Endocrine Abstracts

Background: There are no effective blood biomarkers for 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 prospective multicenter, multinational blinded study.

Material and methods: Study cohorts: (i) bronchopulmonary carcinoids (BPC) (n=99); (ii) healthy controls (n=102); (iii) idiopathic pulmonary fibrosis (IPF) (n=50); (iv) other lung neoplasia (n=101): adenocarcinomas (ACC) (n=41), squamous cell carcinomas (SCC) (n=37), SCLC (n=16) and LCNEC (n=7). BPC were histologically classified as TC (n=62) and AC (n=37). Twenty matched tumor tissue-blood pairs (BPC: n=6; SCLC: n=4; ACC: n=5; SCC: n=5) were evaluated. BPC disease status was based on imaging and RECIST 1.0 criteria. Diagnostic metrics and disease status correlation was evaluated. Upper limit of normal (NETest) was 20. Data is mean±S.D.

Results: NETest levels were elevated in 83% BPCs. NETest levels were significantly increased in BPC (45±25) vs controls (9±8, P<0.0001; AUROC: 0.96±0.01). The accuracy, sensitivity and specificity were: 92%, 84% and 100%. NETest was elevated in SCLC (42±32) and LCNEC (28±7). Based on imaging and RECIST criteria, 21 were progressive, 58 stable and 20 exhibited no evidence of disease. NETest levels accurately distinguished progressive (61±26) from stable disease (35.5±18, P<0.0001). In NED, levels were 13±7. NETest levels were 100% elevated in metastatic disease. This was irrespective of histology (AC: P<0.02; TC: P=0.0006). Levels were significantly lower in non-endocrine lung cancers, ACC (18±21) and SCC (12±11) and benign disease (18±25) than BPC (45±25) (P<0.001). The correlation between paired tumor and blood for BPC was significant (R: 0.83, P<0.0001). The correlation for SCLC (R: 0.68) was significant but not for SCC and ACC (R: 0.25–0.31).

Conclusions: Elevated NETest levels are diagnostic of lung neuroendocrine neoplasia. Blood NETest levels correlate with tumor tissue levels. The levels accurately identify clinical progression as determined by imaging and RECIST criteria. NETest liquid biopsy is an effective diagnostic and has clinical utility in the identification of disease preogression.