Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma

Our plain-English summary of Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma, by B. Ghanim, M.A. Hoda, T. Klikovits, et al (British Journal of Cancer, 2014).

The study

• Authors: B. Ghanim, M.A. Hoda, T. Klikovits, M.P. Winter, A. Alimohammadi, M. Grusch, B. Dome, M. Arns, P. Schenk, M. Jakopovic, M. Samarzija, L. Brcic, M. Filipits, V. Laszlo, W. Klepetko, W. Berger, B. Hegedus
• Journal: British Journal of Cancer
• Published: 2014;110(4):984-90
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients.

Methods: A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees.

Results: In total, 176 MPM patients (mean age: 63.5 years ± 10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (≥ 390 mg dl(-1)) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (≤ 627 mg dl(-1)) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months) when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl(-1)) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS).

Conclusions: Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.

In plain English

This retrospective study at three centres in Austria and Croatia looked at 176 people with malignant pleural mesothelioma (138 men, 38 women, mean age 63.5). The researchers asked whether fibrinogen, a blood protein that rises with inflammation, measured before treatment, was linked to survival. The study did not examine asbestos exposure. Most patients (154, 87.5%) had elevated fibrinogen. Patients at or below the median level of 627 mg/dl had a median survival of 19.1 months (confidence interval 14.5 to 23.7), versus 8.5 months (6.2 to 10.7) for those above it. After accounting for age, sex, stage, tumour type and treatment in 150 patients, high fibrinogen remained linked to a higher risk of death (hazard ratio 1.81, 95% CI 1.23 to 2.65). Among patients who had surgery as part of combined treatment, those with fibrinogen above 750 mg/dl lived a median of 5.3 months, versus 31.3 months for those below it. The authors concluded that fibrinogen is an independent prognostic marker, and that patients with remarkably elevated levels did not benefit from this surgery-based treatment. They called for prospective studies.

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
• Who was studied: 176 patients with histologically verified malignant pleural mesothelioma (mean age 63.5 years, 38 females, 138 males). Patients came from LKH Hochegg (22) and the Medical University of Vienna (91) in Austria, and from University Hospital Center Zagreb (63) in Croatia. The years of the study are not given. 150 patients with complete stage data were used for the multivariate analyses.
• Exposure: Asbestos exposure was not studied. The factor studied was the plasma fibrinogen level measured before treatment at the time of diagnosis. It was analysed by median (627 mg/dl), by clinical cutoff (390 mg/dl) and by 75th percentile (750 mg/dl), in relation to survival and treatment (best supportive care, chemo- and/or radiotherapy, or multimodality therapy including radical surgery).
• Main results:
  • 154 of 176 patients (87.5%) had elevated plasma fibrinogen (390 mg/dl or above) at diagnosis.
  • Patients in the low-fibrinogen group (at or below the median of 627 mg/dl) had a median overall survival of 19.1 months (14.5–23.7). Patients in the high-fibrinogen group had 8.5 months (6.2–10.7).
  • In multivariate analysis (150 patients), high fibrinogen was an independent prognostic factor for death (hazard ratio 1.81, CI 1.23–2.65).
  • Patients in the high-fibrinogen group were more often diagnosed at late stage. Early stage was 5 patients (6.9%) in the high group vs 14 patients (17.9%) in the low group, P=0.04. The high group was also less often treated with multimodality therapy including surgery: 17 (19.5%) vs 37 (41.6%).
  • No significant interaction was found between treatment and fibrinogen grouped by median. Using the 75th percentile (750 mg/dl), the interaction was significant (interaction term 0.034).
  • Among patients receiving multimodality therapy including surgery, those with fibrinogen above the 75th percentile had a median overall survival of 5.3 months, vs 31.3 months for those below it.
  • In 96 patients with both markers available, the area under the ROC curve for predicting death before 13.8 months was 0.771 for CRP and 0.734 for fibrinogen.
• The authors' conclusion: The authors concluded that fibrinogen is a novel independent prognostic biomarker in MPM. They also concluded that patients with remarkably elevated fibrinogen did not benefit from aggressive multimodality therapy including surgery. They stated that further independent and prospective studies are needed.
• Limitations the authors state:
  • Tumour stage information was missing for 26 patients, so the multivariate analyses used 150 patients.
  • No diagnostic CRP level was available for 63 patients, limiting the comparison of CRP and fibrinogen.
  • The authors stated that further independent investigations and prospective studies are needed.
  • The biological basis of fibrinogen's prognostic and predictive power is not known.

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: Biomarker, Pleural Mesothelioma, Overall Survival, confidence interval, Hazard Ratio, Multimodal Therapy.

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