Abstract
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.
Highlights
In one instance (Rabbit 4) the tumour volume contracted after an initial phase of rapid growth (Fig. 5b and c). ctDNA levels increased initially with tumour growth and fell dramatically when the tumour volume declined
Detection of ctDNA has emerged as a promising strategy for tracking tumour burden and assessing response to treatment, yet few studies have been performed to characterize the kinetics of ctDNA release in tumour-bearing subjects with local-regional disease
We have adopted the VX2 rabbit model of papillomavirus-associated HNSCC, which phenotypically mimics the human disease counterpart in terms of its metastatic lymph node spread in an immunocompetent host
Summary
In one instance (Rabbit 4) the tumour volume contracted after an initial phase of rapid growth (Fig. 5b and c). ctDNA levels increased initially with tumour growth and fell dramatically when the tumour volume declined. In one instance (Rabbit 4) the tumour volume contracted after an initial phase of rapid growth (Fig. 5b and c). CtDNA levels increased initially with tumour growth and fell dramatically when the tumour volume declined. The necrotic tumour volume appeared to reflect more closely ctDNA levels during the phase of rapid tumour growth; upon tumour contraction the necrotic tumour volume provided an overestimate of ctDNA levels. This case study illustrates the complex temporal relationship that can exist between tumour growth, necrosis, and ctDNA release
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