Klein Haneveld Mirthe J, van Treijen Mark J C, Pieterman Carolina R C, Dekkers Olaf M, van de Ven Annenienke, de Herder Wouter W, Zandee Wouter T, Drent Madeleine L, Bisschop Peter H, Havekes Bas, Vriens Menno R, Verrijn Stuart Annemarie A, Valk Gerlof D, van Leeuwaarde Rachel S
Department of Endocrine Oncology, University Medical Centre Utrecht, 3584 CX, Utrecht, the Netherlands.
Department of Surgical Oncology, Section of Surgical Endocrinology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
J Clin Endocrinol Metab. 2021 Nov 19;106(12):3515-3525. doi: 10.1210/clinem/dgab569.
Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate.
The aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients.
Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease.
Five of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively.
Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.
无功能性胰腺神经内分泌肿瘤（NF-pNETs）非常普遍，是1型多发性内分泌腺瘤病（MEN1）患者死亡的重要原因。然而，启动pNETs筛查的最佳年龄仍存在争议。
本研究旨在评估年轻MEN1患者中临床相关NF-pNETs的发病年龄。
从荷兰MEN研究组数据库中检索MEN1患者的胰腺影像学数据。采用区间删失生存方法描述年龄相关的外显率，比较生存曲线，并建立参数模型以估计不同年龄发生临床相关NF-pNET的风险。主要目的是评估临床相关NF-pNET（大小≥20mm或快速生长）的发病年龄；次要目的是评估任何大小的NF-pNET和pNET相关转移疾病的发病年龄。
350例患者中有5例在18岁之前发生了临床相关的NF-pNETs，其中2例随后发生了淋巴结转移。在性别、时间框架、MEN1诊断类型或基因型方面，未发现临床相关NF-pNET-free生存率存在差异。发生临床相关肿瘤的风险为1%、2.5%和5%时，估计年龄（中位数，95%CI）分别为9.5（6.5-12.7）、13.5（10.2-16.9）和17.8岁（14.3-21.4）。
基于人群的队列分析表明，13至14岁开始通过胰腺影像学监测NF-pNETs是合理的。应考虑在年轻时进行筛查所带来的心理和医疗负担。
