Endocrine Surgery, Surgical Oncology Program, National Cancer Institute, NIH, Bethesda, Maryland, USA.
Department of Surgical Oncology, Section of Surgical Endocrinology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Endocr Relat Cancer. 2020 Jun;27(6):R145-R161. doi: 10.1530/ERC-19-0372.
Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prognostic factors for risk stratification are limited. This systematic review aims to establish the current state of evidence regarding prognostic factors in MEN1-related NF-pNETs. We systematically searched four databases for studies assessing prognostic value of any factor on NF-pNET progression, development of distant metastases, and/or overall survival. In- and exclusion, critical appraisal and data-extraction were performed independently by two authors according to pre-defined criteria. Thirteen studies (370 unique patients) were included. Prognostic factors investigated were tumor size, timing of surgical resection, WHO grade, methylation, p27/p18 expression by immunohistochemistry (IHC), ARX/PDX1 IHC and alternative lengthening of telomeres. Results were complemented with evidence from studies in MEN1-related pNET for which data could not be separately extracted for NF-pNET and data from sporadic NF-pNET. We found that the most important prognostic factors used in clinical decision making in MEN1-related NF-pNETs are tumor size and grade. NF-pNETs <2 cm may be managed with watchful waiting, while surgical resection is advised for NF-pNETs ≥2 cm. Grade 2 NF-pNETs should be considered high risk. The most promising and MEN1-relevant avenues of prognostic research are multi-analyte circulating biomarkers, tissue-based molecular factors and imaging-based prognostication. Multi-institutional collaboration between clinical, translation and basic scientists with uniform data and biospecimen collection in prospective cohorts should advance the field.
多发性内分泌腺瘤病 1 型（MEN1）患者中，转移性十二指肠胰腺神经内分泌肿瘤（dpNETs）是最重要的与疾病相关的死亡原因。无功能性胰腺神经内分泌肿瘤（NF-pNETs）在 MEN1 中高发且临床表现异质性大。因此，其治疗具有争议性。目前关于预后因素的分层风险评估数据有限。本系统综述旨在评估 MEN1 相关 NF-pNET 中预后因素的现有证据。我们系统性地在四个数据库中检索了评估任何因素对 NF-pNET 进展、远处转移发展和/或总生存的预后价值的研究。根据预先设定的标准，两名作者独立进行了纳入与排除、批判性评价和数据提取。共纳入了 13 项研究（370 例患者）。所研究的预后因素包括肿瘤大小、手术切除时机、世界卫生组织（WHO）分级、甲基化、免疫组织化学（IHC）检测的 p27/p18 表达、ARX/PDX1 IHC 及端粒的非经典延长。结果补充了 MEN1 相关 pNET 研究的数据，这些研究中无法单独提取 NF-pNET 的数据，以及散发性 NF-pNET 的研究数据。我们发现，在 MEN1 相关 NF-pNET 中用于临床决策的最重要的预后因素是肿瘤大小和分级。直径<2cm 的 NF-pNET 可采用密切观察等待，而直径≥2cm 的 NF-pNET 建议行手术切除。2 级 NF-pNET 应被视为高危肿瘤。最有前景且与 MEN1 相关的预后研究途径是多分析物循环生物标志物、组织分子因素和基于影像学的预后预测。临床、转化和基础科学家之间的多机构合作，通过前瞻性队列进行统一的数据和生物样本收集，应能推动该领域的发展。
