Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota.
Nuclear Medicine Division, Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota.
J Nucl Med. 2024 Oct 1;65(10):1584-1590. doi: 10.2967/jnumed.124.267964.
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.
我们的目的是探索用于预测接受 [Lu]Lu-DOTATATE 治疗的胃肠胰腺神经内分泌肿瘤（GEP-NETs）患者治疗反应的定量成像标志物。这样做可以使我们能够及时切换到更有效的治疗方法，从而避免时间和资源的浪费，并最大限度地减少毒性。
回顾性选择了接受 4 次 [Lu]Lu-DOTATATE 治疗的无法切除或转移性、进展性、高分化、受体阳性的 GEP-NETs 患者。使用治疗结束时的 SPECT/CT 图像，我们计算了所有可见肿瘤的最大直径，以计算肿瘤负担评分（TBS）。选择了最多 4 个靶病变并进行半自动分割。测量了靶病变峰计数和脾脏峰计数，并计算了归一化峰计数。计算了整个治疗过程中 TBS（ΔTBS）和归一化峰计数（ΔnPC）相对于第一次治疗的变化。使用第三个月的 CT 评估治疗反应，并将其分为进展性疾病（PD）或非 PD。
共纳入 27 例患者（7 例 PD，20 例非 PD）。PD 组和非 PD 组之间的 ΔTBS、ΔTBS 和 ΔTBS（其中第二次-第一次、第三次-第一次和第四次-第一次表示第二次和第一次、第三次和第一次、第四次和第一次 [Lu]Lu-DOTATATE 治疗周期之间的扫描次数）之间存在显著差异（中位数分别为 0.043 比-0.049、0.08 比-0.116 和 0.109 比-0.123[ = 0.023， = 0.002，<0.001]）。ΔnPC 显示出显著的组间差异（平均值，-0.107 比-0.282； = 0.033）；ΔnPC 和 ΔnPC 未达到统计学意义（平均值，-0.122 比-0.312 和-0.183 比-0.405[ = 0.117 和 0.067]）。在最佳阈值下，ΔTBS 的曲线下面积（AUC）为 0.957，达到 100%的灵敏度和 80%的特异性。ΔTBS 和 ΔTBS 的 AUC 分别为 0.793 和 0.893，灵敏度分别为 71.4%和 85%，特异性分别为 85%和 95%。ΔnPC、ΔnPC 和 ΔnPC 的 AUC 分别为 0.764、0.693 和 0.679；灵敏度分别为 71.4%、71.4%和 100%；特异性分别为 75%、70%和 35%。
ΔTBS 和 ΔnPC 可以在第二次治疗时预测 [Lu]Lu-DOTATATE 的反应。
