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A multigenomic liqu...
A multigenomic liquid biopsy biomarker for neuroendocrine tumor disease outperforms CgA and has surgical and clinical utility
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- Modlin, I. M. (författare)
- Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA.
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- Kidd, M. (författare)
- Wren Labs, Branford, CT USA.
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- Falconi, M. (författare)
- IRCCS San Raffaele Sci Inst, Dept Surg, Milan, Italy.
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- Filosso, P. L. (författare)
- Univ Turin, Dept Surg Sci, Turin, Italy.
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- Frilling, A. (författare)
- Imperial Coll London, Dept Surg & Canc, London, England.
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- Malczewska, A. (författare)
- Med Univ Silesia, Dept Endocrinol & Neuroendocrine Tumours, Katowice, Poland.
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- Toumpanakis, C. (författare)
- Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
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- Valk, G. (författare)
- Univ Med Ctr Utrecht, Dept Endocrine Oncol, Utrecht, Netherlands.
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- Pacak, K. (författare)
- NIH, Med Neuroendocrinol, Bldg 10, Bethesda, MD 20892 USA.
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- Bodei, L. (författare)
- Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA.
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- Öberg, Kjell, 1946- (författare)
- Uppsala universitet,Endokrin tumörbiologi
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Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA Wren Labs, Branford, CT USA. (creator_code:org_t)
- Elsevier, 2021
- 2021
- Engelska.
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 32:11, s. 1425-1433
- Relaterad länk:
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http://hdl.handle.ne...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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: MannWhitney 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/Ga-68-SSA-PET) 91%. Presurgery, all NETs (n = 153) were positive (100%). After palliative R1/R2 surgery (n = 51) all (100%) remained elevated. After curative RO-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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- NETest
- biomarker
- neuroendocrine tumor
- NET
- Chromogranin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Modlin, I. M.
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Kidd, M.
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Falconi, M.
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Filosso, P. L.
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Frilling, A.
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Malczewska, A.
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Toumpanakis, C.
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Valk, G.
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Pacak, K.
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Bodei, L.
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Öberg, Kjell, 19 ...
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Uppsala universitet