Dynamics of cell-free tumour DNA correlate with treatment response of head and neck cancer patients receiving radiochemotherapy.

• ctDNA can be detected in the majority of patients with locally advanced HNSCC. • ctDNA was correlated with gross tumour volume before treatment start. • Concentration of ctDNA was correlated with treatment response and disease recurrence. • Monitoring of ctDNA/cvDNA is a promising non-invasive biomarker for patients with HNSCC under RCTX. Definitive radiochemotherapy (RCTX) with curative intent is one of the standard treatment options in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Despite this intensive therapy protocol, disease recurrence remains an issue. Therefore, we tested the predictive capacity of liquid biopsies as a novel biomarker during RCTX in patients with HNSCC. We sequenced the tumour samples of 20 patients with locally advanced HNSCC to identify driver mutations. Subsequently, we performed a longitudinal analysis of circulating tumour DNA (ctDNA) dynamics during RCTX. Deep sequencing and UMI-based error suppression for the identification of driver mutations and HPV levels in the plasma enabled treatment-response monitoring prior, during and after RCTX. In 85% of all patients ctDNA was detectable, showing a significant correlation with the gross tumour volume (p -value 0.032). Additionally, the tumour allele fraction in the plasma was negatively correlated with the course of treatment (p -value <0.05). If ctDNA was detectable at the first follow-up, disease recurrence was seen later on. Circulating HPV DNA (cvDNA) could be detected in three patients at high levels, showing a similar dynamic behaviour to the ctDNA throughout treatment, and disappeared after treatment. Monitoring RCTX treatment-response using liquid biopsy in patients with locally advanced HNSCC is feasible. CtDNA can be seen as a surrogate marker of disease burden, tightly correlating with the gross tumour volume prior to the treatment start. The observed kinetic of ctDNA and cvDNA showed a negative correlation with time and treatment dosage in most patients. [ABSTRACT FROM AUTHOR]