Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS).
Pleural mesothelioma (PM) is often presaged by benign asbestos-associated pleural inflammation (AAPI), offering a unique window of opportunity for translational research. The PREDICT-Meso International Accelerator Network is leveraging this natural history to perform target identification and develop novel therapies for early-stage or pre-invasive disease. This requires assembly of a unique bioresource of longitudinal human tissue samples spanning the terminal stages of PM evolution, development of preclinical models for drug screening and reliable tools for risk prediction in patients presenting with AAPI.
Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS) is a prospective, multicentre observational study, comprising two arms (A and B), with a nested MRI substudy in arm A. Arm A will recruit 300 AAPI patients and perform 6-monthly surveillance for 2 years. Suspicion of PM evolution will prompt repeat biopsy and banking, delivering a primary objective of ≥38 longitudinal AAPI-PM tissue pairs. This target reflects a projected PM evolution rate of 14% (95% CI 10.5 to 19.2) derived from a prior multicentre feasibility trial. Multiomic risk profiling will be performed in arm A, using blood proteomics, exhaled breath metabolomics and perfusion MRI. Arm B will recruit 300 patients with suspected PM, permitting collection of multiregion pleural biopsies in patients spanning AAPI and PM timepoints for evaluation of anatomical heterogeneity. Where possible, patients in arm B diagnosed with AAPI will be recruited to arm A for 2-year surveillance +/- repeat biopsy in subsequent PM evolution cases. Pleural fluid will be collected in arm B for cell-line generation and diagnostic biomarker evaluation. Exhaled breath will be collected in arm B for diagnostic biomarker evaluation.
The study has ethical approval (REC Ref 21/WS/0120). Results will be disseminated via peer-reviewed journals and national/international scientific conferences. Tissues, data and derived omics will be shared via the PREDICT-Meso Research Tissue Bank (REC Ref 21/WS/0011).
ISRCTN22929761.
Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS) is a prospective, multicentre observational study, comprising two arms (A and B), with a nested MRI substudy in arm A. Arm A will recruit 300 AAPI patients and perform 6-monthly surveillance for 2 years. Suspicion of PM evolution will prompt repeat biopsy and banking, delivering a primary objective of ≥38 longitudinal AAPI-PM tissue pairs. This target reflects a projected PM evolution rate of 14% (95% CI 10.5 to 19.2) derived from a prior multicentre feasibility trial. Multiomic risk profiling will be performed in arm A, using blood proteomics, exhaled breath metabolomics and perfusion MRI. Arm B will recruit 300 patients with suspected PM, permitting collection of multiregion pleural biopsies in patients spanning AAPI and PM timepoints for evaluation of anatomical heterogeneity. Where possible, patients in arm B diagnosed with AAPI will be recruited to arm A for 2-year surveillance +/- repeat biopsy in subsequent PM evolution cases. Pleural fluid will be collected in arm B for cell-line generation and diagnostic biomarker evaluation. Exhaled breath will be collected in arm B for diagnostic biomarker evaluation.
The study has ethical approval (REC Ref 21/WS/0120). Results will be disseminated via peer-reviewed journals and national/international scientific conferences. Tissues, data and derived omics will be shared via the PREDICT-Meso Research Tissue Bank (REC Ref 21/WS/0011).
ISRCTN22929761.
Authors
Neilly Neilly, MacPherson MacPherson, Alexander Alexander, Walker Walker, Kelly Kelly, Roche Roche, Abugassa Abugassa, Allan Allan, Ashraf Ashraf, Aujayeb Aujayeb, Bibby Bibby, Bilancia Bilancia, Corcoran Corcoran, Chetty Chetty, Conroy Conroy, Craig Craig, Crook Crook, D'Souza D'Souza, Daneshvar Daneshvar, DeFoneska DeFoneska, Denniston Denniston, Fallon Fallon, Ferguson Ferguson, Gatheral Gatheral, Griffiths Griffiths, Haris Haris, Hashim Hashim, Ionescu Ionescu, Kadwani Kadwani, Macdougall Macdougall, Maclay Maclay, Mann Mann, Maskell Maskell, Morrison Morrison, Panchal Panchal, Prudon Prudon, Rahman Rahman, Sudhir Sudhir, Ramsaroop Ramsaroop, Reddy Reddy, Reid Reid, Sage Sage, Short Short, Stanton Stanton, Succony Succony, Tsaknis Tsaknis, Tsim Tsim, Cowell Cowell, Lamote Lamote, Blyth Blyth
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