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Abstract：
Purpose: This study aims to elucidate the role of quantitative SSTR-PET metrics and clinicopathological biomarkers in the progression-free survival (PFS) and overall survival (OS) of neuroendocrine tumors (NETs) treated with peptide receptor radionuclide therapy (PRRT). Methods: A retrospective analysis including 91 NET patients (M47/F44; age 66 years, range 34-90 years) who completed four cycles of standard 177Lu-DOTATATE was conducted. SSTR-avid tumors were segmented from pretherapy SSTR-PET images using a semiautomatic workflow with the tumors labeled based on the anatomical regions. Multiple image-based features including total and organ-specific tumor volume and SSTR density along with clinicopathological biomarkers including Ki-67, chromogranin A (CgA) and alkaline phosphatase (ALP) were analyzed with respect to the PRRT response. Results: The median OS was 39.4 months (95% CI: 33.1-NA months), while the median PFS was 23.9 months (95% CI: 19.3-32.4 months). Total SSTR-avid tumor volume (HR = 3.6; P = 0.07) and bone tumor volume (HR = 1.5; P = 0.003) were associated with shorter OS. Also, total tumor volume (HR = 4.3; P = 0.01), liver tumor volume (HR = 1.8; P = 0.05) and bone tumor volume (HR = 1.4; P = 0.01) were associated with shorter PFS. Furthermore, the presence of large lesion volume with low SSTR uptake was correlated with worse OS (HR = 1.4; P = 0.03) and PFS (HR = 1.5; P = 0.003). Among the biomarkers, elevated baseline CgA and ALP showed a negative association with both OS (CgA: HR = 4.9; P = 0.003, ALP: HR = 52.6; P = 0.004) and PFS (CgA: HR = 4.2; P = 0.002, ALP: HR = 9.4; P = 0.06). Similarly, number of prior systemic treatments was associated with shorter OS (HR = 1.4; P = 0.003) and PFS (HR = 1.2; P = 0.05). Additionally, tumors originating from the midgut primary site demonstrated longer PFS, compared to the pancreas (HR = 1.6; P = 0.16), and those categorized as unknown primary (HR = 3.0; P = 0.002). Conclusion: Image-based features such as SSTR-avid tumor volume, bone tumor involvement, and the presence of large tumors with low SSTR expression demonstrated significant predictive value for PFS, suggesting potential clinical utility in NETs management. Moreover, elevated CgA and ALP, along with an increased number of prior systemic treatments, emerged as significant factors associated with worse PRRT outcomes.
摘要：
目的：本研究旨在阐明定量SSTR-PET指标和临床病理生物标志物在接受肽受体放射性核素治疗（PRRT）的神经内分泌肿瘤（NETs）的无进展生存期（PFS）和总生存期（OS）中的作用。方法:回顾性分析91例NET患者(M47/F44；年龄66岁，范围34-90年），谁完成了四个周期的标准177Lu-DOTATATE进行。使用半自动工作流程从治疗前SSTR-PET图像中分割出SSTR-狂热肿瘤，并根据解剖区域标记肿瘤。针对PRRT反应分析了多种基于图像的特征，包括总的和器官特异性的肿瘤体积和SSTR密度以及临床病理生物标志物，包括Ki-67，嗜铬粒蛋白A（CgA）和碱性磷酸酶（ALP）。结果:中位OS为39.4个月(95%CI:33.1-NA个月),而中位PFS为23.9个月(95%CI:19.3-32.4个月).SSTR总肿瘤体积（HR=3.6；P=0.07）和骨肿瘤体积（HR=1.5；P=0.003）与较短的OS相关。此外，肿瘤总体积（HR=4.3；P=0.01），肝肿瘤体积（HR=1.8;P=0.05）和骨肿瘤体积（HR=1.4;P=0.01）与较短的PFS相关。此外，SSTR摄取低的大病灶体积与OS(HR=1.4;P=0.03)和PFS(HR=1.5;P=0.003)相关.在生物标志物中，基线CgA和ALP升高与OS(CgA:HR=4.9;P=0.003,ALP:HR=52.6;P=0.004)和PFS(CgA:HR=4.2;P=0.002,ALP:HR=9.4;P=0.06)均呈负相关.同样，既往系统治疗次数与较短的OS(HR=1.4;P=0.003)和PFS(HR=1.2;P=0.05)相关.此外,源自中肠原发部位的肿瘤显示出更长的PFS，与胰腺相比（HR=1.6；P=0.16），和那些分类为未知的原发性（HR=3.0；P=0.002）。结论：基于图像的特征，如SSTR-avid肿瘤体积，骨肿瘤受累，并且具有低SSTR表达的大肿瘤的存在证明了PFS的显着预测价值，提示NETs管理中潜在的临床效用。此外，CGA和ALP升高，随着先前系统治疗的数量增加，成为与PRRT结果较差相关的重要因素。
