• I M Modlin, M Kidd, M Falconi, P L Filosso, A Frilling, A Malczewska, C Toumpanakis, G Valk, K Pacak, L Bodei, and K Oberg.
• Yale University School of Medicine, New Haven, CT, USA.
• Ann. Oncol. 2021 Aug 11.

BackgroundBiomarkers are key tools in cancer management. In neuroendocrine tumors (NETs), Chromogranin A (CgA) was considered acceptable as a biomarker. We assessed the clinical efficacy of a multigenomic blood biomarker (NETest) to CgA over a 5-year period.MethodsAn observational, prospective, cross-sectional, multicenter, multinational, comparative cohort assessment. Cohort #1: NETest evaluation in NETs (1,684) and cancers, benign diseases, controls (731). Cohort #2: (n=1,270): matched analysis of NETest/CgA in a sub-cohort of NETs (n=922) vs. other diseases and controls (n=348). Disease status was assessed by RECIST. NETest measurement: qPCR (ULN: 20), CgA (EuroDiagnostica, ULN: 108ng/mL).StatisticsMann-Whitney U-test, AUROC, Chi2 and McNemar's test.ResultsCohort #1: NETest diagnostic accuracy was 91% (p<0.0001) and identified pheochromocytomas (98%), small intestine (94%), pancreas (91%), lung (88%), gastric (80%) and appendix (79%). NETest reflected grading: G1: 40±1, G2 (50±1) and G3 (52±1). Loco-regional disease levels were lower (38±1) than metastatic (52±1, p<0.0001). NETest accurately stratified RECIST-assessed disease extent: no disease (21±1), stable (43±2), progressive (62±2) (p<0.0001). NETest concordance with imaging (CT/MRI/68Ga-SSA-PET) 91%. Pre-surgery, all NETs (n=153) were positive (100%). After palliative R1/R2 surgery (n=51) all (100%) remained elevated. After curative R0-surgery (n=102), NETest levels were normal in 81(70%) with no recurrence at 2 years. In the 31 (30%) with elevated levels, 25 (81%) recurred within 2 years. Cohort #2: NETest diagnostic accuracy was 87% and CgA 54% (p<0.0001). NETest was more accurate than CgA for grading (Chi2=7.7, OR=18.5) and metastatic identification (Chi2=180, OR=8.4). NETest identified progressive disease (95%) vs CgA (57%, p<0.0001). Imaging concordance for NETest was 91% vs. CgA (46%) (p<0.0001). Recurrence prediction after surgery was NETest-positive in >94% vs. CgA 11%.ConclusionNETest accurately diagnoses NETs and is an effective surrogate marker for imaging, grade, metastases and disease status compared to CgA. A multigenomic liquid biopsy is an accurate biomarker of NET disease.Copyright © 2021. Published by Elsevier Ltd.

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