A serum mesothelin level is a prognostic indicator for patients with malignant mesothelioma in routine clinical practice

Our plain-English summary of A serum mesothelin level is a prognostic indicator for patients with malignant mesothelioma in routine clinical practice, by M. Linch, S. Gennatas, S. Kazikin, et al (BMC Cancer, 2014).

The study

• Authors: M. Linch, S. Gennatas, S. Kazikin, J. Iqbal, R. Gunapala, K. Priest, J. Severn, A. Norton, B. Ayite, J. Bhosle, M. O'Brien, S. Popat
• Journal: BMC Cancer
• Published: 2014;14:674
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant mesothelioma (MM) carries a poor prognosis and response rates to palliative chemotherapy remain low. Identifying patients with MM that are unlikely to respond to chemotherapy could prevent futile treatments and improve patient quality of life. Studies have suggested that soluble mesothelin is a potential biomarker for early diagnosis and prognosis of MM. We set out to explore the utility of serum mesothelin in routine clinical practice.

Methods: We conducted a prospective exploratory study of serum mesothelin levels in 53 consecutive patients with MM at our institution between April 2009 and February 2011. Survival was assessed and analysed by mesothelin level as both continuous and categorical variables using Cox regression models. Differences in response rate between treatment groups were assessed by the Kruskal-Wallis Test.

Results: All 53 patients, who had been given study information agreed to participate. The patients' median age was 69 (range 24-90). Median mesothelin level was 2.7 nM and this value was used to dichotomize categories: ≤2.7 nM (low) and >2.7 nM (high). The progression free survival (PFS) for low vs high mesothelin was 8.0 vs 5.1 months (HR 1.8, p-0.058). When mesothelin was accessed as a continuous variable for PFS the HR was 1.03 (95% CI: 1.01-1.06; p=0.013). The overall survival (OS) for low vs high mesothelin was 17.2 vs 11.3 months (HR 1.9, p=0.088). When mesothelin was assessed as a continuous variable for OS the HR was 1.02 (95% CI: 0.99 - 1.04; p=0.073). Thirty patients received chemotherapy of which 18 had a pre-chemotherapy serum mesothelin level. In these 18 patients, the pre-chemotherapy mesothelin level did not correlate with response.

Conclusions: A single random sample provides information about patient prognosis but does not predict treatment response. We suggest further prospective validation of mesothelin testing as a prognostic biomarker.

In plain English

At the Royal Marsden Hospital in London, the authors measured blood levels of the protein mesothelin in 53 patients with malignant mesothelioma (49 pleural, 4 peritoneal) between April 2009 and February 2011. The study did not examine asbestos exposure. The median level was 2.7 nM, and patients were split into low (2.7 nM or less) and high (above 2.7 nM) groups. Treated as a continuous measure, higher mesothelin was significantly associated with shorter progression-free survival, the time to progression or death (hazard ratio 1.03 per unit, 95% CI 1.01 to 1.06). Median progression-free survival was 8.0 months in the low group and 5.1 months in the high group. Median overall survival was 17.2 months in the low group and 11.3 months in the high group. Neither group difference was statistically significant, and neither was the continuous result for overall survival. In 18 patients tested before chemotherapy, mesothelin levels did not differ significantly by treatment response. The authors said this part was underpowered. They concluded that a single sample gives prognostic information but does not predict treatment response.

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: Prospective exploratory study at a single institution, carried out as a service evaluation
• Who was studied: 53 patients with histologically confirmed malignant mesothelioma at the Royal Marsden Hospital, London, tested between April 2009 and February 2011. Of these, 49 had pleural and 4 had peritoneal mesothelioma, 46 had epithelioid histology, 36 were men and 17 women, and the mean age was 69 (range 24 to 90).
• Exposure: Not an asbestos exposure study. The factor examined was a single random serum mesothelin level, measured with the Mesomark ELISA kit and expressed in nmol/L. No fiber types or occupational exposures are reported.
• Main results:
  • Progression-free survival was measured from the date of mesothelin measurement to disease progression or death.
  • Across the 53 patients, the mean serum mesothelin was 6.6 nM (range 0.3 to 102.5 nM) and the median was 2.7 nM. The median was used to define the low and high groups.
  • Progression-free survival, mesothelin as a continuous variable: HR 1.03 (95% CI 1.01 to 1.06; p = 0.013). Each unit increase in mesothelin raised the hazard of progression by 3%.
  • Progression-free survival, high (above 2.7 nM) vs low (2.7 nM or less): HR 1.8 (95% CI 0.9 to 3.2; p = 0.059). Median progression-free survival was 8.0 months in the low group and 5.1 months in the high group.
  • Overall survival, mesothelin as a continuous variable: HR 1.02 (95% CI 0.99 to 1.04; p = 0.073), not statistically significant.
  • Overall survival, high vs low group: HR 1.9 (95% CI 0.9 to 4.1; p = 0.088). Median overall survival was 17.2 months in the low group (2.7 nM or less) and 11.3 months in the high group (above 2.7 nM). The authors described high levels as non-significantly associated with shorter overall survival.
  • Among 18 patients with a mesothelin level taken before chemotherapy: 0 complete responses, 5 (28%) partial responses, 11 (61%) stable disease and 2 (11%) progressive disease. Pre-chemotherapy mesothelin levels did not differ significantly between the response groups.
• The authors' conclusion: The authors concluded that a single random sample provides information about patient prognosis but does not predict treatment response. They suggested further prospective validation of mesothelin testing as a prognostic biomarker.
• Limitations the authors state:
  • The analysis of response to chemotherapy, based on 18 patients, was underpowered to detect a difference.
  • The study was small and carried out at a single institution, and larger prospective studies are needed to validate the results.
  • Covariates such as renal function were not accounted for. Kidney impairment can raise mesothelin levels.
  • Survival was counted from the date of mesothelin sampling, which may underestimate true progression-free and overall survival.
  • Outcomes were not analysed by chemotherapy regimen because numbers were small.

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: Mesothelin, Mesothelioma, Prognosis, Palliative Care, Chemotherapy, Quality of Life, Biomarker, Overall Survival.

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