Circulating Transcript Analysis (NETest) in GEP-NETs Treated With Somatostatin Analogs Defines Therapy

Journal of Clinical Endocrinology and Metabolism - Tập 100 Số 11 - Trang E1437-E1445 - 2015
Jarosław B. Ćwikła1, Lisa Bodei2, Agnieszka Kolasińska-Ćwikła3, A Sankowski4, Irvin M. Modlin5, Mark Kidd6
1Department of Radiology, Faculty of Medical Sciences (J.Ć.), University of Warmia and Mazury, Olsztyn 10-558, Poland
2Division of Nuclear Medicine (L.B.), European Institute of Oncology, Milan 20141, Italy
3Department of Oncology (A.K.-Ć.), Maria Skłodowska-Curie Memorial Cancer Center, Institute of Oncology, Warsaw 44-101, Poland
4Department of Radiology (A.S.), Hospital Ministry of Internal Affairs, Warsaw 02-507, Poland
5Keewaydin Consulting, Inc. (I.M.M.), Woodbridge, Connecticut 06525
6Wren Laboratories (M.K.), Branford, Connecticut 06405

Tóm tắt

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 (11 mo) 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 Chromogranin A (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 (P < .0001). Prospective set: 28 patients (26/28 SD) undergoing standard SSA. Grading: 12 G1, 16 G2. SSA Response: progression-free survival: 315 days: 14 (50%) SD, 14 (50%) PD. NETest: Twenty had elevated (≥80%) values; 14 developed PD; six, SD. CgA: Twelve of 28 exhibited elevated baseline values and/or subsequent >25% 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.

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Tài liệu tham khảo

Modlin, 2008, Gastroenteropancreatic neuroendocrine tumours, Lancet Oncol, 9, 61, 10.1016/S1470-2045(07)70410-2

Klöppel, 2009, ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification, Neuroendocrinology, 90, 162, 10.1159/000182196

Lawrence, 2010, New pharmacologic therapies for gastroenteropancreatic neuroendocrine tumors, Gastroenterol Clin North Am, 39, 615, 10.1016/j.gtc.2010.08.013

Pavel, 2013, Systemic therapeutic options for carcinoid, Semin Oncol, 40, 84, 10.1053/j.seminoncol.2012.11.003

Kanakis, 2012, Biochemical markers for gastroenteropancreatic neuroendocrine tumours (GEP-NETs), Best Pract Res Clin Gastroenterol, 26, 791, 10.1016/j.bpg.2012.12.006

Giandomenico, 2013, Improving the diagnosis and management of neuroendocrine tumors: Utilizing new advances in biomarker and molecular imaging science, Neuroendocrinology, 98, 16, 10.1159/000348832

Sundin, 2012, Therapeutic monitoring of gastroenteropancreatic neuroendocrine tumors: The challenges ahead, Neuroendocrinology, 96, 261, 10.1159/000342270

Falconi, 2012, ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: Well-differentiated pancreatic non-functioning tumors, Neuroendocrinology, 95, 120, 10.1159/000335587

Bodei, 2014, The future of nuclear medicine imaging of neuroendocrine tumors: On a clear day one might see forever, Eur J Nucl Med Mol Imaging, 41, 2189, 10.1007/s00259-014-2836-1

Modlin, 2014, Neuroendocrine tumor biomarkers: Current status and perspectives, Neuroendocrinology, 100, 265, 10.1159/000368363

Frilling, 2012, Neuroendocrine tumor disease: An evolving landscape, Endocr Relat Cancer, 19, R163, 10.1530/ERC-12-0024

Modlin, 2010, Chromogranin A—biological function and clinical utility in neuro endocrine tumor disease, Ann Surg Oncol, 17, 2427, 10.1245/s10434-010-1006-3

Marotta, 2012, Limitations of Chromogranin A in clinical practice, Biomarkers, 17, 186, 10.3109/1354750X.2012.654511

Kulke, 2011, Future directions in the treatment of neuroendocrine tumors: Consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting, J Clin Oncol, 29, 934, 10.1200/JCO.2010.33.2056

Welin, 2009, Elevated plasma chromogranin A is the first indication of recurrence in radically operated midgut carcinoid tumors, Neuroendocrinology, 89, 302, 10.1159/000179900

Kidd, 2015, Blood and tissue neuroendocrine tumor gene cluster analysis correlate, define hallmarks and predict disease status, Endocr Relat Cancer, 22, 561, 10.1530/ERC-15-0092

Modlin, 2014, A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection, Endocr Relat Cancer, 21, 615, 10.1530/ERC-14-0190

Shapiro, 1999, The interpretation of diagnostic tests, Stat Methods Med Res, 8, 113, 10.1177/096228029900800203

Frank, 2003, Clinical biomarkers in drug discovery and development, Nat Rev Drug Discov, 2, 566, 10.1038/nrd1130

Caplin, 2014, Lanreotide in metastatic enteropancreatic neuroendocrine tumors, N Engl J Med, 371, 224, 10.1056/NEJMoa1316158

Rinke, 2009, Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: A report from the PROMID Study Group, J Clin Oncol, 27, 4656, 10.1200/JCO.2009.22.8510

Ćwikła, 2008, Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs, J Nucl Med, 49, 1060, 10.2967/jnumed.107.046961

Kwekkeboom, 2010, Somatostatin-receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors, Endocr Relat Cancer, 17, R53, 10.1677/ERC-09-0078

Sankowski, 2012, The clinical value of MRI using single-shot echoplanar DWI to identify liver involvement in patients with advanced gastroenteropancreatic-neuroendocrine tumors (GEP-NETs), compared to FSE T2 and FFE T1 weighted image after i.v. Gd-EOB-DTPA contrast enhancement, Med Sci Monit, 18, MT33, 10.12659/MSM.882719

Modlin, 2013, The Identification of gut neuroendocrine tumor disease by multiple synchronous transcript analysis in blood, Plos One, e63364, 10.1371/journal.pone.0063364

Modlin, 2014, Gut neuroendocrine tumor blood qPCR fingerprint assay: Characteristics and reproducibility, Clin Chem, 52, 419

Stridsberg, 2003, A comparison between three commercial kits for chromogranin A measurements, J Endocrinol, 177, 337, 10.1677/joe.0.1770337

Stridsberg, 1995, Measurements of chromogranin A, chromogranin B (secretogranin I), chromogranin C (secretogranin II) and pancreastatin in plasma and urine from patients with carcinoid tumours and endocrine pancreatic tumours, J Endocrinol, 144, 49, 10.1677/joe.0.1440049

Bosman, 2010, WHO classification of tumours of the digestive system, 4th ed

Hanley, 1982, The meaning and use of the area under a receiver operating characteristic (ROC) curve, Radiology, 143, 29, 10.1148/radiology.143.1.7063747

Hanley, 1983, A method of comparing the areas under receiver operating characteristic curves derived from the same cases, Radiology, 148, 839, 10.1148/radiology.148.3.6878708

de Mestier, 2014, Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: State of the art, Endocr Relat Cancer, 21, R105, 10.1530/ERC-13-0365

Lindholm, 2011, Biomarkers and molecular imaging in gastroenteropancreatic neuroendocrine tumors, Horm Metab Res, 43, 832, 10.1055/s-0031-1287794

Oberg, 2011, Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours, Endocr Relat Cancer, 18, S17, 10.1530/ERC-10-0280

Massironi, 2010, Plasma chromogranin A response to octreotide test: Prognostic value for clinical outcome in endocrine digestive tumors, Am J Gastroenterol, 105, 2072, 10.1038/ajg.2010.154

Massironi, 2014, Chromogranin A in diagnosing and monitoring patients with gastroenteropancreatic neuroendocrine neoplasms: A large series from a single institution, Neuroendocrinology, 100, 240, 10.1159/000369818

Jensen, 2013, Chromogranin A is a sensitive marker of progression or regression in ileo-cecal neuroendocrine tumors, Scand J Gastroenterol, 48, 70, 10.3109/00365521.2012.733953

Rindi, 2014, The 2010 WHO classification of digestive neuroendocrine neoplasms: A critical appraisal four years after its introduction, Endocr Pathol, 25, 186, 10.1007/s12022-014-9313-z

Whitman, 2006, Catecholamine-secreting metastatic carcinoid as differential diagnosis in pheochromocytoma: Clinical, laboratory, and imaging clues in the search for the lurking neuroendocrine tumor (NET), Ann N Y Acad Sci, 1073, 59, 10.1196/annals.1353.007

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Journal of Clinical Endocrinology and Metabolism

Tập 100 Số 11

E1437-E1445

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