Early Identification of Residual Disease After Neuroendocrine Tumor Resection Using a Liquid Biopsy Multigenomic mRNA Signature (NETest)

Published on May 18, 2021in Annals of Surgical Oncology4.061
· DOI :10.1245/S10434-021-10021-1
Irvin M. Modlin81
Estimated H-index: 81
(Yale University),
Mark Kidd66
Estimated H-index: 66
+ 14 AuthorsAlexandra Kitz2
Estimated H-index: 2
Introduction Surgery is the only cure for neuroendocrine tumors (NETs), with R0 resection being critical for successful tumor removal. Early detection of residual disease is key for optimal management, but both imaging and current biomarkers are ineffective post-surgery. NETest, a multigene blood biomarker, identifies NETs with >90% accuracy. We hypothesized that surgery would decrease NETest levels and that elevated scores post-surgery would predict recurrence. Methods This was a multicenter evaluation of surgically treated primary NETs (n = 153). Blood sampling was performed at day 0 and postoperative day (POD) 30. Follow-up included computed tomography/magnetic resonance imaging (CT/MRI), and messenger RNA (mRNA) quantification was performed by polymerase chain reaction (PCR; NETest score: 0-100; normal ≤20). Statistical analyses were performed using the Mann-Whitney U-test, Chi-square test, Kaplan-Meier survival, and area under the receiver operating characteristic curve (AUROC), as appropriate. Data are presented as mean ± standard deviation. Results The NET cohort (n = 153) included 57 patients with pancreatic cancer, 62 patients with small bowel cancer, 27 patients with lung cancer, 4 patients with duodenal cancer, and 3 patients with gastric cancer, while the surgical cohort comprised patients with R0 (n = 102) and R1 and R2 (n = 51) resection. The mean follow-up time was 14 months (range 3-68). The NETest was positive in 153/153 (100%) samples preoperatively (mean levels of 68 ± 28). In the R0 cohort, POD30 levels decreased from 62 ± 28 to 22 ± 20 (p 20 had image-identifiable recurrence. An NETest score of >20 predicted recurrence with 100% sensitivity and correlated with residual disease (Chi-square 17.1, p Conclusion The preoperative NETest accurately identified all NETs (100%). All resections decreased NETest levels and a POD30 NETest score >20 predicted radiologically recurrent disease with 94% accuracy and 100% sensitivity. R0 resection appears to be ineffective in approximately 30% of patients. NET mRNA blood levels provide early objective genomic identification of residual disease and may facilitate management.
#1Mark KiddH-Index: 66
#1Mark KiddH-Index: 5
Last. Irvin M. ModlinH-Index: 81
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BACKGROUND: The NETest is a multi-gene assay comprising 51 circulating neuroendocrine tumor specific transcripts. The quotient of the 51-gene assay is based upon an ensemble of machine learning algorithms. Eight cancer hallmarks or "omes" (apoptome, epigenome, growth factor signalome, metabolome, proliferome, plurome, secretome SSTRome) represent 29 genes. The NETest is an accurate diagnostic (>90%) but its prognostic utility has not been assessed. In this study, we describe expansion of the NET...
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#1Anna MalczewskaH-Index: 12
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BACKGROUND: There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions, the clinical utility of the NETest as a liquid biopsy in an ENETS Centre of Excellence and compared its utility with chromogranin A (CgA). Methods Cohorts: Gastroenteropancreatic (GEP)-NEN (n=253), bronchopulmonary (BP)-NEN (n=64), thymic NEN (n=1), colon cancer (n=37), NSCLC (n=63), benign lung disease (n=59...
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BACKGROUND: Surgery remains the only treatment for the cure of pancreatic neuroendocrine tumors (PanNETs). Biomarkers to identify the completeness of resection and predict recurrence are lacking. OBJECTIVE: The aims of this study were to evaluate if the blood measurement of neuroendocrine gene transcripts (NETest) was diagnostic of PanNETs, and whether NETest blood levels could identify complete resection. We compared transcript analysis with the biomarker chromogranin A (CgA). METHODS: This was...
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#1Kjell ÖbergH-Index: 116
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Abstract Biomarkers that are secretory monoanalyte products of GEP (gastro-entero-pancreatic) and BP (broncho-pulmonary) or lung NETs (neuroendocrine tumors) have significant limitations in clinical utility. The assessment of secretory activity provides little information in regard to tumor biology. Furthermore, ∼50% of NETs have measurable secretory products. Molecular genomic identification in blood (NETest liquid biopsy) of the regulators of tumor biology provide multianalyte, real-time asses...
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