A multigenomic liquid biopsy biomarker for neuroendocrine tumor disease outperforms CgA and has surgical and clinical utility
| Autor: | M. Kidd, P.L. Filosso, Karel Pacak, A. Frilling, I. M. Modlin, Anna Malczewska, Lisa Bodei, Christos Toumpanakis, Massimo Falconi, Gerlof D. Valk, Kjell Öberg |
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| Přispěvatelé: | Dr. Heinz-Horst Deichmann Stiftung |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty endocrine system NETest biomarker neuroendocrine tumor NET Chromogranin Neuroendocrine tumors NETest biomarker neuroendocrine tumor NET Chromogranin Article McNemar's test Internal medicine medicine Biomarkers Tumor Humans 1112 Oncology and Carcinogenesis Oncology & Carcinogenesis Prospective Studies Liquid biopsy biology Surrogate endpoint business.industry Liquid Biopsy Chromogranin A Hematology medicine.disease Pancreatic Neoplasms Neuroendocrine Tumors Cross-Sectional Studies Response Evaluation Criteria in Solid Tumors Cohort biology.protein Biomarker (medicine) Neoplasm Recurrence Local business |
| Zdroj: | Ann Oncol |
| Popis: | BACKGROUND: Biomarkers are key tools in cancer management. In neuroendocrine tumors (NETs), Chromogranin A (CgA) was considered acceptable as a biomarker. We compared the clinical efficacy of a multigenomic blood biomarker (NETest) to CgA over a 5-year period. PATIENTS AND METHODS: An observational, prospective, cross-sectional, multicenter, multinational, comparative cohort assessment. Cohort 1: NETest evaluation in NETs (n = 1684) and cancers, benign diseases, controls (n = 731). Cohort 2: (n = 1270): matched analysis of NETest/CgA in a sub-cohort of NETs (n = 922) versus other diseases and controls (n = 348). Disease status was assessed by response evaluation criteria in solid tumors (RECIST). NETest measurement: qPCR [upper limit of normal (ULN: 20)], CgA (EuroDiagnostica, ULN: 108 ng/ml). STATISTICS: Mann-Whitney U-test, AUROC, chi-square and McNemar' test. RESULTS: Cohort 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). Locoregional 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%. Presurgery, 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 (chi-square = 7.7, OR = 18.5) and metastatic identification (chi-square = 180, OR = 8.4). NETest identified progressive disease (95%) versus CgA (57%, P < 0.0001). Imaging concordance for NETest was 91% versus CgA (46%) (P < 0.0001). Recurrence prediction after surgery was NETest-positive in >94% versus CgA 11%. CONCLUSION: NETest 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. |
| Databáze: | OpenAIRE |
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