Pretreatment serum C-reactive protein levels predict benefit from multimodality treatment including radical surgery in malignant pleural mesothelioma: a retrospective multicenter analysis

Our plain-English summary of Pretreatment serum C-reactive protein levels predict benefit from multimodality treatment including radical surgery in malignant pleural mesothelioma: a retrospective multicenter analysis, by B. Ghanim, M.A. Hoda, M.P. Winter, et al (Annals of Surgery, 2012).

The study

• Authors: B. Ghanim, M.A. Hoda, M.P. Winter, T. Klikovits, A. Alimohammadi, B. Hegedus, B. Dome, M. Grusch, M. Arns, P. Schenk, W. Pohl, C. Zielinski, M. Filipits, W. Klepetko, W. Berger
• Journal: Annals of Surgery
• Published: 2012;256(2):357-62
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: To evaluate the prognostic and predictive relevance of pretreatment serum C-reactive protein (CRP) in malignant pleural mesothelioma (MPM) patients.

Background: MPM is a rare but aggressive disease with poor treatment outcome. Therapeutic decision is challenging, and predictive biomarkers for better treatment stratification are urgently needed.

Methods: Clinical data, including survival and pretreatment CRP levels, were retrospectively collected from 115 patients with histologically proven MPM. Patients with any evidence for infectious disease were excluded. The association between CRP levels and survival was analyzed using Cox models adjusted for clinical and pathological factors.

Results: Median pretreatment CRP of all patients was 1.19 mg/dL (range: 0.00-22.62 mg/dL). Patients with elevated CRP levels (≥1 mg/dL; n = 62, 53.9%) had a significantly shorter overall survival compared with those with normal CRP (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.82-4.33; P < 0.001). In multivariate survival analyses, elevated CRP was confirmed as an independent prognostic factor in MPM (HR 2.07, 95% CI 1.23-3.46; P = 0.01). Most interestingly, we observed a significant interaction between CRP and treatment modality (P < 0.001). Among patients with normal CRP levels, radical tumor resection within multimodality therapy was associated with distinctly prolonged overall survival when compared with treatment protocols without surgery (HR 7.26, 95% CI 3.40-15.49; P < 0.001). In contrast among patients with elevated CRP, no survival benefit was achieved by radical surgery within multimodality approaches (HR 0.911, 95% CI 0.53-1.58; P = 0.74).

Conclusions: Our results suggest that multimodality regimens including radical resection increase survival selectively in MPM patients with normal pretreatment serum CRP levels.

In plain English

This retrospective study reviewed 115 malignant pleural mesothelioma patients at three Austrian and Hungarian centers, 1994 to 2010. It asked whether pretreatment C-reactive protein (CRP), a routine inflammation blood test, predicted survival. Asbestos exposure was not studied. CRP was elevated (1 mg/dL or higher) in 62 of 115. Median survival was 9.04 months (95% CI 6.86 to 11.22) with elevated CRP and 25.28 months (95% CI 9.79 to 40.78) with normal CRP. In 100 patients, after adjusting for other clinical factors, elevated CRP remained linked to higher risk of death (hazard ratio 2.07, 95% CI 1.23 to 3.46). With normal CRP, patients having radical surgery within combined treatment survived a median 35.93 months (95% CI 31.57 to 40.30), versus 9.73 months (95% CI 7.73 to 11.74) with chemotherapy and/or radiotherapy alone. With elevated CRP, median survival was 7.86 months (95% CI 4.91 to 10.81) with surgery and 9.63 months (95% CI 8.45 to 10.81) without. This difference was not statistically significant. Treatment choice was not standardized, the authors noted. They concluded CRP needs prospective validation before use in selecting patients for surgery.

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 clinical records, using survival analysis (Kaplan-Meier curves and Cox regression)
• Who was studied: 115 patients with histologically proven malignant pleural mesothelioma: 65 at the Medical University of Vienna, 15 at Landesklinik Hochegg (Austria) and 35 at the National Koranyi Institute, Budapest (Hungary). They were drawn from a database of 249 patients and were referred between 1994 and 2010. Patients with infections were excluded. Patients given surgery alone, palliative treatment only or best supportive care were also excluded.
• Exposure: Asbestos exposure was not examined. The study looked at two factors. The first was pretreatment serum CRP level (normal below 1 mg/dL, elevated at 1 mg/dL or higher). The second was treatment type: radical surgery within multimodality treatment (n = 51) versus chemotherapy and/or radiotherapy alone (n = 64).
• Main results:
  • Across all 115 patients, median pretreatment CRP was 1.19 mg/dL (range 0.00 to 22.62 mg/dL). CRP was elevated in 62 (53.9%) of the 115 patients.
  • For all patients, median overall survival was 11.24 months (95% CI 8.38 to 14.11 months). During the observation period, 101 of the 115 patients died.
  • In the unadjusted analysis, patients with elevated CRP had a higher risk of death than patients with normal CRP: HR 2.81, 95% CI 1.82 to 4.33, P less than 0.001.
  • Median survival was 9.04 months (95% CI 6.86 to 11.22) for patients with elevated CRP and 25.28 months (95% CI 9.79 to 40.78) for patients with normal CRP.
  • The adjusted analysis covered 100 patients with complete data. Three factors were independent survival predictors: elevated CRP (HR 2.07, 95% CI 1.23 to 3.46, P = 0.01), nonepitheloid histology (HR 1.70, 95% CI 1.04 to 2.80), and chemo- and/or radiotherapy compared with surgery within multimodality treatment (HR 2.34, 95% CI 1.36 to 4.04). Age, sex and stage were not independent predictors.
  • The authors found a statistically significant interaction between CRP and treatment type (P less than 0.001).
  • Among patients with normal CRP, median survival was 35.93 months (95% CI 31.57 to 40.30) with radical surgery within multimodality treatment and 9.73 months (95% CI 7.73 to 11.74) with chemo- and/or radiotherapy alone. For patients with normal CRP who did not receive surgery, the hazard ratio was 7.26 (95% CI 3.40 to 15.49; P less than 0.001).
  • Among patients with elevated CRP, median survival was 7.86 months (95% CI 4.91 to 10.81) with surgery within multimodality treatment and 9.63 months (95% CI 8.45 to 10.81) with chemo- and/or radiotherapy alone (HR 0.911, 95% CI 0.53 to 1.58; P = 0.74).
  • Elevated CRP was associated with late-stage disease. Late stage was found in 80.6% of patients with elevated CRP and 58.5% of patients with normal CRP (P = 0.02).
  • When white blood cell (leukocyte) count was added to the adjusted model, CRP remained an independent prognostic marker.
• The authors' conclusion: The authors concluded that their results suggest radical surgery within multimodality treatment increases survival selectively in patients with normal pretreatment CRP. They added that prospective validation is needed before CRP can be recommended for selecting patients for surgery.
• Limitations the authors state:
  • Treatment allocation was not standardized; it depended on the attending physician's decision.
  • No defined performance status (a measure of patients' general physical condition) was available for the whole cohort.

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, Biomarker, Overall Survival, Hazard Ratio, confidence interval, Multimodal Therapy.

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