Prognostication and monitoring of mesothelioma using biomarkers: a systematic review

Our plain-English summary of Prognostication and monitoring of mesothelioma using biomarkers: a systematic review, by D.T. Arnold, D. De Fonseka, F.W. Hamilton, et al (British Journal of Cancer, 2017).

The study

• Authors: D.T. Arnold, D. De Fonseka, F.W. Hamilton, N.M. Rahman, N.A. Maskell
• Journal: British Journal of Cancer
• Published: 2017;116(6):731-741
• Type of article: Systematic review
• Cited by: 45 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Radiological markers of treatment response and prognostication in malignant pleural mesothelioma have limitations due to the morphology of the disease. Serum or pleural fluid biomarkers that could act as an adjunct to radiological assessment would be of significant value. The aim of this review was to collate and summarise the literature relating to this topic.

Methods: A systematic review was performed on the databases Pubmed and EMBASE to identify relevant studies. Two independent researchers read the abstracts and used the Quality in Prognostic Studies tool to assess the quality of the evidence.

Results: Forty-five studies were identified from the current literature. Twenty studies investigated the role of serum soluble mesothelin with majority suggesting that it has variable utility as a baseline test but when measured serially correlates with treatment response and prognosis. Several studies demonstrated that serum osteopontin correlated with survival at baseline. Other biomarkers have shown prognostic utility in individual studies but are yet to be reproduced in large cohort studies.

Conclusions: From the available literature no serum or pleural fluid biomarker was identified that could be recommended currently for routine clinical practice. However, a falling serum soluble mesothelin might correlate with treatment response and improved survival.

In plain English

This was a systematic review, not a new study of patients. The authors searched the PubMed and EMBASE databases for English-language papers up to 30 June 2016. They looked for papers on whether substances (biomarkers) in blood or in the fluid around the lungs could predict survival or track treatment response in malignant pleural mesothelioma. Two reviewers screened 1325 abstracts and included 45 studies. Because the studies differed so much, the authors did not combine their results. Blood soluble mesothelin was the most studied biomarker, in 20 studies with a total of 1578 patients. Its usefulness as a single test before treatment varied. All eight studies that measured it repeatedly during treatment found that falling levels went along with response on scans and/or longer survival. Several studies linked starting blood osteopontin levels with survival. No study found blood fibulin-3 to be a significant predictor of survival at the start. The authors concluded that no blood or pleural fluid biomarker could currently be recommended for routine clinical practice. They noted that many included studies had a moderate to high risk of bias.

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: Systematic review of published studies (no meta-analysis), with study quality assessed by two reviewers using the Quality in Prognostic Studies (QUIPS) tool
• Who was studied: 45 published studies of patients with proven malignant pleural mesothelioma (MPM). In each, a serum or pleural fluid biomarker was measured and compared with survival or treatment response. They were drawn from 1325 abstracts (English-language, PubMed and EMBASE, up to 30 June 2016). Studies with fewer than 10 MPM patients, conference abstracts and letters were excluded.
• Exposure: Not asbestos exposure. The review examined blood (serum or plasma) and pleural fluid biomarkers, mainly soluble mesothelin, megakaryocyte potentiating factor, osteopontin, fibulin-3, hyaluronic acid and VEGF, as markers of prognosis and treatment response.
• Main results:
  • Serum/plasma soluble mesothelin was the most studied biomarker: 20 studies (18 prospective, 2 retrospective) with a total of 1578 patients. Pleural fluid soluble mesothelin was examined separately in five studies with a total of 371 patients.
  • In the reviewed studies, serum soluble mesothelin had variable usefulness as a single test before treatment, but when measured repeatedly it correlated with treatment response and prognosis.
  • All eight reviewed studies of repeated serum soluble mesothelin testing found a correlation between falling levels and radiological response and/or improved overall survival.
  • Several reviewed studies found that serum osteopontin before treatment correlated with survival. In one of them (Grigoriu et al 2007, 96 MPM patients), baseline serum osteopontin was related to overall survival at multivariate analysis, with a hazard ratio of 3.46 (CI 1.1 to 10.9).
  • None of the six reviewed studies of serum/plasma fibulin-3 found it to be a significant marker of prognosis at baseline.
  • Other biomarkers showed prognostic usefulness in individual studies, but this had not yet been reproduced in large cohort studies.
• The authors' conclusion: The authors concluded that no serum or pleural fluid biomarker could currently be recommended for routine clinical practice. They added that a falling serum soluble mesothelin might correlate with treatment response and improved survival, but further studies are required.
• Limitations the authors state:
  • The quality of included studies varied, and many had a moderate to high risk of bias due to study attrition or lack of reporting of confounding factors.
  • Patients within studies received different treatments, a major confounder that multivariate analysis can only partly adjust for.
  • Differences between studies in biomarker cut-offs, tumour histology, treatments and outcome measures meant the results were not meta-analysed.
  • The studies of repeated soluble mesothelin testing focused on chemotherapy patients, with only 34 surgical patients.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Biomarker, Systematic Review, Pleural Mesothelioma, Mesothelin, Prognosis, Osteopontin.

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