High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy

Our plain-English summary of High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy, by S.C. Kao, N. Pavlakis, R. Harvie, et al (Clinical Cancer Research, 2010).

The study

• Authors: S.C. Kao, N. Pavlakis, R. Harvie, J.L. Vardy, M.J. Boyer, N. van Zandwijk, S.J. Clarke
• Journal: Clinical Cancer Research
• Published: 2010;16(23):5805-13
• Cited by: 267 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Asbestos-induced chronic inflammation is implicated in the pathogenesis of malignant mesothelioma (MM). We have investigated blood neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, as a prognostic factor in MM patients.

Experimental Design: Patients with MM who had systemic therapy at participating institutes were studied. Potential prognostic factors such as age, gender, performance status, histologic subtype, and baseline laboratory parameters, including NLR, were analyzed. Overall survival from commencement of therapy was determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed with significant factors (P ≤ 0.05) to determine their independent effect.

Results: A total of 173 MM patients undergoing systemic therapy including 119 patients receiving first-line therapy and 54 patients receiving second- or third-line therapy were included in this retrospective evaluation. Forty-two percent of patients had an elevated NLR at baseline. The following variables were predictive of survival: female gender (P = 0.044), epithelioid histologic subtype (P < 0.001), baseline white blood cell count less than 8.3 × 10⁹/L (P = 0.008), baseline platelet count 400 × 10⁹/L or less (P = 0.05), and NLR of 5 or less (P < 0.001). After multivariate analysis, histologic epithelioid subtype [hazard ratio (HR) = 2.0; 95% confidence interval (CI) = 1.3-2.9; P = 0.001], and NLR less than 5 (HR = 2.7; 95% CI = 1.8-3.9; P < 0.001) remained independent predictors. The 1-year survival rate was 60% versus 26%, whereas the 2-year survival rate was 34% versus 10% for NLR less than 5 and 5 or greater, respectively. In the separate analyses of chemotherapy-naive and previously treated patient groups, NLR was an independent predictor of survival in both groups.

Conclusion: Our results indicate that NLR is an independent predictor of survival for patients with MM undergoing systemic therapy.

©2010 AACR.

In plain English

This retrospective study looked at whether a simple blood measure, the neutrophil-to-lymphocyte ratio (NLR: neutrophil count divided by lymphocyte count), was linked to survival in 173 malignant mesothelioma patients starting systemic (drug) therapy at Sydney hospitals in Australia. Of these, 119 were receiving first-line treatment and 54 had been treated before. An NLR of 5 or greater was considered elevated, and 42% of patients had an elevated NLR before treatment. Median overall survival was 16.7 months with an NLR below 5 and 6.6 months with an NLR of 5 or greater. One-year survival was 60% versus 26%, and two-year survival was 34% versus 10%. After allowing for other factors, NLR (hazard ratio 2.7, 95% confidence interval 1.8 to 3.9) and epithelioid tumor subtype (hazard ratio 2.0, 1.3 to 2.9) remained independent predictors of survival. NLR also remained an independent predictor separately in first-line and in previously treated patients. The authors concluded that an NLR less than 5 was an independent predictor of longer survival. They stated that the findings require validation in an independent series of patients with standardized treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of a series of malignant mesothelioma patients receiving systemic therapy (consecutive clinic patients plus clinical trial patients), with survival analysis (Kaplan-Meier and multivariate Cox regression)
• Who was studied: 173 patients with malignant mesothelioma in New South Wales, Australia. They were consecutive patients who started chemotherapy from January 2004 to February 2009 at Sydney Cancer Centre, plus patients enrolled in clinical trials since 1999 at Sydney Cancer Centre and Royal North Shore Hospital. 119 received first-line therapy and 54 received second- or third-line therapy. 141 were male and 32 female.
• Exposure: The study did not examine asbestos exposure. The factor studied was the baseline blood neutrophil-to-lymphocyte ratio (absolute neutrophil count divided by absolute lymphocyte count), with 5 or greater counted as elevated. Other factors examined were age, gender, performance status, histologic subtype, stage and other blood counts. Treatments included pemetrexed, cisplatin, carboplatin, gemcitabine, thalidomide, imatinib and others.
• Main results:
  • 42% of patients had an elevated NLR (5 or greater) at baseline (73 of 173 in Table 2; 95 had NLR below 5).
  • All patients: median overall survival was 16.7 months for NLR below 5 versus 6.6 months for NLR of 5 or greater (P less than 0.001).
  • All patients: 1-year survival was 60% for NLR below 5 versus 26% for NLR of 5 or greater; 2-year survival was 34% versus 10%.
  • All patients, multivariate analysis: epithelioid subtype (HR 2.0; 95% CI 1.3 to 2.9; P = 0.001) and the NLR grouping (HR 2.7; 95% CI 1.8 to 3.9; P less than 0.001) were independent predictors of survival. Gender, white blood cell count, platelet count and treatment status were significant in univariate analysis but not in multivariate analysis.
  • First-line (chemotherapy-naive) patients: median overall survival was 19.2 months for NLR below 5 versus 6.6 months for NLR of 5 or greater. In multivariate analysis only epithelioid subtype (HR 2.6; 95% CI 1.5 to 4.5) and NLR (HR 3.2; 95% CI 1.9 to 5.2) were predictive of survival.
  • First-line patients: 75% of those with a normal NLR survived 12 months or more, and 61% of those with an elevated NLR lived less than 12 months.
  • Previously treated (second- or third-line) patients: only NLR was an independent predictor of survival (HR 2.1; 95% CI 1.1 to 3.9; P = 0.028). Median overall survival was 10.4 versus 3.8 months for NLR below 5 versus 5 or greater.
  • Subgroup of 65 patients with abnormal baseline NLR: 28 (43%) had their NLR normalize after one cycle of therapy. Their median overall survival was 7.8 months versus 5.0 months for patients whose NLR stayed abnormal (P = 0.034).
  • Thalidomide subgroup: NLR and CRP were significant prognostic markers in univariate analysis. White blood cell count, platelet count, IL-6, IL-6 soluble receptor, mGPS and VEGF were not. NLR remained significant in multivariate analysis (HR 2.3; 95% CI 1.3 to 4.3; P = 0.007).
  • Exploratory analysis in 63 thalidomide patients: NLR was not associated with IL-6, IL-6 soluble receptor or VEGF. NLR correlated with white blood cell count (r = 0.581) and CRP (r = 0.438). Weight loss was associated with higher baseline NLR (r = 0.37, P = 0.021).
• The authors' conclusion: The authors concluded that an NLR less than 5 was an independent predictor of longer survival for patients with malignant mesothelioma undergoing systemic therapy. They added that the low cost and easy availability of a full blood count favor its use in clinical practice.
• Limitations the authors state:
  • The findings require validation in an independent series of patients with standardized treatment. Such cohorts may be hard to access because chemotherapy studies have not routinely collected lymphocyte counts.
  • The CALGB prognostic score could not be included because of incomplete clinical information, so NLR could not be directly compared with it.
  • Much staging data was missing, and only 6 patients had early-stage disease. The authors suggest this may explain why clinical stage did not predict prognosis.
  • Higher clinical stage showed a trend toward elevated NLR that did not reach statistical significance. The authors say this may be partly due to difficulties classifying stage in mesothelioma and the limited sample size.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Prognosis, Malignant Mesothelioma, Systemic Therapy, Chronic Inflammation, Inflammation, Performance Status, Histological Subtype, Overall Survival.

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