Tumor-Informed Circulating Tumor DNA Monitoring for Predicting Outcomes in Patients With Head and Neck Squamous Cell Carcinoma.
- 1University of Nevada, Reno School of Medicine, Reno, Nevada.
- 2Department of Oncology, Natera, Inc., Austin, Texas.
- 3William N. Pennington Cancer Institute, Reno, Nevada.
Abstract
Despite advances in treatments, nearly half of the patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence. Early recurrence detection is critical for enabling timely curative interventions and improving survival outcomes. Here, we evaluated circulating tumor DNA (ctDNA) testing post-definitive treatment to detect molecular residual disease (MRD) and predict outcomes in patients with HNSCC. This retrospective study included a real-world cohort of 97 patients with stage I to IV HNSCC undergoing ctDNA testing using a personalized, tumor-informed assay (Signatera, Natera, Inc). Longitudinal plasma samples (n = 500) were collected pretreatment, in the early postdefinitive local treatment setting (within 3 months of completing definitive local treatment, before adjuvant treatment), and during postdefinitive treatment surveillance (after adjuvant therapy [if given] or postcompletion of definitive local treatment until recurrence). Median patient follow-up was 22 (2-56) months. ctDNA-based MRD positivity in the early postdefinitive local treatment setting was significantly associated with inferior progression-free survival (PFS) (hazard ratio [HR], 6.39; P = .0002) and overall survival (OS) (HR, 25.72; P = .003). Longitudinally, MRD positivity during the postdefinitive treatment surveillance window was associated with significantly shorter PFS (HR, 38.87; P < .0001) and OS (HR, 14.37; P = .014) and preceded radiographic progression by a median of 4.3 (0.62-21.91) months. The increased risk of recurrence for patients who were MRD-positive was observed across all pathologic stages, regardless of p16 status. In multivariate analysis, MRD positivity postdefinitive treatment was the only clinicopathologic factor significantly associated with PFS (HR, 38.29; P < .001). In patients with stage I to IV HNSCC, ctDNA-based MRD positivity after definitive local therapy and adjuvant treatment is associated with disease recurrence and poor survival outcomes.
Related
- A tumor–immune balance index from stem-like circulating tumor cells is associated with outcomes after yttrium-90 radioembolization for hepatocellular carcinoma
- Whole-genome sequencing-based tumor-informed circulating tumor DNA monitoring for early detection of recurrence in patients with solid tumors
- Sequencing-informed, patient-specific droplet digital PCR assays for circulating tumor DNA monitoring in recurrent or metastatic head and neck cancer: a pilot study
- Circulating microRNA as biomarkers for predicting cladribine response in multiple sclerosis
- Sensitive Glioma Detection and Recurrence Monitoring Using a Machine Learning Model Based on Circulating Monocytes
BibTeX
@article{denney2026tumorinformed,
title = {{Tumor-Informed Circulating Tumor DNA Monitoring for Predicting Outcomes in Patients With Head and Neck Squamous Cell Carcinoma.}},
author = {Sydney F Denney and George Laliotis and Charuta C Palsuledesai and Giby V George and Michael Krainock and Minetta C Liu and Abhinand V Peddada},
journal = {Advances in radiation oncology},
year = {2026},
month = oct,
doi = {10.1016/j.adro.2026.102205},
url = {https://europepmc.org/article/MED/42999361},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Tumor-Informed Circulating Tumor DNA Monitoring for Predicting Outcomes in Patients With Head and Neck Squamous Cell Carcinoma.
AU - Sydney F Denney
AU - George Laliotis
AU - Charuta C Palsuledesai
AU - Giby V George
AU - Michael Krainock
AU - Minetta C Liu
AU - Abhinand V Peddada
PY - 2026
DA - 2026/10/30
JO - Advances in radiation oncology
DO - 10.1016/j.adro.2026.102205
UR - https://europepmc.org/article/MED/42999361
AB - Despite advances in treatments, nearly half of the patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence. Early recurrence detection is critical for enabling timely curative interventions and improving survival outcomes. Here, we evaluated circulating tumor DNA (ctDNA) testing post-definitive treatment to detect molecular residual disease (MRD) and predict outcomes in patients with HNSCC. This retrospective study included a real-world cohort of 97 patients with stage I to IV HNSCC undergoing ctDNA testing using a personalized, tumor-informed assay (Signatera, Natera, Inc). Longitudinal plasma samples (n = 500) were collected pretreatment, in the early postdefinitive local treatment setting (within 3 months of completing definitive local treatment, before adjuvant treatment), and during postdefinitive treatment surveillance (after adjuvant therapy [if given] or postcompletion of definitive local treatment until recurrence). Median patient follow-up was 22 (2-56) months. ctDNA-based MRD positivity in the early postdefinitive local treatment setting was significantly associated with inferior progression-free survival (PFS) (hazard ratio [HR], 6.39; P = .0002) and overall survival (OS) (HR, 25.72; P = .003). Longitudinally, MRD positivity during the postdefinitive treatment surveillance window was associated with significantly shorter PFS (HR, 38.87; P < .0001) and OS (HR, 14.37; P = .014) and preceded radiographic progression by a median of 4.3 (0.62-21.91) months. The increased risk of recurrence for patients who were MRD-positive was observed across all pathologic stages, regardless of p16 status. In multivariate analysis, MRD positivity postdefinitive treatment was the only clinicopathologic factor significantly associated with PFS (HR, 38.29; P < .001). In patients with stage I to IV HNSCC, ctDNA-based MRD positivity after definitive local therapy and adjuvant treatment is associated with disease recurrence and poor survival outcomes.
SN - 2452-1094
ER -