Department of Medicine, Stanford University School of Medicine, Stanford, California.
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University School of Medicine, Stanford, California; and.
J Nucl Med. 2019 Jul;60(7):882-891. doi: 10.2967/jnumed.118.217851. Epub 2019 Mar 8.
The diagnosis and subsequent therapy of neuroendocrine neoplasms (NENs) have long relied on somatostatin receptor (SSTR) expression. The field of theranostics now uses newer SSTR-based PET imaging with Ga-DOTATATE or Ga-DOTATOC as a prerequisite for the administration of peptide receptor radionuclide therapy (PRRT). In the United States, Food and Drug Administration approval of Lu-DOTATATE, a form of PRRT, in 2018 for use in gastroenteropancreatic NENs was obtained on the basis of prolonged progression-free survival versus high-dose octreotide long-acting release in a phase III clinical trial of well-differentiated midgut NENs. Well-differentiated grade 1 and grade 2 NENs have a low proliferation index (Ki-67 < 20%) and longer overall survival (>10 y), whereas higher-grade (grade 3 [G3]) NENs have a high Ki-67 (>20%) and shorter overall survival (<1 y). Here, we present a review on the role of SSTR-based imaging and PRRT in G3 NENs, including a discussion of well-differentiated G3 NENs, the newest histologic classification. Some studies suggest that G3 NENs are less likely to be positive on SSTR-based imaging (but more likely on F-FDG PET) than are well-differentiated NENs, but these data are limited. We found only 13 studies mentioning the use of PRRT in G3 NENs and a total of only 151 patients across these studies in whom radiologic response was measured. Of these 151 patients, 99 (66%) demonstrated at least stable disease or a partial response, indicating that some G3 NENs can be responsive to PRRT. We suggest that patients with G3 NENs should receive both F-FDG PET and SSTR-based imaging to aid in both diagnosis and treatment selection, as positivity on SSTR-based imaging helps with patient identification for PRRT and discordance may suggest important clues to tumor biology and prognosis. However, prospective studies are needed to fully understand the role of PRRT in G3 NENs, especially in well- versus poorly differentiated G3 disease.
神经内分泌肿瘤（NENs）的诊断和随后的治疗长期依赖于生长抑素受体（SSTR）的表达。在治疗诊断学领域，现在使用新的基于 SSTR 的 Ga-DOTATATE 或 Ga-DOTATOC PET 成像作为肽受体放射性核素治疗（PRRT）的给药前提。在美国，基于 Lu-DOTATATE（一种 PRRT 形式）在 III 期临床试验中与高剂量奥曲肽长效释放相比可延长无进展生存期，于 2018 年获得了美国食品和药物管理局批准，用于治疗胃肠胰神经内分泌肿瘤。分化良好的中肠神经内分泌肿瘤的低增殖指数（Ki-67<20%）和较长的总生存期（>10 年），而高级别（G3）NENs 的 Ki-67 较高（>20%），总生存期较短（<1 年）。在这里，我们回顾了基于 SSTR 的成像和 PRRT 在 G3 NENs 中的作用，包括对分化良好的 G3 NENs 的讨论，这是最新的组织学分类。一些研究表明，与分化良好的 NENs 相比，G3 NENs 基于 SSTR 的成像（但更可能基于 F-FDG PET）阳性的可能性较低，但这些数据有限。我们仅发现 13 项研究提到了 G3 NENs 中 PRRT 的使用，并且在这些研究中，总共只有 151 名患者的放射学反应得到了测量。在这 151 名患者中，99 名（66%）至少表现为稳定疾病或部分缓解，这表明一些 G3 NENs 可以对 PRRT 有反应。我们建议 G3 NENs 患者应同时接受 F-FDG PET 和基于 SSTR 的成像，以辅助诊断和治疗选择，因为基于 SSTR 的成像阳性有助于识别适合 PRRT 的患者，而不一致可能提示肿瘤生物学和预后的重要线索。然而，需要前瞻性研究来充分了解 PRRT 在 G3 NENs 中的作用，特别是在分化良好的 G3 疾病与分化不良的 G3 疾病之间的作用。
