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Endocrine Abstracts (2020) 72 P1 | DOI: 10.1530/endoabs.72.P1


Post-operative NETest scores detect residual NET disease and accurately predicts tumor recurrence in R0

Irvin Modlin1, Mark Kidd2, Kjell Oberg3, Massimo Falconi4, Pier Luigi Filosso5, Andrea Frilling6, Anna Malczewska7, Ronald Salem1, Christos Toumpanakis8, Faidon-Marios Laskaratos8, Stefano Partelli4, Matteo Roffinella5, Claudia von Arx8, Beata Kos-Kudla7, Lisa Bodei9, Ignat Drozdov2 & Alexandra Kitz2

1Yale University, New Haven, Connecticut, USA; 2Wren Laboratories, Branford, Connecticut, USA; 3University Hospital, Uppsala, Sweden; 4San Rafaelle IRCCS, Milan, Italy; 5University of Torino, Turin, Italy; 6Imperial College, London, UK; 7Medical University of Silesia, Katowice, Poland; 8Royal Free Hospital, London, UK; 9Memorial Sloan Kettering Cancer Center, New York, USA

Introduction: Surgery is the only cure for neuroendocrine tumor (NET) disease. R0 resection is critical for successful tumor resection. Early detection of residual disease is key for optimal management. Both imaging and current biomarkers have intrinsic limitations and are largely ineffective up to 3 months post-surgery. NETest, a multigene blood biomarker test, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would detect residual disease (after R1/R2) and could be used to predict recurrence in R0.

Methods: Multicenter evaluation of surgically treated primary NETs (n=153). Blood sampling at D0 and POD30. Follow-up including CT/MRI. mRNA quantification by PCR and algorithmic analysis (NETest score: 0–100; normal<20). Statistics: Mann-Whitney U-test, Chi2, Kaplan-Meier survival, AUROC. Mean±S.E.M.

Results: NET-cohort (n=153): 57 pancreatic, 62 small bowel, 27 lung, 4 duodenal, 3 gastric. Surgery: R0 (n=102), R1and R2 (n=51). Follow-up: mean 14 months (range 3–68). Preop 153/153 NETest-positive (68±28). R1/R2 Cohort: Score decreased (73±26 to 52±27). At POD30, 100% were elevated (P<0.0001). R0 Cohort: POD30 levels decreased from 62±28 to 22±20 (P<0.0001). 30% (31/102) remained elevated: 28% lung, 29% pancreas, 27% small bowel and 1/3 gastric. Recurrence: By 12 months, 24/31 (74%) with POD30 NETest>20 had image-identifiable recurrence. NETest>20 predicted recurrence with 100% sensitivity and correlated highly (Chi2=17.1, P<0.0001) with residual disease. AUROC analysis identified AUC=0.96 (P<0.0001) for recurrence-prediction.

Conclusion: A liquid biopsy (NETest) genomic biomarker for neuroendocrine tumors is 100% accurate for tumor diagnosis. All resections decreased NETest levels. NETest>20 at POD30 predicted radiologically recurrent disease with 93% accuracy and 100% sensitivity. R0 resection appears to be ineffective in ˜30%. NET mRNA blood levels provide early objective genomic identification of residual disease and may facilitate management.