Quantitative 68Ga-DOTATATE PET/CT Parameters for the Prediction of Therapy Response in Patients with Progressive Metastatic Neuroendocrine Tumors Treated with 177Lu-DOTATATE
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abstract
The aim of this study was to determine whether quantitative PET parameters on baseline 68Ga-DOTATATE PET/CT and interim PET (iPET) performed before the second cycle of therapy are predictive of the therapy response and progression-free survival (PFS). Methods: Ninety-one patients with well-differentiated neuroendocrine tumors (mean Ki-67 index, 8.3%) underwent 68Ga-DOTATATE PET/CT to determine suitability for peptide receptor radionuclide therapy as part of a prospective multicenter study. The mean follow-up was 12.2 mo. Of the 91 patients, 36 had iPET. The tumor metrics evaluated were marker lesion-based measures (mean SUVmax and ratio of the mean lesion SUVmax to the SUVmax in the liver or the SUVmax in the spleen), segmented 68Ga-DOTATATE tumor volumes (DTTVs), SUVmax and SUVmean obtained with the liver and spleen as thresholds, and heterogeneity parameters (coefficient of variation, kurtosis, and skewness). The Wilcoxon rank sum test was used for the association between continuous variables and the therapy response, as determined by the clinical response. Univariable and multivariable Cox proportional hazards models were used for the association with PFS. Results: There were 71 responders and 20 nonresponders. When marker lesions were used, higher mean SUVmax and ratio of the mean lesion SUVmax to the SUVmax in the liver were predictors of the therapy response (P = 0.018 and 0.024, respectively). For DTTV parameters, higher SUVmax and SUVmean obtained with the liver as a threshold and lower kurtosis were predictors of a favorable response (P = 0.025, 0.0055, and 0.031, respectively). The latter also correlated with a longer PFS. The iPET DTTV SUVmean obtained with the liver as a threshold and the ratio of mean SUVmax obtained from target lesions at iPET to baseline PET correlated with the therapy response (P = 0.024 and 0.048, respectively) but not PFS. From the multivariable analysis with adjustment for age, primary site, and Ki-67 index, the mean SUVmax (P = 0.019), ratio of the mean lesion SUVmax to the SUVmax in the liver (P = 0.018), ratio of the mean lesion SUVmax to the SUVmax in the spleen (P = 0.041), DTTV SUVmean obtained with the liver (P = 0.0052), and skewness (P = 0.048) remained significant predictors of PFS. Conclusion: The degree of somatostatin receptor expression and tumor heterogeneity, as represented by several metrics in our analysis, were predictive of the therapy response or PFS. Changes in these parameters after the first cycle of peptide receptor radionuclide therapy did not correlate with clinical outcomes.
