Endocrine Abstracts (2016) 46 P8 | DOI: 10.1530/endoabs.46.P8

Blood measurement of neuroendocrine gene transcripts defines the effectiveness of operative resection and ablation strategies

Irvin M Modlin1, Andrea Frilling2, Ronald R Salem3, Daniele Alaimo4, Panagiotis Drymousis2, Harpreet S Wasan2, Stephen Callahan4, Omar Faiz5, Lei Weng2, Nancy Teixeira4, Lisa Bodei4, Ignat Drozdov4 & Mark Kidd4


1Emeritus Prof, Yale University School of Medicine, New Haven, USA; 2Department of Surgery and Cancer, Imperial College London, London, UK; 3Department of Surgery, Yale University School of Medicine, New Haven, USA; 4Wren Laboratories, Branford, USA; 5Department of Colorectal Surgery, St Mark’s Hospital, London, UK.


Background: Surgery is the only curative treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but the prediction of residual disease/recurrence is limited in the absence of optimal biomarkers. We examined whether a blood-based multianalyte neuroendocrine gene transcript assay (NETest) would define tumor cytoreduction and therapeutic efficacy.

Methods: The NETest is a polymerase chain reaction–based analysis of 51 genes. Disease activity is scaled 0–100%; minimal <14%, low 14–47%, and high >47%. A total of 35 GEP-NETs in 2 groups were evaluated. I: after surgery (R0, n=15; residual, n=12); II: nonsurgery (n=8: embolization with gel-foam alone [bland: n=3]), transarterial chemoembolization (n=2), and radiofrequency embolization (n=3). Measurement (quantitative real-time-polymerase chain reaction) and chromogranin A (CgA; enzyme-linked immunosorbent assay) were undertaken preoperatively and 1 month after treatment.

Results: NETest score was increased in 35 (100%) preoperatively; 14 (40%) had increased CgA (χ2=30, P<2×10−8). Resection reduced NETest from 80±5% to 29%±5, (P<.0001). CgA decrease was insignificant (14.3±1.6 U/L to 12.2±1.7 U/L). NETest decreases correlated with diminished tumor volume (R2=0.29, P=0.03). Cytoreduction significantly reduced NETest from 82±3% to 41%±6, P<.0001). CgA was not decreased (21.4±5.5 U/L to 18.4±10.1 U/L). Four (36%) of 11 R0s with increased NETest at 1 month developed positive imaging (sensitivity 100%, specificity 20%). One hundred percent (ablated group) were transcript- and image-positive.

Conclusion: Blood NET transcripts delineate surgical resection/cytoreduction and facilitate identification of residual disease. (Work published).

Keywords: Blood NET transcripts, NETest, gastroenteropancreatic neuroendocrine tumors