Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma

Our plain-English summary of Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma, by S. Iser, S. Hintermair, A. Varga, et al (Cancers, 2023).

The study

• Authors: S. Iser, S. Hintermair, A. Varga, A. Çelik, M. Sayan, A. Kankoç, N. Akyürek, B. Öğüt, P. Bertoglio, E. Capozzi, P. Solli, L. Ventura, D. Waller, M. Weber, E. Stubenberger, B. Ghanim
• Journal: Cancers
• Published: 2023;16(1)
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers' prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.

In plain English

This retrospective study from several centers examined 98 patients with pleural mesothelioma confirmed by tissue diagnosis. The authors compared routine blood tests, taken before diagnosis or surgery, and the treatments given with how long patients lived. The blood tests included platelets, hemoglobin, white-cell counts and C-reactive protein (CRP, an inflammation marker). The article did not measure asbestos exposure. Median survival for the whole group was 19.4 months. Patients treated with surgery plus other therapy survived a median of 26.1 months, compared with 3.2 months for those given best supportive care. Patients with a platelet count at or below 280 G/L survived a median of 26.1 months, compared with 11.7 months for those above it. In an adjusted analysis of 83 patients, four factors were each linked to a higher risk of death: non-epithelioid tumor type, no surgery, platelets above 280 G/L, and CRP above 1 mg/dL. Leukocyte, neutrophil and lymphocyte counts showed no significant link. The authors concluded that decisions about lung-sparing surgery may not depend as heavily on inflammatory markers as previously thought. They named the retrospective design and the high share of surgical patients as limitations.

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: retrospective multicenter study of patient records (survival analysis)
• Who was studied: 98 patients with histologically proven pleural mesothelioma: 25 female and 73 male, mean age 64.9 years. 84 had epithelioid tumors and 14 had non-epithelioid tumors (8 biphasic, 6 sarcomatoid). The authors work at centers in Austria, Turkey, Italy and the UK, but the participating departments are listed only in a supplementary table that is not included. The treatment period is not stated.
• Exposure: Asbestos exposure was not measured. The study examined blood markers from samples taken before the intervention (before diagnosis or surgery): leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, the NLR, LMR and PLR ratios, and CRP. It also examined clinical factors, including treatment. 65 patients had multimodal therapy, 9 had surgery alone, 7 had chemo-, radio- or immunotherapy, and 17 had best supportive care.
• Main results:
  • Median overall survival for all 98 patients was 19.4 months (CI 12.1 to 26.7).
  • Median survival by treatment was 26.1 months for multimodal therapy, 11.7 months for surgery alone, 9.2 months for chemo-, radio- or immunotherapy, and 3.2 months for best supportive care (p less than 0.001).
  • Patients who had cytoreductive surgery (n = 74) had a median survival of 25.5 months, compared with 3.8 months for patients without surgery (n = 24) (p less than 0.001).
  • Patients with hemoglobin above 12 g/dL survived a median of 24.2 months, compared with 15 months for those at or below 12 g/dL (p = 0.021).
  • Patients with platelets at or below the median of 280 G/L survived a median of 26.1 months, compared with 11.7 months for those above it (p less than 0.001).
  • Patients with a platelet-lymphocyte ratio (PLR) at or below the median of 195.6 survived a median of 25.5 months, compared with 12.3 months for those above it (p = 0.023).
  • In the multivariate model (n = 83), non-epithelioid histology had a hazard ratio for death of 3.45 (95% CI 1.60 to 7.40, p = 0.002) compared with epithelioid histology.
  • In the multivariate model, no surgery had a hazard ratio for death of 3.04 (95% CI 1.43 to 6.43, p = 0.004) compared with cytoreductive surgery.
  • In the multivariate model, platelets above 280 G/L had a hazard ratio of 2.01 (95% CI 1.09 to 3.70, p = 0.025). CRP above 1 mg/dL had a hazard ratio of 1.76 (95% CI 1.03 to 3.00, p = 0.039).
  • Histology did not reach statistical significance in the univariate analyses (p = 0.053 and p = 0.056).
  • Leukocytes, lymphocytes, neutrophils, the NLR and the LMR were not significant in any analysis.
  • When patients were split by surgery, CRP level did not significantly change survival among surgical patients (p = 0.699) or among non-surgical patients (p = 0.120). The authors said CRP alone may not be considered prognostic in this analysis.
• The authors' conclusion: The authors concluded that the decision to have lung-sparing surgery may not depend as heavily on inflammatory parameters as previously thought. They said the survival of surgically treated patients supports further research on surgery, especially combined with biomarkers.
• Limitations the authors state:
  • The retrospective design created problems with treatment allocation and with the completeness of laboratory data.
  • The study worked with thoracic surgical centers, so surgical patients far outnumbered conservatively treated patients. This must be considered when comparing survival between treatments.
  • Biomarker levels were measured only at specific time points.
  • There were few biphasic and sarcomatoid cases, so the authors merged them into one non-epithelioid group.
  • Leukocyte, monocyte, LMR and CRP values were missing for some patients and could not be recovered.

Topics

Medical terms in this study, explained in our Lexicon: Biomarker, Pleural Mesothelioma, Inflammation, Histology, Overall Survival, Pleurectomy/Decortication (P/D), Epithelioid, Non-epithelioid.

Related studies

• Ki67 Tumor Expression Predicts Treatment Benefit Achieved by Macroscopic Radical Lung-Preserving Surgery in Pleural Mesothelioma-A Retrospective Multicenter Analysis — S. Hintermair, S. Iser, et al. (2024)
• Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems — J.G. Edwards, K.R. Abrams, et al. (2000)
• Validation of prognostic factors in malignant pleural mesothelioma: a retrospective analysis of data from patients seeking compensation from the New South Wales Dust Diseases Board — S.C. Kao, J. Vardy, et al. (2013)
• Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases — D.B. Chapel, J.J. Schulte, et al. (2021)
• External validation of prognostic indices for overall survival of malignant pleural mesothelioma — Y. Kataoka, Y. Yamamoto, et al. (2017)
• Soluble mesothelin related peptides (SMRP) and osteopontin as protein biomarkers for malignant mesothelioma: analytical validation of ELISA based assays and characterization at mRNA and protein levels — A.J. Rai, R.M. Flores, et al. (2010)

Browse more research in Cancers, or return to medical research.