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

Cancer. 2014 Mar 1;120(5):711-21. doi: 10.1002/cncr.28493. Epub 2013 Nov 21.


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.

Keywords: Response Evaluation Criteria In Solid Tumors (RECIST); computed tomography; computed tomography (CT) attenuation; interobserver variability; intraobserver variability; renal cell carcinoma; tumor shrinkage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Carcinoma, Renal Cell / diagnostic imaging*
  • Carcinoma, Renal Cell / drug therapy*
  • Female
  • Humans
  • Kidney Neoplasms / diagnostic imaging*
  • Kidney Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Observer Variation
  • Tomography, X-Ray Computed*
  • Treatment Outcome


  • Angiogenesis Inhibitors