Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials.

Background: Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients with bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[F]fluoro-D-glucose (F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.In this study, nine patients with 38 bone lesions were imaged with F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified as the maximum tumor voxel normalized by dose and body weight (SUVmax) and the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals of SUVmax and SULpeak were used to determine limits of F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with F-FDG before and after standard-of-care therapy for response assessment.

Results: The mean relative difference of SUVmax in 38 bone tumors of the first cohort was 4.3%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and -16.3%, respectively. The F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria changed the status of 3 patients compared to standard the standard Positron Emission Tomography Response Criteria in Solid Tumors of ±30% SULpeak.

Conclusions: In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using F-FDG uptake, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial F-FDG imaging in clinical trials investigating bone lesions from these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.