title: A serum mesothelin level is a prognostic indicator for patients with malignant mesothelioma in routine clinical practice.
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.
authors.forename: Mark
authors.initials: M
authors.lastname: Linch
authors.forename: Spyridon
authors.initials: S
authors.lastname: Gennatas
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kazikin
authors.forename: Jhangir
authors.initials: J
authors.lastname: Iqbal
authors.forename: Ranga
authors.initials: R
authors.lastname: Gunapala
authors.forename: Kathryn
authors.initials: K
authors.lastname: Priest
authors.forename: Joanne
authors.initials: J
authors.lastname: Severn
authors.forename: Alison
authors.initials: A
authors.lastname: Norton
authors.forename: Bee
authors.initials: B
authors.lastname: Ayite
authors.forename: Jaishree
authors.initials: J
authors.lastname: Bhosle
authors.forename: Mary
authors.initials: M
authors.lastname: O'Brien
authors.affiliation: Royal Marsden Hospital, Fulham Road, SW3 6JJ London, Surrey, UK. Sanjay.Popat@rmh.nhs.uk.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Popat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D008297:Male; D000090204:Mesothelin; D008654:Mesothelioma / Q000097:blood* / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D000090204:Mesothelin