Neutrophil-to-lymphocyte ratio in malignant pleural fluid: Prognostic significance.

Natalia Popowicz,Hui Min Cheah,Cynthia Gregory,Y C Gary Lee,Alina Miranda,Ian M Dick,Jenette Creaney,Luka Brcic

doi:10.1371/journal.pone.0250628

Abstract

Predicting survival of patients with malignant pleural effusions (MPEs) is notoriously difficult. A robust prognostic marker can guide clinical decision making. The neutrophil-to-lymphocyte ratio (NLR) in blood has been shown to predict survival in many cancers. Pleural fluid bathes the malignant pleural tissues, thus the NLR of the pleural fluid may reflect more closely the local tumour environment. The objective of this study was to explore the prognostic significance of pleural effusion NLR for MPE. We analysed matched effusion and blood from 117 patients with malignant and 24 with benign pleural effusions. Those who had received recent chemotherapy or had a pleurodesis were excluded. Neutrophil and lymphocyte counts in effusions were performed by manual review of cytospin cell preparations by trained observers. Clinical data were extracted from a state-wide hospital database. We found significantly fewer neutrophils (expressed as percentage of total leukocyte count) in pleural fluid than in corresponding blood (9% vs 73%; p<0.001). The NLR was an order of magnitude lower in pleural fluid than in corresponding blood: median [IQR] = 0.20 [0.04–1.18] vs 4.9 [3.0–8.3], p<0.001. Correlation between blood and pleural fluid NLR in MPE patients was moderate (rs = 0.321, p<0.001). In univariate analysis, NLR (>0.745)) in malignant pleural fluid was predictive of poorer survival (HR = 1.698 [1.0054–2.736]; p = 0.030), and remained significant after adjustment for age, sex, presence of a chest drain, cancer type, concurrent infection and subsequent treatment with chemotherapy (HR = 1.786 [1.089–2.928]; p = 0.022). Patients with pleural fluid NLR > 0.745 had a significantly shorter median survival of 130 (95% CI 0–282) days compared to 312 (95% CI 195–428) days for pleural NLR < 0.745, p = 0.026. The NLR in blood was also predictive of poorer survival in MPE patients (HR = 1.959 [1.019–3.096]; p<0.001). The proportion of neutrophils in pleural fluid was predictive of prognosis more strongly than lymphocytes. This study provides evidence that NLR in malignant effusions can predict survival, and therefore may provide prognostic information for this cohort. This prognostic association in the fluid is driven by the presence of neutrophils.

Highlights

Malignant pleural effusion (MPE) often indicates advanced, disseminated malignancy
The present study describes the pleural fluid neutrophil-to-lymphocyte ratio (NLR) compared with blood NLR in patients with MPE with various underlying aetiologies and provides evidence that pleural NLR is predictive of survival
This study of pleural fluid NLR finds that the proportion and distribution of neutrophils and lymphocytes differed considerably between the blood and pleural fluid suggesting that the NLR in malignant pleural effusion pleural immune/inflammatory responses are, in part, compartmentalized

Summary

Introduction

Malignant pleural effusion (MPE) often indicates advanced, disseminated malignancy. MPE most commonly develops due to lung, breast, gastrointestinal and gynaecological cancers as well as malignant mesothelioma (MM). Shortness of breath from the underlying pleural effusion is the most common presenting symptom and is often relieved by pleural fluid drainage. Prognosis of patients with MPE can range from 1 to 18 months and can be dependent on the underlying aetiology and cancer staging [1, 2]. Symptom control is the primary goal of MPE management and can be achieved through a number of invasive procedures. Treatment choices including chemotherapy or effusion control strategy, may be guided by prognosis. These procedures may not be appropriate for patients with a poor prognosis where palliative approaches and thoracentesis can provide transient relief of symptoms in the short-term whilst minimising discomfort. Stratifying patients with MPE based on survival is essential to facilitate appropriate treatment choices

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