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

Mark D.J. Neilly; Alexandrea MacPherson; Laura Alexander; Nicola Walker; Caroline Kelly; Joshua Roche; Emad Abugassa; Liam Allan; Adeel Ashraf; Avinash Aujayeb; Anna Bibby; Rocco Bilancia; John Corcoran; Mahendran Chetty; Kevin Conroy; Christopher Craig; Rebecca Crook; Alveena D’Souza; Cyrus Daneshvar; Duneesha DeFoneska; Poppy Denniston; Janet Fallon; Katie Ferguson; Timothy Gatheral; Andrew Lloyd Griffiths; Mohammed Haris; Mohammed Hashim; Alina Ionescu; Owais Kadwani; Michelle Macdougall; John D. Maclay; Oliver Nesfield Mann; Nick Maskell; Morvern Morrison; Rakesh Panchal; Benjamin Prudon; Najib M. Rahman; Rajini Sudhir; Sudarshan Ramsaroop; Raja Reddy; Phil Reid; Elizabeth Sage; Philip Short; Andrew E. Stanton; Laura Succony; Georgios Tsaknis; Selina Tsim; Gordon Cowell; Kevin Lamote; Kevin G. Blyth

doi:10.1136/bmjresp-2025-004045

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

Mark D.J. Neilly
, Alexandrea MacPherson
, Laura Alexander
, Nicola Walker
, Caroline Kelly
, Joshua Roche
, Emad Abugassa
, Liam Allan
, Adeel Ashraf
, Avinash Aujayeb
, Anna Bibby
, Rocco Bilancia
, John Corcoran
, Mahendran Chetty
, Kevin Conroy
, Christopher Craig
, Rebecca Crook
, Alveena D’Souza
, Cyrus Daneshvar
, Duneesha DeFoneska

Poppy Denniston, Janet Fallon, Katie Ferguson, Timothy Gatheral, Andrew Lloyd Griffiths, Mohammed Haris, Mohammed Hashim, Alina Ionescu, Owais Kadwani, Michelle Macdougall, John D. Maclay, Oliver Nesfield Mann, Nick Maskell, Morvern Morrison, Rakesh Panchal, Benjamin Prudon, Najib M. Rahman, Rajini Sudhir, Sudarshan Ramsaroop, Raja Reddy, Phil Reid, Elizabeth Sage, Philip Short, Andrew E. Stanton, Laura Succony, Georgios Tsaknis, Selina Tsim, Gordon Cowell, Kevin Lamote, Kevin G. Blyth

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	e004045
Number of pages	10
Journal	BMJ Open Respiratory Research
Volume	13
Issue number	1
DOIs	https://doi.org/10.1136/bmjresp-2025-004045
Publication status	Published - 1 Jul 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Asbestos Induced Lung Disease
Mesothelioma
Pleural Disease

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1136/bmjresp-2025-004045Licence: CC BY

Fina Published VersionFinal published version, 1.3 MBLicence: CC BY

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Neilly, M. D. J., MacPherson, A., Alexander, L., Walker, N., Kelly, C., Roche, J., Abugassa, E., Allan, L., Ashraf, A., Aujayeb, A., Bibby, A., Bilancia, R., Corcoran, J., Chetty, M., Conroy, K., Craig, C., Crook, R., D’Souza, A., Daneshvar, C., ... Blyth, K. G. (2026). Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS). BMJ Open Respiratory Research, 13(1), Article e004045. https://doi.org/10.1136/bmjresp-2025-004045

@article{0401b13fbecd4b09afeca7d862200d27,

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

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.",

keywords = "Asbestos Induced Lung Disease, Mesothelioma, Pleural Disease",

author = "Neilly, \{Mark D.J.\} and Alexandrea MacPherson and Laura Alexander and Nicola Walker and Caroline Kelly and Joshua Roche and Emad Abugassa and Liam Allan and Adeel Ashraf and Avinash Aujayeb and Anna Bibby and Rocco Bilancia and John Corcoran and Mahendran Chetty and Kevin Conroy and Christopher Craig and Rebecca Crook and Alveena D{\textquoteright}Souza and Cyrus Daneshvar and Duneesha DeFoneska and Poppy Denniston and Janet Fallon and Katie Ferguson and Timothy Gatheral and Griffiths, \{Andrew Lloyd\} and Mohammed Haris and Mohammed Hashim and Alina Ionescu and Owais Kadwani and Michelle Macdougall and Maclay, \{John D.\} and Mann, \{Oliver Nesfield\} and Nick Maskell and Morvern Morrison and Rakesh Panchal and Benjamin Prudon and Rahman, \{Najib M.\} and Rajini Sudhir and Sudarshan Ramsaroop and Raja Reddy and Phil Reid and Elizabeth Sage and Philip Short and Stanton, \{Andrew E.\} and Laura Succony and Georgios Tsaknis and Selina Tsim and Gordon Cowell and Kevin Lamote and Blyth, \{Kevin G.\}",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.",

year = "2026",

month = jul,

day = "1",

doi = "10.1136/bmjresp-2025-004045",

language = "English",

volume = "13",

journal = "BMJ Open Respiratory Research",

issn = "2052-4439",

publisher = "BMJ Publishing Group",

number = "1",

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Neilly, MDJ, MacPherson, A, Alexander, L, Walker, N, Kelly, C, Roche, J, Abugassa, E, Allan, L, Ashraf, A, Aujayeb, A, Bibby, A, Bilancia, R, Corcoran, J, Chetty, M, Conroy, K, Craig, C, Crook, R, D’Souza, A, Daneshvar, C, DeFoneska, D, Denniston, P, Fallon, J, Ferguson, K, Gatheral, T, Griffiths, AL, Haris, M, Hashim, M, Ionescu, A, Kadwani, O, Macdougall, M, Maclay, JD, Mann, ON, Maskell, N, Morrison, M, Panchal, R, Prudon, B, Rahman, NM, Sudhir, R, Ramsaroop, S, Reddy, R, Reid, P, Sage, E, Short, P, Stanton, AE, Succony, L, Tsaknis, G, Tsim, S, Cowell, G, Lamote, K & Blyth, KG 2026, 'Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS)', BMJ Open Respiratory Research, vol. 13, no. 1, e004045. https://doi.org/10.1136/bmjresp-2025-004045

Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS). / Neilly, Mark D.J.; MacPherson, Alexandrea; Alexander, Laura et al.
In: BMJ Open Respiratory Research, Vol. 13, No. 1, e004045, 01.07.2026.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Protocol for Mesothelioma Observational study of Risk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy (Meso-ORIGINS)

AU - Neilly, Mark D.J.

AU - MacPherson, Alexandrea

AU - Alexander, Laura

AU - Walker, Nicola

AU - Kelly, Caroline

AU - Roche, Joshua

AU - Abugassa, Emad

AU - Allan, Liam

AU - Ashraf, Adeel

AU - Aujayeb, Avinash

AU - Bibby, Anna

AU - Bilancia, Rocco

AU - Corcoran, John

AU - Chetty, Mahendran

AU - Conroy, Kevin

AU - Craig, Christopher

AU - Crook, Rebecca

AU - D’Souza, Alveena

AU - Daneshvar, Cyrus

AU - DeFoneska, Duneesha

AU - Denniston, Poppy

AU - Fallon, Janet

AU - Ferguson, Katie

AU - Gatheral, Timothy

AU - Griffiths, Andrew Lloyd

AU - Haris, Mohammed

AU - Hashim, Mohammed

AU - Ionescu, Alina

AU - Kadwani, Owais

AU - Macdougall, Michelle

AU - Maclay, John D.

AU - Mann, Oliver Nesfield

AU - Maskell, Nick

AU - Morrison, Morvern

AU - Panchal, Rakesh

AU - Prudon, Benjamin

AU - Rahman, Najib M.

AU - Sudhir, Rajini

AU - Ramsaroop, Sudarshan

AU - Reddy, Raja

AU - Reid, Phil

AU - Sage, Elizabeth

AU - Short, Philip

AU - Stanton, Andrew E.

AU - Succony, Laura

AU - Tsaknis, Georgios

AU - Tsim, Selina

AU - Cowell, Gordon

AU - Lamote, Kevin

AU - Blyth, Kevin G.

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

PY - 2026/7/1

Y1 - 2026/7/1

N2 - 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.

AB - 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.

KW - Asbestos Induced Lung Disease

KW - Mesothelioma

KW - Pleural Disease

UR - https://www.scopus.com/pages/publications/105043535578

U2 - 10.1136/bmjresp-2025-004045

DO - 10.1136/bmjresp-2025-004045

M3 - Article

C2 - 42386348

AN - SCOPUS:105043535578

SN - 2052-4439

VL - 13

JO - BMJ Open Respiratory Research

JF - BMJ Open Respiratory Research

IS - 1

M1 - e004045

ER -

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

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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