{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:11:00Z","timestamp":1789171860212,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme United Kingdom","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","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":[[2026,9]]},"abstract":"<jats:p>\n                    Accurate prediction of lack of benefit from pembrolizumab in patients with metastatic urothelial cancer (mUC) is an unmet need. We investigated the dynamics of circulating tumor DNA (ctDNA) load, estimated using the modified fast aneuploidy screening test\u2010sequencing system (mFast\u2010SeqS), as a potential biomarker for early on\u2010treatment identification of treatment response. A total of 104 patients with mUC treated with pembrolizumab from two prospective biomarker discovery trials were included and mFast\u2010SeqS was performed on paired blood samples collected at baseline and on\u2010treatment. Patients with a high on\u2010treatment aneuploidy score (\u2265\u20095,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200926) had a shorter median OS than patients with a low (&lt;\u20095) score (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200976) (3 vs 17\u2009months:\n                    <jats:italic>P<\/jats:italic>\n                    \u2010value&lt;\u20090.001). Patients with an increased (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910), stable (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200966), or decreased (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200928) on\u2010treatment score relative to their baseline score had a median PFS of 1.5, 4.0, and 8.3\u2009months, respectively. Median OS was 3.0, 11.1, and 18.7\u2009months, respectively. In patients with mUC treated with pembrolizumab, the on\u2010treatment mFast\u2010SeqS\u2010based ctDNA level and its dynamics relative to baseline are independent prognostic markers that can be used to identify patients that are unlikely to benefit from pembrolizumab.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70272","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T10:46:45Z","timestamp":1781606805000},"page":"2175-2187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal genome\u2010wide aneuploidy measurements in circulating cell\u2010free\n                    <scp>DNA<\/scp>\n                    to predict lack of benefit from pembrolizumab in patients with metastatic urothelial cancer"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0005-1697","authenticated-orcid":false,"given":"Youssra","family":"Salhi","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3111-4268","authenticated-orcid":false,"given":"Stavros","family":"Makrodimitris","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"van Wilpe","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"te Paske","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"de Weerd","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corine M.","family":"Beaufort","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans M.","family":"Westgeest","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Amphia Hospital Breda  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Voortman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen J. B.","family":"Aarts","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, GROW Research Institute for Oncology and Reproduction Maastricht University Medical Center+  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Rijnders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Franciscus Gasthuis &amp; Vlietland Rotterdam  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid A. M.","family":"van der Veldt","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"de Wit","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niven","family":"Mehra","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M.","family":"Wilting","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie G. J.","family":"Robbrecht","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute  Rotterdam The 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