Molecular Genomic Assessment Of Neuroendocrine Tumor Disease Using A Blood-based Mrna Signature Predicts Tumor Recurrence With 93% Accuracy
*Irvin M Modlin1, *Mark Kidd2, *Andrea Frilling3, *Massimo Falconi4, *Pier Luigi Filosso5, *Anna Malczewska6, *Ignat A Drozdov2, *Alexandra Kitz2, Edward L Kaplan7
1Yale University, New Haven, CT;2Wren Laboratories, Branford, CT;3Imperial College London, London, United Kingdom4Ospedale San Raffaele IRCCS, Milan, Italy5University of Torino, Turin, Italy6Medical University of Silesia, Katowice, Poland7The University of Chicago Medicine, Chicago, IL
OBJECTIVE(S): Identification of residual disease after neuroendocrine tumor (NET) resection is important to facilitate management. Post-surgery imaging is insensitive and current biomarkers ineffective. We examined whether NETest, a multigene blood biomarker, was diagnostic of NETs, correlated with surgical resection and could predict recurrence. Data were compared to CgA.
METHODS: Multicenter evaluation of lung, small bowel, duodenal, gastric and pancreas NET resections (n=103). 1ml blood collected at D0 and POD30. Transcript quantification by PCR (NETest score: normal: <20), CgA by NeoELISA (normal<109ng/mL). Analyses: Wilcoxon paired test, Chi2, McNemar’s test.
NETs: 47 pancreatic, 26 small bowel, 26 lung, 2 appendix, 1 duodenum, 1 gastric. Surgery: R0 (83), R1/R2 (20). Follow-up: mean=12months. NETest D0: 103/103 (100%)-positive. CgA: 23/103 (22%)-positive. Chi2=78, p<0.0001. POD30 R0: NETest: decreased 59±28 to 26±23 (p<0.0001). 37% (31/83) were elevated. CgA: decreased 101±120 to 80±79 (p<0.03) with 18% (15/83) elevated. R1/R2: POD 30. NETest: decreased 79±20 to 40±22 with 100% (20/20) elevated. CgA: surgery had no effect (75±38 to 67±50) and 10% (2/20) positive. R0 Recurrence (n=25): NETest: Elevated POD30 score 25/25 (100%) exhibited image-identifiable recurrence at 12months. With normal score (0/52) were image-positive. Chi2=56, p<0.0001. NETscore elevation at POD30 predicted recurrence with 93% accuracy. CgA: Of 25 recurrences, 2 (8%) had elevated CgA levels.
CONCLUSIONS: NETest diagnosis is more accurate than CgA (100% vs 23%). After R0 NETest decreased significantly. An elevated NETest on POD30 predicted recurrence with 93% accuracy compared to CgA (8%). NET mRNA blood levels have clinical utility and identify residual disease prior to imaging.
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