{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:29:08Z","timestamp":1790173748496,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,9,8]],"date-time":"2018-09-08T00:00:00Z","timestamp":1536364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013041","name":"Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA006973"],"award-info":[{"award-number":["P30 CA006973"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>Melanoma currently lacks a reliable blood\u2010based biomarker of disease activity, although circulating tumor<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>(ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>) may fill this role. We investigated the clinical utility (i.e., impact on clinical outcomes and interpretation of radiographic data) of measuring ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>in patients with metastatic or high\u2010risk resected melanoma. Patients were prospectively accrued into \u2265\u00a01 of three cohorts, as follows. Cohort A: patients with radiographically measurable metastatic melanoma who underwent comparison of ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>measured by a<jats:styled-content style=\"fixed-case\">BEAM<\/jats:styled-content>ing digital<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>assay to tissue mutational status and total tumor burden; when appropriate, determinations about initiation of targeted therapy were based on ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>data. Cohorts B and C: patients with<jats:styled-content style=\"fixed-case\">BRAF<\/jats:styled-content>\u2010 or<jats:styled-content style=\"fixed-case\">NRAS<\/jats:styled-content>\u2010mutant melanoma who had either undergone surgical resection of high\u2010risk disease (cohort B) or were receiving or had received medical therapy for advanced disease (cohort C). Patients were followed longitudinally with serial ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>measurements with contemporaneous radiographic imaging to ascertain times to detection of disease activity and progressive disease, respectively. The sensitivity and specificity of the ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>assay were 86.8% and 100%, respectively. Higher tumor burden and visceral metastases were found to be associated with detectable ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>. In two patients in cohort A, ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>test results revealed a targetable mutation where tumor testing had not; both patients experienced a partial response to targeted therapy. In four of 30 patients with advanced melanoma, ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>assessments indicated evidence of melanoma activity that predicted radiographic evidence of disease progression by 8, 14, 25, and 38\u00a0weeks, respectively. Ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>was detectable in three of these four patients coincident with radiographic evaluations that alone were interpreted as showing no evidence of neoplastic disease. Our findings provide evidence for the clinical utility of integrating ct<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>data in managing patients with melanoma in a real\u2010world setting.<\/jats:p>","DOI":"10.1002\/1878-0261.12373","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T14:11:32Z","timestamp":1534428692000},"page":"1661-1672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["From validity to clinical utility: the influence of circulating tumor<scp>DNA<\/scp>on melanoma patient management in a real\u2010world setting"],"prefix":"10.1002","volume":"12","author":[{"given":"Steven P.","family":"Rowe","sequence":"first","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Luber","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Bioinformatics Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Makell","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Brothers","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Santmyer","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan D.","family":"Schollenberger","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Quinn","sequence":"additional","affiliation":[{"name":"Sysmex Inostics Inc. Mundelein IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Edelstein","sequence":"additional","affiliation":[{"name":"Sysmex Inostics Inc. Mundelein IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick S.","family":"Jones","sequence":"additional","affiliation":[{"name":"Sysmex Inostics Inc. Mundelein IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen B.","family":"Bleich","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Sharfman","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan J.","family":"Lipson","sequence":"additional","affiliation":[{"name":"Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.15855"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.030"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.49.8691"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007094"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.044"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213261"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9839"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11219"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"e0166354","DOI":"10.1371\/journal.pone.0166354","article-title":"Performance of streck cfDNA blood collection tubes for liquid biopsy testing","volume":"11","author":"Diaz IM","year":"2016","journal-title":"PLoS One"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth898"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1789"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e32831993cc"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiographics.10.4.2198632"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-017-3674-8"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx363.045"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113205"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5788"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1260"},{"key":"e_1_2_10_21_1","first-page":"449","article-title":"Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma","volume":"63","author":"Kelderman S","year":"2014","journal-title":"Cancer Immunol Immunother"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-017-0902-9"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx717"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx026"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.5332"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-014-0042-0"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30578-2"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708539"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11156"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13397"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3519"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.70"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-017-9660-6"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0605"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx017"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0321"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2017.05.033"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30074-8"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00520-1"},{"issue":"3","key":"e_1_2_10_40_1","first-page":"30","article-title":"Identification and management of toxicities from immune checkpoint\u2010blocking drugs","volume":"28","author":"Teply BA","year":"2014","journal-title":"Oncology (Williston Park)"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3511"},{"key":"e_1_2_10_42_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.16.00009","article-title":"Circulating tumor DNA analysis and functional imaging provide complementary approaches for comprehensive disease monitoring in metastatic melanoma","volume":"1","author":"Wong SQ","year":"2017","journal-title":"JCO Precis Oncol"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029336"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2F1878-0261.12373","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.12373","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/1878-0261.12373","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/1878-0261.12373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T08:28:07Z","timestamp":1720513687000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/1878-0261.12373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,8]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/1878-0261.12373"],"URL":"https:\/\/doi.org\/10.1002\/1878-0261.12373","archive":["Portico"],"relation":{},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,8]]},"assertion":[{"value":"2018-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}