Progress and challenges in Mesothelioma: From bench to bedside

Our plain-English summary of Progress and challenges in Mesothelioma: From bench to bedside, by K.G. Blyth, D.J. Murphy (Respiratory Medicine, 2018).

The study

• Authors: K.G. Blyth, D.J. Murphy
• Journal: Respiratory Medicine
• Published: 2018;134:31-41
• Type of article: Review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant Pleural Mesothelioma (MPM) is currently an incurable cancer with a typical survival of 1 year from the time of diagnosis. The recent genomic and transcriptomic characterization of MPM presents new opportunities and challenges for MPM researchers. Recent advances in clinical and laboratory diagnostics, and proposals for an updated, data-driven, staging system, also present new challenges for clinicians and hospital services involved in MPM care. The aim of this review is first to introduce the reader to the topic of MPM, a disease that is causally linked to prior, typically occupational, exposure to asbestos fibres. Secondly, we will discuss MPM from the clinical and laboratory perspectives, including reviews of current and evolving therapies and our present understanding of the molecular basis of the disease. Finally, we will attempt to identify critical knowledge gaps that currently prevent more effective treatment, including the challenges involved in early detection and chemoprophylaxis.

Copyright © 2017 Elsevier Ltd. All rights reserved.

In plain English

This article is mainly a narrative review of published research. The authors, from Glasgow, reviewed research on malignant pleural mesothelioma (MPM). They described it as an incurable cancer causally linked to prior, typically occupational, exposure to asbestos fibres. They searched PubMed for references from 2000 onward. The review covered diagnosis, staging, treatments and the genetics of the disease. Among the studies it described, a genomic analysis of 216 MPM tumours found few mutations and no smoking-related mutation pattern. A meta-analysis found that the mesothelin blood test had 32% sensitivity at 95% specificity. A figure also presented the authors' own retrospective data on 404 patients diagnosed in the West of Scotland between 2008 and 2017. Survival data were available for 370 of them. The 342 who had both survival data and a recorded sub-type were analysed. In that group, survival was longest with epithelioid, intermediate with biphasic and shortest with sarcomatoid MPM. The authors stated that surgery currently has no proven therapeutic role and that current tools are not accurate enough for a screening programme. They concluded that much progress had been made over the last decade and that more is expected.

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: Mainly a narrative review of published literature on malignant pleural mesothelioma, written from clinical and laboratory perspectives. One figure also presents the authors' own retrospective analysis of patient survival data from the West of Scotland.
• Who was studied: Published studies on malignant pleural mesothelioma, found through PubMed, the authors' own libraries and recent meeting abstracts, limited to references since 2000. A figure adds retrospective data on 404 patients diagnosed with MPM in the West of Scotland between January 2008 and April 2017.
• Exposure: Not an exposure study. The review describes MPM as causally linked to prior, typically occupational, asbestos exposure, and notes that the link was validated in workers exposed mainly to crocidolite and amosite.
• Main results:
  • Authors' own West of Scotland data: of 404 patients, 370 had survival data. 28 without a recorded histological sub-type were excluded, leaving 342 in the sub-type analysis. Survival was longest in epithelioid, intermediate in biphasic and shortest in sarcomatoid MPM. Compared with epithelioid MPM, the hazard ratio for death was 1.93 for sarcomatoid MPM (p less than 0.0001) and 1.75 for biphasic MPM.
  • The review described a published genomic study of 216 MPM cases. That study found few protein-altering mutations and no smoking-related DNA-damage signature. A DNA-damage pattern from reactive oxygen species predominated, which the review called consistent with known effects of asbestos fibres.
  • The review cited a large meta-analysis reporting that the mesothelin blood test had 32% sensitivity at 95% specificity.
  • The review cited the randomised MARS feasibility trial, which reported excess mortality in the extra-pleural pneumonectomy arm (adjusted hazard ratio 2.75, interval 1.21 to 6.26, p = 0.016). The authors stated that surgery has, at present, no proven therapeutic role in MPM.
  • Drawing on the literature, the authors inferred that in new MPM cases only about one-third of patients have visible pleural plaques. Only about two-thirds have a positive mesothelin test or a CT scan with obvious signs of pleural malignancy. They concluded that the detection tools needed for an accurate screening programme do not currently exist.
  • The review described a transgenic mouse model of asbestos-induced peritoneal mesothelioma. In that model, anti-inflammatories and anti-oxidants did not show useful preventive (chemoprophylactic) effects.
• The authors' conclusion: The authors concluded that there had been much progress in MPM over the last decade, including an updated staging system, clinical trials of therapies, better diagnostic tools and the first detailed characterisation of the tumour genome. They expected further progress. They identified knowledge gaps in drug development, early detection and chemoprophylaxis.

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: Mesothelioma, Pleural Mesothelioma, Staging.

Related studies

• Malignant pleural mesothelioma: from the bench to the bedside — P. Astoul, E. Roca, et al. (2012)
• Translating mesothelioma molecular genomics and dependencies into precision oncology-based therapies — T.K. Hinz, L.E. Heasley (2020)
• Translational advances in pleural malignancies — G.T. Stathopoulos (2011)
• Loco-regional staging of malignant pleural mesothelioma by integrated 18F-FDG PET/MRI — D.J. Murphy, S.M. Mak, et al. (2019)
• Challenges and controversies in the diagnosis of malignant mesothelioma: Part 2. Malignant mesothelioma subtypes, pleural synovial sarcoma, molecular and prognostic aspects of mesothelioma, BAP1, aquaporin-1 and microRNA — D.W. Henderson, G. Reid, et al. (2013)
• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)

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