{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:14:40Z","timestamp":1787786080820,"version":"build-2784847793"},"reference-count":32,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["110962"],"award-info":[{"award-number":["110962"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Eye salvaging therapy of malignant melanomas of the uvea can preserve the eye in most cases, but still about half of patients die from metastatic disease. Previous analyses of cell\u2010free DNA from plasma had shown detectable levels of tumor\u2010specific\n                      <jats:italic>GNAQ<\/jats:italic>\n                      \/\n                      <jats:italic>GNA11<\/jats:italic>\n                      mutations in patients with the clinical diagnosis of progressive disease. However, data on the\n                      <jats:bold>time<\/jats:bold>\n                      span that elapses from the detection of ctDNA in plasma to the clinical detection of metastases (diagnostic lead time) are missing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined 135 patients with uveal melanoma. Cell\u2010free DNA was isolated from a total of 807 blood samples which were taken over a period of up to 41\u00a0months and analyzed for the presence of\n                      <jats:italic>GNAQ<\/jats:italic>\n                      \/\n                      <jats:italic>GNA11<\/jats:italic>\n                      mutations by deep amplicon sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010one of the 135 patients developed metastases or recurrence. A ctDNA signal was identified in the plasma of 17 of the 21 patients. In 10 patients, this ctDNA signal preceded the clinical diagnosis of metastasis by 2\u201310\u00a0months. In 10 other patients, a ctDNA signal was only detected in samples obtained shortly before or after radiotherapy. The presence of a ctDNA signal in 16 of the remaining 125 patients was linked to clinical manifestation of metastases (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014) or tumor recurrence (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a02) with a sensitivity and specificity of 80% and 96%, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Detection of ctDNA in plasma can provide a diagnostic lead time over the clinical diagnosis of metastases or tumor recurrence. Longer lead times are to be expected if intervals between sampling are shortened.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.4153","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T03:02:56Z","timestamp":1626922976000},"page":"5974-5982","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Early detection of metastatic uveal melanoma by the analysis of tumor\u2010specific mutations in cell\u2010free plasma DNA"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6088-6929","authenticated-orcid":false,"given":"Claudia H. D.","family":"Le Guin","sequence":"first","affiliation":[{"name":"Department of Ophthalmology University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Bornfeld","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos E.","family":"Bechrakis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyla","family":"Jabbarli","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Hospital Essen University Duisburg\u2010Essen Essen 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