Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study

Our plain-English summary of Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study, by K. Hollevoet, J. Van Cleemput, J. Thimpont, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: K. Hollevoet, J. Van Cleemput, J. Thimpont, P. De Vuyst, L. Bosquée, K. Nackaerts, P. Germonpré, S. Vansteelandt, Y. Kishi, J.R. Delanghe, J.P. van Meerbeeck
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(5):889-95
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study aims to examine the longitudinal behavior of SM and MPF in controls to gain insight in the optimal use of these biomarkers in screening.

Methods: Asbestos-exposed individuals, with no malignant disease at inclusion, were surveilled for 2 years with annual measurements of SM and MPF. Fixed thresholds were set at 2.10 nmol/L for SM and 13.10 ng/ml for MPF. Longitudinal biomarker analysis, using a random intercept model, estimated the association with age and glomerular filtration rate (GFR), and the intraclass correlation. The latter represents the proportion of total biomarker variance accounted for by the between-individual variance.

Results: A total of 215 participants were included, of whom 179 and 137 provided a second sample and third sample, respectively. Two participants with normal SM and MPF levels presented afterward with mesothelioma and lung cancer, respectively. Participants with elevated biomarker levels were typically older and had a lower GFR. During follow-up, biomarker levels significantly increased. Longitudinal analysis indicated that this was in part due to aging, while changes in GFR had a less pronounced effect on serial biomarker measurements. SM and MPF had a high intraclass correlation of 0.81 and 0.78, respectively, which implies that a single biomarker measurement and fixed threshold are suboptimal in screening.

Conclusions: The longitudinal behavior of SM and MPF in controls indicates that a biomarker-based screening approach can benefit from the incorporation of serial measurements and individual-specific screening rules, adjusted for age and GFR. Large-scale validation remains nevertheless mandatory to elucidate whether such an approach can improve the early detection of mesothelioma.

In plain English

This Belgian prospective study followed 215 people with past professional asbestos exposure and no malignancy at enrolment for 2 years. It measured mesothelioma blood markers soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) yearly. Second and third samples came from 179 and 137 participants. Both markers rose significantly during follow-up. Part of this rise was due to aging: the model estimated each extra year of age raised geometric mean SM by 18% (95% CI 15 to 20%) and MPF by 14% (95% CI 12 to 17%). Kidney function changes had a smaller effect, significant only for SM. Most variation was between people, not within a person over time (intraclass correlation 0.81 for SM, 0.78 for MPF). One of three participants who developed cancer had stage III epithelioid pleural mesothelioma, with normal, stable marker levels. The authors concluded that a single measurement with a fixed threshold is suboptimal for screening; serial, individual-specific rules adjusted for age and kidney function could help but need large-scale validation. They noted the study was too small and short for mesothelioma's rarity and long latency.

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: prospective longitudinal cohort study with annual blood biomarker measurements over 2 years
• Who was studied: 215 individuals in Belgium with professional asbestos exposure and no malignant disease. They were enrolled between November 2007 and July 2010 through the Belgian Occupational Diseases Fund, four respiratory medicine departments, and two companies with a history of asbestos processing. 18 were female at baseline. 126 (59%) had a benign asbestos-related condition: pleural plaques n=71, diffuse pleural thickening n=39, other lesions mainly asbestosis n=16. 89 (41%) had no radiologically obvious asbestos-related lesions.
• Exposure: Past professional asbestos exposure, estimated in fiber years by standardized questionnaire; fiber types not specified. Fiber years were estimated in 204 participants. The median was 40.0 fiber years (22.0 to 116.8) in those with a benign asbestos-related condition and 15.8 fiber years (6.1 to 40.6) in healthy asbestos-exposed participants.
• Main results:
  • Of the 215 participants, 179 (84%) gave a second blood sample and 137 (64%) a third. The median follow-up was 12.2 and 24.2 months respectively.
  • Using fixed thresholds (SM 2.10 nmol/L, MPF 13.10 ng/ml), 20 participants had an elevated SM level and 21 an elevated MPF level at baseline or follow-up; 14 had both above threshold. At each sampling point, those with elevated levels were significantly older and had a lower GFR than those with normal levels.
  • Three participants presented a malignancy during follow-up. One was a stage III epithelioid pleural mesothelioma in a participant with pleural plaques whose biomarker levels were normal and stable (SM 1.76 then 1.61 nmol/L; MPF 10.56 then 10.00 ng/ml). A participant with fatal lung cancer had normal baseline levels. Elevated levels were seen only in the participant with prostate cancer and in one who had a paralyzing stroke.
  • In all participants, fiber years did not show an independent association with SM, MPF, or GFR in multiple regression; only age was independently associated. The authors stated that biomarker levels were not useful to estimate past asbestos exposure.
  • SM and MPF levels increased significantly during follow-up in the 137 participants with all three samples. Across all participants sampled at each time point, median SM was 0.96, 1.18 and 1.21 nmol/L, and median MPF was 6.64, 7.60 and 8.40 ng/ml, at baseline, first and second follow-up.
  • In the longitudinal model (participants who developed a malignancy excluded), a 1-year increase in age was estimated to raise geometric mean SM by 18% (95% CI 15 to 20%) and MPF by 14% (95% CI 12 to 17%).
  • The effect of GFR was significant only for SM: a decrease of 10 ml/min/1.73 m2 raised geometric mean SM by 4% (95% CI 1 to 6%).
  • Aging accounted for 22% of within-individual SM variance and 15% of MPF variance; changes in GFR explained only 1% for both.
  • The intraclass correlation was 0.81 for SM and 0.78 for MPF.
• The authors' conclusion: The authors concluded that, given the effect of age and GFR and the large between-individual variance, a single biomarker measurement with a fixed threshold is suboptimal in screening. They said a screening approach could benefit from serial measurements and individual-specific rules, but large-scale validation is still needed to see whether this improves early detection of mesothelioma.
• Limitations the authors state:
  • The authors stated that the size of the study population and the length of follow-up were not in proportion to mesothelioma's low incidence and long latency. They said the finding that a participant with normal levels developed mesothelioma is therefore of limited relevance.
  • The number of follow-up samples decreased after initial inclusion.
  • The authors attributed GFR's limited impact most likely to GFR changing little in 2 years. They suggested that larger GFR changes over a longer period could have a more pronounced effect.

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, Biomarker, Cohort Study, Mesothelin, Lung Cancer.

Related studies

• The effect of clinical covariates on the diagnostic and prognostic value of soluble mesothelin and megakaryocyte potentiating factor — K. Hollevoet, K. Nackaerts, et al. (2012)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Diagnostic performance of soluble mesothelin and megakaryocyte potentiating factor in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2010)
• Comparison of the diagnostic accuracy of the MSLN gene products, mesothelin and megakaryocyte potentiating factor, as biomarkers for mesothelioma in pleural effusions and serum — J. Creaney, S. Sneddon, et al. (2013)
• Combined serum mesothelin and plasma osteopontin measurements in malignant pleural mesothelioma — A. Cristaudo, A. Bonotti, et al. (2011)
• Individual predictors of increased serum mesothelin in asbestos-exposed workers — R. Filiberti, P. Marroni, et al. (2013)

Browse more research in Journal of Thoracic Oncology, or return to medical research.