采用基于血液的 mRNA 标志物（NETest）进行分子基因组评估具有成本效益，并且具有 94%的准确性预测神经内分泌肿瘤的复发。

Molecular Genomic Assessment Using a Blood-based mRNA Signature (NETest) is Cost-effective and Predicts Neuroendocrine Tumor Recurrence With 94% Accuracy.

机构信息

Yale University School of Medicine, New Haven, CT.

Wren Laboratories, Branford, CT.

出版信息

Ann Surg. 2021 Sep 1;274(3):481-490. doi: 10.1097/SLA.0000000000005026.

DOI:10.1097/SLA.0000000000005026

PMID:34183517

Abstract

INTRODUCTION

Identification of residual disease after neuroendocrine tumor (NET) resection is critical for management. Post-surgery imaging is insensitive, expensive, and current biomarkers ineffective. We evaluated whether the NETest, a multigene liquid biopsy blood biomarker, correlated with surgical resection and could predict recurrence.

METHODS

Multicenter evaluation of NET resections over 24 months (n = 103): 47 pancreas, 26 small bowel, 26 lung, 2 appendix, 1 duodenum, 1 stomach. Surgery: R0 (83), R1/R2 (20). One millilitre of blood was collected at D0 and posroperative day (POD) 30. Transcript quantification by polymerase chain reaction (normal: ≤20), CgA by NEOLISA (normal ≤108 ng/mL). Standard-of-care (SoC) follow-up costs were calculated and compared to POD30 NETest-stratification approach. Analyses: Wilcoxon-paired test, Chi-square test.

D BIOMARKERS

NETest: 103 of 103 (100%)-positive, whereas 23 of 103 (22%) were CgA-positive (Chi-square = 78, P < 0.0001).In the R0 group, the NETest decreased 59 ± 28 to 26 ± 23 (P < 0.0001); 36% (30/83) remained elevated. No significant decrease was evident for CgA. In the R1/R2 group the NETest decreased but 100% remained elevated. CgA levels did not decrease.An elevated POD30 NETest was present in R0 and 25 (83%) developed radiological recurrences. Normal score R0 s (n = 53) did not develop recurrence (Chi-square = 56, P < 0.0001). Recurrence prediction was 94% accurate with the NETest.

COST EVALUATION

Using the NETest to stratify postoperative imaging resulted in a cost-savings of 42%.

CONCLUSION

NETest diagnosis is more accurate than CgA (100% vs 22%). Surgery significantly decreased NETest. An elevated POD30 NETest predicted recurrence with 94% accuracy and post-surgical POD30 NETest follow-up stratification decreased costs by 42%. CgA had no surgical utility. Further studies would define the accuracy and cost-effectiveness of the NETest in the detection of postoperative recurrent disease.

摘要

简介

识别神经内分泌肿瘤 (NET) 切除术后的残留疾病对于治疗至关重要。术后影像学检查不敏感，费用昂贵，且目前的生物标志物无效。我们评估了 NETest 是否为一种多基因液体活检血液生物标志物，与手术切除相关，并能预测复发。

方法

在 24 个月内对 103 例 NET 切除术进行了多中心评估：47 例胰腺，26 例小肠，26 例肺，2 例阑尾，1 例十二指肠，1 例胃。手术：R0（83 例），R1/R2（20 例）。在 D0 和术后第 30 天（POD30）采集 1 毫升血液。通过聚合酶链反应（正常：≤20）定量转录物，通过 NEOLISA（正常：≤108ng/mL）定量 CgA。计算了标准治疗（SoC）随访的费用，并与 POD30NETest 分层方法进行了比较。分析：Wilcoxon 配对检验，卡方检验。

结果

NETest：103 例中的 103 例（100%）呈阳性，而 103 例中的 23 例（22%）呈 CgA 阳性（卡方=78，P<0.0001）。在 R0 组中，NETest 从 59±28 降至 26±23（P<0.0001）；36%（30/83）仍升高。CgA 水平未见明显下降。在 R1/R2 组中，NETest 虽有所下降，但 100%仍升高。CgA 水平未下降。R0 患者 POD30 时 NETest 升高，25 例（83%）出现影像学复发。R0 中正常评分（n=53）无复发（卡方=56，P<0.0001）。NETest 对复发的预测准确率为 94%。

成本评估

使用 NETest 对术后影像学进行分层，可节省 42%的成本。

结论

NETest 诊断比 CgA（100%比 22%）更准确。手术显著降低了 NETest。术后第 30 天升高的 NETest 对复发的预测准确率为 94%，术后第 30 天的 NETest 随访分层降低了 42%的成本。CgA 对手术无实用价值。进一步的研究将确定 NETest 在检测术后复发疾病方面的准确性和成本效益。