68Ga-DOTATATE PET/CT for the early prediction of response to somatostatin receptor-mediated radionuclide therapy in patients with well-differentiated neuroendocrine tumors.

Abstract

We aimed to evaluate (68)Ga-DOTATATE PET/CT for the early prediction of time to progression and clinical outcome after a first cycle of peptide receptor radionuclide treatment (PRRT) in a cohort of patients with well-differentiated neuroendocrine tumors. Thirty-three consecutive patients (22 men and 11 women; mean age +/- SD, 57.8 +/- 12.1 y) were investigated at baseline and again 3 mo after initiation of the first cycle of PRRT. (68)Ga-DOTATATE receptor expression was assessed using 2 measures of standardized uptake value (SUV): maximum SUV (SUV(max)) and tumor-to-spleen SUV ratio (SUV(T/S)). Percentage change in SUV scores after PRRT relative to baseline (DeltaSUV) was calculated. After completing 1-3 cycles of PRRT, patients entered the follow-up study, for estimation of time to progression. According to the Response Evaluation Criteria in Solid Tumors, progression was defined on the basis of contrast-enhanced CT. Clinical symptoms, as well as the tumor markers chromogranin A and neuron-specific enolase, were also recorded during regular follow-up visits. The 23 of 31 patients with decreased SUV(T/S) after the first PRRT cycle had longer progression-free survival than did the 8 of 31 patients with stable or increased scores (median survival not reached vs. 6 mo, P = 0.002). For the 18 of 33 patients showing a reduction in SUV(max), there was no significant difference in progression-free survival (median survival not reached vs. 14 mo, P = 0.22). Multivariate regression analysis identified SUV(T/S) as the only independent predictor for tumor progression during follow-up. In the 17 of 33 patients with clinical symptoms before PRRT, DeltaSUV(T/S) correlated with clinical improvement (r = 0.52, P < 0.05), whereas DeltaSUV(max) did not (r = 0.42, P = 0.10). Changes in the tumor markers (chromogranin A and neuron-specific enolase) did not predict DeltaSUV scores, clinical improvement, or time to progression. Decreased (68)Ga-DOTATATE uptake in tumors after the first cycle of PRRT predicted time to progression and correlated with an improvement in clinical symptoms among patients with well-differentiated neuroendocrine tumors; DeltaSUV(T/S) was superior to DeltaSUV(max) for prediction of outcome.