Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications

作者：Tomoko Akaike, Manisha Thakuria, Ann W. Silk, Daniel S. Hippe, Song Y. Park, Naomi So, Nolan J. Maloney, Lindsay Gunnell, Alec Eschholz, Emily Kim, Sumi Sinha, Evan Hall, Shailender Bhatia, Sunil Reddy, Angel Rodriguez, Alexey Aleshin, Jacob Choi, Kenneth Y. Tsai, Sue S. Yom, Siegrid S. Yu, Jaehyuk Choi, Sunandana Chandra, Paul Nghiem, Lisa C. Zaba · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.23.02054 · 被引用次数：30 · 研究领域：Polyomavirus and related diseases、Bacteriophages and microbial interactions、Lung Cancer Research Studies

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with ...