Tasks and Experiences of the Prospective, Longitudinal, Multicenter MoMar (Molecular Markers) Study for the Early Detection of Mesothelioma in Individuals Formerly Exposed to Asbestos Using Liquid Biopsies

Our plain-English summary of Tasks and Experiences of the Prospective, Longitudinal, Multicenter MoMar (Molecular Markers) Study for the Early Detection of Mesothelioma in Individuals Formerly Exposed to Asbestos Using Liquid Biopsies, by D.G. Weber, S. Casjens, K. Wichert, et al (Cancers, 2023).

The study

• Authors: D.G. Weber, S. Casjens, K. Wichert, M. Lehnert, D. Taeger, H.P. Rihs, T. Brüning, G. Johnen, The MoMar Study Group
• Journal: Cancers
• Published: 2023;15(24)
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is an aggressive cancer, strongly associated with prior exposure to asbestos. Commonly, tumors are detected at late stages of the disease. Detection at early stages might be meaningful, because therapies might be more effective when the tumor burden is relatively low and the tumor has not spread to distant sites. Circulating biomarkers in blood might be a promising tool to improve the early detection of mesothelioma, but for screening in asymptomatic subjects, candidate biomarkers need to be validated in appropriate studies. This study was conducted to assess the performance of biomarkers in liquid biopsies to detect mesothelioma at early stages. Over a period of 10 years, 2769 volunteers formerly exposed to asbestos were annually examined and liquid biopsies were collected. A follow-up was completed 17 months after the last blood collection. The article provides a detailed overview of our lessons learned and experiences of conducting a prospective, longitudinal, multicenter study. The existing cohort of individuals at risk is highly suitable for the validation of blood-based biomarkers for the early detection of mesothelioma as well as lung cancer.

In plain English

This article described how the German MoMar study was organized and run, and reported an updated analysis of two blood markers for detecting mesothelioma before diagnosis. From 2008 to 2018, 2769 volunteers formerly exposed to asbestos (99.3% men) were recruited and gave blood at roughly yearly examinations. Citing their earlier publication, the authors reported 40 incident mesothelioma cases and 64 incident lung cancer cases in the cohort. For the biomarker analysis, 32 mesothelioma cases with a blood sample taken between 13 months and three weeks before diagnosis were compared with 172 matched asbestos-exposed controls from the same cohort. Levels of calretinin and mesothelin were higher in the cases. With the test set so that 98% of controls tested negative, calretinin picked up 34% of cases, mesothelin 25%, and the two combined 44%. The authors concluded that the combination was validated for detecting mesothelioma about one year before the usual diagnosis based on symptoms. They noted that too few women took part to give reliable information about women, and that tumor location and stage at each blood draw were unknown.

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: Report on the methods and experiences of a prospective, longitudinal, multicenter cohort study, including an updated nested case-control analysis of blood biomarkers
• Who was studied: 2769 volunteers formerly exposed to asbestos, recruited 2008 to 2018 at 26 study centers in Germany (mostly Northern Germany) from a German Social Accident Insurance surveillance program. 2749 (99.3%) were men and 20 (0.7%) were women. Median age at entry was 73 years (range 43 to 94).
• Exposure: Former asbestos exposure; fiber types were not specified. Participants had recognized benign asbestos-associated diseases such as asbestosis, pleural effusions and pleural plaques. Median duration of exposure was 27 years (range 1 to 60), based on 2652 participants with exposure information.
• Main results:
  • Whole cohort: 40 incident mesothelioma cases were registered as of March 2019. Compared with the number expected in the general population, the risk was 17.6 (95% CI 12.57 to 23.96). This figure was taken from the authors' earlier publication.
  • Whole cohort: 64 incident lung cancer cases were observed, a risk of 1.27 (95% CI 0.99 to 1.62) compared with the general population. This figure was also taken from the earlier publication.
  • Biomarker analysis: of 43 mesothelioma cases (40 incident and 3 prevalent), 32 had a blood sample taken between 13 months and three weeks before diagnosis. The median interval from blood collection to diagnosis was 7 months.
  • Median calretinin was 0.40 ng/mL in the 32 prediagnostic mesothelioma cases and 0.18 ng/mL in the 172 controls. Median mesothelin was 1.43 nmol/L in the cases and 1.03 nmol/L in the controls.
  • The differences between prediagnostic mesothelioma cases and controls were statistically significant for calretinin (p less than 0.0001) and for mesothelin (p = 0.0005).
  • Area under the curve was 0.80 (95% CI 0.70 to 0.90) for calretinin and 0.69 (95% CI 0.59 to 0.80) for mesothelin. For the combination of both markers, the article printed "0.86 (range 0.86–0.68)".
  • At a predefined specificity of 98%, sensitivity was 34% for calretinin, 25% for mesothelin and 44% for the two combined. The initial 2018 analysis had reported 46%.
  • Sample quality: of 242 randomly selected plasma samples, 240 (99.2%) were below the hemolysis threshold.
  • After the study period was doubled to ten years, 14,939 person-years were recorded, against 10,000 expected.
• The authors' conclusion: The authors concluded that the combination of calretinin and mesothelin was validated for early detection of mesothelioma about one year before the usual symptom-based diagnosis. They also concluded that the cohort is suitable for validating biomarkers for mesothelioma and lung cancer.
• Limitations the authors state:
  • Only 20 of the 2769 participants were women, too few to give reliable information about women.
  • The location and stage of the tumor at the time of each blood sample were unknown and could not be related to biomarker levels.
  • Delayed processing of individual plasma samples could not be ruled out.
  • A nested case-control analysis has less statistical power than the full cohort because the sample is smaller.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Tumor Burden, Biomarker, Lung Cancer.

Related studies

• Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies — D.G. Weber, S. Casjens, et al. (2020)
• Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin - a case-control comparison nested into a prospective cohort of asbestos-exposed workers — G. Johnen, K. Burek, et al. (2018)
• Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study — D.G. Weber, A. Brik, et al. (2019)
• Performance of biomarkers SMRP, CA125, and CYFRA 21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos — M. Gube, D. Taeger, et al. (2011)
• Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study — K. Hollevoet, J. Van Cleemput, et al. (2011)
• Is it useful to combine sputum cytology and low-dose spiral computed tomography for early detection of lung cancer in formerly asbestos-exposed power industry workers? — M.K. Felten, L. Knoll, et al. (2014)

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