Biomarkers in malignant pleural mesothelioma: current status and future directions

Our plain-English summary of Biomarkers in malignant pleural mesothelioma: current status and future directions, by T. Ahmadzada, G. Reid, S. Kao (Journal of Thoracic Disease, 2018).

The study

• Authors: T. Ahmadzada, G. Reid, S. Kao
• Journal: Journal of Thoracic Disease
• Published: 2018;10(Suppl 9):S1003-S1007
• Type of article: Editorial, Comment
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

This invited editorial commented on a review of mesothelioma biomarkers by Sun, Vaynblat and Pass (Ann Transl Med 2017). The authors described malignant pleural mesothelioma (MPM) as an uncommon, aggressive tumour associated with asbestos exposure. It is often diagnosed late, typical survival is around 1 year, and treatment options are limited. They summarised evidence on blood-based markers. Soluble mesothelin (SMRP) was the only clinically validated, FDA-approved blood biomarker, but a meta-analysis reported 32% sensitivity at 95% specificity. Meta-analyses reported osteopontin sensitivity of 65% and specificity of 81% (360 cases), and fibulin-3 sensitivity of 62% at 82% specificity (468 cases). A hyperacetylated isoform of HMGB1 distinguished MPM patients from asbestos-exposed and healthy controls in one study. SMRP, osteopontin and HMGB1 were associated with poor prognosis but had not been prospectively validated. The authors also discussed inflammation-based scores and microRNAs, including a six-miRNA signature that predicted survival beyond 20 months with 92.3% accuracy after extrapleural pneumonectomy and 71.9% after pleurectomy/decortication. No predictive biomarkers had been recommended for clinical practice, including for bevacizumab or nintedanib. PD-L1 was described as a robust prognostic marker, and one retrospective study suggested an association with pembrolizumab response. The authors concluded that promising biomarkers required independent validation, that international collaboration was important, and that more research should focus on predictive biomarkers.

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 article is an invited editorial, not an original study. The authors commented on a review of mesothelioma biomarkers by Sun and colleagues. They described the state of research on biomarkers, measurable signs in blood or tumour tissue that might help manage malignant pleural mesothelioma (MPM). As background, they noted that MPM is associated with asbestos exposure; asbestos itself was not studied.

Citing other researchers' work, they wrote that soluble mesothelin (SMRP) was the only blood-based biomarker clinically validated and FDA-approved for mesothelioma. It was indicated for monitoring patients already diagnosed with epithelioid or biphasic mesothelioma. However, a meta-analysis reported its sensitivity as 32% at 95% specificity. Cited meta-analyses reported 65% sensitivity and 81% specificity for osteopontin (360 MPM cases), and 62% sensitivity at 82% specificity for fibulin-3 (468 MPM cases).

They wrote that no predictive biomarkers had been recommended for clinical practice. They also wrote that high tumour PD-L1 expression had been consistently associated with poor prognosis. The authors concluded that there was still a long way to go, that promising markers all required independent validation, and that more research should focus on predictive biomarkers.

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: Invited editorial commenting on a published review (Sun et al.) of biomarkers for mesothelioma; no original data
• Who was studied: No study population; the editorial discusses published research on tumour and blood biomarkers in malignant pleural mesothelioma (MPM), prompted by a review by Sun et al.
• Exposure: Not studied; asbestos exposure is mentioned only as background, as the exposure with which MPM is associated
• Main results:
  • The authors stated that soluble mesothelin (SMRP) was the only blood-based biomarker clinically validated and FDA-approved for mesothelioma.
  • The authors stated that SMRP is marketed as MESOMARK and indicated for monitoring patients already diagnosed with epithelioid or biphasic mesothelioma.
  • Citing a meta-analysis (not this article's own data), the authors reported a sensitivity of 32% at 95% specificity for SMRP and described its clinical usefulness as limited.
  • Citing a meta-analysis of 360 MPM cases, the authors reported a diagnostic sensitivity of 65% and a specificity of 81% for osteopontin.
  • Citing a meta-analysis of 468 MPM cases, the authors reported a diagnostic sensitivity of 62% at 82% specificity for fibulin-3, and said it needed further prospective validation.
  • The authors stated that SMRP, osteopontin and HMGB1 had been associated with poor prognosis, but that none was used routinely in clinic for this purpose, because most had not been validated prospectively.
  • The authors stated that no predictive biomarkers (markers of who will benefit from a treatment) had been recommended for clinical practice.
  • The authors stated that high tumour PD-L1 expression had been consistently associated with poor prognosis in MPM, but that its role in predicting response to checkpoint inhibitors was yet to be prospectively defined.
• The authors' conclusion: The authors concluded that there is still a long way to go in discovering and implementing biomarkers in MPM, that promising diagnostic and prognostic markers all require independent validation, and that more research should focus on predictive biomarkers.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Mesothelioma, Asbestos Exposure, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Meta-Analysis, Osteopontin.

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