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Reliable prediction of survival in advanced-stage hepatocellular carcinoma treated with sorafenib: comparing 1D and 3D quantitative tumor response criteria on MRI

  • Oncology
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To compare 1D and 3D quantitative tumor response criteria applied to DCE-MRI in patients with advanced-stage HCC undergoing sorafenib therapy to predict overall survival (OS) early during treatment.

Methods

This retrospective analysis included 29 patients with advanced-stage HCC who received sorafenib for at least 60 days. All patients underwent baseline and follow-up DCE-MRI at 81.5 ± 29.3 days (range 35–140 days). Response to sorafenib was assessed in 46 target lesions using 1D criteria RECIST1.1 and mRECIST. In addition, a segmentation-based 3D quantification of absolute enhancing lesion volume (vqEASL) was performed on the arterial phase MRI, and the enhancement fraction of total tumor volume (%qEASL) was calculated. Accordingly, patients were stratified into groups of disease control (DC) and disease progression (DP). OS was evaluated using Kaplan-Meier curves with log-rank test and Cox proportional hazards regression model.

Results

The Kaplan-Meier analysis revealed that stratification of patients in DC vs. DP according to mRECIST (p = 0.0371) and vqEASL (p = 0.0118) successfully captured response and stratified OS, while stratification according to RECIST and %qEASL did not correlate with OS (p = 0.6273 and p = 0.7474, respectively). Multivariable Cox regression identified tumor progression according to mRECIST and qEASL as independent risk factors of decreased OS (p = 0.039 and p = 0.006, respectively).

Conclusions

The study identified enhancement-based vqEASL and mRECIST as reliable predictors of patient survival early after initiation of treatment with sorafenib. This data provides evidence for potential advantages 3D quantitative, enhancement-based tumor response analysis over conventional techniques regarding early identification of treatment success or failure.

Key Points

• Tumor response criteria on MRI can be used to predict survival benefit of sorafenib therapy in patients with advanced HCC.

• Stratification into DC and DP using mRECIST and vqEASL significantly correlates with OS (p = 0.0371 and p = 0.0118, respectively) early after initiation of sorafenib, while stratification according to RECIST and %qEASL did not correlate with OS (p = 0.6273 and p = 0.7474, respectively).

• mRECIST (HR = 0.325, p = 0.039. 95%CI 0.112–0.946) and qEASL (HR = 0.183, p = 0.006, 95%CI 0.055–0.613) are independent prognostic factors of survival in HCC patients undergoing sorafenib therapy.

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Abbreviations

%qEASL:

Percent-based qEASL

1D:

One-dimensional

3D:

Three-dimensional

95%CI:

95% confidence interval

BCLC:

Barcelona Liver Cancer Staging System

BL:

Baseline

CR:

Complete response

DC:

Disease control

DCE-MRI:

Dynamic contrast-enhanced magnetic resonance imaging

DP:

Disease progression

ECOG:

Eastern Cooperative Oncology Group

eTV:

Enhancing tumor volume

FDA:

US Food and Drug Administration

FU:

Follow-up

HCC:

Hepatocellular carcinoma

HR:

Hazard ratio

LI-RADS:

Liver Imaging Reporting and Data System

OS:

Overall survival

PR:

Partial response

PVT:

Portal vein thrombus

qEASL:

Quantitative European Association for the Study of the Liver

SD:

Stable disease

TKI:

Tyrosine kinase inhibitors

TTV:

Total tumor volume

VEGFR2:

Vascular endothelial growth factor receptor 2

vqEASL:

Volume-based qEASL

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Acknowledgments

We thank Isabel Schobert for her support.

Funding

This study received funding by the National Institute of Health (R01 CA206180).

Author information

Authors and Affiliations

  1. Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA

    Luzie A. Doemel, Julius Chapiro, Fabian Laage Gaupp, Lynn Jeanette Savic, Ahmet S. Kucukkaya, Alexandra Petukhova, Jonathan Tefera, Tal Zeevi, MingDe Lin & Todd Schlachter

  2. Institute of Radiology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität and Berlin Institute of Health, 10117, Berlin, Germany

    Luzie A. Doemel, Lynn Jeanette Savic, Ahmet S. Kucukkaya, Alexandra Petukhova & Jonathan Tefera

  3. Digestive Disease Section, Yale Liver Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA

    Ariel Jaffe & Mario Strazzabosco

  4. Division of Medical Oncology, Department of Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA

    Timil Patel & Stacey M. Stein

  5. Yale Cancer Center, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA

    Timil Patel & Stacey M. Stein

Authors
  1. Luzie A. Doemel
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  2. Julius Chapiro
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Corresponding author

Correspondence to Julius Chapiro.

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Guarantor

The scientific guarantor of this publication is J. Chapiro.

Conflict of interest

M. Lin is a Visage Imaging employee. J. Chapiro and M. Strazzabosco acknowledge the support of the Clinical and Translational Core of the Liver Center (DK034989, Silvio Conte Digestive Disease Centers). All other authors of this manuscript declare no relationship with any companies whose products or services may be related to the subject of matter of the article.

Statistics and biometry

Statistical advice was provided by Lawrence Staib, PhD, Yale School of Medicine and Dr. rer. nat. Konrad Neumann, Charité-Universitätsmedizin, Berlin.

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Written informed consent was waived by the Institutional Review Board.

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Institutional Review Board approval was obtained.

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Doemel, L.A., Chapiro, J., Laage Gaupp, F. et al. Reliable prediction of survival in advanced-stage hepatocellular carcinoma treated with sorafenib: comparing 1D and 3D quantitative tumor response criteria on MRI. Eur Radiol 31, 2737–2746 (2021). https://doi.org/10.1007/s00330-020-07381-9

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  • DOI: https://doi.org/10.1007/s00330-020-07381-9

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