Tirosh Amit, Papadakis Georgios Z, Millo Corina, Hammoud Dima, Sadowski Samira M, Herscovitch Peter, Pacak Karel, Marx Stephen J, Yang Lily, Nockel Pavel, Shell Jasmine, Green Patience, Keutgen Xavier M, Patel Dhaval, Nilubol Naris, Kebebew Electron
Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Sackler Faculty of Medicine, Tel Aviv University, Israel.
PET Imaging Center, National Institutes of Health Clinical Center, Bethesda, Maryland; Institute of Computer Science (ICS), Foundation for Research and Technology Hellas (FORTH), Crete, Greece.
Gastroenterology. 2018 Mar;154(4):998-1008.e1. doi: 10.1053/j.gastro.2017.11.008. Epub 2017 Nov 16.
BACKGROUND & AIMS: Survival times vary among patients with neuroendocrine tumors (NETs) - even among those with the same site, stage, and grade of primary tumor. This makes it difficult to select treatment for patients with unresectable NETs because some patients can survive decades without treatment. Gallium-DOTATATE positron emission tomography with computed tomography (Ga-DOTATATE PET/CT) is a sensitive imaging technique for detection of NETs. We investigated the prognostic accuracy of Ga-DOTATATE PET/CT-based analysis of tumor volume in patients with NETs.
We performed a prospective study of 184 patients with NETs (128 [69.6%] with metastases and 11 patients [6.0%] with locally advanced disease) at the National Institutes of Health Clinical Center (Bethesda, MD) from 2013 through 2017. All patients underwent Ga-DOTATATE PET/CT image analysis and total Ga-DOTATATE-Avid tumor volume (Ga-DOTATATE TV) was determined. We also measured fasting serum chromogranin A, neuron-specific enolase, gastrin, glucagon, vasoactive intestinal peptide, pancreatic polypeptide, and 24-hour urinary 5-hydroxyindoleacetic acid levels in all patients. Disease progression was defined as a new lesion or a growth of a known lesion during the interval between baseline Ga-DOTATATE PET/CT scan and follow-up imaging (14.0 ± 6.1 months; range, 1-35 months). The primary outcomes were progression-free survival (PFS) and disease-specific mortality during a median follow-up time of 18 months (range, 4-35 months).
We found an inverse correlation between quartiles of Ga-DOTATATE TV and PFS (P = .001) and disease-specific survival (P = .002). A Ga-DOTATATE TV of 7.0 mL or more was associated with higher odds of disease progression (hazard ratio, 3.0; P = .04). A Ga-DOTATATE TV of 35.8 mL or more was associated with increased risk of disease-specific death (hazard ratio, 10.6) in multivariable analysis (P = .01), as well as in subgroup analysis of patients with pancreatic NETs.
In a prospective study, we demonstrated the prognostic utility of Ga-DOTATATE TV in a large cohort of patients with NETs, in terms of PFS and disease-specific mortality.
神经内分泌肿瘤(NETs)患者的生存时间各不相同,即使是那些原发性肿瘤部位、分期和分级相同的患者也是如此。这使得为无法切除的NETs患者选择治疗方案变得困难,因为有些患者未经治疗也能存活数十年。镓[68Ga] DOTATATE正电子发射断层扫描联合计算机断层扫描(Ga-DOTATATE PET/CT)是一种检测NETs的敏感成像技术。我们研究了基于Ga-DOTATATE PET/CT分析肿瘤体积对NETs患者的预后准确性。
2013年至2017年,我们在美国国立卫生研究院临床中心(马里兰州贝塞斯达)对184例NETs患者进行了一项前瞻性研究(128例[69.6%]有转移,11例[6.0%]有局部晚期疾病)。所有患者均接受Ga-DOTATATE PET/CT图像分析,并确定总的Ga-DOTATATE摄取肿瘤体积(Ga-DOTATATE TV)。我们还测量了所有患者的空腹血清嗜铬粒蛋白A、神经元特异性烯醇化酶、胃泌素、胰高血糖素、血管活性肠肽、胰多肽以及24小时尿5-羟吲哚乙酸水平。疾病进展定义为在基线Ga-DOTATATE PET/CT扫描与随访成像之间的间隔期内出现新病灶或已知病灶增大(14.0±6.1个月;范围1 - 35个月)。主要结局是在中位随访时间18个月(范围4 - 35个月)内的无进展生存期(PFS)和疾病特异性死亡率。
我们发现Ga-DOTATATE TV四分位数与PFS(P = .001)和疾病特异性生存率(P = .002)之间呈负相关。Ga-DOTATATE TV为7.0 mL或更大与疾病进展几率较高相关(风险比,3.0;P = .04)。在多变量分析中(P = .01)以及在胰腺NETs患者的亚组分析中,Ga-DOTATATE TV为35.8 mL或更大与疾病特异性死亡风险增加相关(风险比,10.6)。
在一项前瞻性研究中,我们证明了Ga-DOTATATE TV在一大群NETs患者中对PFS和疾病特异性死亡率方面的预后价值。