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In this trial, we evaluated the efficacy of first\u2010line envafolimab plus chemotherapy in SCLC patients with LM and explored potential predictive biomarkers. Patients received envafolimab in combination with chemotherapy for four cycles, followed by envafolimab monotherapy until disease progression or unacceptable toxicity. The primary endpoint was progression\u2010free survival (PFS). Secondary endpoints included safety, objective response, overall survival, and identification of predictive biomarkers. Whole\u2010exome sequencing (WES), transcriptome sequencing, DNA methylation sequencing, circulating tumor DNA (ctDNA) analysis, and cell\u2010free DNA (cfDNA) methylation sequencing were performed on tumor tissues and peripheral blood samples. The objective response rate (ORR) was 75.9%, the disease control rate (DCR) was 100%, and the median PFS was 4.3 months. Granulocyte turnover and TNFRSF9 expression emerged as key indicators across transcriptomic and epigenomic analyses, and were associated with prognosis and liver dysfunction. cfDNA\u2010based assessment of granulocyte turnover reflected both liver damage and tumor dynamics, suggesting its potential for real\u2010time monitoring. These findings suggest that granulocyte activity may contribute to an immunosuppressive tumor microenvironment and serve as a predictive marker for treatment stratification in SCLC with LM.<\/jats:p>","DOI":"10.1002\/mco2.70925","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:16:09Z","timestamp":1786950969000},"source":"Crossref","is-referenced-by-count":0,"title":["Dynamic Granulocyte Turnover Inferred From cfDNA Methylation Predicts Immunotherapy Benefit in Liver\u2010Metastatic Small Cell Lung Cancer: A Prospective Biomarker Study"],"prefix":"10.1002","volume":"7","author":[{"given":"Ning","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine\u2010Oncology Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan 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