Dynamic Changes in Circulating Tumor DNA During Immunotherapy for Head and Neck Cancer: SHIZUKU-HN Study

Area of Science:

• Oncology
• Molecular Diagnostics
• Biomarker Research

Background:

• Immune checkpoint inhibitors (ICIs) show limited durable response rates (20%) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
• Circulating tumor DNA (ctDNA) has emerged as a potential non-invasive biomarker for cancer monitoring.
• Current utilization of ctDNA testing in HNSCC is low (7% in Japan's C-CAT database).

Purpose of the Study:

• To evaluate ctDNA as a real-time biomarker for monitoring treatment response in HNSCC patients receiving ICIs.
• To correlate ctDNA dynamics with tumor volume and radiographic changes.
• To identify genetic mutations via ctDNA that may indicate treatment resistance.

Main Methods:

• Prospective analysis of serial plasma samples from 27 HNSCC patients undergoing ICIs (SHIZUKU-HN study).
• Guardant360 assay used to assess ctDNA variant allele frequency (VAF) and genetic mutations.
• Tumor volume quantified using 3D CT reconstruction; comparison with Japan's C-CAT database (n=2255).

Main Results:

• Mean ctDNA VAF significantly correlated with tumor volume (Spearman's ρ = 0.70, p = 0.001).
• ctDNA changes often preceded radiographic progression, indicating early treatment response or resistance.
• Disappearance of BRAF/APC mutations in partial responders and detection of EGFR/PIK3CA amplifications via ctDNA suggested resistance mechanisms.

Conclusions:

• ctDNA serves as a dynamic and sensitive biomarker for real-time monitoring of HNSCC treatment response to ICIs.
• ctDNA analysis provides early insights into treatment efficacy and can identify emerging resistance mechanisms.
• This approach supports personalized ICI therapy strategies for HNSCC patients.