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Hepatobiliary MR contrast agent uptake as a predictive biomarker of aggressive features on pathology and reduced recurrence-free survival in resectable hepatocellular carcinoma: comparison with dual-tracer 18F-FDG and 18F-FCH PET/CT

  • Hepatobiliary-Pancreas
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Abstract

Objectives

To compare the performance of the quantitative analysis of the hepatobiliary phase (HBP) tumor enhancement in gadobenate dimeglumine (Gd-BOPTA)–enhanced MRI and of dual-tracer 18F-FDG and 18F-fluorocholine (FCH) PET/CT for the prediction of tumor aggressiveness and recurrence-free survival (RFS) in resectable hepatocellular carcinoma (HCC).

Methods

This retrospective, IRB approved study included 32 patients with 35 surgically proven HCCs. All patients underwent Gd-BOPTA-enhanced MRI including delayed HBP images, 18F-FDG PET/CT, and (for 29/32 patients) 18F-FCH PET/CT during the 2 months prior to surgery. For each lesion, the lesion-to-liver contrast enhancement ratio (LLCER) on MRI HBP images and the SUVmax tumor-to-liver ratio (SUVT/L) for both tracers were calculated. Their predictive value for aggressive pathological features—including the histological grade and microvascular invasion (MVI)—and RFS were analyzed and compared using area under receiver operating characteristic (AUROC) curves and Cox regression models, respectively.

Results

The AUROCs for the identification of aggressive HCCs on pathology with LLCER, 18F-FDG SUVT/L, and 18F-FCH SUVT/L were 0.92 (95% CI 0.78, 0.98), 0.89 (95% CI 0.74, 0.97; p = 0.70), and 0.64 (95% CI 0.45, 0.80; p = 0.035). At multivariate Cox regression analysis, LLCER was identified as an independent predictor of RFS (HR (95% CI) = 0.91 (0.84, 0.99), p = 0.022). LLCER − 4.72% or less also accurately predicted moderate-poor differentiation grade (Se = 100%, Sp = 92.9%) and MVI (Se = 93.3%, Sp = 60%) and identified patients with poor RFS after surgical resection (p = 0.030).

Conclusions

HBP tumor enhancement after Gd-BOPTA injection may help identify aggressive HCC pathological features, and patients with reduced recurrence-free survival after surgical resection.

Key Points

• In patients with resectable HCC, the quantitative analysis of the HBP tumor enhancement in Gd-BOPTA-enhanced MRI (LLCER) accurately identifies moderately-poorly differentiated and/or MVI-positive HCCs.

• After surgical resection for HCC, patients with LLCER − 4.72% or less had significantly poorer recurrence-free survival than patients with LLCER superior to − 4.72%.

• Gd-BOPTA-enhanced MRI with delayed HBP images may be suggested as part of pre-surgery workup in patients with resectable HCC.

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Abbreviations

18F-FDG:

18F-Fluorodeoxyglucose

18F-FCH:

18F-Fluorocholine

AUROC:

Area under the ROC curve

CI:

Confidence interval

ESG:

Edmonson Steiner grade

Gd-BOPTA:

Gadobenate dimeglubine

HBP:

Hepatobiliary phase

HCC:

Hepatocellular carcinoma

HR:

Hazard ratios

IRB:

Institutional Review Board

LLCER:

Lesion-to-liver contrast enhancement ratio

MVI:

Microvascular invasion

NPV:

Negative predictive value

PET/CT:

Positron emission tomography-CT

PPV:

Positive predictive value

RFS:

Recurrence-free survival

ROI:

Region of interest

VIBE:

Volumetric interpolated breath-hold examination

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Funding

The authors state that this work has not received any funding.

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Authors and Affiliations

  1. Service d’Imagerie Médicale, AP-HP, Hôpitaux Universitaires Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France

    Sébastien Mulé, François Legou, Athena Galletto Pregliasco, Rym Kharrat, Vania Tacher, Hicham Kobeiter & Alain Luciani

  2. Faculté de Médecine, Université Paris Est Créteil, Créteil, France

    Sébastien Mulé, Julien Calderaro, Alexis Laurent, Giuliana Amaddeo, Vania Tacher, Hicham Kobeiter, Emmanuel Itti & Alain Luciani

  3. INSERM IMRB, U 955, Equipe 18, Créteil, France

    Sébastien Mulé, Julien Calderaro, Giuliana Amaddeo, Vania Tacher & Alain Luciani

  4. Service de Médecine Nucléaire, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France

    Julia Chalaye & Emmanuel Itti

  5. Laboratoire des Signaux et Systèmes, Université Paris-Saclay, Gif sur Yvette, France

    Arthur Tenenhaus

  6. Service d’anatomie et cytologie pathologiques, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France

    Julien Calderaro

  7. Service de chirurgie digestive et hépato-bilio-pancréatique, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France

    Alexis Laurent

  8. Service d’Hépatologie, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France

    Giuliana Amaddeo & Hélène Regnault

Authors
  1. Sébastien Mulé
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  2. Julia Chalaye
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  3. François Legou
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  7. Alexis Laurent
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  14. Alain Luciani
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Corresponding author

Correspondence to Sébastien Mulé.

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Guarantor

The scientific guarantor of this publication is Pr. Alain Luciani.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise (Dr. Arthur Tenenhaus).

Informed consent

Written informed consent was not required for this study due to the retrospective design and the non-interventional nature of the study. All patients were informed in writing of the study protocol and objectives.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• Retrospective

• Cross-sectional study

• Performed at one institution

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Mulé, S., Chalaye, J., Legou, F. et al. Hepatobiliary MR contrast agent uptake as a predictive biomarker of aggressive features on pathology and reduced recurrence-free survival in resectable hepatocellular carcinoma: comparison with dual-tracer 18F-FDG and 18F-FCH PET/CT. Eur Radiol 30, 5348–5357 (2020). https://doi.org/10.1007/s00330-020-06923-5

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  • DOI: https://doi.org/10.1007/s00330-020-06923-5

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