小肠神经内分泌肿瘤（Si-NET）通常被研究为一组均匀的群体。增殖指数Ki-67影响预后并确定肿瘤等级。我们假设，与G1肿瘤相比，Ki-67较高的Si-NET二级（G2）肿瘤可能不那么适合已建立的治疗转移性疾病。我们对212名在瑞典两家医院接受治疗的Si-NET G2患者进行了回顾性队列研究，时间跨度为20年（2000-2019年）。首次生长抑素类似物（SSA）治疗的中位癌特异性生存期为77个月。单一用药的SSA给药的中位进展无病生存期（PFS）为12.4个月，而所有接受第一线SSA治疗的患者的中位PFS为19个月。对于放射学进展患者，SSA剂量升级后的PFS为6个月。在Ki-67为3-5％、5-10％和10-20％的患者中单独研究了SSA和肽受体放射性核素治疗（PRRT）的治疗效果。对于SSA，更高的Ki-67水平PFS显著缩短（分别为31、18和10个月），而PRRT的PFS只有小差别（分别是29、25和25个月）。连续用干扰素-α（IFNα），依维莫司和化疗的中位PFS为6、5和9个月。IFNα似乎对生长抑素受体表达较低的肿瘤有效。总之，尽管其增殖指数比G1肿瘤高，已建立的治疗方法似乎在Si-NET G2中有效。然而，SSA的疗效在较高的Ki-67水平下减少，但PRRT的疗效则只有小幅下降。SSA剂量升级提供了有限的疾病稳定。

Small intestinal neuroendocrine tumours (Si-NET) are often studied as a uniform group. Proliferation index Ki-67 influences prognosis and determines tumour grade. We hypothesized that Si-NET grade 2 (G2) tumours, which have a higher Ki-67 than G1 tumours, might benefit less from established treatments for metastatic disease. We conducted a retrospective cohort study of 212 patients with metastatic Si-NET G2 treated in two Swedish hospitals during 20 years (2000-2019). Median cancer-specific survival on first-line somatostatin analogues (SSA) was 77 months. Median progression-free survival (PFS) was 12.4 months when SSA was given as monotherapy and 19 months for all patients receiving first-line SSA. PFS after SSA dose escalation was 6 months in patients with radiological progression. Treatment efficacies of SSA and peptide receptor radionuclide treatment (PRRT) were studied separately in patients with Ki-67 of 3-5%, 5-10% and 10-20%. For SSA, PFS was significantly shorter at higher Ki-67 levels (31, 18 and 10 months, respectively), while there was only a minor difference in PFS for PRRT (29, 25 and 25 months). Median PFS for sequential treatment with interferon-alpha (IFNα), everolimus and chemotherapy was 6, 5 and 9 months. IFNα seemed to be effective in tumours with low somatostatin-receptor expression. In conclusion, established treatments appeared effective in Si-NET G2, despite their higher proliferation index compared to G1 tumours. However, efficacy of SSA but not PRRT was reduced at higher Ki-67 levels. SSA dose escalation provided limited disease stabilization.