Role of Cell-Free DNA in Relapsed Head and Neck Cancer

Abstract Introduction Owing to the aggressive biology of head and neck squamous cell carcinoma (HNSCC), new biomarkers that can facilitate the diagnosis and tracking of tumour growth are the need of the hour. Liquid biopsy has emerged as an easier tool than tissue biopsy to monitor the emergence of treatment resistance or the recurrence of disease at the molecular level. Objectives To assess the role of cell-free DNA (cfDNA) as a biomarker for relapsed HNSCC. Materials and Methods This study is a Phase 2 interventional study (NCT: CTRI/2020/02/023378) that assessed the response rates of a new triplet drug regimen in refractory or relapsed HNSCC. Thirty-five patients underwent blood sampling before the commencement of therapy and at 3 months of treatment. Isolation of cfDNA was done using magnetic beads (molecular weight near 170 kb) for quantification. Results Twenty-eight patients had comparable data at baseline and after 3 months of treatment. The mean cfDNA reading at baseline was 8.9 ng/μL (range: 2.6 -7.3 ng/μL) of blood. The cfDNA concordance with clinical and radiological outcomes was 54.2%. The patients who responded to therapy were compared over time with patients who did not respond. Repeated measures testing found a significant difference (p 1?4 0.0035) in changes to the cfDNA levels of these two groups. Conclusion This study posits the potential value of liquid biopsy in the treatment of recurrent HNSCC. Our findings prove the clinical relevance as well as limitations of cfDNA, which warrant extrapolation in an upfront setting too.