NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

Abstract

Background: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript “liquid biopsy” (NETest) in BPC for diagnosis and monitoring of the disease status. Aim: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. Material and Methods: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. Results: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25–0.31). Conclusions: Elevated ­NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.

Utility of a ready-to-use PCR system for neuroendocrine tumor diagnosis

“…To validate that the PSP-NETest was an effective liquid biopsy, we directly compared matched tumor tissue and blood samples. The concordance was highly significant (R: 0.71–0.82, p <0.0001) and similar to what has been previously reported for the liquid-based assay [25, 34]. These data confirm that the PSP detects circulating tumor transcripts and functions as a bona fide liquid biopsy.…”

“…The NETest can also distinguish stable from progressive disease and monitor the effectiveness of medical treatment [10]. Given that our approach has been independently validated [34, 37], we anticipate that usage will become widespread. Clinical application and usage of this molecular assay will be facilitated by the PSP approach we describe.…”

The Challenge of Evaluating Response to Peptide Receptor Radionuclide Therapy in Gastroenteropancreatic Neuroendocrine Tumors: The Present and the Future

“…These results have been further validated in several independent studies [ 67 , 68 , 69 , 70 , 71 , 72 ]. In particular, van Treijen et al [ 71 ] emphasize the potential role of liquid biopsy as a marker of persistent disease after therapy or relapse during follow-up.…”

Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

“…In this sense, precision medicine has gained particular attention in the oncology field [3]. Molecular profiling can be applied to gain insight into the alterations underlying tumorigenesis [4], contributing to the identification of diagnostic and prognostic biomarkers, and to the selection of treatments considering individual variability.…”