Design considerations for using PET as a response measure in single site and multicenter clinical trials.

RATIONALE AND OBJECTIVES: Positron emission tomography (PET) is used to evaluate response to therapy with increasing interest in having PET provide endpoints for clinical trials. Here we demonstrate impacts of PET measurement error and choice of quantification method on clinical trial design. MATERIALS AND METHODS: Sample size was calculated for two-arm randomized trials with percent change in (18)F-fluorodeoxyglucose (FDG) PET uptake as an efficacy endpoint. Two methods of uptake quantification were considered: standardized uptake values (SUVs) and kinetic measures from dynamic imaging. Calculations assumed a 20 percentage point difference in treatment groups' average percent change, and yielded 80% power at α = 0.05. The range of precision (10%-40%) in PET uptake measures was based on review of the literature. The range of SUV sensitivities (50%-100%) relative to kinetic analyses was based on a study of 75 locally advanced breast cancer patients. RESULTS: Sample sizes increased from 8 to 126 as PET precision worsened from 10% to 40% at full measurement sensitivity to true change. In a subgroup with low initial FDG uptake, a sample size of 126 was required under 20% standard deviation using clinical SUVs. More sophisticated imaging quantification could reduce this sample size to 32. CONCLUSIONS: The dependence of sample size on measurement precision and the sensitivity of imaging measures to true change should be considered in single site and multicenter PET trials to avoid underpowered studies with inconclusive results. Sophisticated PET imaging methods that are more sensitive to changes in uptake may be advantageous in early studies with limited patient numbers.