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Page 2 of 11 Yoneoka et al. Hepatoma Res 2020;6:67 I http://dx.doi.org/10.20517/2394-5079.2020.57

Keywords: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, transarterial radioembolization,
hepatocellular carcinoma

INTRODUCTION
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth most common
[1]
cause of cancer-related death worldwide . In the United States, the overall prognosis for HCC is poor,
[2]
with a 5-year survival rate of 10% . Generally accepted curative therapies include liver resection or
transplantation. Unfortunately, patients with advanced disease are usually not amenable to surgical
intervention. For patients with unresectable tumors, transarterial chemoembolization (TACE) or
transarterial radioembolization (TARE) with yttrium-90 (Y90) can be considered to treat or downstage
disease to qualify for curative surgery. Although TACE has been the mainstay of treatment for intermediate-
stage tumors, TARE has a distinct advantage in that it can be used in portal venous thrombosis and has a
[3-5]
better adverse effect profile with similar efficacy to TACE .

Response to TARE is measured by the modified response evaluation criteria in solid tumors (mRECIST)
[6]
using either contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) .
Depending on individual center protocols, initial images are performed 1 to 3 months post-treatment.
Unfortunately, tumors that are non-responsive to TARE may progress while waiting for subsequent
imaging. Therefore, prognostic biomarkers are needed to help predict which patients will benefit from
TARE.

The serum marker alpha-fetoprotein (AFP), widely used as a screening tool for HCC, has been shown to
[7,8]
have prognostic value in treatment . However, AFP is also elevated in non-tumor environments and is
[9]
not particularly sensitive for small tumors . Liquid biopsy, which detects circulating tumor cells or nucleic
[10]
acids, is a promising alternative to AFP but is not yet widely available . Recently, inflammatory markers
such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have gained
popularity as prognostic indicators in cancer [11-14] . While the mechanism behind these markers is not
precisely understood, a proinflammatory environment along with thrombocytosis has been associated with
tumor growth and survival [15-17] .

Previous studies have highlighted the clinical utility of NLR and PLR as prognostic markers for HCC after
liver resection, transplantation, and TACE [12,14,18-20] . However, the use of NLR in combination with PLR for
TARE has not been well established. This study aimed to understand the prognostic value of NLR and PLR
in patients who received TARE as a first-line therapy for HCC.

METHODS
Patients
This was a retrospective review from a prospectively collected database of 1,442 patients diagnosed with
HCC from 1993 to 2019. All patients were referred to a group of hepatobiliary surgeons affiliated with a
tertiary medical center in Hawaii that has the only liver center and liver transplant program in the state.
This surgical group evaluates approximately 60%-70% of all the cases of HCC in Hawaii and includes
referrals from the American territories of the Pacific Basin. We selected patients who received TARE as a
primary treatment for HCC. Patients were excluded if they had a previous liver resection, liver transplant,
any systemic therapy or locoregional therapy prior to TARE. Patients were also excluded if they received
adjuvant therapy following TARE but prior to follow-up imaging. Patients who had initial follow-up later
than 12 months were additionally excluded. We included patients who had two separate TARE treatments
for bilateral or extensive disease. These Y90 treatments were typically done about 1 month apart, and