{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:21:38Z","timestamp":1780431698145,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Conventional imaging assesses therapy response in stage IV solid-tumor patients in 8- to 12-week intervals, delaying detection of non-responders. We evaluated a quantitative PCR (qPCR) assay that interrogates size-distributed cell-free DNA (cfDNA) fragments to provide earlier insights into treatment efficacy. Methods: In this prospective study, 128 patients with metastatic lung, breast, or colorectal cancer provided plasma 12\u201321 days after the first dose of a new systemic regimen. The qPCR targets multi-copy retrotransposon element fragments of greater than 80 bp, greater than 105 bp, and greater than 265 bp, as well as an internal control. A model integrates these quantities into a Progression Score (PS) ranging from 0 to 100; higher values indicate probable disease progression. Results: The PS model yielded an area under (AUC) the receiver-operating-characteristic (ROC) curve of 0.93 for predicting radiographic progression at first imaging. Scores were strongly bimodal: 92% of patients with PS &gt; 90 progressed, whereas 95% with PS &lt; 10 did not. Intermediate scores (10\u201390) comprised a mixed cohort. Assay performance was unaffected by tumor genomic profile. Conclusions: This cfDNA-based Progression Score (PS) assay enables tumor- and therapy-agnostic, non-invasive monitoring of treatment response as early as two weeks after initiation. By flagging ineffective regimens well before standard imaging, the test can accelerate clinical decision-making, reduce exposure to futile therapy, and potentially improve outcomes in stage IV cancer. Early treatment plan changes may also avoid the high costs of ineffective treatments, prevent downstream toxicity-related hospitalizations, and free up limited imaging and infusion-suite capacity\u2014yielding savings for patients, payers, and healthcare systems.<\/jats:p>","DOI":"10.3390\/cancers17213583","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:02:03Z","timestamp":1762419723000},"page":"3583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Cell-Free DNA Fragmentomic Assay and Its Application for Monitoring Disease Progression in Real Time for Stage IV Cancer Patients"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-1941","authenticated-orcid":false,"given":"Sudhir K.","family":"Sinha","sequence":"first","affiliation":[{"name":"Cadex Genomics, Redwood City, CA 94062, USA"},{"name":"InnoGenomics, New Orleans, LA 70148, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Brown","sequence":"additional","affiliation":[{"name":"InnoGenomics, New Orleans, LA 70148, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Knopf","sequence":"additional","affiliation":[{"name":"Sutter Health, Berkeley, CA 94704, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hall","sequence":"additional","affiliation":[{"name":"Cadex Genomics, Redwood City, CA 94062, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Shannon","sequence":"additional","affiliation":[{"name":"BioRankings, Saint Louis, MO 63108, USA"},{"name":"Division of General Medicine & Geriatrics, Washington University School of Medicine, Saint Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Haack","sequence":"additional","affiliation":[{"name":"Cadex Genomics, Redwood City, CA 94062, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.22465\/juo.234600060003","article-title":"The Current State and Future of Plasma Cell-Free DNA Analysis in Urologic Malignancies","volume":"21","author":"Akamatsu","year":"2023","journal-title":"Korean J. 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