Circulating transcript analysis (NETest) in GEP-NETs treated with somatostatin analogs defines therapy

Context: Early and precise delineation of therapeutic responses are key issues in neuroendocrine neoplasm/tumor management. Imaging is currently used but exhibits limitations in sensitivity and specificity. The utility of biomarkers is unclear. Objective, Setting, and Design: This prospective cohort study (11mo)sought to determine whether measurements of circulating neuroendocrine tumor transcripts (NETest) predict responses to somatostatin analogs (SSAs). Patients: The test set consisted of 35 SSA-treated gastroenteropancreatic-NETs (RECISTevaluated). The prospective set consisted of 28 SSA-treated Grade 1-Grade 2 GEP-NETs. Intervention(s): Whole blood for transcript analysis (NETest) and plasma for ChromograninA(CgA) (baseline), were collected every 4 weeks (prior to SSA injection). Morphologic (multidetector computed tomography/MRI) and functional imaging (99mTc-[HYNIC, Tyr3]-Octreotide) was undertaken at entry and 6-month intervals until progression (RECIST 1.0). Main Outcome Measure(s): Treatment response. Results: Test set: NETest (≥80%; scale, 0-100%) differentiated stable (SD) and progressive (PD) disease (P25% increase; eight developed PD; four, SD. NETest (P=.002) and grade (P=.054) were the only factors associated with treatment response. Multiple regression analysis established that the NETest could predict disease progression (P=.0002). NETest changes occurred significantly earlier (146 d prior to progression vs 56 d CgA; P <.0001; χ2 = 19) and in more patients (100 vs 57%; P <.02). Conclusions: NETest values (80-100%) were more accurate and occurred at a significantly earlier time point than CgA and predicted SSA treatment response.