F-032
BLOOD MEASUREMENT OF NEUROENDOCRINE GENE TRANSCRIPTS IS DIAGNOSTIC FOR BRONCHOPULMONARY CARCINOID AND IDENTIFIES THE EFFECTIVENESS OF SURGICAL RESECTION Free

Objectives: Defining bronchopulmonary neuroendocrine tumours (BPNETs) management is difficult since imaging, histology and biomarkers (Chromogranin A) are limited in predicting malignancy and assessing therapy. Biopsies are invasive and often difficult to interpret. We therefore developed a NET multigene blood test (NETest) to diagnose and assess BPNET management.

Methods: Material: Cohort I (retrospective): BPNET (n=108; progressive n=34, stable n=74); Cohort II (prospective surgery): BPNET (n=12; typical carcinoid (n=9), atypical (n=1), LCNEC (n=2)). Cohort III controls: normal (n=90) and lung disease (COPD: n=18; adenocarcinoma n=7, squamous n=5). Cohort II bloods were pre surgery, POD 1, 5, 7 and 30. BP-NETest measurement: qPCR (0-100% scale: normal <25%, stable ≤40%, intermediate 40-70%, progressive ≥70%). CgA (ELISA; normal <109 ng/ml) was the comparator. Analysis: Cohort I/III: 2-tailed Mann-Whitney U-test, ROC-statistics; Cohort II: Wilcoxon-matched pairs, 1-way ANOVA.

Results: Cohort I: All BPNETs (n=108) were positive. Controls (n=90) 6±1%, stable (n=74) - levels 38±3%; progressive (n=34): 74±5%; (P < 0.0001). AUC for NET vs controls: 0.94±0.03 (P<0.0001). CgA was positive in 41% and not different to controls. Cohort II: NETest was positive in all; pre-surgical: 81±12% [typical (78±9%), atypical (100%), LCNEC (84 + 3%)]. For all patients: POD1 (66±10%), POD5 (65±11%), POD7 (38±3%, P=0.015) and POD30 (35±3%, P<0.01). One-way ANOVA analysis was significant (F = 11.2, P < 0.0001). At 30 days, levels had decrease in all patients by 230%±33%. CgA was positive in only 33% (pre-surgery) and not informative (one-way ANOVA: F = 0.88, P=0.51). Cohort III: NETest controls: 6±1%; COPD 24±1%, adenocarcinoma 12±2% and squamous cancers 16±3%. AUC vs BPNETs: 0.90±0.03 (P<0.0001).

Conclusions: Blood NET gene levels identified BPNETs in 100%. NETest differentiated controls, benign or malignant lung disease (>93%). Resection decreased blood values in all patients. CgA was of no clinical utility. Given the accuracy/sensitivity of NET transcript measurement, we predict that follow-up NETest levels will prognosticate residual disease and recurrence post-surgery.

Disclosure: K. Chung and M. Kidd: Employees of Wren Laboratories.