biostudies-literatureRuiz-Torres DANIH HHS298https://www.ebi.ac.uk/biostudies/studies/S-EPMC12373877biostudies-literatureUnknown9(1)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.NPJ precision oncologyPersonalized circulating tumor DNA dynamics inform survival and response to immune checkpoint blockade in recurrent/metastatic head and neck cancer.PMC123738775K23DE029811Ruiz-Torres DARoberts TFaden DLWirth LJGates LMendel JChevalier AEfthymiou VMurray CBryan MEPipinikas CStott SLFisch ASPatel MJMerkin RDPark JCfalsePersonalized circulating tumor DNA dynamics inform survival and response to immune checkpoint blockade in recurrent/metastatic head and neck cancer.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.2025-01-01T00:00:00Z2025 Aug2026-05-08T06:54:00.491Z2026-04-07T23:31:35.173ZS-EPMC123738774084689610.1038/s41698-025-01084-4