Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis

Our plain-English summary of Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis, by Y. Zhuo, L. Lin, S. Wei, et al (Medicine, 2016).

The study

• Authors: Y. Zhuo, L. Lin, S. Wei, M. Zhang
• Journal: Medicine
• Published: 2016;95(52):e5706
• Type of article: Meta-analysis
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Lactate dehydrogenase (LDH) as a hypoxia-regulator plays a vital role in alternative metabolic pathways of cancer cells. Numerous studies have assessed the prognostic value of elevated pretreatment LDH in malignant mesothelioma (MM). However, the results have been largely inconsistent. Hence, the aim of current study was to investigate the prognostic value of pretreatment LDH levels in patients with MM by performing a meta-analysis of relevant studies.

Methods: A literature search for English language studies, which investigated the association of LDH levels with overall survival (OS) in malignant mesothelioma, was performed in the electronic databases, PubMed, Medline, Embase, and Web of Science. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated. Heterogeneity was assessed using Cochran Q and I statistics. Sensitivity analysis, meta-regression model, and subgroup analysis were performed to trace the source of heterogeneity, if applicable.

Results: A total of 9 studies with a combined study population of 1977 patients came within the purview of this meta analysis. Pooled HR for OS in patients with high LDH level was 1.68 (95% CI = 1.36-2.00). Significant heterogeneity was observed in the included studies (I = 54.1%, P = 0.026). Sensitivity analysis after sequential exclusion of 1 study at a time, and meta-regression with inclusion of 6 confounding factors failed to identify the source of heterogeneity. However, in the subgroup analysis, it was found that the publication of Nojiri et al was the origin of heterogeneity. When omitted the publication of Nojiri et al, the pooled HR of the rest 8 studies was 1.83 (95% CI = 1.45-2.20, I = 0.0%, P = 0.723). Egger test and funnel plots excluded the possibility of publication bias affecting the results of the current meta-analysis.

Conclusion: A negative association was observed between high LDH levels and poor overall survival in the current study. Our findings suggest that pretreatment LDH level could serve as a useful predictor of prognosis in patients with malignant mesothelioma.

In plain English

This was a meta-analysis, a study that pooled results from earlier research. The authors searched four databases for English-language studies, published up to April 3, 2016, on whether the blood level of an enzyme, lactate dehydrogenase (LDH), measured before treatment, was linked to overall survival in patients with malignant mesothelioma. Nine studies with 1977 patients in total were included. Across all nine, high LDH gave a pooled hazard ratio for overall survival of 1.68 (95% CI 1.36 to 2.00), which the authors read as a worse outlook. However, results varied significantly between studies. The authors traced this variation to one study (Nojiri et al). Without that study, the pooled hazard ratio for the other eight was 1.83 (95% CI 1.45 to 2.20). Tests found no sign of publication bias. The authors concluded that pretreatment LDH could serve as a useful predictor of prognosis in malignant mesothelioma. They noted limitations including a modest total sample, inconsistent LDH cut-off values, a mix of adjusted and unadjusted results, and the English-language restriction. The study did not analyze asbestos exposure.

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: Systematic review and meta-analysis of published studies (retrospective and prospective) on pretreatment serum LDH and overall survival
• Who was studied: 9 studies, published 1998 to 2015, with a combined 1977 patients with malignant mesothelioma. Seven studies covered pleural disease only and two covered mixed disease sites. Databases were searched up to April 3, 2016.
• Exposure: Pretreatment serum LDH level above versus below each study's cut-off value (500 IU/L in most studies; 229 or 230 IU/L in others). Asbestos exposure was not analyzed.
• Main results:
  • All 9 studies combined (random-effects model): the pooled hazard ratio for overall survival with elevated LDH was 1.68 (95% CI 1.36 to 2.00). Heterogeneity between studies was significant (I-squared 54.1%, P = 0.026).
  • With the Nojiri et al study left out, the pooled hazard ratio for the remaining 8 studies was 1.83 (95% CI 1.45 to 2.20), with no heterogeneity (I-squared 0.0%, P = 0.723).
  • Of the 9 included studies, 4 had reported negative results and 5 had reported positive results.
  • The pooled result stayed stable when studies were excluded one at a time.
  • Meta-regression found no significant association between the hazard ratio and age, publication year, disease site, LDH cut-off value, type of study or variable type.
  • The Egger test found no significant publication bias (P = 0.832).
• The authors' conclusion: The authors concluded that pretreatment LDH level could serve as a useful predictor of prognosis in patients with malignant mesothelioma. They described the link between high LDH and poor survival as a 'negative association'.
• Limitations the authors state:
  • There was significant heterogeneity across the included studies.
  • The total sample was modest, which may increase the risk of bias and lower statistical power.
  • The studies spanned 1998 to 2015, and treatment strategies may have changed over that period.
  • Limiting the search to English-language studies may have caused selection bias.
  • Both univariate and multivariate results were pooled, and univariate analysis tends to overestimate effect size.
  • The included studies used inconsistent LDH cut-off values.
  • The included prospective and retrospective studies are less reliable than prospective randomized trials.

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: Lactate Dehydrogenase (LDH), Malignant Mesothelioma, Meta-Analysis, Hypoxia, Overall Survival, Hazard Ratio, confidence interval, Confounding.

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