{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:52:12Z","timestamp":1787017932037,"version":"build-2736575974"},"reference-count":59,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2021]]},"abstract":"<b><i>Background:<\/i><\/b> There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions in an ENETS Center of Excellence (CoE), the clinical utility of the NETest as a liquid biopsy and compared its utility with chromogranin A (CgA) measurement. <b><i>Methods:<\/i><\/b> The cohorts were: gastroenteropancreatic NEN (GEP\u00adNEN; <i>n<\/i> = 253), bronchopulmonary NEN (BPNEN; <i>n<\/i> = 64), thymic NEN (<i>n<\/i> = 1), colon cancer (<i>n<\/i> = 37), non-small-cell lung cancer (NSCLC; <i>n<\/i> = 63), benign lung disease (<i>n<\/i> = 59), and controls (<i>n<\/i> = 86). In the GEPNEN group, 164 (65%) had image-positive disease (IPD, <i>n<\/i> = 135) or were image-negative but resection-margin\/biopsy-positive (<i>n<\/i> = 29), and were graded as G1 (<i>n<\/i> = 106), G2 (<i>n<\/i> = 49), G3 (<i>n<\/i> = 7), or no data (<i>n<\/i> = 2). The remainder (<i>n<\/i> = 71) had no evidence of disease (NED). In the BPNEN group, 43\/64 (67%) had IPD. Histology revealed typical carcinoids (TC, <i>n<\/i> = 14), atypical carcinoids (AC, <i>n<\/i> = 14), small-cell lung cancer (SCLC, <i>n<\/i> = 11), and large-cell neuroendocrine carcinoma (LCNEC, <i>n<\/i> = 4). Disease status (stable or progressive) was evaluated according to RECIST v1.1. Blood sampling involved NETest (<i>n<\/i> = 563) and NETest\/CgA analysis matched samples (<i>n<\/i> = 178). NETest was performed by PCR (on a scale of 0\u2013100), with a score \u226520 reflecting a disease-positive status and &#x3e;40 reflecting progressive disease. CgA positivity was determined by ELISA. Samples were deidentified and measurements blinded. The Kruskal-Wallis, Mann-Whitney U, and McNemar tests, and the area under the curve (AUC) of the receiver-operating characteristics (ROC) were used in the statistical analysis. <b><i>Results:<\/i><\/b> In the GEPNEN group, NETest was significantly higher (34.4 \u00b1 1.8, <i>p<\/i> &#x3c; 0.0001) in disease-positive patients than in patients with NED (10.5 \u00b1 1, <i>p<\/i> &#x3c; 0.0001), colon cancer patients (18 \u00b1 4, <i>p<\/i> &#x3c; 0.0004), and controls (7 \u00b1 0.5, <i>p<\/i> &#x3c; 0.0001). Sensitivity for detecting disease compared to controls was 89% and specificity was 94%. NETest levels were increased in G2 vs. G1 (39 \u00b1 3 vs. 32 \u00b1 2, <i>p<\/i> = 0.02) and correlated with stage (localized: 26 \u00b1 2 vs. regional\/distant: 40 \u00b1 3, <i>p<\/i> = 0.0002) and progression (55 \u00b1 5 vs. 34 \u00b1 2 in stable disease, <i>p<\/i> = 0.0005). In the BPNEN group, diagnostic sensitivity was 100% and levels were significantly higher in patients with bronchopulmonary carcinoids (BPC; 30 \u00b1 1.3) who had IPD than in controls (7 \u00b1 0.5, <i>p<\/i> &#x3c; 0.0001), patients with NED (24.1 \u00b1 1.3, <i>p<\/i> &#x3c; 0.005), and NSCLC patients (17 \u00b1 3, <i>p<\/i> = 0.0001). NETest levels were higher in patients with poorly differentiated BPNEN (LCNEC + SCLC; 59 \u00b1 7) than in those with BPC (30 \u00b1 1.3, <i>p<\/i> = 0.0005) or progressive disease (57.8 \u00b1 7), compared to those with stable disease (29.4 \u00b1 1, <i>p<\/i> &#x3c; 0.0001). The AUC for differentiating disease from controls was 0.87 in the GEPNEN group and 0.99 in BPC patients (<i>p<\/i> &#x3c; 0.0001). Matched CgA analysis was performed in 178 patients. In the GEPNEN group (<i>n<\/i> = 135), NETest was significantly more accurate for detecting disease (99%) than CgA positivity (53%; McNemar test \u03c7<sup>2<\/sup> = 87, <i>p<\/i> &#x3c; 0.0001). In the BPNEN group (<i>n<\/i> = 43), NETest was significantly more accurate for disease detection (100%) than CgA positivity (26%; McNemar\u2019s test \u03c7<sup>2<\/sup> = 30, <i>p<\/i> &#x3c; 0.0001). <b><i>Conclusions:<\/i><\/b> The NETest is an accurate diagnostic for GEPNEN and BPNEN. It exhibits tumor biology correlation with grading, staging, and progression. CgA as a biomarker is significantly less accurate than NETest. The NETest has substantial clinical utility that can facilitate patient management.<\/jats:p>","DOI":"10.1159\/000508106","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T17:00:33Z","timestamp":1587747633000},"page":"304-319","source":"Crossref","is-referenced-by-count":22,"title":["Prospective Evaluation of the NETest as a Liquid Biopsy for Gastroenteropancreatic and Bronchopulmonary Neuroendocrine Tumors: An ENETS Center of Excellence Experience"],"prefix":"10.1159","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-4832","authenticated-orcid":false,"given":"Anna","family":"Malczewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Witkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"W\u00f3jcik-Giertuga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Ku\u015bnierz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Bocian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Rydel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Robek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Pierzcha\u0142a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Malczewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Le\u015b-Zieli\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Czy\u017cewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Ziora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Pilch-Kowalczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Zaj\u0119cki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Kos-Kud\u0142a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1159\/000493319"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1159\/000443167"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.05.006"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21493"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1159\/000443170"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.3049"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1159\/000367850"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1159\/000358727"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1159\/000504605"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2018.05.002"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.14"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1159\/000368363"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2016.01.002"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3109\/1354750X.2012.654511"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1159\/000500525"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpb.2018.09.016"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11815"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.currproblcancer.2018.08.004"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13514"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.125529"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax7392"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063364"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-14-0190"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1159\/000336089"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0727"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00740"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.4_suppl.222"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1159\/000497037"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1530\/EC-19-0030"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2019.11.003"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2792"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-015-3250-z"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1016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