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.
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.
Authors: Lisa Bodei; Mark S Kidd; Aviral Singh; Wouter A van der Zwan; Stefano Severi; Ignat A Drozdov; Anna Malczewska; Richard P Baum; Dik J Kwekkeboom; Giovanni Paganelli; Eric P Krenning; Irvin M Modlin Journal: Eur J Nucl Med Mol Imaging Date: 2019-12-14 Impact factor: 9.236
Authors: A Malczewska; A Procner; A Walter; K Kusnierz; W Zajecki; H Aslanian; B Kos-Kudla Journal: BMC Gastroenterol Date: 2020-07-23 Impact factor: 3.067
Authors: Mark Kidd; Ignat A Drozdov; Somer Matar; Nicole Gurunlian; Nicholas J Ferranti; Anna Malczewska; Philip Bennett; Lisa Bodei; Irvin M Modlin Journal: PLoS One Date: 2019-06-27 Impact factor: 3.240
Authors: Angela Lamarca; Hamish Clouston; Jorge Barriuso; Mairéad G McNamara; Melissa Frizziero; Was Mansoor; Richard A Hubner; Prakash Manoharan; Sarah O'Dwyer; Juan W Valle Journal: J Clin Med Date: 2019-10-05 Impact factor: 4.241