Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study

Our plain-English summary of Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study, by S. Tsim, C. Kelly, L. Alexander, et al (BMJ Open, 2016).

The study

• Authors: S. Tsim, C. Kelly, L. Alexander, C. McCormick, F. Thomson, R. Woodward, J.E. Foster, D.B. Stobo, J. Paul, N.A. Maskell, A. Chalmers, K.G. Blyth
• Journal: BMJ Open
• Published: 2016;6(11):e013324
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

Methods And Analysis: Serum and plasma (for SOMAscan and fibulin-3, respectively) will be collected at presentation, prior to pleural biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of MPM/non-MPM cases will depend on the incidence of MPM in the study population (estimated at 13-20%). Identical sampling and storage protocols will be used in 22 recruiting centres and histological confirmation sought in all cases. Markers will be measured using the SOMAscan proteomic assay (SomaLogic) and a commercially available fibulin-3 ELISA (USCN Life Science). The SE in the estimated sensitivity and specificity will be <5% for each marker and their performance will be compared with serum mesothelin. Blood levels will be compared with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested substudy. The prognostic value of each marker will be assessed and a large bioresource created.

Ethics And Dissemination: The study has been approved by the West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management Group meets on a monthly basis. Results will be published in peer-reviewed journals, presented at international meetings and disseminated to patient groups.

Trial Registration Number: ISRCTN10079972, Pre-results.

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In plain English

This article is a study protocol. It described how the DIAPHRAGM study was planned to be carried out and reported no results. DIAPHRAGM was designed as a prospective, multicentre observational study. Blood samples were to be taken from patients at first presentation, before any pleural biopsy or pleurodesis: serum for the SOMAscan protein test and plasma for fibulin-3. The aim was to find out whether these markers give clinically useful information for diagnosing malignant pleural mesothelioma and for judging a patient's outlook (prognosis). The planned sample was 83 to 120 patients with malignant pleural mesothelioma, at least 480 patients with pleural disease other than mesothelioma, and 109 asbestos-exposed controls. The authors stated that the final number of mesothelioma patients, and therefore the statistical power available for the study's main question, would not be known until recruitment was complete.

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: Protocol for a prospective, multicentre observational study of diagnostic and prognostic blood markers. No results are reported.
• Who was studied: Planned: 83 to 120 patients with malignant pleural mesothelioma (MPM), at least 480 patients with non-MPM pleural disease, and 109 asbestos-exposed controls.
• Exposure: This is not an asbestos exposure study. The things being tested are blood markers taken at presentation, before pleural biopsy or pleurodesis: serum for the SOMAscan proteomic test and plasma for fibulin-3. No fiber types are studied.
• Limitations the authors state:
  • The final number of participants with malignant pleural mesothelioma, and therefore the statistical power to test the primary objective, would not be known until recruitment was complete.

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: Biomarker, Mesothelioma, Diaphragm, Pleural Mesothelioma, Thoracoscopy, Clinical Trial, Fibulin-3, Pleural Biopsy.

Related studies

• The Its Not JUST Idiopathic pulmonary fibrosis Study (INJUSTIS): description of the protocol for a multicentre prospective observational cohort study identifying biomarkers of progressive fibrotic lung disease — F. Khan, I. Stewart, et al. (2019)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• Biomarkers in malignant mesothelioma: diagnostic and prognostic role of soluble mesothelin-related peptide — N. Dipalma, V. Luisi, et al. (2011)
• Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases — S. Tsim, L. Alexander, et al. (2021)
• Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study — K. Hollevoet, J. Van Cleemput, et al. (2011)
• Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin — G. Ak, Y. Tada, et al. (2017)

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