Abstract
Overexpression of somatostatin receptors (SSTRs) in patients with neuroendocrine neoplasms (NENs) is used for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Noninvasive visualization and quantification of SSTR density is possible by SSTR imaging (SRI) using PET. Recently, we introduced (64)Cu-DOTATATE for SRI, and we hypothesized that uptake of this tracer could be associated with overall survival (OS) and progression-free survival (PFS). Methods: We evaluated patients with NENs who underwent (64)Cu-DOTATATE PET/CT SRI in 2 prospective studies. Tracer uptake was determined as the maximal SUV (SUV(max)) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of (64)Cu-DOTATATE SUV(max) for OS and PFS. Specificity, sensitivity, and accuracy were calculated for prediction of outcome at 24 mo after (64)Cu-DOTATATE PET/CT. Results: In total, 128 patients with NENs were included and followed for a median of 73 mo (range, 1-112 mo). During follow-up, 112 experienced disease progression, and 69 died. The optimal cutoff for (64)Cu-DOTATATE SUV(max) was 43.3 for prediction of PFS, with a hazard ratio of 0.56 (95% confidence interval, 0.38-0.84) for patients with an SUV(max) of more than 43.3. However, no significant cutoff was found for prediction of OS. In multiple Cox regression adjusted for age, sex, primary tumor site, and tumor grade, the SUV(max) cutoff hazard ratio was 0.50 (range, 0.32-0.77) for PFS. The accuracy was moderate for predicting PFS (57%) at 24 mo after (64)Cu-DOTATATE PET/CT. Conclusion: In this first study to report the association of (64)Cu-DOTATATE PET/CT and outcome in patients with NENs, tumor SSTR density as visualized with (64)Cu-DOTATATE PET/CT was prognostic for PFS but not OS. However, the accuracy of prediction of PFS at 24 mo after (64)Cu-DOTATATE PET/CT SRI was moderate, limiting the value on an individual-patient basis.