Patients with neuroendocrine neoplasms (NENs) have heterogeneous somatostatin receptor expression, with highly differentiated lesions having higher expression. Receptor expression of the total tumor burden may be visualized by somatostatin receptor imaging, such as with ⁶⁴Cu-DOTATATE PET/CT. Assessment of maximal lesion uptake is associated with progression-free survival (PFS) but not overall survival (OS). We hypothesized that the lesion with the lowest, rather than the highest, ⁶⁴Cu-DOTATATE uptake would be more prognostic, and we developed a semiautomatic method for evaluating this hypothesis. Methods: Patients with NENs underwent ⁶⁴Cu-DOTATATE PET/CT. A standardized semiautomatic tumor delineation method was developed and used to identify the lesion with the lowest uptake, that is, with the lowest SUV_mean. Additionally, we assessed total tumor volume derived from the semiautomatic tumor delineation. Kaplan–Meier and Cox regression analyses were used to determine whether there was any association with OS and PFS. Results: In 116 patients with NENs, median PFS (95% CI) was 23 mo (range, 20–31 mo) and median OS was 85 mo (range, 68–113 mo). Minimum SUV_mean and total tumor volume were significantly associated with PFS and OS in univariate Cox regression analyses, whereas SUV_max was significant only for PFS. In multivariate Cox analyses, both minimum SUV_mean and total tumor volume remained statistically significant. Minimum SUV_mean and total tumor volume were then dichotomized by their median, and patients were categorized into 4 groups: high or low total tumor volume and high or low minimum SUV_mean. Patients with a low total tumor volume and high minimum SUV_mean had a hazard ratio of 0.32 (95% CI, 0.20–0.51) for PFS and 0.24 (95% CI, 0.13–0.43) for OS, both with P values of less than 0.001 (reference: high total tumor volume and low minimum SUV_mean). Conclusion: We propose a standardized semiautomatic tumor delineation method to identify the lesion with the lowest ⁶⁴Cu-DOTATATE uptake and total tumor volume. Assessment of the lowest, rather than the highest, lesion uptake greatly increases prognostication by ⁶⁴Cu-DOTATATE PET/CT. Combining lesion uptake and total tumor volume, we derived a novel prognostic classification system for patients with NENs.

神经内分泌肿瘤（NEN）患者的生长抑素受体表达存在异质性，高度分化的病灶表达较高。总肿瘤负荷的受体表达可以通过生长抑素受体成像可视化，例如使用⁶⁴ Cu-DOTATATE PET/CT。最大病变吸收的评估与无进展生存期 (PFS) 相关，但与总生存期 (OS) 无关。我们假设⁶⁴ Cu-DOTATATE 摄取量最低而非最高的病变预后更好，我们开发了一种半自动方法来评估这一假设。方法： NEN 患者接受⁶⁴ Cu-DOTATATE PET/CT。开发了一种标准化的半自动肿瘤勾画方法，并用于识别摄取最低的病变，即具有最低 SUV_{平均值的病变}。此外，我们还评估了半自动肿瘤勾画得出的总肿瘤体积。 Kaplan-Meier 和 Cox 回归分析用于确定是否与 OS 和 PFS 存在任何关联。结果：在 116 名 NEN 患者中，中位 PFS (95% CI) 为 23 个月（范围，20-31 个月），中位 OS 为 85 个月（范围，68-113 个月）。在单变量 Cox 回归分析中，最小 SUV_平均值和总肿瘤体积与 PFS 和 OS 显着相关，而 SUV _max仅与 PFS 显着相关。在多变量 Cox 分析中，最小 SUV_平均值和总肿瘤体积仍然具有统计学意义。 然后将最小 SUV_平均值和总肿瘤体积按中位数二分，将患者分为 4 组：总肿瘤体积高或低以及最小 SUV_平均值高或低。肿瘤总体积较低且最小 SUV_平均值较高的患者，PFS 的风险比为 0.32（95% CI，0.20-0.51），OS 的风险比为 0.24（95% CI，0.13-0.43），两者的P值均小于0.001（参考：总肿瘤体积高，最小 SUV_平均值低）。结论：我们提出了一种标准化的半自动肿瘤勾画方法来识别⁶⁴ Cu-DOTATATE 摄取和总肿瘤体积最低的病灶。对最低而非最高病变摄取的评估可大大提高⁶⁴ Cu-DOTATATE PET/CT 的预后。结合病灶吸收和肿瘤总体积，我们得出了 NEN 患者的新预后分类系统。