title: Observer variability in mesothelioma tumor thickness measurements: defining minimally measurable lesions.
abstract: BACKGROUND
  Single time-point unidimensional tumor thickness measurements define measurable disease for clinical trial inclusion and also constitute a field in the International Association for the Study of Lung Cancer prospective mesothelioma staging database. The modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for mesothelioma did not alter the 10-mm minimum tumor measurement recommendation. However, as computed tomography technology has advanced, we sought to examine whether interobserver agreement was acceptable at smaller tumor thickness in mesothelioma.
  
  
  METHODS
  The primary observer selected 170 discrete measurement sites from 105 thoracic computed tomography scans from 50 consenting patients with pleural mesothelioma. Sites represented a range of tumor thickness, lesion morphology, and location. The outer (parietal) tumor margin was marked at each site and presented to five additional observers, who then selected the visceral margin of the tumor to create a line segment that captured tumor thickness. Relative differences among the observer measurements were estimated using a random-effects analysis of variance model to identify the smallest tumor thickness at which linear measurements could be made reliably.
  
  
  RESULTS
  Systematic bias was observed, with some observers consistently measuring larger or smaller thicknesses than the thickness measured by others. The mean range across all 170 sites was 15.1% of the mean per-site measurement (SD = 9.1%; median range, 13.1%). Measurements acquired at sites with mean tumor thickness less than 7.5 mm demonstrated interobserver variability with a 75th percentile included 20% of the tumor thickness. The 95% confidence interval for relative interobserver measurement differences obtained for mean measurement lengths in the range 5 to 7.5 mm does not exceed the RECIST thresholds.
  
  
  CONCLUSIONS
  This study has implications for the definition of minimally measurable tumor adopted by clinical trial and staging protocols. Although the statistical findings suggest that a reduction in "minimally measurable disease" from 10 mm to 5 or 7.5 mm might be warranted, clinical factors may ultimately dictate the most appropriate definition.
authors.affiliation: Departments of *Radiology and ‖Health Studies, The University of Chicago, Chicago, Illinois; †School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia; and Departments of ‡Medical Oncology and §Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Armato
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
authors.forename: Roslyn J
authors.initials: RJ
authors.lastname: Francis
authors.forename: Masha
authors.initials: M
authors.lastname: Kocherginsky
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Byrne
mesh_terms: D015982:Bias; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008654:Mesothelioma / Q000000981:diagnostic imaging* / Q000473:pathology*; D009367:Neoplasm Staging; D015588:Observer Variation; D010997:Pleural Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D017410:Practice Guidelines as Topic; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden