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 (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. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in ΔTBS_second-first, ΔTBS_third-first, and ΔTBS_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. −0.049, 0.08 vs. −0.116, and 0.109 vs. −0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). ΔnPC_second-first showed significant group differences (mean, −0.107 vs. −0.282; P = 0.033); ΔnPC_third-first and ΔnPC_fourth-first did not reach statistical significance (mean, −0.122 vs. −0.312 and −0.183 vs. −0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, ΔTBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. ΔTBS_second-first and ΔTBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. ΔnPC_second-first, ΔnPC_third-first, and ΔnPC_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: ΔTBS and ΔnPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.