The clinical applications of a multigene liquid biopsy (NETest) in neuroendocrine tumors

Abstract

Purpose There are few effective biomarkers for neuroendocrine tumors. Precision oncology strategies have provided liquid biopsies for real-time and tailored decision-making. This has led to the development of the first neuroendocrine tumor liquid biopsy (the NETest). The NETest represents a transcriptomic signature of neuroendocrine tumor (NETs) that captures tumor biology and disease activity. The data have direct clinical application in terms of identifying residual disease, disease progress and the efficacy of treatment. In this overview we assess the available published information on the metrics and clinical efficacy of the NETest. Material and methods Published data on the NETest have been collated and analyzed to understand the clinical application of this multianalyte biomarker in NETs. Results NETest assay has been validated as a standardized and reproducible clinical laboratory measurement. It is not affected by demographic characteristics, or acid suppressive medication. Clinical utility of the NETest has been documented in gastroenteropancreatic, bronchopulmonary NETs, in paragangliomas and pheochromocytomas. The test facilitates accurate diagnosis of a NET disease, and real-time monitoring of the disease status (stable/progressive disease). It predicts aggressive tumor behavior, identifies operative tumor resection, and efficacy of the medical treatment (e.g. somatostatin analogues), or peptide receptor radionuclide therapy (PRRT). NETest metrics and clinical applications out-perform standard biomarkers like chromogranin A. Conclusions The NETest exhibits clinically competent metrics as an effective biomarker for neuroendocrine tumors. Measurement of NET transcripts in blood is a significant advance in neuroendocrine tumor management and demonstrates that blood provides a viable source to identify and monitor tumor status.

Nordic guidelines 2021 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

“…Overall, s-CgA as a single plasma biomarker is inadequate to predict tumour progression and must be used in association with imaging followup. The role of emerging biomarker panels such as the NETest TM , has to be determined [11]. Depending on the primary tumour and symptoms of the patient, measurement of specific markers, such as gastrin, insulin, c-peptide, pro-insulin, glucagon, VIP, somatostatin, ACTH or calcitonin should be performed.…”

Molecular Signatures and Their Clinical Utility in Pancreatic Neuroendocrine Tumors

“…Minimally invasive liquid biopsy tests for advanced cancers using blood/plasma have been shown to detect tumor-specific mutations in circulating cell-free tumor DNA (ctDNA), and recent data from studies of the NETest have shown successful detection of tumor-specific transcripts in circulating RNA ( 73 , 74 ). Genç et al.…”

Medical Treatment of Gastrointestinal Neuroendocrine Neoplasms

“…There are multiple studies investigating the role of sev-eral biomarkers as well as of genetic and epigenetic alterations, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), histone modifications and miRNAs, as prognostic factors and predictors of response to treatment [71,72]. A recently developed multigene liquid biopsy (NETest), that is based on transcriptomic evaluation of NENs, has been shown to have numerous clinical applications as it may assess the successful surgical removal of a NEN or predict the aggressive tumour behaviour and the efficacy of SSAs and PRRT [73].…”