Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies

Our plain-English summary of Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies, by K.G. Blyth (Thorax, 2015).

The study

• Author: K.G. Blyth
• Journal: Thorax
• Published: 2015;70(4):374
• Type of article: Letter, Comment
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, the author responded to a Thorax study by Creaney et al on fibulin-3 as a diagnostic marker for malignant pleural mesothelioma (MPM). Their results (plasma area under the curve 0.671, sensitivity 21%) were markedly discordant with those of Pass et al, who used the same assay in a similarly designed study (plasma area under the curve 0.974–0.997, sensitivity 97%). The author argued that Creaney et al had not mentioned one possible confounder: inconsistent timing of biomarker measurements in relation to pleural biopsies, pleurodesis and surgical palliation. He cited studies in other cancers showing effects of biopsy, resection and peritumoural inflammation on biomarker expression. He also cited an earlier study that found a small but statistically significant fall in pleural fluid mesothelin after pleurodesis, with enough variation in paired samples to change the diagnostic classification of 2 of 51 patients. Creaney et al had taken measurements 'within 1 month of diagnosis'. In the Pass study, measurements were made in tertiary surgical centres, which the author considered almost certainly followed extensive pleural intervention. He concluded that such inconsistencies introduce systematic error. He called for standardised timing of biomarker sampling, tested in prospective studies with predefined early sampling, rigorous subsequent diagnostics, and data on confounders such as renal function, body mass index, concomitant drugs and inflammatory indices. He stated that the DIAPHRAGM study in the UK and Ireland was adopting this approach.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This was a letter to the editor; it reported no new patient data. The author compared two published studies of one fibulin-3 test for malignant pleural mesothelioma (MPM). Creaney et al reported a plasma area under the curve (AUC) of 0.671 and sensitivity of 21%; Pass et al reported a plasma AUC of 0.974–0.997 and sensitivity of 97%. The author argued that inconsistent sampling times, such as after pleural biopsies, pleurodesis or surgery, may have affected results. Creaney et al reported measuring within 1 month of diagnosis. In the Pass study, the author wrote, sampling almost certainly followed extensive pleural intervention. The author also cited an earlier mesothelin study in which variation between paired samples from patients not undergoing biopsy or pleurodesis led to diagnostic reclassification of 2 of 51 patients. The author called for a standardised approach to the timing of biomarker sampling. The author also called for prospective studies with predefined early sampling and data on confounders such as renal function and body mass index. The author noted that the DIAPHRAGM study in the UK and Ireland was taking this approach.

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: Letter to the editor (correspondence) commenting on published biomarker studies; no new data
• Who was studied: No patients were studied. The letter discussed two published studies of the fibulin-3 biomarker in malignant pleural mesothelioma (MPM), by Creaney et al and by Pass et al.
• Main results:
  • The author reported that Creaney et al found a plasma AUC of 0.671 and a sensitivity of 21% for fibulin-3 in MPM. These figures belong to the Creaney study, not to this letter.
  • The author reported that Pass et al, using the same assay in a similarly designed study, found a plasma AUC of 0.974–0.997 and a sensitivity of 97%. These figures belong to the Pass study, not to this letter.
  • The author argued that because Creaney et al made measurements within 1 month of diagnosis, some samples may have been taken after potentially confounding events such as biopsy or pleurodesis.
  • The author stated that in the Pass study, measurements were made in tertiary surgical centres and almost certainly after extensive pleural intervention.
  • The author cited an earlier study of pleural fluid mesothelin (Davies et al). In that study, variation in paired samples from patients not undergoing biopsy or pleurodesis led to diagnostic reclassification of 2/51 patients. This result belongs to that earlier study.
  • The author recommended collecting data on potential confounders, including renal function, body mass index, concomitant drugs and inflammatory indices.
  • The author stated that the DIAPHRAGM study was adopting this approach and was recruiting across the UK and Ireland.
• The authors' conclusion: The author concluded that inconsistent timing of biomarker sampling introduces systematic error. The author asked MPM researchers and biomarker consortia to consider a standardised approach to the timing of biomarker measurements.

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: Biomarker, Mesothelioma, Thorax, Fibulin-3, Pleural Mesothelioma, Pleurodesis, Biopsy, Inflammation.

Related studies

• Author's response: Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies — J. Creaney, B.W. Robinson (2015)
• Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study — S. Tsim, C. Kelly, et al. (2016)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
• Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma — H.I. Pass, S.M. Levin, et al. (2012)
• FBLN-3 as a biomarker of pleural plaques in workers occupationally exposed to carcinogenic fibers: a pilot study — V. Rapisarda, C. Ledda, et al. (2015)
• Plasma Fibulin-3 as a Potential Biomarker for Patients with Asbestos-Related Diseases in the Han Population — Z. Jiang, S. Ying, et al. (2017)

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