Results & OUtputs

Results

Meso-ORIGINS protocol has been published in BMJ Open Respiratory Research.

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.

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The Meso-ORIGINS feasibility study (IRAS ref 253522, NHS ref GN17ON341), a multi-centre cohort study which concluded in January 2021, demonstrated the feasibility of the Meso-ORIGINS study methods and allowed us to refine the study design for Meso-ORIGINS.
The feasibility study had retrospective and prospective elements and was conducted at 4 UK pleural disease centres (Glasgow, Oxford, Manchester and Bristol).

In the retrospective element, which involved database review at each site, Malignant Pleural Mesothelioma (MPM) evolved, following an initial diagnosis of asbestos associated benign pleural inflammation, in 42 of 257 eligible cases (16% (95%CI 12.3-21.4%)). Of these, MPM evolution was confirmed histologically by repeat biopsy in 36/257 (14% (95% CI 10.5-19.2). In the prospective element, 37 patients were recruited over 12 months at the 4 study centres, exceeding the minimum number needed to demonstrate and adequate recruitment rate (39 patients).

The feasibility study has therefore demonstrated:
a) how many participants are required for the Meso-ORIGINS study (i.e. it has helped us estimate our sample size more precisely)
b) that it should be possible to recruit enough participants in a reasonable amount of time, assuming the number of recruiting centres is scaled up appropriately
c) that potentially eligible participants would be willing to consent to the proposed methods of surveillance, and that a mixture of repeat biopsy methods will be needed.

The results of the feasibility study suggest that the Meso-ORIGINS aims and protocol are achievable and methods are acceptable to participants.