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Prognostic Significance of Neutrophil to Lymphocyte Ratio Dynamics in Patients with Hepatocellular Carcinoma Treated with Radioembolization Using Glass Microspheres

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To study the prognostic significance of neutrophil and lymphocyte dynamics in patients with hepatocellular carcinoma (HCC) treated with radioembolization.

Methods

A retrospective, single-center review of clinical records and treatment parameters (liver volume treated, administered activity, and radiation dose) in consecutive patients who received radioembolization for HCC was performed between August 20, 2015, and May 24, 2019. Neutrophil and lymphocyte variables associated with overall survival (OS) were determined by Barcelona Clinic Liver Cancer (BCLC) stage and were correlated with radioembolization treatment parameters. Statistical methods included Wilcoxon signed-rank test, univariate, and multivariate Cox regression analysis; receiver operating characteristic analysis; and the Kaplan-Meier method.

Results

One hundred sixty-three patients with a median 67.0 years of age were included for analysis. Eighty-one percent of patients received segmental radioembolization with a median treatment dose of 358 Gray (interquartile range 256–497). The post-treatment lymphocyte count decreased significantly in 94.5 % (p < 0.001) of patients but was not predictive of OS (p = 0.248). The pre-procedure neutrophil to lymphocyte ratio (NLRpre) was not predictive of OS (p = 0.891), and the 1-month post-procedure NLR was a borderline independent predictor of OS (p = 0.05). The NLR ratio (NLRR = NLRpost-procedure/NLRpre) (Hazard ratio [HR], 1.31; 95% Cl, 1.04-1.66) and change in NLR (ΔNLR= NLRpost-procedure - NLRpre) (HR, 1.09; 95% CI, 1.02–1.15) were associated with worse OS in BCLC C patients. NLRR (> 3.17) and ΔNLR (> 3.74) were independent predictors when adjusted for tumor presentation, treatment parameters, and liver function. Volume of liver treated and administered activity positively correlated with NLRR and ΔNLR (p < 0.001).

Conclusion

A decrease in lymphocyte count is common after radioembolization, but of little clinical impact. Neither pre-treatment or post-treatment NLR was a predictor of survival in our study population. NLRR and ΔNLR were independent predictors of survival in BCLC stage C disease and had positive correlations with volume of liver tissue treated and administered activity.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AFP:

alpha feto protein

BCLC:

Barcelona Clinic Liver Cancer

CT:

computed tomography

ECOG:

Eastern Cooperative Oncology Group

HCC:

hepatocellular carcinoma

HR:

hazard ratio

MIRD:

medical internal radiation dose

MRI:

magnetic resonance imaging

NLR:

neutrophil-to-lymphocyte ratio

NLRR:

NLRpost-treatment / NLRpre-treatment

ΔNLR:

NLRpost-treatment - NLRpre-treatment

OS:

Overall survival

ROC:

receiver operating characteristic

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Funding

No funding was used for the purpose of this study.

Author information

Authors and Affiliations

  1. Interventional Radiology Department, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China

    Xi Li

  2. Mayo Clinic, Jacksonville, FL, USA

    Xi Li

  3. Division of Vascular/Interventional Radiology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL, 32224, USA

    S. Ali Montazeri, Ricardo Paz-Fumagalli, Carlos A. Padula, Weiping Wang & Beau Toskich

  4. Division of Medical Oncology, Mayo Clinic, Jacksonville, FL, USA

    Kabir Mody

  5. Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Clinic Cancer Center, Rochester, MN, USA

    Lewis R. Roberts

  6. Department of Transplantation, Mayo Clinic, Jacksonville, FL, USA

    Tushar Patel

  7. Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA

    Sunil Krishnan

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  1. Xi Li
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Contributions

X.L., data gathering, manuscript writing, statistical analysis; S.A.M. data gathering, manuscript writing, statistical analysis; R.P., study design, manuscript writing and editing, data interpretation; C.A.P, data gathering, manuscript writing; W.W., manuscript editing; K.M. manuscript editing; L.R.R., manuscript editing and study design; T.P., manuscript editing and study design; S.K., manuscript editing, data interpretation; B.T., data gathering, manuscript writing, data interpretation, study conception and design.

Corresponding author

Correspondence to Beau Toskich.

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Competing Interests

Dr. Krishnan reports grants from NIH, DoD, CPRIT, clinical research support from Celgene, Elekta outside the submitted work. In addition, Dr. Krishnan has patents pending or issued on radiation minibeams and gold nanoparticles. Dr. Mody reports and Research Support: Astrazeneca/Medimmune; Genentech; Senwha Biociences Inc; Basilea Pharma; Agios; Taiho Oncology; Merck KGa Serono; Puma Biotechnology. Consulting: AstraZeneca, Eisai, Bayer, Celgene, Ipsen. Grant Support: SPORE (NCI/NIH P50 CA210964). Dr. Patel reports grants from NIH, during the conduct of the study. Dr. Toskich is an advisor to Boston Scientific, Johnson and Johnson, Astra Zeneca, and Histosonics. Dr. Roberts reports grants from BTG International, grants from National Cancer Institute Grant P50 CA210964, grants from NIH NCATS Grant UL1 TR002377, during the conduct of the study; grants and other from Bayer, grants and other from Exact Sciences, grants and other from Gilead Sciences, grants from GlycoTest, other from GRAIL, Inc., other from QED Therapeutics, Inc., grants from RedHill Biopharma Ltd., grants from TARGET PharmaSolutions, other from TAVEC, grants from Wako Diagnostics, outside the submitted work. Dr. Li reports personal fees from China Scholarship Council, outside the submitted work. Drs. Padula, Wang, Montazeri, and Paz-Fumagalli have nothing to disclose.

Ethics

IRB approved the study. The need for consent was waived due to the retrospective design of the study.

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Xi Li and S. Ali Montazeri were co-first authors.

This article is part of the Topical Collection on Oncology - General.

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Li, X., Montazeri, S.A., Paz-Fumagalli, R. et al. Prognostic Significance of Neutrophil to Lymphocyte Ratio Dynamics in Patients with Hepatocellular Carcinoma Treated with Radioembolization Using Glass Microspheres. Eur J Nucl Med Mol Imaging 48, 2624–2634 (2021). https://doi.org/10.1007/s00259-020-05186-y

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