Quantitative ⁶⁸Ga-Dotatate PET/CT parameters for the prediction of therapy response in patients with progressive metastatic neuroendocrine tumors treated with ¹⁷⁷Lu-Dotatate

PURPOSE: To determine whether quantitative PET parameters on baseline ⁶⁸Ga-DOTATATE PET/CT (bPET) and interim PET (iPET) performed prior to second cycle of therapy are predictive of therapy response and progression free survival (PFS). PATIENTS & METHODS: Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki67, 8.3%) underwent ⁶⁸Ga-DOTATATE PET/CT (DT- PET) to determine suitability for peptide receptor radionuclide therapy (PRRT) as part of a prospective multicenter study. Mean follow-up was 12.2 months. Of them, 36 patients had iPET. Tumor metrics evaluated: 1. Marker lesion-based measures: mean SUVmax and ratio to liver/spleen; 2. Segmented DT tumor volume (DTTV) measures: DTTV; SUVmax and SUVmean using liver and spleen as thresholds; 3. Heterogeneity parameters (coefficient of variance, kurtosis, and skewness). Wilcoxon rank sum test was used for association between continuous variables and therapy response as determined by clinical response. Univariable and multivariable Cox proportional hazards model were used for association with PFS. RESULTS: There were 71 responders and 20 nonresponders. Using marker lesions, higher mean SUVmax and mean SUVmax(Tumor/Liver) were predictors of therapy response (p=0.018 & 0.024, respectively). For DTTV, higher SUVmax and SUVmean using liver as threshold and lower kurtosis were predictors of favorable response (p=0.025, 0.0055 & 0.031, respectively. These also correlated with longer PFS. iPET DTTV SUVmean using liver threshold and ratio iPET mean SUVmax using target lesions correlated with therapy response (p=0.024 & 0.048, respectively) but not PFS. From the multivariable analysis adjusting for age, primary site and Ki67, mean SUVmax (p=0.019), SUVmax T/L (p=0.018), SUVmax T/S (p=0.041), DTTV SUV_mean Liver (p=0.0052) and skewness (p=0.048) remain significant predictors of PFS. CONCLUSION: Degree of somatostatin receptor expression and tumor heterogeneity as represented by several metrics in our analysis are predictive of therapy response and/or PFS. Change in these parameters after first cycle of PRRT did not correlate with clinical outcomes.