{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:21:42Z","timestamp":1793330502148,"version":"4.5.0"},"reference-count":22,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>End-of-treatment (EOT) response evaluation by positron emission tomography (PET) remains suboptimal in patients with large B-cell lymphoma (LBCL), because of its limited positive predictive value (PPV). Circulating tumor DNA (ctDNA)\u2014based measurable residual disease (MRD) detection offers a minimally invasive approach and may improve prognostication. We prospectively evaluated EOT MRD using phased variant enrichment and detection sequencing (PhasED-Seq) in patients with first-line LBCL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients were enrolled in the HOVON-902 prospective cohort and received curative-intent first-line treatment. Phased variants (PVs) were identified and tracked using tumor biopsies or pretreatment plasma. The prognostic significance of EOT ctDNA-MRD status in progression-free survival (PFS) and overall survival (OS) was compared with that of the International Prognostic Index (IPI) and EOT PET-computed tomography (CT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      PV identification was successful in 134 of 136 (99%) using either tissue or plasma. At EOT, 83% of patients were MRD-negative and 17% of patients were MRD-positive. MRD positivity was strongly associated with inferior outcomes: the 3-year PFS was 17% in MRD-positive versus 85% in MRD-negative patients (hazard ratio [HR], 9.8 [95% CI, 5.1 to 19];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 9.63 \u00d7 10\n                      <jats:sup>\u221212<\/jats:sup>\n                      ), and the OS was 43% versus 92%, respectively (HR, 7.7 [95% CI, 3.4 to 17.4];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 1.27 \u00d7 10\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). In multivariate analysis, MRD was an independent prognostic factor when controlling for IPI and EOT PET-CT. MRD positivity had a higher PPV for 2-year PFS than positive PET (68%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      56%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2264 .001), whereas negative predictive value was similar between negative MRD and PET (89%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      88%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .71). MRD positivity was associated with a significantly higher relapse risk within both complete metabolic response (CMR) and non-CMR subgroups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>This study validates ultrasensitive ctDNA-MRD detection using PhasED-Seq in a uniformly treated, prospective real-world LBCL cohort. These findings support further evaluation of MRD integration into clinical response assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01712","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T20:59:10Z","timestamp":1765573150000},"page":"400-409","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Prospective Validation of  Circulating Tumor DNA Measurable Residual Disease After First-Line Therapy in Large B-Cell Lymphoma"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5473-9415","authenticated-orcid":true,"given":"Steven","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hematology, Amsterdam UMC\u2014Location Vrije Universiteit, Cancer Center Amsterdam, Amsterdam, The Netherlands"},{"name":"Department of Pathology, Amsterdam UMC\u2014Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"},{"name":"Divisions of Oncology and Hematology, Department of Medicine, Stanford University, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2740-2873","authenticated-orcid":true,"given":"Marcel","family":"Nijland","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Strobbe","sequence":"additional","affiliation":[{"name":"Gelre Hospital, Zutphen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-9261","authenticated-orcid":true,"given":"Margriet","family":"Oosterveld","sequence":"additional","affiliation":[{"name":"Canisius Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinske","family":"Boersma","sequence":"additional","affiliation":[{"name":"Amphia Hospital, Breda, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Koene","sequence":"additional","affiliation":[{"name":"St Antonius Hospital, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Klerk","sequence":"additional","affiliation":[{"name":"Dijklander Hospital, Hoorn, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"de Jongh","sequence":"additional","affiliation":[{"name":"Albert Schweitzer Hospital, Dordrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad","family":"Koster","sequence":"additional","affiliation":[{"name":"VieCuri Medical Center, Venlo, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2067-6791","authenticated-orcid":true,"given":"Hans","family":"Pruijt","sequence":"additional","affiliation":[{"name":"Jeroen Bosch Ziekenhuis, \u2019s-Hertogenbosch, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein","family":"van der Poel","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7469-7427","authenticated-orcid":true,"given":"Erik","family":"van Werkhoven","sequence":"additional","affiliation":[{"name":"Hemato-Oncology Foundation for Adults in The Netherlands (HOVON), Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helma","family":"Zanders","sequence":"additional","affiliation":[{"name":"Hemato-Oncology Foundation for Adults in The Netherlands (HOVON), Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Dinmohamed","sequence":"additional","affiliation":[{"name":"Netherlands Comprehensive Cancer Organization (IKNL), Enschede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7357-4406","authenticated-orcid":true,"given":"Michiel","family":"Pegtel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam UMC\u2014Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Meek","sequence":"additional","affiliation":[{"name":"Foresight Diagnostics, Inc, Boulder, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4376-2569","authenticated-orcid":true,"given":"Sierra 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