why choose us

300×250 Ad Slot

Research Article: Sequencing-informed, patient-specific droplet digital PCR assays for circulating tumor DNA monitoring in recurrent or metastatic head and neck cancer: a pilot study

Date Published: 2026-10-30

Abstract:
In 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. Nine 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). Sixteen 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. Patient-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.

Introduction:
In 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…

Read more

300×250 Ad Slot