Inflammation-based prognostic indices in malignant pleural mesothelioma

Our plain-English summary of Inflammation-based prognostic indices in malignant pleural mesothelioma, by D.J. Pinato, F.A. Mauri, R. Ramakrishnan, et al (Journal of Thoracic Oncology, 2012).

The study

• Authors: D.J. Pinato, F.A. Mauri, R. Ramakrishnan, L. Wahab, T. Lloyd, R. Sharma
• Journal: Journal of Thoracic Oncology
• Published: 2012;7(3):587-94
• Cited by: 123 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Biomarkers of systemic inflammation have been shown to predict the natural history of MPM; however, this observation lacks independent validation. Our aim was to compare the prognostic performance of three inflammation-based biomarkers in predicting overall survival (OS) in MPM.

Methods: In patients with histologically proven MPM, the inflammation-based prognostic scores modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio were studied and compared with the European Organization for the Research and Treatment of Cancer Prognostic Score (EPS) and other known potential prognostic factors such as gender, histologic subtype, Eastern Cooperative Oncology Group performance status, and baseline blood parameters.

Results: A total of 171 MPM patients presenting to Imperial College NHS Trust were studied. In univariate analyses, the following parameters were predictors of OS: female gender (p = 0.03), epithelioid histology (p = 0.03), normal C-reactive protein (p = 0.03), baseline white blood cell count <8.3 × 10/liter (p = 0.04), EPS (p = 0.003), mGPS (p < 0.001), NLR (p = 0.006), and platelet-to-lymphocyte ratio (p = 0.03). Multivariate survival analysis confirmed the mGPS (hazard ratio = 2.6; p < 0.001) and NLR (hazard ratio = 2.0; p = 0.008), but not the EPS, as independent predictors of OS. Tissue expression of Ki-67 (p < 0.001) and vascular endothelial growth factor (p < 0.001) was higher in a subgroup of patients with high-risk inflammatory scores.

Conclusions: The mGPS and NLR are externally validated prognostic indices in patients with MPM and correlate with sustained neoangiogenesis and increased proliferative index.

In plain English

This retrospective study examined 171 patients with malignant pleural mesothelioma seen at Imperial College NHS Healthcare Trust, London, between 1993 and 2011. It did not measure asbestos exposure. It asked whether blood-test inflammation measures predicted survival. These were the modified Glasgow Prognostic Score (mGPS), the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio, compared with the EORTC prognostic score and other factors. Median overall survival was 9.7 months (95% CI 8.1 to 11.4). Among factors that predicted survival on their own, both mGPS (hazard ratio 2.6, 95% CI 1.6 to 4.2) and NLR (hazard ratio 2.0, 95% CI 1.6 to 3.2) remained independent predictors in a combined analysis. The EORTC score did not. One-year survival was 72%, 35% and 17% for mGPS scores of 0, 1 and 2. Twenty patients were chosen at random for tumor tissue tests. The 10 with high-risk scores showed more cell proliferation and more staining for VEGF, a blood-vessel growth factor. The authors concluded that mGPS and NLR were validated as independent predictors. They noted the retrospective design, missing data and 18-year span, and called for prospective studies.

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 cohort study of prognostic factors for survival, with a small immunohistochemistry (tumor tissue staining) substudy
• Who was studied: 171 patients with histologically proven malignant pleural mesothelioma presenting to the Imperial College NHS Healthcare Trust, London, between 1993 and 2011. They were drawn from 202 identified patients after exclusions for inflammatory disease, second primary tumor, active infection or insufficient follow-up. 84% were male. A random subset of 20 patients (10 per group) had tumor tissue stained.
• Exposure: Asbestos exposure was not assessed. The factors studied were pre-biopsy blood-based inflammation scores: the modified Glasgow Prognostic Score (based on C-reactive protein and albumin), the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio. These were compared with the EORTC prognostic score and other clinical factors.
• Main results:
  • Among the 171 patients, 138 had died by the time of analysis. Median overall survival was 9.7 months (95% CI 8.1 to 11.4).
  • Factors significant in univariate analysis were entered into a stepwise backward Cox model, which removed variables with p greater than 0.10. In that multivariate analysis, mGPS was an independent predictor of overall survival: hazard ratio 2.6, 95% CI 1.6 to 4.2, p less than 0.001.
  • In the same multivariate analysis, NLR was also an independent predictor of overall survival: hazard ratio 2.0, 95% CI 1.6 to 3.2, p = 0.008.
  • The EORTC prognostic score and the other factors examined were not confirmed as independent prognostic factors in multivariate analysis. This included the platelet-to-lymphocyte ratio, although it was significant in univariate analysis.
  • Overall survival at 1 year was 72%, 35% and 17% for patients with mGPS 0, 1 and 2, respectively.
  • Survival at 2 years was 29% for mGPS 0, 17% for mGPS 1 and 4% for mGPS 2.
  • An abnormal mGPS was found in 66% of patients. It was associated with worse performance status, high white cell count, high platelet count and a greater than 10 g/liter hemoglobin difference.
  • In the tissue substudy, group B (high-risk inflammation scores, 10 patients) had a higher Ki-67 proliferative index than group A (low-risk scores, 10 patients): median 55.5 versus 8.5.
  • In the same 20 patients, group B had higher VEGF staining than group A: median immunohistochemical score 225.0 versus 60.0.
• The authors' conclusion: The authors concluded that their analysis validated the mGPS and NLR, but not the platelet-to-lymphocyte ratio, as independent predictors of overall survival in malignant pleural mesothelioma. They described the tissue findings as provocative and said these require further validation.
• Limitations the authors state:
  • The study was retrospective and had a significant amount of missing data.
  • The 18-year study period may have introduced heterogeneity as diagnosis and treatment of mesothelioma improved over time.
  • The Cancer and Leukemia Group B prognostic score could not be compared because clinical information was incomplete.
  • The authors stated that prospective studies are needed to validate the clinical usefulness of these scores.

Topics

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

Medical terms in this study, explained in our Lexicon: Inflammation, Pleural Mesothelioma, Chronic Inflammation, Asbestos Exposure, Biomarker, Overall Survival, Histological Subtype, Performance Status.

Related studies

• 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)
• Existing models, but not neutrophil-to-lymphocyte ratio, are prognostic in malignant mesothelioma — T.M. Meniawy, J. Creaney, et al. (2013)
• Analysis of prognostic factors of patients with malignant peritoneal mesothelioma — W. Yin, G. Zheng, et al. (2018)
• Prognostic value of the lymphocyte-to-monocyte ratio and other inflammatory markers in malignant pleural mesothelioma — A.C. Tanrikulu, A. Abakay, et al. (2016)
• 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)
• 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)

Browse more research in Journal of Thoracic Oncology, or return to medical research.