Existing models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma

Our plain-English summary of Existing models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma, by T.M. Meniawy, J. Creaney, R.A. Lake, et al (British Journal of Cancer, 2013).

The study

• Authors: T.M. Meniawy, J. Creaney, R.A. Lake, A.K. Nowak
• Journal: British Journal of Cancer
• Published: 2013;109(7):1813-20
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Recent studies proposed neutrophil-to-lymphocyte ratio (NLR) as a prognostic biomarker in malignant pleural mesothelioma (MPM). We examined baseline prognostic variables including NLR and the EORTC and CALGB models as predictors of overall survival (OS) in MPM.

Methods: In this retrospective study, 274 consecutive eligible, newly presenting patients with MPM were included. Of these, 159 received chemotherapy, 10 had tri-modality therapy, 2 underwent surgery only and 103 received supportive care alone. Univariate analyses and multivariate Cox models were calculated for OS.

Results: In univariate analysis, poor prognostic factors were: age ≥65 years, nonepithelioid histology, stage III-IV, poor performance status (PS), weight loss, chest pain, low haemoglobin and high platelet count. A baseline NLR≥ 5 did not predict worse OS (hazard ratio (HR) 1.25; P=0.122). On multivariate analysis, age, histology, PS, weight loss, chest pain and platelet count remained significant. The EORTC and CALGB prognostic groups were validated as predictive for OS (HR 1.62; P<0.001 and HR 1.65; P<0.001, respectively).

Conclusion: Our findings validate standard prognostic variables and the existing EORTC and CALGB models, but not NLR, at initial diagnosis of MPM. In guiding patient management at diagnosis, it is important to consider multiple baseline variables that jointly predict survival.

In plain English

This retrospective study examined 274 consecutive patients with malignant pleural mesothelioma diagnosed 2005 to 2010 at, or attending, a Western Australian hospital. Asbestos exposure was not studied. The authors tested whether the blood neutrophil-to-lymphocyte ratio (NLR) and EORTC and CALGB scoring systems predicted survival. Median survival from diagnosis was 13.3 months overall (95% CI 11.6 to 15.1), 15.2 months (13.8 to 17.9) for 169 patients given chemotherapy and 8.3 months (5.7 to 11.1) for 105 not given it. An NLR of 5 or more at diagnosis did not predict shorter survival (hazard ratio 1.25; 95% CI 0.94 to 1.66). The EORTC and CALGB prognostic groups did predict survival (hazard ratios 1.62, 95% CI 1.26 to 2.08, and 1.65, 95% CI 1.36 to 1.99). Age 65 or over, non-epithelioid tumour type, poor performance status, weight loss, chest pain and high platelet count independently predicted shorter survival. The authors concluded that established factors and models, but not NLR at initial diagnosis, were prognostic in this cohort. They noted the retrospective design, possible selection bias and a smaller-than-planned sample.

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 consecutive patients (prognostic factor analysis using Kaplan-Meier and Cox models)
• Who was studied: 274 eligible patients, out of 369 screened, with malignant pleural mesothelioma diagnosed between 1 January 2005 and 31 December 2010. Patients either were diagnosed at or attended Sir Charles Gairdner Hospital, Nedlands, Western Australia. 169 received chemotherapy, including 10 with trimodality therapy. 105 did not: 103 had supportive care alone and 2 had extrapleural pneumonectomy only.
• Exposure: Not asbestos exposure. The factors studied were the baseline blood neutrophil-to-lymphocyte ratio (cutoff 5), the EORTC and CALGB prognostic models, and individual clinical and laboratory variables at diagnosis.
• Main results:
  • Median overall survival from diagnosis was 13.3 months (95% CI 11.6 to 15.1) for all 274 patients. It was 15.2 months (95% CI 13.8 to 17.9) for chemotherapy-treated patients and 8.3 months (95% CI 5.7 to 11.1) for the non-chemotherapy group.
  • In all patients, a baseline NLR of 5 or more was not predictive of overall survival (HR 1.25; 95% CI 0.94 to 1.66; P = 0.122).
  • The EORTC and CALGB prognostic models were each predictive of overall survival: HR 1.62 (95% CI 1.26 to 2.08; P less than 0.001) and HR 1.65 (95% CI 1.36 to 1.99; P less than 0.001), respectively.
  • In multivariate analysis, six factors independently predicted shorter survival: age 65 or over, non-epithelioid histology, poor performance status (ECOG 2 to 3), weight loss, chest pain and a baseline platelet count above 400.
  • A baseline NLR of 5 or more was not predictive of worse survival in chemotherapy-treated patients (n = 169; HR 1.08; 95% CI 0.74 to 1.58; P = 0.69). Nor was it predictive in non-chemotherapy-treated patients (n = 105; HR 1.46; 95% CI 0.95 to 2.25; P = 0.08).
  • Among chemotherapy patients with an NLR above 5 at the start of chemotherapy (66 patients), NLR fell below 5 after one cycle in 47 and stayed elevated in 19. In univariate analysis, normalisation was prognostic for survival from the start of chemotherapy (HR 2.2; 95% CI 1.25 to 4.03).
  • Exploratory analyses of NLR at diagnosis found no significant survival differences using a cutoff of 3, the median value (3.53), or NLR as a continuous variable.
• The authors' conclusion: The authors concluded that their findings validated standard prognostic variables and the existing EORTC and CALGB models, but not NLR, at initial diagnosis of malignant pleural mesothelioma.
• Limitations the authors state:
  • Retrospective design and nonrandomised allocation of treatment groups, which prevented comparison of variables between treatment groups.
  • Selection bias from excluding screened patients with missing values for the markers examined.
  • Results may not apply to patients diagnosed outside this tertiary institution, or to those not fit for or refusing diagnostic testing.
  • No data were collected on albumin or CRP, so these inflammation markers could not be analysed.
  • The study did not reach its planned sample size of 321. The authors state that the higher-than-anticipated event rate preserved its power.
  • It is unknown whether NLR normalisation would remain predictive alongside other markers of chemotherapy response, because those variables were not collected after chemotherapy.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Biomarker, Pleural Mesothelioma, Overall Survival, Chemotherapy, Histology, Performance Status, Hazard Ratio.

Related studies

• Response to comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma' — T.M. Meniawy, J. Creaney, et al. (2014)
• Comment on 'Existing prognostic models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma' — S.C. Kao, N. van Zandwijk, et al. (2014)
• Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy — S.C. Kao, S. Klebe, et al. (2011)
• Malignant pleural mesothelioma: clinical experience and prognostic value of derived neutrophil-to-lymphocyte ratio and PD-L1 expression — L. Gutierrez-Sainz, P. Cruz, et al. (2021)
• High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy — S.C. Kao, N. Pavlakis, et al. (2010)
• Relation between neutrophil/lymphocyte ratio and primary tumor metabolic activity in patients with malign pleural mesothelioma — B.A. Özyürek, Ö. Özmen, et al. (2018)

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