ENETS single center of excellence experience with the NETest: A real-world assessment of 565 patients.

Abstract

605 Background: There is a substantial clinical unmet need for an accurate and effective blood biomarker of NET disease. We therefore evaluated under real-world conditions the clinical utility of the NETest in a NET Center of Excellence and compare it with the biomarker CgA. Methods: Cohorts: GEP-NET (253), BP-NET (49), colon cancer (37), lung cancers (80), benign lung disease (59) and controls (86). GEP-NETs: 164 (65%) had image-detectable disease or were resection-margin (R1) positive. Grading included G1 [106], G2 [49] and G3 [9]. BP-NETs, 28 of 49 (57%) had evidence of disease. Grading was TC [14], AC [14]. Disease status (stable [SD] or progressive [PD]) determined by RECIST 1.1. Blood sampling: NETest ( n= 565) and NETest/CgA matched samples (135). NETest (PCR) (0-100 score) with positive > 20; progressive > 40. CgA (ELISA). All samples deidentified, and measurement/ analyses blinded. Statistics: Mann-Whitney U-test, McNemar’s test and AUROC. Results: GEPNET: NETest was significantly higher (34.4±1.8, p< 0.0001) in NET disease versus no NET disease (10.5±1, p< 0.0001), non-NET disease (18±4, p= 0.0004) or controls (7±0.5, p< 0.0001). Diagnostic sensitivity was 89%, and specificity 94%. NETest levels were not related to grade (G1: 32±2 vs. G2: 38±3, p= 0.09). BPNET: NETest was significantly higher (30±1.3) vs no NET disease (24.1±1.3, p= 0.0049). Diagnostic sensitivity 100%. Levels were elevated vs controls ( p< 0.0001) and non-NET disease (20±2, p= 0.0001). NETest levels were not related to grade (TC 30±2 vs. AC: 30±2, p= NS). Levels were elevated in PD (55±5.5) vs SD (33.6±2, p= 0.0005). AUCs for detecting disease ranged between 0.89 (GEP-NET) to 1.0 (BE-NET) ( p< 0.0001). Matched GEP-NETS (135): NETest was significantly more accurate for detecting NETS (99%) than CgA (53%, McNemar’s test Chi2= 87, p= 0.0001). sensitivity (99%) and specificity (96%) were better than CgA (37% and 96% respectively). Conclusions: The NETest is an accurate diagnostic test for both GEP- and BP-NEN. It defines clinical status (stable or progressive disease). NETest is significantly more accurate than CgA. The multianalyte genomic blood assessment of NET disease provided clinical information of utility in management.