Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS)

Our plain-English summary of Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS), by M.D.J. Neilly, A. MacPherson, L. Alexander, et al (BMJ Open Respiratory Research, 2026).

The study

• Authors: M.D.J. Neilly, A. MacPherson, L. Alexander, N. Walker, C. Kelly, J. Roche, E. Abugassa, L. Allan, A. Ashraf, A. Aujayeb, A. Bibby, R. Bilancia, J. Corcoran, M. Chetty, K. Conroy, C. Craig, R. Crook, A. D'Souza, C. Daneshvar, D. DeFoneska, P. Denniston, J. Fallon, K. Ferguson, T. Gatheral, A.L. Griffiths, M. Haris, M. Hashim, A. Ionescu, O. Kadwani, M. Macdougall, J.D. Maclay, O.N. Mann, N. Maskell, M. Morrison, R. Panchal, B. Prudon, N.M. Rahman, R. Sudhir, S. Ramsaroop, R. Reddy, P. Reid, E. Sage, P. Short, A.E. Stanton, L. Succony, G. Tsaknis, S. Tsim, G. Cowell, K. Lamote, K.G. Blyth
• Journal: BMJ Open Respiratory Research
• Published: 2026;13(1)
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: 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.

Methods And Analysis: 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.

Ethics And Dissemination: 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).

Trial Registration Number: ISRCTN22929761.

© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group.

In plain English

This article is a study protocol. It describes a planned and ongoing UK study, Meso-ORIGINS, and reports no findings on who develops mesothelioma. The prospective, multicentre observational study began recruiting in July 2022 and aims to enrol 600 asbestos-exposed patients at 32 sites in 27 UK cities. Arm A is to follow 300 patients whose pleural biopsy showed asbestos-associated pleural inflammation. Eligible biopsy findings include atypical mesothelial proliferation or mesothelioma in situ, but not confirmed mesothelioma. They are to be checked every 6 months for 2 years, with repeat biopsy at the clinical team's discretion if mesothelioma is suspected, and a subgroup is to have MRI scans. Arm B is to enrol 300 patients with suspected pleural mesothelioma and take biopsies from several places in the chest lining during thoracoscopy. Blood, breath and pleural fluid are also to be banked. The arm A size was based on an earlier feasibility study. In that study, mesothelioma was confirmed in 36 of 257 patients (14%, 95% confidence interval 10.3 to 18.8) after an initial diagnosis of asbestos-associated pleural inflammation. An interim review in March 2025 counted 181 arm B recruits over 33 months.

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: Study protocol for a prospective, multicentre, longitudinal observational study with two arms (A and B) and a nested MRI substudy in arm A; no results are reported
• Who was studied: Planned 600 patients in the UK, all aged 16 or over. Arm A: 300 asbestos-exposed patients with a pleural biopsy in the last year showing asbestos-associated pleural inflammation (for example benign fibrinous pleurisy, non-specific pleuritis, atypical mesothelial proliferation or mesothelioma in situ), excluding any confirmed pleural mesothelioma. Arm B: 300 asbestos-exposed patients with suspected pleural mesothelioma undergoing thoracoscopy. Recruitment began in July 2022, and 32 sites in 27 UK cities were open at the time of writing.
• Exposure: History of asbestos exposure, or imaging compatible with it such as pleural plaques; no fiber types, jobs or doses are specified
• Main results:
  • No study results are reported. At an interim review of recruitment in March 2025, arm B had 181 recruits over 33 months, an average of 5.5 cases per month
  • At the time of writing, the study was open at 32 sites in 27 UK cities
  • The arm A sample size was based on the earlier retrospective, multicentre Meso-ORIGINS feasibility study. In that study, pleural mesothelioma evolution after an initial diagnosis of asbestos-associated pleural inflammation was confirmed histologically in 36 of 257 patients (14%, 95% CI 10.3 to 18.8).
• The authors' conclusion: As a protocol, the article draws no conclusions about mesothelioma risk. The authors stated that the multiomic risk prediction in arm A will inform eligibility criteria for future precision prevention trials
• Limitations the authors state:
  • The authors noted that pleural fluid will often not be available at baseline in arm A, because AAPI patients rarely have an actively draining effusion
  • Planned research-only repeat biopsies in arm A patients without mesothelioma after at least 18 months of follow-up were removed as unfeasible after review of the first 20 patients

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Inflammation, Biopsy, Biomarker.

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