Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK.
Department of Oncology, UCL Cancer Institute, University College London, London, UK.
J Clin Endocrinol Metab. 2021 Mar 8;106(3):872-882. doi: 10.1210/clinem/dgaa822.
Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined.
This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs.
CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death.
The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P < .01) for PanNETs and 5.88 (P < .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P < .03) and 5.09 (P < .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P < .01), whereas 2 or greater CTCs had an HR of 2.25 (P < .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P < .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P < .06).
The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.
循环肿瘤细胞（CTCs）在神经内分泌肿瘤（NETs）患者中可检测到，是准确的预后标志物，尽管最佳阈值尚未确定。
本研究旨在确定胰腺（PanNET）（90 例）和中肠 NETs（109 例）中转移性 PanNET 和中肠 NET 中最佳的 CTC 预后阈值。
使用 CellSearch 对 199 例转移性胰腺（PanNET）（90 例）或中肠 NETs（109 例）患者进行 CTC 计数。对患者进行了至少 3 年的无进展生存期（PFS）和总生存期（OS）随访，直至死亡。
PanNET 和中肠 NETs 中 12 个月时进展的受试者工作特征曲线（ROC）下面积（AUROC）确定最佳 CTC 阈值分别为 1 个或更多和 2 个或更多。在多变量逻辑回归分析中，这些阈值可预测 12 个月的进展，比值比（OR）分别为 6.69（P<0.01）和 5.88（P<0.003）。在 PanNET 和中肠 NETs 中，发现相同的阈值对于预测 36 个月的死亡也是最佳的，比值比（OR）分别为 2.87（P<0.03）和 5.09（P<0.005）。在 PanNET 中用于 PFS 的多变量 Cox 风险回归分析中，1 个或更多 CTC 的风险比（HR）为 2.6（P<0.01），而 2 个或更多 CTC 的 HR 为 2.25（P<0.01）。在 PanNET 中用于 OS 的多变量分析中，1 个或更多 CTC 的 HR 为 3.16（P<0.01），在中肠 NETs 中，2 个或更多 CTC 的 HR 为 1.73（P<0.06）。
预测转移性 PanNET 和中肠 NET 的 PFS 和 OS 的最佳 CTC 阈值分别为 1 和 2。这些阈值可用于临床实践和临床试验中对患者进行分层。
