Abstract
BackgroundMalignant 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.MethodsWe 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.ResultsAll 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.ConclusionsA 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.
Highlights
Malignant mesothelioma (MM) carries a poor prognosis and response rates to palliative chemotherapy remain low
Thirty out of 53 patients received chemotherapy during their management for MM and 18/30 patients had their mesothelin level tested in the month prior to starting chemotherapy
We report the use of serum mesothelin in the assessment of patients with malignant mesothelioma in routine practice
Summary
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. Malignant mesothelioma (MM) is an aggressive cancer of serosal surfaces such as the pleura, peritoneum and rarely the pericardium. Diagnosis of MM is challenging as symptoms and early radiographic signs are often non-specific and their significance can be masked by multiple co-morbidities of this normally older patient. The optimal surgical approach is debated and includes palliative support with or without chemotherapy contingent on co-morbidities
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