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

• Published in: Scientific reports Vol. 7; no. 1; pp. 16723 - 11
• Main Authors: Muhanna, Nidal, Di Grappa, Marco A., Chan, Harley H. L., Khan, Tahsin, Jin, Cheng S., Zheng, Yangqiao, Irish, Jonathan C., Bratman, Scott V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2017; Nature Publishing Group
• Subjects: 45/22; 692/4028/546; 692/4028/67/1857; Animals; Cell-Free Nucleic Acids - blood; Circulating Tumor DNA - genetics; Computed tomography; Contraction; Deoxyribonucleic acid; DNA; Head & neck cancer; Head and Neck Neoplasms - diagnostic imaging; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - surgery; Humanities and Social Sciences; Kinetics; Lymph nodes; Male; Metastases; Metastasis; multidisciplinary; Neoplasm Transplantation; Rabbits; Science; Science (multidisciplinary); Sensitivity and Specificity; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - diagnostic imaging; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - surgery; Surgery; Tomography Scanners, X-Ray Computed; Tumor Burden; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-17079-6

In cancer patients, circulating tumour-derived DNA (ctDNA) levels imperfectly reflect disease burden apparent on medical imaging. Further evaluation of ctDNA levels over time is needed to better understand the correlation with tumour growth and therapeutic response. We describe ctDNA kinetics within an orthotopic, immunocompetent preclinical rabbit model of local-regionally advanced head and neck squamous cell carcinoma (HNSCC). Monitoring primary tumour and metastatic lymph node volume by computed tomography (CT), we observed a correlation between ctDNA levels and tumour burden. We found that ctDNA detection could precede evidence of tumour on CT. Sensitivity and specificity of ctDNA detection in this model was 90.2% (95% C.I.: 76.9–97.3%) and 85.7% (95% C.I.: 67.3–96.0%), respectively. Rapid tumour growth followed by auto-necrosis and tumour volume contraction produced a spike in ctDNA levels, suggesting that viable tumour cells may be required for sustained ctDNA release. Following surgical resection, both ctDNA and total plasma DNA were correlated with recurrent tumour volume. Our results reveal the complex kinetic behaviour of ctDNA and total plasma DNA upon tumour growth or surgery. This pre-clinical model could be useful for future studies focused on elucidating mechanisms of ctDNA release into the circulation from primary and metastatic sites.