{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:44:11Z","timestamp":1792086251670,"version":"4.4.0"},"reference-count":31,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008963","name":"Sociedad Espa\u00f1ola de Oncolog\u00eda M\u00e9dica","doi-asserted-by":"publisher","award":["SEOM_PrinmunoOnco20"],"award-info":[{"award-number":["SEOM_PrinmunoOnco20"]}],"id":[{"id":"10.13039\/501100008963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 have significantly improved outcomes in patients with advanced melanoma. However, the optimal treatment duration remains undefined. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for treatment response monitoring and surveillance and can predict long-term clinical outcomes. Methods: Clinical and ctDNA data from prospectively enrolled patients with stage IV melanoma treated with anti\u2013PD-1-based therapy at a single academic center were retrospectively analyzed. Of the 56 patients eligible, 28 underwent serial ctDNA testing during ICI treatment and follow-up (median 31 months) using a personalized, tumor-informed assay. Landmark analysis at 6 and 9 months was performed to assess progression-free survival (PFS) based on ctDNA status. Multivariable Cox regression was used to identify independent predictors of long-term outcomes. Results: Pre-ICI treatment, 91.7% (11\/12) of evaluable patients were ctDNA-positive. At 6 months, ctDNA negativity or clearance was observed in 47.4% (9\/19), and was strongly associated with improved PFS in the landmark analysis (HR: 10.0, p = 0.03; 2-year PFS: 89% in ctDNA-negative versus 30% in ctDNA-positive groups). At 9 months, persistent ctDNA positivity trended toward worse PFS. Multivariate analysis confirmed ctDNA status at the 6-month landmark timepoint to be an independent predictor of long-term benefit. Conclusions: Tumor-informed ctDNA testing is a robust, non-invasive tool to predict long-term benefit from anti\u2013PD-1-based therapy in advanced melanoma. ctDNA clearance or sustained negativity at 6 months may serve as a surrogate for durable response and could inform individualized treatment discontinuation strategies, and minimize toxicity and cost while maintaining efficacy. These findings, derived from a limited single-center cohort, warrant further exploration and validation in larger studies.<\/jats:p>","DOI":"10.3390\/cancers17233804","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T11:50:13Z","timestamp":1764244213000},"page":"3804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Personalized Circulating Tumor DNA Assay to Assess Long-Term Clinical Benefit in Patients with Advanced Melanoma"],"prefix":"10.3390","volume":"17","author":[{"given":"Clara","family":"Mart\u00ednez-Vila","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednic of Barcelona, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Programa de Doctorat en Medicina i Recerca Translacional, Facultat de Medicina i Ci\u00e8ncies de la Salut, Universitat de Barcelona (UB), c. Casanova, 143, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-6567","authenticated-orcid":false,"given":"Cristina","family":"Teixido","sequence":"additional","affiliation":[{"name":"Molecular Biology CORE Laboratory, Biomedical Diagnostic Centre (CDB), Hospital Cl\u00ednic, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Department of Pathology, Hospital Cl\u00ednic of Barcelona, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Grupo Espa\u00f1ol de Terapias Inmuno-Biol\u00f3gicas en C\u00e1ncer (G\u00c9TICA), Vel\u00e1zquez, 7-3\u00ba Planta, 28001 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednic of Barcelona, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Grupo Espa\u00f1ol de Terapias Inmuno-Biol\u00f3gicas en C\u00e1ncer (G\u00c9TICA), Vel\u00e1zquez, 7-3\u00ba Planta, 28001 Madrid, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rossell\u00f3 149, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3452-7607","authenticated-orcid":false,"given":"Francisco","family":"Aya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednic of Barcelona, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Grupo Espa\u00f1ol de Terapias Inmuno-Biol\u00f3gicas en C\u00e1ncer (G\u00c9TICA), Vel\u00e1zquez, 7-3\u00ba Planta, 28001 Madrid, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rossell\u00f3 149, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumedha","family":"Sudhaman","sequence":"additional","affiliation":[{"name":"Natera, Inc., Austin, TX 78753, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griffin L.","family":"Budde","sequence":"additional","affiliation":[{"name":"Natera, Inc., Austin, TX 78753, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3310-5557","authenticated-orcid":false,"given":"Europa Azucena","family":"Gonz\u00e1lez-Navarro","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rossell\u00f3 149, 08036 Barcelona, Spain"},{"name":"Department of Immunology, Hospital Cl\u00ednic of Barcelona, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3460-0384","authenticated-orcid":false,"given":"Llucia","family":"Alos","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Cl\u00ednic of Barcelona, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rossell\u00f3 149, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0647-3058","authenticated-orcid":false,"given":"Natalia","family":"Castrejon","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Cl\u00ednic of Barcelona, University of Barcelona, Villarroel 170, 08036 Barcelona, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rossell\u00f3 149, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-9171","authenticated-orcid":false,"given":"J. Bryce","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Natera, Inc., Austin, TX 78753, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Krainock","sequence":"additional","affiliation":[{"name":"Natera, Inc., Austin, TX 78753, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8206-5232","authenticated-orcid":false,"given":"Minetta C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Natera, Inc., Austin, TX 78753, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-1957","authenticated-orcid":false,"given":"Ana","family":"Arance","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Cl\u00ednic of Barcelona, Villarroel 170, 08036 Barcelona, Spain"},{"name":"Grupo Espa\u00f1ol de Terapias Inmuno-Biol\u00f3gicas en C\u00e1ncer (G\u00c9TICA), Vel\u00e1zquez, 7-3\u00ba Planta, 28001 Madrid, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Rossell\u00f3 149, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1001\/jamaoncol.2018.4514","article-title":"Survival Outcomes in Patients with Previously Untreated BRAF Wild-Type Advanced Melanoma Treated with Nivolumab Therapy: Three-Year Follow-up of a Randomized Phase 3 Trial","volume":"5","author":"Ascierto","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1200\/JCO.22.01599","article-title":"Seven-Year Follow-Up of the Phase III KEYNOTE-006 Study: Pembrolizumab Versus Ipilimumab in Advanced Melanoma","volume":"41","author":"Robert","year":"2023","journal-title":"J. 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