtained 4–6 weeks after TACE. (C) Axial CE MRI scan obtained 4–6 weeks after TACE. All images were obtained in a 62-year-old male participant with a 5.5-cm hepatocellular carcinoma in segment V of the liver that had residual tumor after TACE, confirmed with re-treatment angiography (reference standard) after identification of residual disease at imaging 1–2 months after TACE. This example shows CE US and CE MRI discordance, with CE US readers correctly identifying this lesion as incompletely treated, while CE MRI readers incorrectly deemed this treatment complete based on posttreatment inflammatory rim enhancement (arrows). Here, CE US revealed the success of TACE earlier and more accurately than CE MRI, with this series demonstrating the high sensitivity of CE US.

Figure 4:

Example of two-dimensional (2D) contrast-enhanced (CE) US and CE MRI discordance. (A) Transverse 2D dual B-mode (left) and CE US (right) image obtained 1–2 weeks after transarterial chemoembolization (TACE). (B) Transverse 2D dual B-mode (left) and CE US (right) images obtained 4–6 weeks after TACE. (C) Axial CE MRI scan 4–6 weeks after TACE. All images were obtained in a 63-year-old male participant with a 2.4-cm hepatocellular carcinoma in segment VIII of the liver who underwent successful TACE with no residual tumor, as confirmed with 4–8-month follow-up CE MRI (reference standard). This is an example of CE US and CE MRI discordance. CE MRI reads correctly noted that this tumor was completely treated, whereas CE US reads incorrectly deemed this lesion incompletely treated based on arterial phase hyperenhancement (arrows). Here, we show the high specificity of CE MRI and CE CT.

Figure 5:

Transverse (A) two-dimensional dual B-mode (left) and contrast-enhanced (CE) US (right) images and corresponding (B) three-dimensional (3D) CE US images in a 71-year-old male participant 11 days after transarterial chemoembolization (TACE) for a 7.1-cm hepatocellular carcinoma in segment VII of the liver. In A, large areas of residual enhancement and peripheral nodularity (arrow) are appreciated in the arterial phase, indicative of a viable residual tumor. In B, 3D CE US enables visualization across multiple sections (4.3-mm thickness, as shown in the top left panel), enabling visualization of various enhancing internal components (arrows).