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© 2014 Linch et al.; licensee BioMed Central Ltd.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.

Introduction Response rates in the palliative treatment of non-small cell lung cancer, with combination platinum-based chemotherapy, vary from 20% to 40%, leaving a large number with either stable or progressive disease. We examined radiographic response after two courses of platinum-based induction chemotherapy to see whether this is an early predictor of outcome. Methods In this retrospective study, 320 patients with stage III/IV NSCLC were identified who received 4 or more courses of first-line platinum-based chemotherapy and attained partial response (PR) or stable disease (SD). Results After two courses, 115 patients attained PR and 205 SD. Cox regression analysis shows that response after two courses of chemotherapy remains an independent significant prognostic factor for survival. The 2-year survival for patients attaining PR after two courses ( n = 115) was 23% compared with 11% ( n = 205) for those with SD ( p = 0.002). Patients who achieve an objective response after two courses also have a better symptomatic response ( p = 0.003) and it was significantly longer ( p = 0.04). Of the 205 with SD, 51 attained PR with four courses, whereas 154 (48%) remained with SD; there was no difference in survival outcome of these two groups. Conclusions These data suggest that NSCLC patients who only have SD after two cycles of first-line chemotherapy have poorer survival outcome and less symptomatic benefit than those in PR. Trials looking at change in management at this point are warranted.