Non-Invasive Imaging Biomarkers to Predict the Hepatopulmonary Shunt Fraction Before Transarterial Radioembolization in Patients with Hepatocellular Carcinoma

Abstract

Purpose

To identify disease-specific profiles comprising patient characteristics and imaging biomarkers on contrast-enhanced (CE)-computed tomography (CT) that enable the non-invasive prediction of the hepatopulmonary shunt fraction (HPSF) in patients with hepatocellular carcinoma (HCC) before resin-based transarterial radioembolization (TARE).

Patients and Methods

This institutional review board-approved (EA2/071/19) retrospective study included 56 patients with HCC recommended for TARE. All patients received tri-phasic CE-CT within 6 weeks prior to an angiographic TARE evaluation study using technetium-99m macroaggregated albumin. Imaging biomarkers representative of tumor extent, morphology, and perfusion, as well as disease-specific clinical parameters, were used to perform data-driven variable selection with backward elimination to generate multivariable linear regression models predictive of HPSF. Results were used to create clinically applicable risk scores for patients scheduled for TARE. Additionally, Cox regression was used to identify independent risk factors for poor overall survival (OS).

Results

Mean HPSF was 13.11% ± 7.6% (range: 2.8– 35.97%). Index tumor diameter (p = 0.014) or volume (p = 0.034) in combination with index tumor non-rim arterial phase enhancement (APHE) (p < 0.001) and washout (p < 0.001) were identified as significant non-invasive predictors of HPSF on CE-CT. Specifically, the prediction models revealed that the HPSF increased with index lesion diameter or volume and showed higher HPSF if non-rim APHE was present. In contrast, index tumor washout was associated with decreased HPSF levels. Independent risk factors of poorer OS were radiogenomic venous invasion and ascites at baseline.

Conclusion

The featured prediction models can be used for the initial non-invasive estimation of HPSF in patients with HCC before TARE to assist in clinical treatment evaluation while potentially sparing ineligible patients from the angiographic shunt evaluation study.

Keywords:

• HCC
• TARE
• SIRT
• liver cancer
• contrast-enhanced computed tomography

Data Sharing Statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Ethics Approval and Informed Consent

This study protocol was reviewed and approved by the institutional review board of the Charité – Universitätsmedizin Berlin (approval number: EA2/071/19), and written informed consent was waived given the retrospective study design. The study was conducted in compliance with the Declaration of Helsinki and honors the herein defined data confidentiality of research subjects. The retrospective study design, methodology, and outcomes did not pose a risk to the health, privacy, rights, or welfare of study participants.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

CAH and LJS are fellows of the BIH Charité (Junior Digital) Clinician Scientist Program funded by the Charité– Universitätsmedizin Berlin and the Berlin Institute of Health. Outside the submitted work, LJS receives research grants from the Berliner Krebsgesellschaft e.V., the Collaborative Research Center (CRC) 1340 “Matrix in Vision” funded by the Deutsche Forschungsgemeinschaft (DFG), and Guerbet. BG reports honoraria and travel support in the last 10 years from Parexel/CALYX, C.R. BARD/BD, SIRTex Medical, St. Jude Medical, COOK, AngioDynamics, Pharmcept, Guerbet, Ewimed, Terumo, Roche, Merck, 3M, Beacon Bioscience/ICON, IPSEN, Bayer, Pfizer, Eisai, MSD, and INARI. The author reports no other conflicts of interest in this work.