The DIAPHRAGM study: Diagnostic and prognostic biomarkers in the rational assessment of Mesothelioma

Introduction: Fibulin-3 (F3) and SOMAscan® (SS) are blood biomarkers with reported sensitivity and specificity >90% for Malignant Pleural Mesothelioma (MPM) but results are limited by inconsistent results and retrospective study design. The primary objective of DIAPHRAGM was to determine the diagnostic performance of F3 and SS in an adequately-powered, prospective study, compared to Mesothelin. Methods: DIAPHRAGM recruited an ‘intention-to-diagnose’ suspected pleural malignancy (SPM) cohort from 22 UK/Irish centres (Dec ’13 – Dec ‘16). Biomarker sampling simulated clinical use and diagnostic assessment was robust (Figure 1). Inclusion criteria were SPM (unilateral pleural effusion/mass), fit for sampling and consent. Patients with recent or in-situ chest drain were excluded. Target sample size was 600 SPM cases (including at least 120 MPM) and 109 asbestos-exposed controls (AEC). Results: 639 SPM and 109 AEC cases were recruited. 156 (24%) SPM patients had MPM, 213 (33 had secondary pleural malignancy and 241 (38%) benign disease. Final diagnoses are awaited in 5% (n=29). Biomarker assays are in progress. Complete results will be available by ERS congress. Conclusion: DIAPHRAGM was an appropriately-designed, multi-centre study that will clearly define the diagnostic performance of F3, SS and Mesothelin in MPM. A large, well-phenotyped bioresource has been created for future biomarker studies.