{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:16:54Z","timestamp":1784233014458,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004257","name":"Helse Vest","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008730","name":"Kreftforeningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008730","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":[[2025,12]]},"abstract":"<jats:p>\n                    We investigated whether DNA methylation and cell\u2010free DNA (cfDNA) fragmentation patterns can improve circulating tumor DNA (ctDNA) detection in advanced pancreatic cancer. In a cohort of 33 patients, ctDNA detection was performed in a tumor\u2010agnostic fashion using DNA methylation, cfDNA fragment lengths, and 4\u2010mer 5\u2032 end motifs. Machine learning models estimating ctDNA levels were built for each individual detection method and their combination. All models significantly differentiated ctDNA levels in patients from healthy individuals (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Using the highest estimated levels in healthy volunteers as cutoffs, ctDNA was detected in 79%, 67%, 67%, and 55% of patients using methylation, fragment length, end motifs, and the combined model, respectively. Univariable Cox regression showed that all ctDNA level estimates were associated with increased hazard ratios (HR, all\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) for progression\u2010free survival (PFS) and overall survival (OS). Multivariable Cox regression confirmed ctDNA levels as an independent predictor of PFS (HR\u2009=\u20091.9,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) and OS (HR\u2009=\u20092.7,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Our findings suggest that machine learning models based on DNA methylation, cfDNA fragment lengths, and cfDNA end motifs can estimate ctDNA levels and predict clinical outcomes in advanced pancreatic cancer.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70116","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T16:59:06Z","timestamp":1756227546000},"page":"3535-3547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Tumor\u2010agnostic detection of circulating tumor\n                    <scp>DNA<\/scp>\n                    in patients with advanced pancreatic cancer using targeted\n                    <scp>DNA<\/scp>\n                    methylation sequencing and cell\u2010free\n                    <scp>DNA<\/scp>\n                    fragmentomics"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-0679","authenticated-orcid":false,"given":"Morten","family":"Lapin","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjersti","family":"Tjensvoll","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"},{"name":"European Liquid Biopsy Society (ELBS)  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin Hestnes","family":"Edland","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satu","family":"Oltedal","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herish","family":"Garresori","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rnar","family":"Gilje","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saga","family":"Ekedal","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trygve","family":"Eftest\u00f8l","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering and Computer Science University of Stavanger  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Terje","family":"Kval\u00f8y","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Physics University of Stavanger  Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Janku","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics The University of Texas MD Anderson Cancer Center  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5847-6752","authenticated-orcid":false,"given":"Oddmund","family":"Nordg\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Stavanger University Hospital  Stavanger Norway"},{"name":"European Liquid Biopsy Society (ELBS)  Hamburg Germany"},{"name":"Department of Chemistry, Bioscience and Environmental Technology, Faculty of Science and Technology University of Stavanger  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