Abstract:

:Overexpression of somatostatin receptors in patients with neuroendocrine neoplasms (NEN) is utilized for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Non-invasive visualization and quantification of somatostatin receptor density is possible by somatostatin receptor imaging (SRI) using positron emission tomography (PET). Recently, we introduced 64Cu-DOTATATE for SRI and we hypothesized that uptake of this tracer could be associated with overall (OS) and progression-free survival (PFS). Methods: We evaluated patients with NEN that had a 64Cu-DOTATATE PET/CT SRI performed in two prospective studies. Tracer uptake was determined as the maximal standardized uptake value (SUVmax) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of 64Cu-DOTATATE SUVmax for OS and PFS. Specificity, sensitivity and accuracy was calculated for prediction of outcome at 24 months after 64Cu-DOTATATE PET/CT. Results: A total of 128 patients with NEN were included and followed for a median of 73 (1-112) months. During follow-up, 112 experienced disease progression and 69 patients died. The optimal cutoff for 64Cu-DOTATATE SUVmax was 43.3 for prediction of PFS with a hazard ratio of 0.56 (95% CI: 0.38-0.84) for patients with SUVmax > 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 SUVmax cutoff hazard ratio was 0.50 (0.32-0.77) for PFS. The accuracy was moderate for predicting PFS (57%) at 24 months after 64Cu-DOTATATE PET/CT. Conclusion: In this first study to report the association of 64Cu-DOTATATE PET/CT and outcome in patients with NEN, tumor somatostatin receptor density visualized with 64Cu-DOTATATE PET/CT was prognostic for PFS but not OS. However, the accuracy of prediction of PFS at 24 months after 64Cu-DOTATATE PET/CT SRI was moderate limiting the value on an individual patient basis.