title: Comparison of central and local serial CT assessments of metastatic renal cell carcinoma patients in a clinical phase IIB study.
abstract: Background Clinical oncological studies attempt to improve precision of data by central radiological assessments. However, it is unclear, to which extent local and central assessments diverge. Purpose To quantify inter-reader variability and the deviation of local from central radiological assessments of computed tomography (CT) scans. Material and Methods This was a sub-study of a randomized clinical phase IIb trial in metastatic renal cell carcinoma (RCC), comparing first-line sorafenib with interferon-alpha-2a (IFN-α-2a). It analyzed agreements of local with central RECIST CT assessments by Cohen's kappa (κ), symmetry tests, deviations in waterfall plots, Bland-Altman plots, and parametric survival analyses. Results The concordance between local and central radiologic review was quantified by κ = 0.53. While local assessment yielded progressive disease (PD) in 18.6%, central assessment classified 22.5% of patient time points as PD exhibiting only a partial overlap with the 18.6% The tumor shrinkage rates in waterfall plots were 68.1% in local and 55.8% in central review (57.8% and 59% by Reader 1 and Reader 2). Bland-Altman plots identified a systematic shift of tumor change rates by -7.5% in local compared to central assessments, that may reflect a systematic tendency of more favorable results in local assessments. The discordance between local and central review was reflected by a time to progression (TTP) hazard ratio (HR) of 1.73 ( P = 0.0003). Conclusion These data suggest that central radiologic review may reduce technical measurement variability in clinical trials, which should be scrutinized in future studies compared to a volumetric reference.
authors.affiliation: 1 Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Universitätsklinikum Köln, Köln, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Felsch
authors.affiliation: 2 Synarc, Inc., Newark, California, USA.
authors.forename: Souhil
authors.initials: S
authors.lastname: Zaim
authors.affiliation: 3 Fraunhofer MEVIS, Institute for Medical Image Computing, Bremen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Dicken
authors.affiliation: 1 Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Universitätsklinikum Köln, Köln, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Lehmacher
authors.affiliation: 4 Bayer HealthCare, Bayer Vital GmbH, Leverkusen, Germany.
authors.forename: Urban J
authors.initials: UJ
authors.lastname: Scheuring
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D003627:Data Interpretation, Statistical; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000627:therapeutic use; D015203:Reproducibility of Results; D012189:Retrospective Studies; D000077157:Sorafenib; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods* / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011994:Recombinant Proteins; D009536:Niacinamide; D000077157:Sorafenib
keywords: RECIST; concordance rate; discordance rate