ImportanceEvidence-based treatment decisions for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) require individualized patient-centered decision-making that accounts for patient and cancer characteristics.ObjectiveTo create an accessible guidance document to educate clinicians and patients on biomarkers informing prognosis and treatment in unresectable or metastatic GEP-NENs.MethodsA multidisciplinary panel in-person workshop was convened to define methods. English language articles published from January 2016 to January 2023 in PubMed (MEDLINE) and relevant conference abstracts were reviewed to investigate prognostic and treatment-informing features in unresectable or metastatic GEP-NENs. Data from included studies were used to form evidence-based recommendations. Quality of evidence and strength of recommendations were determined using the Grading of Recommendations, Assessment, Development and Evaluations framework. Consensus was reached via electronic survey following a modified Delphi method.FindingsA total of 131 publications were identified, including 8 systematic reviews and meta-analyses, 6 randomized clinical trials, 29 prospective studies, and 88 retrospective cohort studies. After 2 rounds of surveys, 24 recommendations and 5 good clinical practice statements were developed, with full consensus among panelists. Recommendations focused on tumor and functional imaging characteristics, blood-based biomarkers, and carcinoid heart disease. A single strong recommendation was made for symptomatic carcinoid syndrome informing treatment in midgut neuroendocrine tumors. Conditional recommendations were made to use grade, morphology, primary site, and urinary 5-hydroxyindoleacetic levels to inform treatment. The guidance document was endorsed by the Commonwealth Neuroendocrine Tumour Collaboration and the North American Neuroendocrine Tumor Society.Conclusions and RelevanceThe study results suggest that select factors have sufficient evidence to inform care in GEP-NENs, but the evidence for most biomarkers is weak. This article may help guide management and identify gaps for future research to advance personalized medicine and improve outcomes for patients with GEP-NENs.

中文翻译：

---

为不可切除或转移性 GEP-NEN 的预后和治疗提供信息的生物标志物


重要性晚期胃肠胰神经内分泌肿瘤 （GEP-NEN） 的循证治疗决策需要以患者为中心的个体化决策，并考虑患者和癌症特征。目的创建一份可访问的指导文件，以教育临床医生和患者了解生物标志物，为不可切除或转移性 GEP-NENs 的预后和治疗提供信息。回顾了 2016 年 1 月至 2023 年 1 月在 PubMed （MEDLINE） 上发表的英文文章和相关会议摘要，以研究不可切除或转移性 GEP-NEN 的预后和治疗信息特征。纳入研究的数据用于形成循证推荐。使用建议分级、评估、开发和评价框架确定证据质量和建议强度。通过采用改进的 Delphi 方法的电子调查达成共识。结果共确定了 131 篇出版物，包括 8 篇系统评价和荟萃分析、6 篇随机临床试验、29 篇前瞻性研究和 88 篇回顾性队列研究。经过 2 轮调查，制定了 24 条建议和 5 份良好临床实践声明，小组成员完全达成共识。建议侧重于肿瘤和功能成像特征、基于血液的生物标志物和类癌心脏病。对症状性类癌综合征提出了一项强有力的建议，为中肠神经内分泌肿瘤的治疗提供信息。有条件地建议使用分级、形态学、原发部位和尿液 5-羟基吲哚乙酸水平来为治疗提供信息。 该指导文件得到了英联邦神经内分泌肿瘤合作组织和北美神经内分泌肿瘤协会的认可。结论和相关性研究结果表明，选择因素有足够的证据为 GEP-NEN 的护理提供信息，但大多数生物标志物的证据较弱。本文可能有助于指导管理并确定未来研究的差距，以推进个性化医疗并改善 GEP-NENs 患者的预后。