生长抑素类似物治疗的胃肠胰神经内分泌肿瘤（GEP-NETs）中的循环转录本分析（NETest）可指导治疗。
Circulating Transcript Analysis (NETest) in GEP-NETs Treated With Somatostatin Analogs Defines Therapy.
作者信息
Ćwikła Jarosław B, Bodei Lisa, Kolasinska-Ćwikła Agnieszka, Sankowski Artur, Modlin Irvin M, Kidd Mark
机构信息
Department of Radiology, Faculty of Medical Sciences (J.Ć.), University of Warmia and Mazury, Olsztyn 10-558, Poland; Division of Nuclear Medicine (L.B.), European Institute of Oncology, Milan 20141, Italy; Department of Oncology (A.K.-Ć.), Maria Skłodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw 44-101, Poland; Department of Radiology (A.S.), Hospital Ministry of Internal Affairs, Warsaw 02-507, Poland; Keewaydin Consulting, Inc. (I.M.M.), Woodbridge, Connecticut 06525; and Wren Laboratories (M.K.), Branford, Connecticut 06405.
出版信息
J Clin Endocrinol Metab. 2015 Nov;100(11):E1437-45. doi: 10.1210/jc.2015-2792. Epub 2015 Sep 8.
CONTEXT
Early and precise delineation of therapeutic responses are key issues in neuroendocrine neoplasm/tumor management. Imaging is currently used but exhibits limitations in sensitivity and specificity. The utility of biomarkers is unclear. objective, setting, and design: This prospective cohort study (11 mo) sought to determine whether measurements of circulating neuroendocrine tumor transcripts (NETest) predict responses to somatostatin analogs (SSAs).
PATIENTS
The test set consisted of 35 SSA-treated gastroenteropancreatic-NETs (RECISTevaluated). The prospective set consisted of 28 SSA-treated Grade 1-Grade 2 GEP-NETs.
INTERVENTION(S): Whole blood for transcript analysis (NETest) and plasma for Chromogranin A (CgA) (baseline), were collected every 4 weeks (prior to SSA injection). Morphologic (multidetector computed tomography/MRI) and functional imaging ((99m)Tc-[HYNIC, Tyr(3)]-Octreotide) was undertaken at entry and 6-month intervals until progression (RECIST 1.0).
MAIN OUTCOME MEASURE(S): Treatment response.
RESULTS
Test set: NETest (≥80%; scale, 0-100%) differentiated stable (SD) and progressive (PD) disease (P < .0001). Prospective set: 28 patients (26/28 SD) undergoing standard SSA. Grading: 12 G1, 16 G2. SSA Response: progression-free survival: 315 days: 14 (50%) SD, 14 (50%) PD. NETest: Twenty had elevated (≥80%) values; 14 developed PD; six, SD. CgA: Twelve of 28 exhibited elevated baseline values and/or subsequent >25% increase; eight developed PD; four, SD. NETest (P = .002) and grade (P = .054) were the only factors associated with treatment response. Multiple regression analysis established that the NETest could predict disease progression (P = .0002). NETest changes occurred significantly earlier (146 d prior to progression vs 56 d CgA; P < .0001; χ(2) = 19) and in more patients (100 vs 57%; P < .02).
CONCLUSIONS
NETest values (80-100%) were more accurate and occurred at a significantly earlier time point than CgA and predicted SSA treatment response.
背景
神经内分泌肿瘤的治疗反应的早期精确界定是其管理中的关键问题。目前使用影像学检查，但在敏感性和特异性方面存在局限性。生物标志物的效用尚不清楚。目的、研究地点和设计：这项前瞻性队列研究（为期11个月）旨在确定循环神经内分泌肿瘤转录本检测（NETest）是否能预测对生长抑素类似物（SSA）的反应。
患者
测试组包括35例接受SSA治疗的胃肠胰神经内分泌肿瘤（根据实体瘤疗效评价标准评估）。前瞻性组包括28例接受SSA治疗的1级至2级胃肠胰神经内分泌肿瘤。
干预措施
每4周（在注射SSA前）采集用于转录本分析的全血（NETest）和用于嗜铬粒蛋白A（CgA）检测的血浆（基线）。在入组时以及每隔6个月进行一次形态学检查（多排螺旋计算机断层扫描/磁共振成像）和功能成像（（99m）Tc-[HYNIC，Tyr（3）]-奥曲肽），直至疾病进展（实体瘤疗效评价标准1.0）。
主要观察指标
治疗反应。
结果
测试组：NETest（≥80%；范围为0-100%）可区分稳定疾病（SD）和疾病进展（PD）（P <.0001）。前瞻性组：28例患者（26/28为SD）接受标准SSA治疗。分级：12例G1级，16例G2级。SSA反应：无进展生存期：315天：14例（50%）为SD，14例（50%）为PD。NETest：20例值升高（≥80%）；14例疾病进展；6例为SD。CgA：28例中有12例基线值升高和/或随后升高>25%；8例疾病进展；4例为SD。NETest（P =.002）和分级（P =.054）是与治疗反应相关唯一因素。多元回归分析表明，NETest可预测疾病进展（P =.0002）。NETest变化出现得明显更早（进展前146天对比CgA为56天；P <.0001；χ² = 19），且涉及更多患者（10%对比57%；P <.02）。
结论
NETest值（80%-100%）比CgA更准确，且出现时间点明显更早，可预测SSA治疗反应。
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