Purpose

Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed.

Patients and methods

We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes.

Results

Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3).

Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative ⁶⁸Gallium(⁶⁸Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (¹⁸FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048).

Conclusion

Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.

中文翻译：

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胃肠胰 3 级神经内分泌肿瘤：单一实体还是异质组？回顾性分析

目的

3 级神经内分泌肿瘤 (NET G3) 是胃肠胰 (GEP) 神经内分泌肿瘤 (NEN) 中的一种新型病理类别，但其临床行为和治疗管理仍然具有挑战性。需要有助于 NET G3 管理的预后和预测因素。

患者和方法

我们对 2015 年至 2020 年所有 Ki-67 > 20%、分化良好的 NET 患者进行了回顾性分析，这些患者在我们的 NEN 专用多学科团队中进行了评估。我们根据 NET G3 诊断时间、放射性示踪剂分布和 Ki-67 对样本进行了划分。我们分析了这些 NET G3 特征与临床结果之间的相关性。

结果

在 3238 份多学科讨论报告中，我们选择了 55 名患者，其中 48 名来自 GEP，7 名来自隐匿性 GEP。在 45 名患者中，NET G3 诊断发生在临床病史开始时（前期-NET G3），而在 10 名患者中，在 NET G1-G2 临床病史期间（晚期-NET G3）。

≤ 30% (34/55) 与 > 30% Ki-67 (21/55) 的患者有更好的总生存期 (OS) ( p  = 0.042)；均质与非均质/阴性⁶⁸镓 ( ⁶⁸ Ga)-DOTA-肽正电子发射断层扫描 (PET)/计算机断层扫描 (CT) 的患者显示出更好的 OS 和显着更好的无进展生存期 (PFS) 的趋势( p  = 0.033)。对于阴性/非均质与均质 18-氟脱氧葡萄糖 ( ¹⁸ FDG)-PET/CT ( p  = 0.027)，观察到更好的 OS。在后期和前期 NET G3 中报告了更好的操作系统的趋势，而后者显示出明显更好的响应率 (RR) ( p  = 0.048)。

结论

我们的研究结果表明，Ki-67 截止、功能成像和 NET G3 诊断时机可能有助于临床医生更准确地选择 NET G3 管理。需要进行前瞻性研究。