Pleural Fluid-to-Blood BNP Ratio May Contribute to Prognosis in Malignant Pleural Mesothelioma

Our plain-English summary of Pleural Fluid-to-Blood BNP Ratio May Contribute to Prognosis in Malignant Pleural Mesothelioma, by V. Tsolaki, G.E. Zakynthinos, S. Zarogiannis, et al (Clinics and Practice, 2023).

The study

• Authors: V. Tsolaki, G.E. Zakynthinos, S. Zarogiannis, P. Zygoulis, I. Kalomenidis, R. Jagirdar, I. Triantafyllou, K.I. Gourgoulianis, D. Makris, E. Zakynthinos
• Journal: Clinics and Practice
• Published: 2023;13(5):1111-1122
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Brain natriuretic peptide (BNP) seems to be produced from malignant mesothelial cells other than cardiomyocytes. We aimed to evaluate whether an increased pleural fluid-to-blood BNP ratio in patients with malignant pleural mesothelioma (MPM) could facilitate prognosis beyond diagnosis.

Materials And Methods: Patients with MPM were included (observational study). One- and two-year survival and factors affecting it were tested. To evaluate the prognostic significance of the natriuretic peptide precursor B (NPPB) gene expression in MPM, we constructed a survival curve from data derived from The Cancer Genome Atlas.

Results: Nineteen consecutive patients with MPM were included (age: 67 (61, 80), male 78.9%). One- and two-year survival were 52.6% and 31.6%, respectively. Age, performance status, and the other variables tested did not differ between survivors and non-survivors. Non-survivors presented higher pleural fluid BNP in two years (699 (210, 5000) vs. 379.5 (5, 567), p = 0.036) and BNP ratios than survivors (1-year: 28.75 (4.05, 150.24) vs. 3.49 (0.3, 26) p = 0.001, 2-years: 22.8 (2.42, 150.24) vs. 3.49 (0.3, 7.76), p = 0.001). One- and two-year survival rates in patients with BNP ratios above/equal to the median value (8.82) were 20% and 0%, and 88.9% and 66.7%, respectively, in patients with BNP ratios below 8.82 (p = 0.006 and p = 0.002, respectively). MPM patients with low NPPB expression presented significantly higher survival rates compared to patients with higher expressions (p = 0.032).

Conclusion: A high pleural fluid/blood BNP ratio, an easily performed in everyday practice, costless biomarker seems to predict poorer survival better than the commonly reported prognostic factors in MPM.

In plain English

This observational study at a hospital in Larissa, Greece, looked at 19 consecutive patients with malignant pleural mesothelioma. Brain natriuretic peptide (BNP) was measured in pleural fluid (fluid around the lungs) and blood at first drainage; one patient was instead measured at a repeat drainage five years after diagnosis. The authors compared the fluid-to-blood ratio between patients who did and did not survive one and two years. Asbestos exposure was recorded as definite or confirmed in 10 patients, possible in 5 and unknown in 4. One-year survival was 52.6% and two-year survival 31.6%. Age, stage, performance status, pleural thickening and several blood tests did not differ between survivors and non-survivors. Non-survivors had higher BNP ratios. Among patients with a ratio at or above the median of 8.82, one-year survival was 20% and two-year survival 0%, compared with 88.9% and 66.7% for those below it. In Cancer Genome Atlas gene data, patients with lower expression of the BNP gene had higher survival. The authors concluded that a higher ratio went with worse survival. They described the results as preliminary, from a small group.

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: Observational study of consecutive patients at one hospital, plus a survival analysis of gene-expression data from The Cancer Genome Atlas (TCGA)
• Who was studied: 19 consecutive patients with malignant pleural mesothelioma at the University Hospital of Larissa, Greece; median age 67 (range 61 to 80)
• Exposure: Asbestos exposure was recorded, but no fiber types or jobs are described: definite/confirmed in 10 of 19 patients (52.6%), possible in 5 (26.3%), unknown in 4 (21%). The factor tested for survival was the ratio of BNP in pleural fluid to BNP in blood. It was measured at the first thoracentesis, except in one patient, who was measured at a repeat thoracentesis five years after diagnosis.
• Main results:
  • At the time of fluid drainage, pleural fluid BNP levels in these patients were about 10 times higher than blood levels, and as much as 150 times higher in some patients.
  • In one patient, BNP was measured five years after the mesothelioma diagnosis, at a repeat thoracentesis for recurrent effusion. This patient had the only ratio below 1 (0.3) and was alive 6330 days after diagnosis.
  • For all 19 patients, one-year survival was 52.6% and two-year survival 31.6%. Age, TNM stage, performance status, degree of pleural thickening, LDH, albumin and CRP did not differ between survivors and non-survivors.
  • Two-year survivors had lower blood white cell counts (p = 0.022).
  • Blood (serum) BNP did not differ significantly between survivors and non-survivors.
  • At two years, pleural fluid BNP was higher in non-survivors (n = 13) than in survivors (n = 6). The medians (minimum, maximum) were 699 (210, 5000) vs. 379.5 (5, 567) pg/mL, p = 0.036.
  • Non-survivors had higher fluid-to-blood BNP ratios than survivors. At one year (9 non-survivors vs. 10 survivors) the medians were 28.75 (4.05, 150.24) vs. 3.49 (0.3, 26), p = 0.001. At two years (13 non-survivors vs. 6 survivors) they were 22.8 (2.42, 150.24) vs. 3.49 (0.3, 7.76), p = 0.001.
  • Patients with a BNP ratio at or above the median of 8.82 had 20% one-year and 0% two-year survival. Patients with a ratio below 8.82 had 88.9% one-year and 66.7% two-year survival (log-rank p = 0.006 and p = 0.002).
  • Three patients had a biopsy, and all three had the epithelioid type. Their BNP ratios and survival were: ratio 2.42 with survival of 476 days, ratio 22.82 with 256 days, and ratio 150.24 with 135 days.
  • In The Cancer Genome Atlas mesothelioma data, patients with low expression of the NPPB gene (the gene for the BNP precursor) had significantly higher survival than patients with higher expression (p = 0.032). The number of patients in this dataset is not given.
• The authors' conclusion: The authors concluded that the pleural fluid-to-blood BNP ratio measured at the initial assessment separated survivors from non-survivors, and that the higher the ratio, the worse the survival.
• Limitations the authors state:
  • The authors suggest the small sample size may explain why commonly reported prognostic factors showed no differences.
  • Histological subtype was known for only three patients, all epithelioid. Most diagnoses were based on cytology of the pleural fluid.
  • The authors describe the results as preliminary and say they need confirmation in larger studies.
  • The authors state that their ideas about whether BNP affects pleural fibrosis or tumor growth are speculative.

Topics

Medical terms in this study, explained in our Lexicon: Prognosis, Pleural Mesothelioma, Mesothelial Cells, Performance Status, Biomarker.

Related studies

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• Malignant mesothelioma cells secrete natriuretic peptides: Data and diagnostic clinical implications — V. Tsolaki, S. Zarogiannis, et al. (2020)
• Preoperative neutrophil-to-lymphocyte ratio correlates with PD-L1 expression in immune cells of patients with malignant pleural mesothelioma and predicts prognosis — R. Okita, N. Kawamoto, et al. (2023)
• Utility of hyaluronic acid in pleural fluid for differential diagnosis of pleural effusions: likelihood ratios for malignant mesothelioma — S. Atagi, M. Ogawara, et al. (1997)
• The use of pleural fluid sCD44v6/std ratio for distinguishing mesothelioma from other pleural malignancies — J.M. Porcel, A. Esquerda, et al. (2011)
• The importance of serum and pleural fluid level of vascular endothelial growth factor (VEGF) and VEGF fluid/serum ratio in the differential diagnosis of malignant mesothelioma-related pleural effusion — Y. Düzköprü, Z. Oruç, et al. (2017)

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