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Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE

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Abstract

Objectives

To investigate the predictive value of quantifiable imaging and inflammatory biomarkers in patients with hepatocellular carcinoma (HCC) for the clinical outcome after drug-eluting bead transarterial chemoembolization (DEB-TACE) measured as volumetric tumor response and progression-free survival (PFS).

Methods

This retrospective study included 46 patients with treatment-naïve HCC who received DEB-TACE. Laboratory work-up prior to treatment included complete and differential blood count, liver function, and alpha-fetoprotein levels. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were correlated with radiomic features extracted from pretreatment contrast-enhanced magnetic resonance imaging (MRI) and with tumor response according to quantitative European Association for the Study of the Liver (qEASL) criteria and progression-free survival (PFS) after DEB-TACE. Radiomic features included single nodular tumor growth measured as sphericity, dynamic contrast uptake behavior, arterial hyperenhancement, and homogeneity of contrast uptake. Statistics included univariate and multivariate linear regression, Cox regression, and Kaplan–Meier analysis.

Results

Accounting for laboratory and clinical parameters, high baseline NLR and PLR were predictive of poorer tumor response (p = 0.014 and p = 0.004) and shorter PFS (p = 0.002 and p < 0.001). When compared to baseline imaging, high NLR and PLR correlated with non-spherical tumor growth (p = 0.001 and p < 0.001).

Conclusions

This study establishes the prognostic value of quantitative inflammatory biomarkers associated with aggressive non-spherical tumor growth and predictive of poorer tumor response and shorter PFS after DEB-TACE.

Key Points

• In treatment-naïve hepatocellular carcinoma (HCC), high baseline platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with non-nodular tumor growth measured as low tumor sphericity.

• High PLR and NLR are predictive of poorer volumetric enhancement-based tumor response and PFS after DEB-TACE in HCC.

• This set of readily available, quantitative immunologic biomarkers can easily be implemented in clinical guidelines providing a paradigm to guide and monitor the personalized application of loco-regional therapies in HCC.

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Abbreviations

AFP:

Alpha-fetoprotein

ALC:

Absolute lymphocyte count

ALT:

Alanine aminotransferase

ANC:

Absolute neutrophil count

AP:

Alkaline phosphatase

AST:

Aspartate aminotransferase

BCLC:

Barcelona Clinic Liver Cancer

DEB:

Drug-eluting bead

ETB:

Enhancing tumor burden

HCC:

Hepatocellular carcinoma

HIPAA:

Health Insurance Portability and Accountability Act

LI-RADS:

Liver Imaging Reporting and Data System

NLR:

Neutrophil-to-lymphocyte ratio

PFS:

Progression-free survival

PLR:

Platelet-to-lymphocyte ratio

qEASL:

Quantitative European Association for the Study of the Liver

TACE:

Transarterial chemoembolization

TB:

Tumor burden

TME:

Tumor microenvironment

TTV:

Total tumor volume

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We thank Luzie Dömel for her support and Claus Peter Nowak, M.Sc., for providing statistical advice. Dr. Savic is a participant in the BIH-Charité Junior Clinician Scientist Program funded by the Charité – Universiätsmedizin Berlin and the Berlin Institute of Health.

Funding

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

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Author notes

  1. Isabel Schobert and Lynn Jeanette Savic contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology and Biomedical Imaging, Yale School of Medicine, 300 Cedar Street, New Haven, CT, 06520, USA

    Isabel Theresa Schobert, Lynn Jeanette Savic, Julius Chapiro, Khaled Bousabarah, Evan Chen, Fabian Laage-Gaupp, Jonathan Tefera, Nariman Nezami, MingDe Lin, Jeffrey Pollak & Todd Schlachter

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

    Isabel Theresa Schobert, Lynn Jeanette Savic & Jonathan Tefera

  3. Department of Stereotactic and Functional Neurosurgery, University Hospital of Cologne, Cologne, Germany

    Khaled Bousabarah

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  1. Isabel Theresa Schobert
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Correspondence to Julius Chapiro.

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The scientific guarantor of this publication is Julius Chapiro.

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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

Claus Peter Nowak, M.Sc., from the Institute of Biometry and Clinical Epidemiology, Charité Berlin, kindly provided statistical advice for this manuscript.

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Written informed consent was waived by the Institutional Review Board.

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Schobert, I.T., Savic, L.J., Chapiro, J. et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of tumor response in hepatocellular carcinoma after DEB-TACE. Eur Radiol 30, 5663–5673 (2020). https://doi.org/10.1007/s00330-020-06931-5

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