Endocrine Abstracts

Background: The NETest, a neuroendocrine multigene transcript ‘liquid biopsy’, is a novel biomarker for GEP-NETs. Current biomarkers are monoanalyte amines or peptides whereas the NETest is a multianalyte signature providing molecular biological information pertinent to clinical disease.

Aim: Independently validate the utility of the NETest for the diagnosis of GEP-NETs and identification of disease progression.

Material and methods: Cohorts: controls (n=63), histologically confirmed NETs (n=113), pancreatic [PNET]: n=68; small bowel [SINET]: n=45). Disease extent at blood draw: CT (n=110) or ⁶⁸Ga-DOTA-TATE PET/CT (n=72). Image-positive disease was defined as CT or ⁶⁸Ga-PET-positive. Both CT/⁶⁸Ga-PET-negative was considered no evidence of disease (NED). Disease status evaluation was RECIST 1.1-based. NETest assay metrics and disease status were evaluated in image positive disease compared to NED. NETest upper limit of normal: 20. Data is mean±S.D.

Results: Diagnosis: Image-positive disease was present in 102 (PNET: n=60; SINET: n=42) and NED in 11 (PNET: n=8; SINET: n=3). NETest levels were significantly increased (27±23) in all GEP-NETs (n=113), vs controls (8±4, P<0.0001). In image-positive disease, NETest levels were 36±22 and in NED significantly lower (7±5, P<0.0001). NETest elevations in image-positive PNET (41±25) and SINETs (38±23) were comparable. NETest diagnostic metrics: accuracy (94%), sensitivity (99%), specificity (90%). Concordance with imaging: NETest was 92% concordant with CT and 96% concordant with ⁶⁸Ga-PET. In CT-positive (n=68), NETest was elevated in 99% (35±20). In CT-negative (n=42), NETest was normal (14±20) in 83%. In ⁶⁸Ga-PET-positive (n=58), the NETest was elevated (38±24) in 98%. In ⁶⁸Ga-PET-negative (n=14), the NETest was negative in 86% (11±11). There were 11 image-discordant results. There were nine ⁶⁸Ga-PET+ve/CT-ve with NETest positive in 89% and two ⁶⁸Ga-PET-ve/CT+ve with NETest positive. Disease status: Eighteen patients exhibited progressive disease (PD). PD NETest levels were significantly (P<0.003) higher (56±29) than stable disease (30±15).

Conclusions: A positive NETest is an effective diagnostic (>90%) for pancreatic and small bowel NETs. Elevated NETest levels are as effective as imaging in diagnosis. NETest levels accurately identified progression. The NETest may have clinical utility in management of PNET and SINETs.