von Hessert-Vaudoncourt Claus, Maasberg Sebastian, Begum Nehara, Rinke Anja, Pöppel Thorsten, Sipos Bence, Grohe Christian, Fottner Christian, Stintzing Sebastian, Grabowski Patricia
Department of Hematology, Oncology, and Cancer Immunology (CCM), Charité Universitaetsmedizin Berlin, Berlin, Germany.
Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. George, Hamburg, Germany.
Medicine (Baltimore). 2025 Mar 14;104(11):e41853. doi: 10.1097/MD.0000000000041853.
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare malignancies deriving from the endocrine system in the gastrointestinal tract including the pancreas. Prognosis is greatly heterogenous due to its dependency on various factors, most importantly stage and differentiation. Several studies report an alarming rise in incidence in the past decade. Despite there being some therapeutical options, best therapy sequence still needs to be defined, particularly for unresectable and/or intermediate and high-grade NENs. Peptide receptor radionuclide therapy (PRRT) was approved in Europe and USA in 2017 and 2018, respectively. Studies with real-world systematic data on characteristics and treatment patterns of PRRT-receiving patients was non-existent at the time of this writing. In this retrospective study, we identified within the German NET-Registry 203 patients diagnosed with GEP-NEN having received PRRT from 1995 to 2023. We assessed general clinical patient characteristics, disease-specific characteristics, treatments and outcomes. To obtain a more up-to-date picture of treatment modalities and outcomes, a subgroup of the study population was allocated to the "therapy cohort," defined by patients with date of first diagnosis between 2010 and 2023 (open cohort). Mean age of the study population was 58 years (SD 12 years) with 51.7% being men. Most patients had a WHO performance score of 0 to 1 (41.4% and 50.5%, respectively). Most NEN cases were of small intestine/pancreatic origin (46.3% and 45.3%, respectively) and displayed well/moderate differentiation (55.3%). Ki-67 was generally within the 3% to 20% range (57.92%). Most patients presented with metastasis at diagnosis (73.9%). Somatostatin analogs (SSAs), chemotherapy and surgery were the most common non-PRRT therapy options (65.3%, 60.2%, and 50.0%, respectively). PRRT was most often applied as third- or second-line therapy (42.3% and 36.6%, respectively), usually after surgery and/or SSA treatment. As PRRT had been administered using different regimens, tumor response evaluation showed mixed responses. Given the low sample size and considerable amount of missing response data, no correlation analysis between PRRT sequencing and tumor response could be performed. Overall, the clinical characteristics and treatment patterns tend to follow trends observed in other studies or medical guidelines. Finally, this study presents real-world data that more accurately describes GEP-NEN disease in Germany and treatment modalities after PRRT's approval.
胃肠胰神经内分泌肿瘤（GEP-NENs）是起源于包括胰腺在内的胃肠道内分泌系统的罕见恶性肿瘤。由于其预后取决于多种因素，最重要的是分期和分化程度，因此预后差异很大。几项研究报告称，在过去十年中其发病率惊人地上升。尽管有一些治疗选择，但最佳治疗顺序仍有待确定，特别是对于不可切除和/或中高分级的神经内分泌肿瘤。肽受体放射性核素治疗（PRRT）分别于2017年和2018年在欧洲和美国获得批准。在撰写本文时，尚无关于接受PRRT治疗患者的特征和治疗模式的真实世界系统数据的研究。在这项回顾性研究中，我们在德国神经内分泌肿瘤登记处确定了203例在1995年至2023年期间被诊断为GEP-NEN并接受PRRT治疗的患者。我们评估了患者的一般临床特征、疾病特异性特征、治疗方法和治疗结果。为了更全面地了解治疗方式和结果，将研究人群中的一个亚组分配到“治疗队列”，该队列由首次诊断日期在2010年至2023年之间的患者定义（开放队列）。研究人群的平均年龄为58岁（标准差12岁），男性占51.7%。大多数患者的世界卫生组织体能状态评分为0至1（分别为41.4%和50.5%）。大多数神经内分泌肿瘤病例起源于小肠/胰腺（分别为46.3%和45.3%），并表现为高/中分化（55.3%）。Ki-67通常在3%至20%的范围内（57.92%）。大多数患者在诊断时出现转移（73.9%）。生长抑素类似物（SSAs）、化疗和手术是最常见的非PRRT治疗选择（分别为65.3%、60.2%和50.0%）。PRRT最常作为三线或二线治疗应用（分别为42.3%和36.6%），通常在手术和/或SSA治疗之后。由于PRRT采用了不同的治疗方案，肿瘤反应评估显示反应不一。鉴于样本量较小且有大量缺失的反应数据，无法进行PRRT治疗顺序与肿瘤反应之间的相关性分析。总体而言，临床特征和治疗模式倾向于遵循其他研究或医学指南中观察到的趋势。最后，本研究提供了真实世界的数据，更准确地描述了德国的GEP-NEN疾病以及PRRT获批后的治疗方式。
