Target Lesion Selection: An Important Factor Causing Variability of Response Classification in the Response Evaluation Criteria for Solid Tumors 1.1

PURPOSEWe conducted a systematic analysis of factors (manual vs automated and unidimensional vs 3-dimensional size assessment, and impact of different target lesion selection) contributing to variability of response categorization in the Response Evaluation Criteria for Solid Tumors 1.1. PATIENTS AND METHODSA total of 41 female patients (58.1 ± 13.2 years old) with metastatic breast cancer underwent contrast-enhanced thoracoabdominal computed tomography for initial staging and first follow-up after systemic chemotherapy. Data were independently interpreted by 3 radiologists with 5 to 9 years of experience. In addition, response was evaluated by a computer-assisted diagnosis system that allowed automated unidimensional and 3-dimensional assessment of target lesions. RESULTSOverall, between-reader agreement was moderate (κ = 0.53), with diverging response classification observed in 19 of 41 patients (46%). In 25 patients, readers had chosen the same, and in 16, readers had chosen different target lesions. Selection of the same target lesions was associated with a 76% rate of agreement (19/25) with regard to response classification; selection of different target lesions was associated with an 81% rate of disagreement (13/16) (P < 0.001). After dichotomizing response classes according to their therapeutic implication in progressive versus nonprogressive, disagreement was observed in 11 of 41 patients (27%) (κ = 0.57). In 9 of these 11 patients, readers had chosen different target lesions. Disagreement rates due to manual versus automated or unidimensional versus volumetric size measurements were less important (11/41 and 6/41; 27% and 15%, respectively). CONCLUSIONSA major source of variability is not the manual or unidimensional measurement, but the variable choice of target lesions between readers. Computer-assisted diagnosis–based analysis or tumor volumetry can help avoid variability due to manual or unidimensional measurements only but will not solve the problem of target lesion selection.