Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance

Our plain-English summary of Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance, by K. Ferguson, M. Neilson, R. Mercer, et al (BMJ Open, 2023).

The study

• Authors: K. Ferguson, M. Neilson, R. Mercer, J. King, K. Marshall, H. Welch, S. Tsim, N.A. Maskell, N.M. Rahman, M. Evison, K.G. Blyth
• Journal: BMJ Open
• Published: 2023;13(8):e067780
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI).

Design: A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size.

Setting: 4 UK pleural disease centres (February 2019-January 2020).

Participants: Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required ≥2 years follow-up.

Outcome Measures: A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6 months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95% CI). Baseline predictors of evolution were identified using logistic regression.

Results: 296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)).

Conclusions: Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500.

Trial Registration Number: ISRCTN12840870.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

In plain English

This multicentre feasibility study, run at four UK pleural disease centres from February 2019 to January 2020, tested plans for Meso-ORIGINS. That study will follow patients with asbestos-associated pleural inflammation (AAPI) to collect tissue before and after any malignant pleural mesothelioma (MPM) develops. In the prospective part, 39 patients were recruited in 12 months. Of these, 21 had a tissue-confirmed diagnosis, short of the target of 27. Ultrasound suggested repeat local anaesthetic thoracoscopy was technically feasible in 13 of 28 patients assessed (46%), and 24 of 36 (67%) said it was acceptable. In the retrospective part, MPM was confirmed histologically within 2 years in 36 of 257 patients with AAPI (14%, 95% CI 10.3% to 18.8%). Malignant CT features (odds ratio 4.78, 95% CI 2.36 to 9.86) and age (odds ratio 1.06, 95% CI 1.02 to 1.12) were associated with MPM evolution. The authors concluded their initial eligibility criteria were too narrow. The main study will recruit more broadly, allow several rebiopsy methods, and aim for 500 patients instead of 590. They noted possible recall bias and that COVID-19 restrictions prevented 11 follow-up visits.

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: Multicentre mixed-methods feasibility study with a prospective observational element and a retrospective cohort element
• Who was studied: Patients with asbestos-associated pleural inflammation (AAPI) at four UK pleural disease centres (Glasgow, Bristol, Oxford, Manchester). The prospective study had 39 patients recruited February 2019 to January 2020, all male, median age 76. The retrospective study had 257 historical cases with at least 2 years of follow-up, 95% male, median age 72.
• Exposure: Asbestos exposure, established by history or by compatible imaging such as pleural plaques. No fiber types are reported. The condition studied was benign pleural inflammation (for example non-specific pleuritis or benign fibrinous pleurisy) and its later evolution to malignant pleural mesothelioma.
• Main results:
  • Prospective study: 21 of 39 recruits (54%) had a histological diagnosis, so the recruitment target of 27 was not met
  • Prospective study: of 28 patients with ultrasound data, repeat local anaesthetic thoracoscopy (LAT) was judged technically feasible in 13 (46%)
  • Prospective study: rebiopsy by LAT or ultrasound-guided needle biopsy was judged feasible in 16 of 28 (57%)
  • Prospective study, 36 questionnaires: repeat LAT was acceptable to 24 of 36 patients (67%) and needle aspiration to 29 of 36 (81%)
  • Prospective study, post hoc analysis: mesothelioma was later diagnosed in 4 of 39 recruits (10.3%, 95% CI 3.5% to 24.2%)
  • Retrospective study: MPM evolution occurred in 42 of 257 (16%, 95% CI 12.3% to 21.4%) and was confirmed histologically, by repeat biopsy or at postmortem, in 36 of 257 (14%, 95% CI 10.3% to 18.8%)
  • Retrospective study: median time to repeat biopsy was 3.5 months (IQR 2 to 9.5), excluding cases confirmed postmortem
  • Retrospective study, multivariable analysis: age (OR 1.06, 95% CI 1.02 to 1.12) and malignant CT features (OR 4.78, 95% CI 2.36 to 9.86) were independently associated with MPM evolution
  • Based on the 14% histologically confirmed evolution rate, the main study's target sample size was reduced from 590 to 500
• The authors' conclusion: The authors concluded that their initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. It will allow a range of rebiopsy techniques, and its sample size has been reduced to 500.
• Limitations the authors state:
  • Potential for recall bias in the retrospective cohort study, although each centre keeps a prospective database
  • COVID-19 restrictions prevented face-to-face follow-up visits for 11 of 39 prospective participants, reducing the data on LAT feasibility and patient acceptability
  • Technical feasibility of repeat LAT was not tested directly, because that was not considered ethical; it was assessed indirectly using ultrasound markers

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Biopsy, Inflammation, Thoracoscopy, Cohort Study, Histology, Ultrasound, Pleural Mesothelioma.

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