title: Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ISRCTN10079972, Pre-results.
authors.affiliation: Department of Respiratory Medicine, Queen Elizabeth University Hospital, Glasgow, UK.|Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Selina
authors.initials: S
authors.lastname: Tsim
authors.affiliation: Cancer Research UK Glasgow Clinical Trials Unit, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kelly
authors.affiliation: Cancer Research UK Glasgow Clinical Trials Unit, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Alexander
authors.affiliation: Cancer Research UK Glasgow Clinical Trials Unit, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: McCormick
authors.affiliation: Cancer Research UK Glasgow Clinical Trials Unit, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Thomson
authors.affiliation: Glasgow Clinical Research Imaging Facility, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: Rosie
authors.initials: R
authors.lastname: Woodward
authors.affiliation: Glasgow Clinical Research Imaging Facility, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: John E
authors.initials: JE
authors.lastname: Foster
authors.affiliation: Department of Radiology, Queen Elizabeth University Hospital, Glasgow, UK.
authors.forename: David B
authors.initials: DB
authors.lastname: Stobo
authors.affiliation: Cancer Research UK Glasgow Clinical Trials Unit, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Paul
authors.affiliation: Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Nick A
authors.initials: NA
authors.lastname: Maskell
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.|Beatson West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Chalmers
authors.affiliation: Department of Respiratory Medicine, Queen Elizabeth University Hospital, Glasgow, UK.|Institute of Infection, Immunology and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Blyth
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D003430:Cross-Sectional Studies; D016326:Extracellular Matrix Proteins / Q000097:blood*; D058851:GPI-Linked Proteins / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000000981:diagnostic imaging*; D000086002:Mesothelioma, Malignant; D011379:Prognosis; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D012107:Research Design; D012606:Scotland
chemical_list: D014408:Biomarkers, Tumor; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D058851:GPI-Linked Proteins; D000090204:Mesothelin
keywords: Biomarker; Diagnosis; Mesothelioma; Prognosis