The prognosis of high-grade gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is highly variable and reported median overall survival remains low. There is no established standard of care for patients with higher grade 2 (G2) (Ki-67 ≥ 10% and ≤ 20%) and grade 3 (G3) (Ki-67 ≥ 20% and ≤ 55%) GEP-NETs and most of the current treatment regimens, particularly for G3 NETs, are extrapolated from lower-grade GEP-NET treatments or based on data from small retrospective studies. Robust evidence to support treatment recommendations for high-grade NETs, especially in the first-line (1L) setting, is limited and the optimal treatment sequence has not been clearly defined. This review summarizes the latest literature on sequencing of therapies, identifies patient selection considerations for utilizing peptide receptor radionuclide therapy (PRRT), and offers data-driven expert opinions and clinical practice recommendations in high-grade GEP-NETs. As authors, we recommend that all patients with well-differentiated, higher G2 and G3 NETs are evaluated with [68Ga]Ga-DOTA-peptide positron emission tomography (PET) for baseline somatostatin receptor expression and if positive, a 1L treatment option of PRRT should be considered, especially in clinically stable patients. Somatostatin analog therapy may benefit patients with low-volume, indolent disease, and chemotherapy is usually a better fit for patients in visceral crisis, in need of urgent treatment, or with no access to [68Ga]Ga-DOTA-peptide PET. In complex cases, a robust discussion at a multidisciplinary NET tumor board can be beneficial.
高级别胃肠胰神经内分泌肿瘤（GEP-NETs）的预后差异显著，已报道的中位总生存期仍然较低。对于较高级别2级（G2）（Ki-67 ≥ 10% 且 ≤ 20%）和3级（G3）（Ki-67 ≥ 20% 且 ≤ 55%）的GEP-NETs患者，目前尚无既定的标准治疗方案，且现有治疗方案大多从低级别GEP-NETs的治疗中推演而来，或基于小型回顾性研究的数据，尤其对于G3级NETs。支持高级别NETs治疗建议的坚实证据有限，尤其在一线（1L）治疗背景下，最佳治疗顺序尚未明确界定。本文综述总结了关于治疗顺序的最新文献，明确了使用肽受体放射性核素治疗（PRRT）的患者选择考量，并为高级别GEP-NETs提供了数据驱动的专家意见和临床实践建议。作为作者，我们建议所有分化良好、较高级别的G2和G3 NETs患者均应接受[68Ga]Ga-DOTA-肽正电子发射断层扫描（PET）以评估基线生长抑素受体表达情况；若结果为阳性，应考虑将PRRT作为一线治疗选择，尤其对于临床病情稳定的患者。生长抑素类似物治疗可能对低肿瘤负荷、惰性疾病的患者有益，而化疗通常更适合处于内脏危象、需要紧急治疗或无法进行[68Ga]Ga-DOTA-肽PET检查的患者。对于复杂病例，在多学科NET肿瘤委员会进行深入讨论可能有益。
肿瘤(癌症)患者之家