Blood Transcript Profiling for the Detection of Neuroendocrine Tumors: Results of a Large Independent Validation Study.

Published on Dec 4, 2018in Frontiers in Endocrinology5.555
· DOI :10.3389/FENDO.2018.00740
Mark J C van Treijen4
Estimated H-index: 4
(UU: Utrecht University),
Catharina M. Korse2
Estimated H-index: 2
(UU: Utrecht University)
+ 5 AuthorsGerlof D. Valk47
Estimated H-index: 47
(UU: Utrecht University)
Sources
Abstract
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 as the association between tumor characteristics and NETest score. Methods: Whole blood samples from 140 consecutive GEP-NET patients and 113 healthy volunteers were collected. Laboratory investigators were blinded to the origin of the samples. NETest results and chromogranin A (CgA) levels were compared with clinical information including radiological imaging to evaluate the association with tumor characteristics. Results: The median NETest score in NET patients was 33% versus 13% in controls (p <0.0001). The NETest did not correlate with age, gender, tumor location, grade, load or stage. Using the cut-off of 14% NETest sensitivity and specificity were 93% and 56% respectively with an AUC of 0.87. The optimal cut-off for the NETest in our population was 20%, with sensitivity 89% and specificity 72%. The upper limit of normal for CgA was established as 100 µg/l. Sensitivity and specificity of CgA were 56% and 83% with an AUC of 0.76. CgA correlated with age (rs =.388, p<0.001) and tumor load (rs = .458, p< 0.001). Conclusions: The low specificity of the NETest precludes its use as a screening test for GEP-NETs. The superior sensitivity of the NETest over CgA (93% vs. 56%; p < 0.001), irrespective of the stage of the disease, emphasize its potential as a marker of disease presence in follow up as well as an indicator for residual disease after surgery.
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References44
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#2Mark KiddH-Index: 69
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OBJECTIVES: The management of bronchopulmonary neuroendocrine tumours (BPNETs) is difficult, since imaging, histology and biomarkers have a limited value in diagnosis, predicting outcome and defining therapeutic efficacy. We evaluated a NET multigene blood test (NETest) to diagnose BPNETs, assess disease status and evaluate surgical resection. METHODS: (i) Diagnostic cohort: BP carcinoids (n = 118)-typical carcinoid, n = 67 and atypical carcinoid, n = 51; other lung NEN (large-cell neuroendocrin...
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#1Arvind Dasari (University of Texas MD Anderson Cancer Center)H-Index: 26
#2Chan Shen (University of Texas MD Anderson Cancer Center)H-Index: 16
Last. James C. Yao (University of Texas MD Anderson Cancer Center)H-Index: 76
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Importance The incidence and prevalence of neuroendocrine tumors (NETs) are thought to be rising, but updated epidemiologic data are lacking. Objective To explore the evolving epidemiology and investigate the effect of therapeutic advances on survival of patients with NETs. Design, Setting, and Participants A retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results (SEER) program was conducted to evaluate 64 971 patients with...
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#1Xinsa Fu (Southern Medical University)H-Index: 2
#2Congxiang Shen (Southern Medical University)H-Index: 4
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Background The study was aimed to quantitatively detect mRNA levels of the catalytic subunit of telomerase (hTERT) in both peripheral blood and circulating tumor cells (CTCs) of patients with nasopharyngeal carcinoma (NPC) and explore its significance in early diagnosis and treatment of NPC.
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#1Amit Tirosh (NIH: National Institutes of Health)H-Index: 18
#2Georgios Z. Papadakis (FORTH: Foundation for Research & Technology – Hellas)H-Index: 17
Last. Electron Kebebew (GW: George Washington University)H-Index: 68
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To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by (68)Ga DOTATATE PET/CT imaging.
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#1Aldo ScarpaH-Index: 100
#2David K. ChangH-Index: 49
Last. Andrea MafficiniH-Index: 25
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Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are a relatively rare, heterogeneous group of diseases in which important advances have been observed in the diagnosis and treatment as well as in our understanding of the biology and genetics of the disease in recent years. Given the insufficient scientific data available on evidence-based management of GEPNETs and the differences in circumstances in individual countries, a multidisciplinary study group was established to provide guidelines...
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Background/Aims: A key issue in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is early identification and prediction of disease progression. Clinical ev
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#1Tetsuhide Ito (Kyushu University)H-Index: 52
#2Robert T. Jensen (NIH: National Institutes of Health)H-Index: 127
PURPOSE OF REVIEW: The purpose is to review recent advances in molecular imaging of neuroendocrine tumors (NETs), discuss unresolved issues, and review how these advances are affecting clinical management. RECENT FINDINGS: Molecular imaging of NETs underwent a number of important changes in the last few years, leading to some controversies, unresolved issues, and significant changes in clinical management. The most recent changes are reviewed in this article. Particularly important is the rapid ...
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#1Kjell ÖbergH-Index: 117
#2Eric P. KrenningH-Index: 120
Last. Irvin M. Modlin (Yale University)H-Index: 85
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The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in current ...
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#1Lisa Bodei (IEO: European Institute of Oncology)H-Index: 52
#2Mark KiddH-Index: 69
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Background Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a ...
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Background null Biomarkers are key tools in cancer management. In neuroendocrine tumors (NETs), Chromogranin A (CgA) was considered acceptable as a biomarker. We compared the clinical efficacy of a multigenomic blood biomarker (NETest) to CgA over a 5-year period. null null null Patients and methods null An observational, prospective, cross-sectional, multicenter, multinational, comparative cohort assessment. Cohort 1: NETest evaluation in NETs (n = 1684) and cancers, benign diseases, controls (...
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With nearly 10 million deaths, cancer is the leading cause of mortality worldwide. Along with major key parameters that control cancer treatment management, such as diagnosis, resistance to the classical and new chemotherapeutic reagents continues to be a significant problem. Intrinsic or acquired chemoresistance leads to cancer recurrence in many cases that eventually causes failure in the successful treatment and death of cancer patients. Various determinants, including tumor heterogeneity and...
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#3Andrea Frilling (Imperial College London)H-Index: 14
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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Introduction Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence. Methods This was a multicenter ev...
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Rationale: Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response. Our aim was to determine the clinical utility of a combination of surgery, theranostics, and a multigene blood measurement in metastasised SBNEN. Methods: Inclusion criteria were ...
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#1Anna Malczewska (Medical University of Silesia)H-Index: 13
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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 & hist...
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