Prognostic and clinicopathological utility of programmed death-ligand 1 in malignant pleural mesothelioma: A meta-analysis

Our plain-English summary of Prognostic and clinicopathological utility of programmed death-ligand 1 in malignant pleural mesothelioma: A meta-analysis, by F. Zhang, W. Gong (International Immunopharmacology, 2020).

The study

• Authors: F. Zhang, W. Gong
• Journal: International Immunopharmacology
• Published: 2020;83:106481
• Type of article: Meta-analysis
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Programmed death ligand 1 (PD-L1) has been reported to be connected to prognosis in individuals with malignant pleural mesothelioma (MPM), although there is no consensus based on data from previous studies. Accordingly, this quantitative meta-analysis investigated prognostic and clinicopathological utility of PD-L1 in patients with MPM.

Methods: A comprehensive search of the PubMed, Web of Science, Embase, and Cochrane Library databases for articles published up to October 4, 2019 was performed. Studies using immunohistochemical techniques to detect/quantify the expression of PD-L1 in MPM tissue were enrolled in the analysis. The combined hazard ratio (HR) and corresponding 95% confidence interval (CI) was applied to assess the association between PD-L1 expression and overall survival (OS).

Results: A total of 11 studies comprising 1606 patients was included in the present meta-analysis. For OS, pooled data revealed an HR of 1.50 (95% CI 1.32-1.70; p < 0.001), suggesting that patients with PD-L1 overexpression experience inferior OS. Subgroup analysis revealed that elevated PD-L1 remained a significant prognostic indicator for worse OS, irrespective of sample size, cut-off value, ethnicity, and Newcastle-Ottawa Scale score. Moreover, PD-L1 overexpression was associated with non-epithelioid histology (odds ratio 4.30 [95% CI 1.89-9.74]; p < 0.001).

Conclusions: Results of this meta-analysis show that elevated expression of PD-L1 could be a factor predicting poorer survival in patients with MPM.

Copyright © 2020 Elsevier B.V. All rights reserved.

In plain English

This was a meta-analysis, which pools results from earlier published studies. It looked at PD-L1, a protein that can be measured in tumor tissue, in malignant pleural mesothelioma. The authors searched four databases for articles published up to October 4, 2019 and included 11 studies with 1606 patients from the United States, Australia, France, Italy and Spain. All included studies measured PD-L1 in tumor tissue with a staining method called immunohistochemistry. The article did not examine asbestos exposure. Across all studies combined, patients whose tumors showed high PD-L1 had poorer overall survival, with a hazard ratio of 1.50 (95% CI 1.32 to 1.70). This held in subgroups by sample size, cut-off value, the grouping the authors called ethnicity (American, European, Australian), and study quality score. In four studies with 768 patients, high PD-L1 was associated with non-epithelioid tumor types (odds ratio 4.30, 95% CI 1.89 to 9.74). It was not significantly associated with sex, stage or smoking. The authors concluded that high PD-L1 was significantly associated with poor survival. They noted that all included studies were retrospective, used different antibodies and cut-offs, and included no Asian patients.

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: Meta-analysis of published studies, following the PRISMA statement; pooled hazard ratios and odds ratios
• Who was studied: 11 retrospective cohort studies including 1606 patients with malignant pleural mesothelioma, from the United States (3), Australia (3), France (2), Italy (2) and Spain (1), found in PubMed, Web of Science, Embase and Cochrane Library searches for articles published up to October 4, 2019
• Exposure: Not asbestos. The factor studied was PD-L1 expression in tumor cells measured by immunohistochemistry, with positivity cut-offs of at least 5% (6 studies), at least 1% (4 studies) or score 1 (1 study)
• Main results:
  • In all 11 studies (1606 patients), high PD-L1 expression was associated with poorer overall survival: pooled hazard ratio 1.50 (95% CI 1.32–1.70; p less than 0.001), fixed-effects model, heterogeneity I2 = 19.8%
  • The association with worse overall survival remained significant in subgroups by sample size, cut-off value, ethnicity and NOS quality score. The weakest subgroups were Australian studies (HR 1.66, 95% CI 1.00–2.76, p = 0.049) and studies with NOS score 6 or lower (HR 1.68, 95% CI 1.01–2.80, p = 0.044)
  • In 4 studies with 768 patients, high PD-L1 expression was associated with non-epithelioid compared with epithelioid histology: odds ratio 4.30 (95% CI 1.89–9.74; p less than 0.001), random-effects model, heterogeneity I2 = 76.7%
  • No significant associations were found between PD-L1 and sex (OR 0.84, 95% CI 0.57–1.23; 4 studies, 768 patients), stage III to IV versus I to II (OR 1.17, 95% CI 0.76–1.81; 2 studies, 448 patients), or smoking (OR 0.81, 95% CI 0.49–1.34; 2 studies, 333 patients)
  • Sensitivity analysis found that no single study substantially changed the pooled result. Begg's funnel plot was largely symmetric (Begg's p = 0.089), which the authors read as no significant publication bias
• The authors' conclusion: The authors concluded that PD-L1 overexpression was significantly associated with poor survival in malignant pleural mesothelioma and with non-epithelioid histology. They added that larger prospective studies in ethnically diverse populations are needed for validation
• Limitations the authors state:
  • All included studies were retrospective cohort studies, which may have led to selection bias
  • PD-L1 was measured with different antibodies and cut-off points across studies, which may have introduced heterogeneity
  • No included study involved Asian patients

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Meta-Analysis, PD-L1, Prognosis, Hazard Ratio, confidence interval, Overall Survival, Non-epithelioid.

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