NETest liquid biopsy is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease.

<br>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 bronchopulmonary carcinoids (BPC) for diagnosis and monitoring of 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 bronchopulmonary carcinoids (BPC) (n=99), healthy controls (n=102), other lung neoplasia (n=101) including adenocarcinomas (ACC) (n=41), squamous cell carcinomas (SCC) (n=37), SCLC (n=16) and LCNEC (n=7) and idiopathic pulmonary fibrosis (IPF) (n=50). BPC were histologically classified as TC (n=62) and AC (n=37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. Upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data is mean± SD.

RESULTS: NETest levels were significantly increased in BPC (45±25) vs controls (9±8, p<0.0001). The AUROC was 0.96±0.01. The accuracy, sensitivity and specificity were: 92%, 84% and 100%. NETest was also elevated in SCLC (42±32) and LCNECs (28±7). NETest accurately distinguished progressive (61±26) from stable disease (35.5±18, p<0.0001). In BPCs NETest levels were elevated in metastatic disease irrespective of histology (AC: p<0.02; TC: p=0.0006). In non-endocrine lung cancers, ACC (18±21) and SCC (12±11) and benign disease (IPF) (18±25) levels were significantly lower than BPC (p<0.001). Significant correlations were evident between paired tumor and blood 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. <br>.