Inflammation in malignant mesothelioma - friend or foe?

Our plain-English summary of Inflammation in malignant mesothelioma - friend or foe?, by A. Linton, N. van Zandwijk, G. Reid, et al (Annals of Cardiothoracic Surgery, 2012).

The study

• Authors: A. Linton, N. van Zandwijk, G. Reid, S. Clarke, C. Cao, S. Kao
• Journal: Annals of Cardiothoracic Surgery
• Published: 2012;1(4):516-22
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

This review examined published evidence on the relationship between local and systemic inflammation and survival in patients with malignant pleural mesothelioma (MPM), and considered possible therapeutic implications. The authors noted that asbestos fibre exposure occupies the central pathogenic role in MPM. In tumour tissue, cited studies found that two features were associated with longer survival: a marked chronic inflammatory response in the stroma (median overall survival 19.4 vs. 15.0 months) and high levels of tumour-infiltrating CD8+ lymphocytes. Macrophages, mostly of the immunoregulatory M2 phenotype, were associated with poorer survival in non-epithelial tumours. For systemic inflammation, the review summarised studies in which several markers were associated with reduced survival: a high blood neutrophil-lymphocyte ratio (NLR ≥5; HR 2.7 in 173 patients receiving systemic therapy), elevated C-reactive protein, low albumin, high monocyte and platelet counts, elevated LDH, and the modified Glasgow prognostic score. Patients whose abnormal NLR normalised after one cycle of systemic therapy survived longer than those whose NLR remained high (7.8 vs. 5.0 months). The authors concluded that inflammatory biomarkers can provide valuable prognostic information. They added that prospective validation and clinically useful cut-off values are needed before these markers enter routine practice. They also discussed possible uses in predicting treatment outcome, recognising chemotherapy futility, identifying patients at risk of cachexia, and guiding immunotherapy research.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a narrative review of published evidence on how inflammation relates to survival in patients with malignant pleural mesothelioma (MPM), and what this might mean for treatment. It reported no new patient data. One study it described, of 175 patients with the epithelial subtype, found longer median overall survival in patients with a marked chronic inflammatory response around the tumour (19.4 vs. 15.0 months). Two series of patients who had extrapleural pneumonectomy linked high numbers of CD8+ lymphocytes in the tumour with better survival. Macrophages in non-epithelial tumours were linked with poorer survival. In blood tests, other studies linked shorter survival with a high neutrophil-to-lymphocyte ratio (5 or more, in 173 patients), raised C-reactive protein, low albumin, raised LDH and high platelet counts. The authors concluded that inflammatory biomarkers can give valuable prognostic information. They added that these markers need prospective validation before use in clinical practice. The review did not study asbestos exposure. It described asbestos fibre exposure as the central cause of MPM and said the resulting changes in immune cells may weaken immunity against the tumour.

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: Narrative review of published studies (the article is labelled a Perspective); no new data
• Who was studied: Patients with malignant pleural mesothelioma (MPM) in the published studies reviewed; the review itself studied no patients
• Exposure: Not studied. In its introduction, citing another paper, the review describes asbestos fibre exposure as the central cause of MPM and says the resulting alteration of immune-competent cells may reduce tumour immunity; no fiber types are named
• Main results:
  • In a reviewed study of 175 patients with epithelial-subtype MPM, patients with a marked chronic inflammatory response in the stroma (tissue around the tumour) had longer median overall survival than those with a low response: 19.4 vs. 15.0 months (P=0.01).
  • In two reviewed series of MPM patients who had extrapleural pneumonectomy, high levels of tumour-infiltrating CD8+ lymphocytes were associated with improved survival on multivariate analysis (HR=0.27-0.38; P less than 0.05).
  • In a reviewed study of tumour samples, macrophages in non-epithelial tumours were negatively correlated with survival (P=0.008). This was not found in epithelial tumours (P=0.7).
  • In a reviewed study of 173 patients who had systemic therapy, a high baseline blood neutrophil-to-lymphocyte ratio (5 or more) was independently associated with reduced overall survival (HR=2.7; 95% CI: 1.8-3.9; P less than 0.001).
  • In the same study, patients whose abnormal baseline ratio returned to normal after one cycle of therapy survived longer than those whose ratio stayed high: 7.8 vs. 5.0 months (P=0.03).
  • In a reviewed study of 363 Turkish patients with MPM, LDH above 500 IU/L (HR=2.24; 95% CI: 1.585-3.168) and platelet count above 420 x 10^3 per microlitre (HR=1.33; 95% CI: 1.009-1.757) were associated with reduced median survival on multivariate analysis.
  • In a reviewed retrospective study of 115 patients with MPM, C-reactive protein of 1 mg/dL or more was an independent indicator of poor prognosis (HR=2.07; 95% CI: 1.23-3.46; P=0.001).
  • In a reviewed cohort of 278 patients admitted for palliative surgery for MPM, albumin below 35 g/L was independently associated with a decline in survival (HR=2.415; 95% CI: 1.70-3.44; P less than 0.0001).
  • In a reviewed study, the modified Glasgow prognostic score (based on C-reactive protein and albumin) was a better predictor than either C-reactive protein or albumin alone on multivariate analysis (HR=2.6; 95% CI: 1.6-4.2; P less than 0.001).
• The authors' conclusion: The authors concluded that inflammatory biomarkers can provide valuable prognostic information in MPM. Some local inflammatory cells (CD8+ T lymphocytes) are associated with better prognosis and others (M2 macrophages) with poorer survival. A systemic inflammatory response (raised CRP and NLR) is associated with poorer prognosis. Prospective validation is required before these markers are used in clinical practice.
• Limitations the authors state:
  • The authors state that clinically useful cut-off values for inflammatory markers require further study and validation.
  • The authors note that the link between NLR normalisation after one cycle of therapy and survival has not been validated in other MPM studies.
  • The authors state that how inflammation causes MPM to develop is beyond the scope of the review.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Mesothelioma, Pleural Mesothelioma, Median Overall Survival, Macrophage, Systemic Therapy, Biomarker, Chemotherapy.

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