title: Intraobserver and interobserver variability in computed tomography size and attenuation measurements in patients with renal cell carcinoma receiving antiangiogenic therapy: implications for alternative response criteria.
abstract: BACKGROUND
  Alternative response criteria have been proposed in patients with metastatic renal cell carcinoma (mRCC) who are receiving vascular endothelial growth factor (VEGF)-targeted therapy, including 10% tumor shrinkage as an indicator of response/outcome. However, to the authors' knowledge, intraobserver and interobserver measurement variability have not been defined in this setting. The objective of the current study was to determine intraobserver and interobserver agreement of computed tomography (CT) size and attenuation measurements to establish reproducible response indicators.
  
  
  METHODS
  Seventy-one patients with mRCC with 179 target lesions were enrolled in phase 2 and phase 3 trials of VEGF-targeted therapies and retrospectively studied with Institutional Review Board approval. Two radiologists independently measured the long axis diameter and mean attenuation of target lesions at baseline and on follow-up CT. Concordance correlation coefficients and Bland-Altman plots were used to assess intraobserver and interobserver agreement.
  
  
  RESULTS
  High concordance correlation coefficients (range, 0.8602-0.9984) were observed in all types of measurements. The 95% limits of agreement for the percentage change of the sum longest diameter was -7.30% to 7.86% for intraobserver variability, indicating that 10% tumor shrinkage represents a true change in tumor size when measured by a single observer. The 95% limits of interobserver variability were -16.3% to 15.4%. On multivariate analysis, the location of the lesion was found to significantly contribute to interobserver variability (P = .048). The 95% limits of intraobserver agreement for the percentage change in CT attenuation were -18.34% to 16.7%.
  
  
  CONCLUSIONS
  In patients with mRCC who are treated with VEGF inhibitors, 10% tumor shrinkage is a reproducible radiologic response indicator when baseline and follow-up studies are measured by a single radiologist. Lesion location contributes significantly to measurement variability and should be considered when selecting target lesions.
authors.affiliation: Department of Imaging, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Krajewski
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.forename: Yoko
authors.initials: Y
authors.lastname: Franchetti
authors.forename: Nikhil H
authors.initials: NH
authors.lastname: Ramaiya
authors.forename: Annick D
authors.initials: AD
authors.lastname: Van den Abbeele
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D015588:Observer Variation; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Response Evaluation Criteria In Solid Tumors (RECIST); computed tomography; computed tomography (CT) attenuation; interobserver variability; intraobserver variability; renal cell carcinoma; tumor shrinkage