Quantitative SPECT/CT Metrics in Early Prediction of [Lu]Lu-DOTATATE Treatment Response in Gastroenteropancreatic Neuroendocrine Tumor Patients.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (ΔTBS) and changes in normalized peak count (ΔnPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in ΔTBS, ΔTBS, and ΔTBS (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. -0.049, 0.08 vs. -0.116, and 0.109 vs. -0.123 [ = 0.023, = 0.002, and < 0.001], respectively). ΔnPC showed significant group differences (mean, -0.107 vs. -0.282; = 0.033); ΔnPC and ΔnPC did not reach statistical significance (mean, -0.122 vs. -0.312 and -0.183 vs. -0.405 [ = 0.117 and 0.067], respectively). At the optimal threshold, ΔTBS exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. ΔTBS and ΔTBS reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. ΔnPC, ΔnPC, and ΔnPC showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. ΔTBS and ΔnPC can predict [Lu]Lu-DOTATATE response by the second treatment session.