Cell-Free DNA Kinetics in a Pre-Clinical Model of Head and Neck Cancer

Area of Science:

• Oncology
• Molecular Biology
• Medical Imaging

Background:

• Circulating tumour-derived DNA (ctDNA) levels in cancer patients do not always correlate with disease burden shown on medical imaging.
• Longitudinal evaluation of ctDNA is crucial for understanding its relationship with tumor growth and treatment efficacy.

Purpose of the Study:

• To investigate ctDNA kinetics in an immunocompetent preclinical rabbit model of locally advanced head and neck squamous cell carcinoma (HNSCC).
• To correlate ctDNA levels with tumor burden, assess ctDNA detection sensitivity and specificity, and understand ctDNA dynamics during tumor progression and after resection.

Main Methods:

• Established an orthotopic, immunocompetent rabbit model of HNSCC.
• Monitored primary tumor and metastatic lymph node volumes using computed tomography (CT).
• Quantified ctDNA levels and total plasma DNA over time, correlating them with tumor burden and surgical outcomes.

Main Results:

• Observed a correlation between ctDNA levels and tumor burden, with ctDNA detection sometimes preceding CT evidence of tumors.
• Achieved high sensitivity (90.2%) and specificity (85.7%) for ctDNA detection in this model.
• Noted a spike in ctDNA during rapid tumor growth followed by auto-necrosis, suggesting viable tumor cells are needed for sustained release.
• Found ctDNA and total plasma DNA levels correlated with recurrent tumor volume post-surgery.

Conclusions:

• ctDNA kinetics are complex and dynamically influenced by tumor growth, necrosis, and surgical intervention.
• This preclinical HNSCC model provides a valuable platform for studying ctDNA release mechanisms.
• ctDNA holds potential as a biomarker for monitoring disease burden and treatment response in HNSCC.