Sequencing-informed, patient-specific droplet digital PCR assays for circulating tumor DNA monitoring in recurrent or metastatic head and neck cancer: a pilot study
Abstract
BackgroundIn recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), early identification of treatment response remains challenging because imaging may be delayed or confounded by treatment-related changes and atypical response patterns under immunotherapy. Serial circulating tumor DNA (ctDNA) analysis may provide a minimally invasive measure of tumor dynamics and complement conventional imaging. We therefore investigated the feasibility and clinical relevance of patient-specific droplet digital PCR (ddPCR)-based ctDNA monitoring.MethodsNine patients with R/M HNSCC underwent tumor genomic profiling using FoundationOne® CDx as part of routine clinical care. Patient-specific single-nucleotide variants, including pathogenic or likely pathogenic variants and technically suitable variants of uncertain significance, were selected for ddPCR assay development. Plasma samples were collected before and/or during systemic treatment, and ctDNA kinetics were assessed in relation to radiologic response, progression-free survival (PFS), and overall survival (OS).ResultsSixteen single-target ddPCR assays were successfully established and combined into ten patient-specific single- or multi-target assay configurations. A total of 21 plasma samples were analyzed, and technically valid measurements were obtained for all samples. Pretreatment plasma was available for seven patients, of whom three (42.9%) had detectable ctDNA. Across all time points, ctDNA was detected at least once in six of nine patients (66.7%). Among the six patients with serial sampling, ctDNA kinetics showed descriptive agreement with radiologic assessment in five (83.3%). The single patient with increasing ctDNA developed progressive disease, whereas decreasing or stable ctDNA was accompanied by partial response or stable disease in four patients; one patient showed a mixed radiologic response. In an exploratory descriptive comparison, the single patient with increasing ctDNA had shorter observed PFS and OS than the five patients with decreasing or stable ctDNA levels. Given the group size of one patient, this observation is hypothesis-generating and does not establish a prognostic association.ConclusionsPatient-specific ddPCR-based ctDNA monitoring was technically feasible and showed agreement with radiologic assessment in most evaluable patients. These proof-of-concept findings support prospective evaluation of patient-specific ddPCR as a focused approach for longitudinal monitoring in R/M HNSCC; its comparative clinical utility and cost-effectiveness remain to be established.
Related
- Whole-genome sequencing-based tumor-informed circulating tumor DNA monitoring for early detection of recurrence in patients with solid tumors
- Primary-Tumor Transcriptomic Signatures Associated with Circulating Tumor Cells Status in Breast Cancer: From CTC-Negative Remodeling to CTC-Associated Metastatic Programs
- Impact of previous nivolumab treatment on the response to taxanes in patients with recurrent/metastatic head and neck squamous cell carcinoma
- Actionable genetic landscape and dynamics in circulating DNA from 12,827 patients with metastatic breast cancer.
- Case Report: Prolonged survival with short-course triplet induction and dual maintenance in recurrent/metastatic cervical cancer
BibTeX
@article{amodio2026sequencinginformed,
title = {{Sequencing-informed, patient-specific droplet digital PCR assays for circulating tumor DNA monitoring in recurrent or metastatic head and neck cancer: a pilot study}},
author = {Luca Leonardo Amodio and Lea Grossmann and Stefanie Gächter and Marta Nowak and Myriam Schaufelberger and Christina Mennicke and Sepehr Rahmani-Khajouei and Martin Zoche and Holger Moch and Achim Weber and Ralph Fritsch and Tomas Brezina and Saskia Hussung},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1984504},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1984504},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sequencing-informed, patient-specific droplet digital PCR assays for circulating tumor DNA monitoring in recurrent or metastatic head and neck cancer: a pilot study
AU - Luca Leonardo Amodio
AU - Lea Grossmann
AU - Stefanie Gächter
AU - Marta Nowak
AU - Myriam Schaufelberger
AU - Christina Mennicke
AU - Sepehr Rahmani-Khajouei
AU - Martin Zoche
AU - Holger Moch
AU - Achim Weber
AU - Ralph Fritsch
AU - Tomas Brezina
AU - Saskia Hussung
PY - 2026
DA - 2026/10/30
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1984504
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1984504
AB - BackgroundIn recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), early identification of treatment response remains challenging because imaging may be delayed or confounded by treatment-related changes and atypical response patterns under immunotherapy. Serial circulating tumor DNA (ctDNA) analysis may provide a minimally invasive measure of tumor dynamics and complement conventional imaging. We therefore investigated the feasibility and clinical relevance of patient-specific droplet digital PCR (ddPCR)-based ctDNA monitoring.MethodsNine patients with R/M HNSCC underwent tumor genomic profiling using FoundationOne® CDx as part of routine clinical care. Patient-specific single-nucleotide variants, including pathogenic or likely pathogenic variants and technically suitable variants of uncertain significance, were selected for ddPCR assay development. Plasma samples were collected before and/or during systemic treatment, and ctDNA kinetics were assessed in relation to radiologic response, progression-free survival (PFS), and overall survival (OS).ResultsSixteen single-target ddPCR assays were successfully established and combined into ten patient-specific single- or multi-target assay configurations. A total of 21 plasma samples were analyzed, and technically valid measurements were obtained for all samples. Pretreatment plasma was available for seven patients, of whom three (42.9%) had detectable ctDNA. Across all time points, ctDNA was detected at least once in six of nine patients (66.7%). Among the six patients with serial sampling, ctDNA kinetics showed descriptive agreement with radiologic assessment in five (83.3%). The single patient with increasing ctDNA developed progressive disease, whereas decreasing or stable ctDNA was accompanied by partial response or stable disease in four patients; one patient showed a mixed radiologic response. In an exploratory descriptive comparison, the single patient with increasing ctDNA had shorter observed PFS and OS than the five patients with decreasing or stable ctDNA levels. Given the group size of one patient, this observation is hypothesis-generating and does not establish a prognostic association.ConclusionsPatient-specific ddPCR-based ctDNA monitoring was technically feasible and showed agreement with radiologic assessment in most evaluable patients. These proof-of-concept findings support prospective evaluation of patient-specific ddPCR as a focused approach for longitudinal monitoring in R/M HNSCC; its comparative clinical utility and cost-effectiveness remain to be established.
SN - 2234-943X
ER -