{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T10:26:17Z","timestamp":1791627977010,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019714","name":"Foundation Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019714","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":[[2025,11]]},"abstract":"<jats:p>Immune checkpoint inhibitors are important for treatment across tumor types but are not universally effective in controlling disease. Early understanding of tumor response, or lack thereof, can inform treatment decisions. This study evaluates changes in circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB) for associations with response to programmed cell death 1 ligand 1 (PD\u2010L1) blockade. We sequenced cell\u2010free DNA collected at the start of therapy, on treatment, and at the end of therapy for 153 patients treated with atezolizumab as part of the pan\u2010tumor MyPathway study (NCT02091141). ctDNA tumor fraction (TF) and bTMB were assessed for correlation with progression\u2010free survival (PFS) and overall survival (OS). We found that molecular response (MR, \u226550% decrease in TF at cycle 3\u2009day 1) was associated with improved PFS (9.7 vs 1.5\u2009months from C3D1; HR\u2009=\u20090.27) and OS (21.1 vs 14.3\u2009months from C3D1; HR\u2009=\u20090.44). These findings were consistent when limited to patients with stable disease (SD; PFS HR\u2009=\u20090.55; OS HR\u2009=\u20090.39). bTMB was correlated with tissue\u2010based TMB (tTMB) when TF was high (\u22651%), but not with OS in this cohort. In total, 61% of baseline samples had predicted clonal hematopoiesis (CH) variants. No correlation between maximum variant allele frequency (maxVAF) of predicted CH and TF was seen. In summary, MR is associated with outcomes for patients treated with atezolizumab and could stratify patients with SD. While CH was common, maxVAF for CH variants was not associated with ctDNA TF. Quantification of ctDNA enables therapy response monitoring and is critical for interpretation of bTMB as a proxy for tTMB.<\/jats:p>","DOI":"10.1002\/1878-0261.70054","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T12:43:45Z","timestamp":1748436225000},"page":"3060-3078","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Circulating tumor\n                    <scp>DNA<\/scp>\n                    monitoring and blood tumor mutational burden in patients with metastatic solid tumors treated with atezolizumab"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4299-3018","authenticated-orcid":false,"given":"Charles","family":"Swanton","sequence":"first","affiliation":[{"name":"Cancer Evolution and Genome Instability Laboratory The Francis Crick Institute  London UK"},{"name":"Department of Oncology University College London Hospitals  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7838-2526","authenticated-orcid":false,"given":"Russell W.","family":"Madison","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc.  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