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CELL-FREE DNA AND CLINICAL CHARACTERISTICS IN PATIENTS WITH SMALL INTESTINAL OR PANCREATIC NEUROENDOCRINE TUMORS
Neuroendocrinology ( IF 4.1 ) Pub Date : 2021-01-18 , DOI: 10.1159/000514457
Stine Karlsen Oversoe 1, 2 , Boe Sandahl Sorensen 3 , Elizaveta Mitkina Tabaksblat 4 , Henning Gronbaek 1 , Jens Kelsen 1
Affiliation  

Background: Neuroendocrine tumors (NETs) are rare and characterized by a heterogeneous clinical course and an unmet need for better prognostic markers. Plasma cell-free DNA (cfDNA) has prognostic value in other malignancies but is not previously investigated in NETs. We studied cfDNA levels in patients with mainly low grade small intestinal (siNET) or pancreatic NET (pNET) and evaluated the prognostic potential of cfDNA. Material and methods: We included 70 NET patients, siNET(n=50) and pNET(n=20). Plasma cfDNA levels were determined by droplet digital PCR for the Beta-2-microglobulin gene every six months during a period of three years, including in a subgroup of 19 patients during Peptide Receptor Radionuclide Therapy (PRRT) therapy. Results: CfDNA levels were higher in both siNET and pNET compared to a previously established healthy cohort (p<0.0001). cfDNA levels did not predict overall survival (crude HR 0.95 (0.57-1.58), p=0.837, adjusted for smoking status HR 0.77 (0.51-1.17), p=0.22). The impact of cfDNA level on progression-free survival showed different trends in siNET and pNET. There was no effect of PRRT treatment on cfDNA levels and no difference in cfDNA levels between patients with and without progressive disease after PRRT (ANOVA p=0.66). CfDNA levels were significantly higher in never-smokers and previous smokers than in current smokers (p=0.029). Conclusion: cfDNA levels are higher in NET patients than in healthy controls, however, there was no association with prognosis, and cfDNA levels were unaffected by PRRT. Our observations suggest that cfDNA levels are not associated with the disease course in low-grade NET in contrast to other malignancies.


中文翻译:

小肠或胰腺神经内分泌肿瘤患者的无细胞 DNA 和临床特征

背景:神经内分泌肿瘤(NETs)是罕见的,其特点是临床过程异质性和对更好预后标志物的需求未得到满足。血浆游离 DNA (cfDNA) 在其他恶性肿瘤中具有预后价值,但之前未在 NETs 中进行过研究。我们研究了主要患有低级别小肠 (siNET) 或胰腺 NET (pNET) 的患者的 cfDNA 水平,并评估了 cfDNA 的预后潜力。材料和方法:我们包括 70 名 NET 患者,siNET(n=50) 和 pNET(n=20)。在三年的时间里,每六个月通过液滴数字 PCR 测定 Beta-2-微球蛋白基因的血浆 cfDNA 水平,包括在肽受体放射性核素治疗 (PRRT) 治疗期间的 19 名患者亚组。结果:与之前建立的健康队列相比,siNET 和 pNET 中的 CfDNA 水平更高(p<0.0001)。cfDNA 水平不能预测总生存期(原始 HR 0.95 (0.57-1.58),p=0.837,根据吸烟状况调整后 HR 0.77 (0.51-1.17),p=0.22)。cfDNA 水平对无进展生存期的影响在 siNET 和 pNET 中显示出不同的趋势。PRRT 治疗对 cfDNA 水平没有影响,并且 PRRT 后患有和未患有疾病进展的患者之间的 cfDNA 水平没有差异(ANOVA p=0.66)。从不吸烟者和既往吸烟者的 CfDNA 水平显着高于当前吸烟者(p=0.029)。结论:NET 患者的 cfDNA 水平高于健康对照组,但与预后无关,且 cfDNA 水平不受 PRRT 的影响。
更新日期:2021-01-18
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