Article Text

Download PDFPDF

Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study
  1. Selina Tsim1,2,
  2. Caroline Kelly3,
  3. Laura Alexander3,
  4. Carol McCormick3,
  5. Fiona Thomson3,
  6. Rosie Woodward4,
  7. John E Foster4,
  8. David B Stobo5,
  9. Jim Paul3,
  10. Nick A Maskell6,
  11. Anthony Chalmers2,7,
  12. Kevin G Blyth1,8
  1. 1Department of Respiratory Medicine, Queen Elizabeth University Hospital, Glasgow, UK
  2. 2Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
  3. 3Cancer Research UK Glasgow Clinical Trials Unit, UK
  4. 4Glasgow Clinical Research Imaging Facility, Queen Elizabeth University Hospital, Glasgow, UK
  5. 5Department of Radiology, Queen Elizabeth University Hospital, Glasgow, UK
  6. 6Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK
  7. 7Beatson West of Scotland Cancer Centre, Glasgow, UK
  8. 8Institute of Infection, Immunology and Inflammation, University of Glasgow, Glasgow, UK
  1. Correspondence to Dr Kevin G Blyth; kevin.blyth{at}ggc.scot.nhs.uk

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.

  • Mesothelioma
  • Biomarker
  • Diagnosis
  • Prognosis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Footnotes

  • Contributors ST and JEF contributed to the conception or design of the work; data acquisition, analysis and interpretation of data for the work. CK contributed to the design of the work; analysis and interpretation of data for the work. LA and DBS contributed to the design of the work and interpretation of data for the work. CM, FT and RW contributed to the design of the work; data acquisition, analysis or interpretation of data for the work. JP contributed to the conception and design of the work; data analysis or interpretation of data for the work. NAM contributed to the design of the work; data analysis and interpretation of data for the work. AC contributed to the conception and design of the work; interpretation of data for the work. ST, CK, LA, CM, FT, RW, JEF, DBS, JP, NAM and AC were involved in revising the work critically for important intellectual content, final approval of the version to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. KGB provided principal contribution to the conception and design of the work; data acquisition, analysis and interpretation of data for the work; drafting the work; final approval of the version to be published; and agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This work was supported by the Chief Scientist's Office of the Scottish Government (Project Grant ETM/285) and the West of Scotland Lung Cancer Research Group (Award September 2015). KGB is part-funded by NHS Research Scotland.

  • Competing interests SomaLogic have provided funding for all SOMAscan assays.

  • Ethics approval The study protocol, all documents and amendments have been approved by the West of Scotland Research Ethics Service (Ref: 13/WS/0240).

  • Provenance and peer review Not commissioned; externally peer reviewed.