January 8, 2022

Abstract

Purpose

A high recurrence rate following ablative therapy of hepatocellular carcinoma (HCC) necessitates routine follow-up imaging (secondary surveillance) to facilitate early re-treatment. We evaluate our unique secondary surveillance algorithm (with use of alternating MRI and CEUS) by assessment of the relative diagnostic accuracy of MRI and CEUS in detection of residual/recurrent tumor. Potential benefits of alternating surveillance are compared to the use of MRI alone.

Materials and methods

This prospective observational IRB approved study included 231 patients with 354 treated tumors between January 2017 and June 2020. Treated lesions underwent secondary surveillance for a minimum of 7 months and up to 3 years, median follow-up 14 months. Secondary surveillance involved MRI performed at 1 month after treatment, followed by CEUS and MRI at alternate 3-month intervals (i.e., CEUS at month 4, MRI at month 7, etc.), for a total of 2 years. An equivocal finding on one imaging modality triggered expeditious evaluation with the alternate modality. Arterial phase hyperenhancement and washout comprise the classic features of recurrent tumor on both modalities.

Results

A total of 746 MRI and 712 CEUS examinations were performed, and a total of 184 tumor recurrences detected, MRI (n = 82) and CEUS (n= 102) (p = 0.19). There was no difference in the sensitivity (71.0–85.0% and 80.9–92.0%), specificity (97.4–99.2% and 98.5–99.9%), and area under the ROC curve (0.85–0.92 and 0.91–0.96) between MRI and CEUS, respectively. 23 of 82 recurrent tumors identified on MRI were equivocal and confirmed with expedited CEUS. 9 equivocal cases on MRI were disproved by expedited CEUS. On CEUS, 1 of the 102 recurrent tumors was equivocal and confirmed on MRI, and 2 equivocal CEUS cases were disproved by MRI.

Conclusion

MRI and CEUS performed similarly in our secondary surveillance algorithm for HCC in their ability to detect tumor recurrence, and showed no significant difference in their relative diagnostic test accuracy measures. Of greater interest, equivocal results on MRI (typically due to difficulty in distinguishing tumor recurrence from post-treatment change/ shunting) were either confirmed or disproven by CEUS in all cases. Secondary surveillance of treated HCC with alternating MRI and CEUS shows equivalent performance of each modality. CEUS resolves equivocal MRI and optimally demonstrates APHE and washout in tumor recurrence.

Introduction

The past decades have been witness to a tremendous improvement in the long-term survival of patients with hepatocellular carcinoma (HCC) [1]. The major reason for this includes the successful implementation of primary surveillance for high risk patients, generally performed with grayscale ultrasound every 6 months [2]. This facilitates early tumor detection, and therefore earlier intervention. Additionally, the emergence of minimally invasive image-guided therapies has facilitated the treatment of non-surgical candidates (nearly 90% of patients), for whom previously a diagnosis of HCC was indicative of impending doom [3]. After decades of painstaking effort at successful management of primary HCC, an emerging challenge relates to tumor recurrence, which occurs in approximately 50% of patients following potentially curative therapy and is prognostically detrimental [4].

The high likelihood of tumor recurrence following initial therapy has prompted major international liver societies, including the American Association for Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), and the Asian Pacific Association for the Study of the Liver (APASL), to formulate guidelines for post-treatment imaging follow-up [5–7]. These “secondary surveillance” guidelines include recommendations on timing and choice of imaging modality following HCC treatment, with the objectives of early detection and re-treatment of residual/recurrent tumor, which has ultimately been shown to improve long-term survival [4, 8]. Recommendations from the major international liver societies for secondary surveillance include imaging follow-up every 3–6 months with either computed tomography (CT) or magnetic resonance imaging (MRI) [5–7]. Contrast-enhanced ultrasound (CEUS) meanwhile, only recently approved in North America for liver imaging, is suggested as a possible second-line diagnostic tool as its ability to evaluate the entire liver is generally felt to be limited [5–7].

Our diagnostic imaging team in a large tertiary center has more than a decade of experience with CEUS for imaging of HCC, and is integrally involved in weekly multidisciplinary rounds for management of complex patients. With regards to secondary surveillance, initially we used CEUS primarily in conjunction with MRI to resolve indeterminate findings. Over many years, CEUS and more importantly, the powerful combination of MRI and CEUS, were recognized as having an invaluable contribution to the secondary surveillance of HCC. This led to institutional implementation of a unique alternating secondary surveillance algorithm (Fig. 1) in approximately 2016. In this algorithm, we perform MRI one month after HCC treatment, followed by CEUS and MRI performed at alternating three-month intervals.

The current manuscript is the culmination of a multi-year prospective evaluation of our unique alternating secondary surveillance algorithm, in which our objectives are to assess the relative diagnostic accuracy of MRI and CEUS in detection of residual or tumor recurrence, and additionally to identify and describe potential benefits of alternating secondary surveillance compared to secondary surveillance with MRI alone.

Continue reading: https://doi.org/10.1007/s00261-021-03331-1

Authors: Sanjay Bansal, Fangshi Lu, Levi Frehlich, Jason K. Wong, Kelly W. Burak, Stephanie R. Wilson, Department of Radiology, University of Calgary (Canada)

Abdominal Radiology (2022) 47:618–629;

Read full text at: https://doi.org/10.1007/s00261-021-03331-1

Funding: Partial research support and equipment from Samsung.
Data and material available upon request.
Declarations: Conflict of interest All authors declare that they have no conflict of interest.

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as longas you give appropriate credit to the original author(s) and the source,provide a link to the Creative Commons licence, and indicate if changeswere made. The images or other third party material in this article areincluded in the article’s Creative Commons licence, unless indicatedotherwise in a credit line to the material. If material is not included inthe article’s Creative Commons licence and your intended use is notpermitted by statutory regulation or exceeds the permitted use, you willneed to obtain permission directly from the copyright holder. To view acopy of this licence, visit http://creativecommons. org/licenses/by/4.0/.