Quantitative SPECT/CT Metrics in Early Prediction of [¹⁷⁷Lu]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 [¹⁷⁷Lu]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. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [¹⁷⁷Lu]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 (∆TBS) and changes in normalized peak count (∆nPC) 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. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in ∆TBS_second-first, ∆TBS_third-first, and ∆TBS_fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [¹⁷⁷Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. 20.049, 0.08 vs. 20.116, and 0.109 vs. 20.123 [P 5 0.023, P 5 0.002, and P, 0.001], respectively). ∆nPC_second-first showed significant group differences (mean, 20.107 vs. 20.282; P 5 0.033); ∆nPC_third-first and ∆nPC_fourth-first did not reach statistical significance (mean, 20.122 vs. 20.312 and 20.183 vs. 20.405 [P 5 0.117 and 0.067], respectively). At the optimal threshold, ∆TBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. ∆TBS_second-first and ∆TBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. ∆nPC_second-first, ∆nPC_third-first, and ∆nPC_fourth-first 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. Conclusion: ∆TBS and ∆nPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.