Blood Molecular Genomic Analysis Predicts the Disease Course of Gastroenteropancreatic Neuroendocrine Tumor Patients: A Validation Study of the Predictive Value of the NETest®.

Published on Jan 1, 2021in Neuroendocrinology4.914
· DOI :10.1159/000509091
Mark J C van Treijen4
Estimated H-index: 4
,
Dennis van der Zee2
Estimated H-index: 2
+ 8 AuthorsGerlof D. Valk47
Estimated H-index: 47
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Abstract
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 strongest predictor of PD. CgA had lower utility. The NETest® anticipates RECIST defined disease status up to one year before imaging alterations are apparent.
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Background The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy—liquid biopsy—to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). Patients and methods A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analys...
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#1Gitta Boons (University of Antwerp)H-Index: 4
#2Timon Vandamme (University of Antwerp)H-Index: 7
Last. Ken Op de Beeck (University of Antwerp)H-Index: 23
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High-throughput analysis, including next-generation sequencing and microarrays, have strongly improved our understanding of cancer biology. However, genomic data on rare cancer types, such as neuroendocrine neoplasms, has been lagging behind. Neuroendocrine neoplasms (NENs) develop from endocrine cells spread throughout the body and are highly heterogeneous in biological behavior. In this challenging disease, there is an urgent need for new therapies and new diagnostic, prognostic, follow-up and...
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#1Alberto Carmona-Bayonas (University of Murcia)H-Index: 14
Last. Rocio Garcia-Carbonero (Complutense University of Madrid)H-Index: 29
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PURPOSESomatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from ...
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#1Eric LiuH-Index: 1
#2Scott Paulson (Texas Oncology)H-Index: 1
Last. Lisa Bodei (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 25
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BACKGROUND: The clinical relevance of molecular biomarkers in oncology management has been recognized in breast and lung cancers. We evaluated a blood-based multigene assay for management of neuroendocrine tumors (NETs) in a real-world study (U.S. registry NCT02270567). Diagnostic accuracy and relationship to clinical disease status in two cohorts (treated and watch-and-wait) were evaluated. MATERIALS AND METHODS: Patients with NETs (n = 100) were followed for 6-12 months. Patients' primary tumo...
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#1Anna Malczewska (Medical University of Silesia)H-Index: 13
#2Magdalena Witkowska (Medical University of Silesia)H-Index: 2
Last. Beata Kos-Kudła (Medical University of Silesia)H-Index: 31
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Introduction: Current monoanalyte biomarkers are ineffective in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). NETest, a novel multianalyte signature, provides molecular information relev ...
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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: 47
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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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#1Cansu Guney GencH-Index: 4
Last. Irvin M. Modlin (Yale University)H-Index: 85
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Background: Recurrence of pancreatic neuroendocrine tumors (pNET) after surgery is common. Strategies to detect recurrence have limitations. We investigated the role of clinical criteria and the multigene polymerase chain reaction–based NETest during post-operative follow-up of pNET. Methods: We studied 3 groups of resections: R0 with no recurrence (n = 11), R0 with recurrence (n = 12), and R1 with no recurrence (n = 12). NETest levels (>40%) were compared with chromogranin A (CgA) and clinicopa...
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#1Günter Klöppel (TUM: Technische Universität München)H-Index: 54
#2Stefano La Rosa (UNIL: University of Lausanne)H-Index: 41
In 1983, a monoclonal antibody, Ki67, was generated, that labeled the nuclei of proliferating non-neoplastic and neoplastic cells. The name Ki67 derived from the city of Kiel (Ki) where the antibody was produced in the university department of pathology and refers to the number of the original clone (67). Systematic assessment of the proliferative activity of tumors using Ki67 started in the 1990s, when Ki67, which only worked on frozen tissue, was complemented by the antibody MIB-1 that also wo...
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#1Vincenzo MarottaH-Index: 19
#2Maria Chiara Zatelli (University of Ferrara)H-Index: 54
Last. Antongiulio FaggianoH-Index: 56
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: Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assa...
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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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Cited By6
Newest
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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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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#6Andrea Frilling (ICL: Imperial College London)H-Index: 14
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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#1Anja Rinke (University of Marburg)H-Index: 23
#2Christoph J. Auernhammer (LMU: Ludwig Maximilian University of Munich)H-Index: 31
Last. Thomas M. Gress (University of Marburg)H-Index: 82
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Gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) comprises clinically as well as prognostically diverse tumour entities often diagnosed at late stage. Current classification provides a uniform terminology and a Ki67-based grading system, thereby facilitating management. Advances in the study of genomic and epigenetic landscapes have amplified knowledge of tumour biology and enhanced identification of prognostic and potentially predictive treatment subgroups. Translation of this genomic a...
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#1Anna Malczewska (Medical University of Silesia)H-Index: 13
#2Kjell Öberg (Uppsala University Hospital)H-Index: 117
Last. Beata Kos-Kudła (Medical University of Silesia)H-Index: 31
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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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