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Lymphocyte to monocyte ratio-based nomogram for predicting outcomes of hepatocellular carcinoma treated with sorafenib

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Abstract

Background

The ability of the pretreatment lymphocyte to monocyte ratio (LMR) to predict outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib is not conclusively determined.

Methods

We retrospectively studied patients treated with sorafenib for HCC in two tertiary referral centres in Asia and North America. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Predictive factors for the outcomes were determined by Cox proportional hazards models. A risk assessment tool was developed.

Results

Compared to the North America cohort, the Asia cohort was more heavily pretreated (72.1% vs. 35.2%; p < 0.001), had higher hepatitis B virus infection (87.6% vs. 5.6%; p < 0.001), and more distant metastases (83.2% vs. 25.4%; p < 0.001). Lower monocyte count in the Asia cohort (median 462.7 vs. 600.0/μL; p = 0.023) resulted in a higher LMR (median 2.6 vs. 1.8; p < 0.001). High LMR was associated with a significantly higher OS [hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.81‒0.97; p = 0.007]. This was confirmed in a sensitivity analysis including patients treated in Asia only (HR 0.89; 95% CI 0.81‒0.97; p = 0.010). An OS nomogram was constructed with the following variables selected in the multivariate Cox model: LMR, treatment location, previous treatment, performance status, alpha-fetoprotein, lymph node metastasis, and Child‒Pugh score. The concordance score was 0.71 (95% CI, 0.67‒0.75). LMR did not predict PFS.

Conclusion

LMR measured before sorafenib administration predicts OS in advanced HCC patients. Our OS nomogram, incorporating LMR, can be offered to clinicians to improve their ability to assess prognosis, strengthen the prognosis-based decision-making, and inform patients in the clinic.

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Abbreviations

LMR:

Lymphocyte to monocyte ratio

TAM:

Tumor-associated macrophages

HCC:

Hepatocellular carcinoma

OS:

Overall survival

PFS:

Progression-free survival

SD:

Standard deviation

IQR:

Interquartile ranges

HR:

Hazard ratio

HBV:

Hepatitis B virus

ECOG:

Eastern Cooperative Oncology Group

PT:

Prothrombin time

AFP:

Alpha-fetoprotein

TIL:

Tumor-infiltrating lymphocytes

ALT:

Alanine aminotransferase

HCV:

Hepatitis C virus

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Funding

National Institutes of Health to LRR (R01 CA 186566), the Mayo Clinic Hepatobiliary SPORE (P50 CA 210964), the Mayo Clinic Cancer Center (P30 CA 15083), the Mayo Clinic Center for Clinical and Translational Science (UL1 TR 002377).

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Author notes

  1. Yeonjung Ha and Mohamed A. Mohamed Ali contributed equally to this article.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA

    Yeonjung Ha, Mohamed A. Mohamed Ali, Sally Bampoh, Kenneth A. Valles, Mohamad Mady, Venkata R. Missula, Kritika Prasai & Lewis R. Roberts

  2. Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea

    Yeonjung Ha, Han Chu Lee & Kang Mo Kim

  3. Department of Gastroenterology, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13496, South Korea

    Yeonjung Ha

  4. Division of Biomedical Statistics and Informatics, Mayo Clinic Health Sciences Research, 205 Third Street SW, Rochester, MN, 55905, USA

    Molly M. Petersen, William S. Harmsen & Terry M. Therneau

  5. Department of Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea

    Baek-Yeol Ryoo

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  1. Yeonjung Ha
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Contributions

YH—conceptualisation, data curation, investigation, and wiring—original draft; MAMA—conceptualisation, data curation, and writing—original draft; MMP—formal analysis, methodology, and writing—review and editing; WSH—formal analysis, methodology, and writing—review and editing; TMT—formal analysis, methodology, and writing—review and editing; HCL—writing—review and editing, BYR—writing—review and editing; SB—data curation; KAV—data curation; MM—data curation; VRM—data curation; KP—data curation.

Corresponding authors

Correspondence to Lewis R. Roberts or Kang Mo Kim.

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Conflict of interest

Dr. Lewis Roberts has received grant support from ARIAD Pharmaceuticals, Bayer, BTG International, Exact Sciences, Gilead Sciences, Glycotest Inc., RedHill Inc., Target PharmaSolutions, and Wako Diagnostics; he has provided advisory services to Bayer, Exact Sciences, Gilead Sciences, GRAIL Inc., QED Therapeutics and TAVEC. The other authors have no conflicts of interests to declare.

Informed consent in human subjects

The institutional review board of the Asan Medical Center (approval number: 2019-0685) and the Mayo Clinic (approval number: 15-006298) granted a waiver of informed consent and approval of this observational study with deidentified data.

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12072_2020_10076_MOESM1_ESM.tif

Supplemental Digital Content 1 Kaplan–Meier estimate of overall survival in the entire cohort. CI, Confidence Interval (TIF 72 kb)

12072_2020_10076_MOESM2_ESM.tif

Supplemental Digital Content 2 Kaplan–Meier estimate of progression-free survival in the entire cohort. CI, Confidence Interval (TIF 70 kb)

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Supplemental Digital Content 7 Overall survival nomogram in Asia cohort (TIF 1230 kb)

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Ha, Y., Mohamed Ali, M.A., Petersen, M.M. et al. Lymphocyte to monocyte ratio-based nomogram for predicting outcomes of hepatocellular carcinoma treated with sorafenib. Hepatol Int 14, 776–787 (2020). https://doi.org/10.1007/s12072-020-10076-4

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