Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS) – A personalised analysis of circulating cell-free tumour DNA

Introduction Circulating cell-free tumour DNA (ctDNA) is an emerging biomarker but has not yet been studied sufficiently for head and neck squamous cell carcinoma (HNSCC). The detection of ctDNA as a marker of minimal residual disease following curative-intent treatment holds promise for identifying patients at an increased risk of relapse, who may benefit from adjuvant radio(chemo)therapy or facilitate close monitoring with repeat resection if needed.

Materials & Methods We conducted a single-centre prospective cohort study to investigate ctDNA in patients with p16-negative HNSCC who received primary surgical treatment with curative intent. Whole exome sequencing was performed on formalin-fixed paraffin-embedded tumour tissue to a median depth of 250x. We utilised RaDaR™, a highly sensitive personalised assay using deep sequencing of up to 48 tumor-specific variants. The RaDaR™ assay was used to analyse serial pre- and post-operative plasma samples for evidence of minimal residual disease and recurrence.

Results In a subset of 21 patients analysed, personalised panels were designed with between 20 and 52 somatic variants (median 48). Preliminary data shows 100% ctDNA detection in baseline samples taken prior to surgery. 131 longitudinal samples were assessed for evidence of ctDNA. In post-surgery samples, ctDNA could be detected at levels as low as 0.0005% allele frequency. In all cases with clinical recurrence to date (5/5), ctDNA was detected prior to progression, with lead times ranging from 108 to 298 days.

Conclusion This study illustrates the potential of ctDNA as a biomarker in HNSCC and demonstrates the feasibility of personalised ctDNA assays for the detection of minimal residual disease post-treatment and for monitoring for early detection of relapse.

Publication History

Article published online:
24 May 2022