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Multicenter Study
. 2021 Sep 1;274(3):481-490.
doi: 10.1097/SLA.0000000000005026.

Molecular Genomic Assessment Using a Blood-based mRNA Signature (NETest) is Cost-effective and Predicts Neuroendocrine Tumor Recurrence With 94% Accuracy

Irvin M Modlin  1 , Mark Kidd  2 , Andrea Frilling  3 , Massimo Falconi  4 , Pier Luigi Filosso  5 , Anna Malczewska  6 , Alexandra Kitz  2
Affiliations
Multicenter Study

Molecular Genomic Assessment Using a Blood-based mRNA Signature (NETest) is Cost-effective and Predicts Neuroendocrine Tumor Recurrence With 94% Accuracy

Irvin M Modlin et al. Ann Surg. .

Abstract

Introduction: Identification of residual disease after neuroendocrine tumor (NET) resection is critical for management. Post-surgery imaging is insensitive, expensive, and current biomarkers ineffective. We evaluated whether the NETest, a multigene liquid biopsy blood biomarker, correlated with surgical resection and could predict recurrence.

Methods: Multicenter evaluation of NET resections over 24 months (n = 103): 47 pancreas, 26 small bowel, 26 lung, 2 appendix, 1 duodenum, 1 stomach. Surgery: R0 (83), R1/R2 (20). One millilitre of blood was collected at D0 and posroperative day (POD) 30. Transcript quantification by polymerase chain reaction (normal: ≤20), CgA by NEOLISA (normal ≤108 ng/mL). Standard-of-care (SoC) follow-up costs were calculated and compared to POD30 NETest-stratification approach. Analyses: Wilcoxon-paired test, Chi-square test.

D biomarkers: NETest: 103 of 103 (100%)-positive, whereas 23 of 103 (22%) were CgA-positive (Chi-square = 78, P < 0.0001).In the R0 group, the NETest decreased 59 ± 28 to 26 ± 23 (P < 0.0001); 36% (30/83) remained elevated. No significant decrease was evident for CgA. In the R1/R2 group the NETest decreased but 100% remained elevated. CgA levels did not decrease.An elevated POD30 NETest was present in R0 and 25 (83%) developed radiological recurrences. Normal score R0 s (n = 53) did not develop recurrence (Chi-square = 56, P < 0.0001). Recurrence prediction was 94% accurate with the NETest.

Cost evaluation: Using the NETest to stratify postoperative imaging resulted in a cost-savings of 42%.

Conclusion: NETest diagnosis is more accurate than CgA (100% vs 22%). Surgery significantly decreased NETest. An elevated POD30 NETest predicted recurrence with 94% accuracy and post-surgical POD30 NETest follow-up stratification decreased costs by 42%. CgA had no surgical utility. Further studies would define the accuracy and cost-effectiveness of the NETest in the detection of postoperative recurrent disease.

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Conflict of interest statement

Conflict of Interest Statement: M.F.: research grants and advisory role for J&J, Novartis, Ipsen, AAA, Mylan, and Celgene; A.F.: advisory roles for Novartis, Ipsen, and SIRTEXl; I.M.M.: consultant for Wren Laboratories; M.K. and A.K. are employees of Wren Laboratories; E.L.K., P.L.F., and A.M. have no disclosures. The authors report no conflicts of interest.

References

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    1. Öberg K. The genesis of the neuroendocrine tumors concept: from Oberndorfer to 2018. Endocrinol Metab Clin North Am 2018; 47:711–731.
    1. Merola E, Pavel ME, Panzuto F, et al. Functional imaging in the follow-up of enteropancreatic neuroendocrine tumors: clinical usefulness and indications. J Clin Endocrinol Metab 2017; 102:1486–1494.

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