Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
ENETS Neuroendocrine Tumor Center of Excellence, Rigshospitalet, Copenhagen, Denmark.
J Nucl Med. 2020 Oct;61(10):1491-1497. doi: 10.2967/jnumed.119.240143. Epub 2020 Feb 28.
Overexpression of somatostatin receptors (SSTRs) in patients with neuroendocrine neoplasms (NENs) is used for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Noninvasive visualization and quantification of SSTR density is possible by SSTR imaging (SRI) using PET. Recently, we introduced Cu-DOTATATE for SRI, and we hypothesized that uptake of this tracer could be associated with overall survival (OS) and progression-free survival (PFS). We evaluated patients with NENs who underwent Cu-DOTATATE PET/CT SRI in 2 prospective studies. Tracer uptake was determined as the maximal SUV (SUV) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of Cu-DOTATATE SUV for OS and PFS. Specificity, sensitivity, and accuracy were calculated for prediction of outcome at 24 mo after Cu-DOTATATE PET/CT. In total, 128 patients with NENs were included and followed for a median of 73 mo (range, 1-112 mo). During follow-up, 112 experienced disease progression, and 69 died. The optimal cutoff for Cu-DOTATATE SUV was 43.3 for prediction of PFS, with a hazard ratio of 0.56 (95% confidence interval, 0.38-0.84) for patients with an SUV of more than 43.3. However, no significant cutoff was found for prediction of OS. In multiple Cox regression adjusted for age, sex, primary tumor site, and tumor grade, the SUV cutoff hazard ratio was 0.50 (range, 0.32-0.77) for PFS. The accuracy was moderate for predicting PFS (57%) at 24 mo after Cu-DOTATATE PET/CT. In this first study to report the association of Cu-DOTATATE PET/CT and outcome in patients with NENs, tumor SSTR density as visualized with Cu-DOTATATE PET/CT was prognostic for PFS but not OS. However, the accuracy of prediction of PFS at 24 mo after Cu-DOTATATE PET/CT SRI was moderate, limiting the value on an individual-patient basis.
在神经内分泌肿瘤 (NENs) 患者中，生长抑素受体 (SSTR) 的过度表达既用于诊断，也用于治疗。受体密度可能反映肿瘤分化程度，因此与预后相关。SSTR 成像 (SRI) 使用 PET 可以实现 SSTR 密度的非侵入性可视化和定量。最近，我们引入了 Cu-DOTATATE 用于 SRI，我们假设这种示踪剂的摄取与总生存期 (OS) 和无进展生存期 (PFS) 相关。我们在 2 项前瞻性研究中评估了接受 Cu-DOTATATE PET/CT SRI 的 NEN 患者。每个患者的最大 SUV (SUV) 用于确定示踪剂摄取。使用对数秩检验进行 Kaplan-Meier 分析以确定 Cu-DOTATATE SUV 对 OS 和 PFS 的预测价值。计算了特异性、敏感性和准确性，以预测 Cu-DOTATATE PET/CT 后 24 个月的结果。共有 128 名 NEN 患者入组，中位随访时间为 73 个月（范围为 1-112 个月）。随访期间，112 例患者出现疾病进展，69 例患者死亡。预测 PFS 的最佳 Cu-DOTATATE SUV 截断值为 43.3，SUV 大于 43.3 的患者的风险比为 0.56（95%置信区间，0.38-0.84）。然而，未发现预测 OS 的显著截断值。在调整年龄、性别、原发肿瘤部位和肿瘤分级的多 Cox 回归中，SUV 截断值的风险比为 0.50（范围为 0.32-0.77）用于预测 PFS。在接受 Cu-DOTATATE PET/CT 后 24 个月预测 PFS 的准确性为 57%，属于中度。在这项首次报道 NEN 患者 Cu-DOTATATE PET/CT 与预后关联的研究中，Cu-DOTATATE PET/CT 显示的肿瘤 SSTR 密度与 PFS 相关，但与 OS 无关。然而，Cu-DOTATATE PET/CT SRI 后 24 个月预测 PFS 的准确性为中度，限制了其在个体患者中的价值。
