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.

Conflict of Interest

Der Erstautor weist auf folgenden Interessenkonflikt hin K.H., S.H., C.P., K.M., P.E. and G.M. are employees and shareholders of Inivata Ltd (Cambridge, UK).

Publication History

Article published online:
24 May 2022