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<p>Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is an aggressive disease with limited predictive biomarkers, often leading to ineffective treatments and unnecessary toxicity. Circulating tumor DNA (ctDNA) provides a promising real-time, non-invasive tool for monitoring disease activity. In this study, we analyzed 137 plasma samples from 16 patients with R/M HNSCC receiving immune checkpoint blockade (ICB), using a tumor-informed, highly sensitive next-generation sequencing assay (RaDaR, NeoGenomics). Serial ctDNA monitoring was performed at baseline and throughout treatment, and its association with clinical outcomes, including disease control, three-year overall survival (OS), and progression-free survival (PFS), was evaluated through univariable and multivariable analyses. ctDNA negativity during treatment was significantly associated with improved disease control (OR 21.7, 95% CI 1.86–754.88, <i>p</i> = 0.0317), three-year OS (HR 0.04, 95% CI 0.00–0.47, <i>p</i> = 0.0103), and PFS (HR 0.03, 95% CI 0.00–0.37, <i>p</i> = 0.0057). Early increases in ctDNA levels correlated with disease progression. Our findings suggest that ctDNA negativity, regardless of PD-L1 expression, ICB regimen, or line of therapy, is a strong predictor of favorable outcomes in R/M HNSCC.</p>

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Personalized circulating tumor DNA dynamics inform survival and response to immune checkpoint blockade in recurrent/metastatic head and neck cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月22日

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  • Daniel A. Ruiz-Torres,
  • Ross D. Merkin,
  • Michael E. Bryan,
  • Julia Mendel,
  • Vasileios Efthymiou,
  • Thomas Roberts,
  • Manisha J. Patel,
  • Jong C. Park,
  • Amber Chevalier,
  • Clodagh Murray,
  • Lisa Gates,
  • Christodoulos Pipinikas,
  • Shannon L. Stott,
  • Adam S. Fisch,
  • Lori J. Wirth,
  • Daniel L. Faden

摘要

Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is an aggressive disease with limited predictive biomarkers, often leading to ineffective treatments and unnecessary toxicity. Circulating tumor DNA (ctDNA) provides a promising real-time, non-invasive tool for monitoring disease activity. In this study, we analyzed 137 plasma samples from 16 patients with R/M HNSCC receiving immune checkpoint blockade (ICB), using a tumor-informed, highly sensitive next-generation sequencing assay (RaDaR, NeoGenomics). Serial ctDNA monitoring was performed at baseline and throughout treatment, and its association with clinical outcomes, including disease control, three-year overall survival (OS), and progression-free survival (PFS), was evaluated through univariable and multivariable analyses. ctDNA negativity during treatment was significantly associated with improved disease control (OR 21.7, 95% CI 1.86–754.88, p = 0.0317), three-year OS (HR 0.04, 95% CI 0.00–0.47, p = 0.0103), and PFS (HR 0.03, 95% CI 0.00–0.37, p = 0.0057). Early increases in ctDNA levels correlated with disease progression. Our findings suggest that ctDNA negativity, regardless of PD-L1 expression, ICB regimen, or line of therapy, is a strong predictor of favorable outcomes in R/M HNSCC.