NETest is superior to chromogranin A in neuroendocrine neoplasia: a prospective ENETS CoE analysis.

Published on Jan 1, 2021in Endocrine connections2.592
· DOI :10.1530/EC-20-0417
Anna Malczewska12
Estimated H-index: 12
(Medical University of Silesia),
Kjell Öberg116
Estimated H-index: 116
(Uppsala University Hospital),
Beata Kos-Kudła31
Estimated H-index: 31
(Medical University of Silesia)
Sources
Abstract
Introduction The absence of a reliable, universal biomarker is a significant limitation in neuroendocrine neoplasia (NEN) management. We prospectively evaluated two CgA assays, (NEOLISA, EuroDiagnostica) and (CgA ELISA, Demeditec Diagnostics (DD)) and compared the results to the NETest. Methods NEN cohort (n = 258): pancreatic, n = 67; small intestine, n = 40; appendiceal, n = 10; rectal, n = 45; duodenal, n = 9; gastric, n = 44; lung, n = 43. Image-positive disease (IPD) (n = 123), image & histology- negative (IND) (n = 106), and image-negative and histology positive (n = 29). CgA metrics: NEOLISA, ULN: 108 ng/mL, DD: ULN: 99 ng/mL. Data mean ± s.e.m. NETest: qRT-PCR – multianalyte analyses, ULN: 20. All samples de-identified and assessed blinded. Statistics: Mann–Whitney U-test, Pearson correlation and McNemar-test. Results CgA positive in 53/258 (NEOLISA), 32 (DD) and NETest-positive in 157/258. In image- positive disease (IPD, n = 123), NEOLISA-positive: 33% and DD: 19%. NETest-positive: 122/123 (99%; McNemar’s Chi2= 79–97, P < 0.0001). NEOLISA was more accurate than DD (P = 0.0003). In image- negative disease (IND), CgA was NEOLISA-positive (11%), DD (8%), P = NS, and NETest (33%). CgA assays could not distinguish progressive (PD) from stable disease (SD) or localized from metastatic disease (MD). NETest was significantly higher in PD (47 ± 5) than SD (29 ± 1, P = 0.0009). NETest levels in MD (35 ± 2) were elevated vs localized disease (24 ± 1.3, P = 0.008). Conclusions NETest, a multigenomic mRNA biomarker, was ~99% accurate in the identification of NEN disease. The CgA assays detected NEN disease in 19–33%. Multigenomic blood analysis using NETest is more accurate than CgA and should be considered the biomarker standard of care.
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Last. Gerlof D. ValkH-Index: 40
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Reliable prediction of disease status is a major challenge in managing gastroenteropancreatic neuroendocrine tumors (GEP-NET). The aim of the study was to validate the NETest®, a blood molecular genomic analysis, for predicting the course of disease in individual patients compared to Chromogranin A (CgA). NETest® (normal ≤20%) and CgA (normal 140ng/ml), NPV and PPV were 83% and 52%. CgA could not predict PD in watchful waiting or NED subgroups. The NETest® reliably predicted SD and was the stron...
6 CitationsSource
#1Mark KiddH-Index: 5
#2Alexandra KitzH-Index: 2
Last. Irvin M Modlin (Yale University)H-Index: 3
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BACKGROUND: The NETest is a multi-gene assay comprising 51 circulating neuroendocrine tumor specific transcripts. The quotient of the 51-gene assay is based upon an ensemble of machine learning algorithms. Eight cancer hallmarks or "omes" (apoptome, epigenome, growth factor signalome, metabolome, proliferome, plurome, secretome SSTRome) represent 29 genes. The NETest is an accurate diagnostic (>90%) but its prognostic utility has not been assessed. In this study, we describe expansion of the NET...
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#1Wook Lee (Inha University)H-Index: 6
#2De-Shuang Huang (Tongji University)H-Index: 71
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Cancer is a complex and heterogeneous disease with many possible genetic and environmental causes. The same treatment for patients of the same cancer type often results in different outcomes in terms of efficacy and side effects of the treatment. Thus, the molecular characterization of individual cancer patients is increasingly important to find an effective treatment. Recently a few methods have been developed to construct cancer sample-specific gene networks based on the difference in the mRNA...
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#1Anna MalczewskaH-Index: 12
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BACKGROUND: There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions, the clinical utility of the NETest as a liquid biopsy in an ENETS Centre of Excellence and compared its utility with chromogranin A (CgA). Methods Cohorts: Gastroenteropancreatic (GEP)-NEN (n=253), bronchopulmonary (BP)-NEN (n=64), thymic NEN (n=1), colon cancer (n=37), NSCLC (n=63), benign lung disease (n=59...
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#1Irvin M Modlin (Yale University)H-Index: 3
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#1Bradon R. McDonald (TGen: Translational Genomics Research Institute)H-Index: 16
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Longitudinal analysis of circulating tumor DNA (ctDNA) has shown promise for monitoring treatment response. However, most current methods lack adequate sensitivity for residual disease detection during or after completion of treatment in patients with nonmetastatic cancer. To address this gap and to improve sensitivity for minute quantities of residual tumor DNA in plasma, we have developed targeted digital sequencing (TARDIS) for multiplexed analysis of patient-specific cancer mutations. In ref...
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#1Anna Malczewska (Medical University of Silesia)H-Index: 12
#2Lisa Bodei (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 25
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Context: Early cancer detection is critical to optimize treatment. This is particularly problematic in neuroendocrine tumors (NETs), which exhibit an ∼5-year diagnostic delay due to covert symptoms, limitations in imaging, and circulating biomarkers. Despite development of continuous monitoring strategies utilizing advanced modalities [CT/MRI or 68Gallium positron emission tomography (PET)/CT] or a repertoire of monoanalyte biomarkers [e.g., chromogranin A (CgA), pancreastatin, serotonin], detec...
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#1Mark J C van Treijen (UU: Utrecht University)H-Index: 4
#2Catharina M. Korse (UU: Utrecht University)H-Index: 2
Last. Gerlof D. Valk (UU: Utrecht University)H-Index: 40
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Background: Available neuroendocrine biomarkers are considered to have insufficient accuracy to discriminate patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) from healthy controls. Recent studies have demonstrated a potential role for circulating neuroendocrine specific transcripts analysis - the NETest - as a more accurate biomarker for NETs compared to available biomarkers. This study was initiated to independently validate the discriminative value of the NETest as well ...
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#1William E. Gibson (VUMC: Vanderbilt University Medical Center)H-Index: 2
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Summary Pathologic examination of hepatic metastasectomies from patients with metastatic small intestinal or pancreatic neuroendocrine tumor frequently reveals micrometastases undetectable by radiologic or macroscopic gross examination. This finding raises the possibility that undetectable micrometastases remain in these patients after metastasectomy. Here we examined liver resections for micrometastases and assessed their impact on prognosis. Hepatic metastasectomies from 65 patients with neuro...
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#1Irvin M. Modlin (Yale University)H-Index: 81
#2Mark KiddH-Index: 66
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: The neuroendocrine neoplasms test (NETest) is a multianalyte liquid biopsy that measures neuroendocrine tumor gene expression in blood. This unique signature precisely defines the biological activity of an individual tumor in real time. The assay meets the 3 critical requirements of an optimal biomarker: diagnostic accuracy, prognostic value, and predictive therapeutic assessment. NETest performance metrics are sensitivity and specificity and in head-to-head comparison are 4-fold to 10-fold mo...
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#1Irvin M. Modlin (Yale University)H-Index: 81
#2Mark KiddH-Index: 66
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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...
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Abstract Biomarkers that are secretory monoanalyte products of GEP (gastro-entero-pancreatic) and BP (broncho-pulmonary) or lung NETs (neuroendocrine tumors) have significant limitations in clinical utility. The assessment of secretory activity provides little information in regard to tumor biology. Furthermore, ∼50% of NETs have measurable secretory products. Molecular genomic identification in blood (NETest liquid biopsy) of the regulators of tumor biology provide multianalyte, real-time asses...
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