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Neutrophil–lymphocyte ratio predicts survival in patients with advanced cholangiocarcinoma on chemotherapy

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Abstract

The blood neutrophil-to-lymphocyte ratio (NLR) is reported to be a prognostic marker in several cancers. However, the prognostic role of NLR in patients with advanced cholangiocarcinoma on chemotherapy is unknown. A total of 221 patients with pathologically confirmed locally advanced or metastatic cholangiocarcinoma receiving first-line palliative chemotherapy were enrolled. Associations between baseline clinical and laboratory variables including NLR and survival were investigated. Patients were classified into two groups according to the NLR level (≤5 vs. >5). Median overall survival (OS) and time to progression (TTP) in patients with NLR ≤ 5 were 10.9 and 6.7 months, respectively, and 6.8 and 4.1 months in patients with NLR > 5 (P < 0.001, P = 0.002, respectively). In multivariate analysis, number of cycles of chemotherapy was a significant predictor of longer OS (HR 0.86, P < 0.001), whereas adverse prognostic factors for OS were CA 19-9 > 300 (HR 1.43, P = 0.025), CEA > 5 (HR 1.44, P = 0.029), higher stage (HR 1.69, P = 0.004), and NLR > 5 (HR 1.87, P < 0.001). NLR > 5 was also associated with reduced TTP (HR 1.66, P = 0.007). Among 50 patients with initial NLR > 5, 33 patients had NLR ≤ 5 after two cycles of chemotherapy and they had significantly better survival than the others (HR 0.48, P = 0.015). NLR independently predicts survival in patients with advanced cholangiocarcinoma undergoing chemotherapy. Considering cost-effectiveness and easy availability, NLR may be a useful biomarker for prognosis prediction.

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Abbreviations

CA 19-9:

Carbohydrate antigen 19-9

CCA:

Cholangiocarcinoma

CEA:

Carcinoembryonic antigen

CI:

Confidence interval

CR:

Complete response

CRP:

C-reactive protein

dNLR:

Derived neutrophil–lymphocyte ratio

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

NLR:

Neutrophil–lymphocyte ratio

NSAIDs:

Nonsteroidal anti-inflammatory drugs

OS:

Overall survival

PD:

Progressive disease

PFS:

Progression-free survival

PR:

Partial response

SD:

Stable disease

TTP:

Time to progression

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Author contributions

Sang Hyub Lee involved in conception and design; Ban Seok Lee, Dong Kee Jang, Kwang Hyun Chung, Jun Hyuk Son collected and assembled of data; Sang Hyub Lee, Ji Kon Ryu, Yong-Tae Kim provided study materials or patients; Ban Seok Lee, Woo Hyun Paik involved in data analysis and interpretation; Ban Seok Lee, Sang Hyub Lee, Woo Hyun Paik wrote the manuscript; All authors finally approved the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea

    Ban Seok Lee, Sang Hyub Lee, Jun Hyuk Son, Dong Kee Jang, Kwang Hyun Chung, Ji Kon Ryu & Yong-Tae Kim

  2. Department of Internal Medicine, Kyungpook National University Medical Center, Daegu, South Korea

    Ban Seok Lee

  3. Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, South Korea

    Yoon Suk Lee

  4. Department of Internal Medicine, Inje University Ilsan Paik Hospital, Koyang, South Korea

    Woo Hyun Paik

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Lee, B.S., Lee, S.H., Son, J.H. et al. Neutrophil–lymphocyte ratio predicts survival in patients with advanced cholangiocarcinoma on chemotherapy. Cancer Immunol Immunother 65, 141–150 (2016). https://doi.org/10.1007/s00262-015-1780-7

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