Abstract 884P
Background
Head and neck squamous cell carcinoma (HNSCC) remains a substantial burden to global health with 5-year survival of <50%. Despite improvements in treatments for HNSCC, many patients develop recurrences. Circulating cell-free tumour DNA (ctDNA) is a recently identified biomarker available from blood samples which remains largely uncharacterised in the context of surgical treatment of HNSCC patients.
Methods
We conducted Liquid Biopsy for Minimal Residual Disease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS), a single-center 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 FFPE tumour tissue. We utilised RaDaR™, a highly sensitive personalised assay using deep sequencing of up to 48 tumor-specific variants. The RaDaR™ assay demonstrated 95% sensitivity at 0.001% median variant allele frequency (AF) in analytical validation studies and was used to analyse serial pre- and post-operative plasma samples for evidence of minimal residual disease and recurrence.
Results
In 17 patients analysed to evaluate the performance of RaDaR™, personalised panels were designed with between 19 and 52 somatic variants (median 48). Preliminary data shows 100% ctDNA detection in baseline samples taken prior to surgery. 106 longitudinal samples were assessed for evidence of ctDNA. In post-surgery samples, ctDNA could be detected at levels as low as 0.0006% AF. In all cases with clinical recurrence to date (5/5), ctDNA was detected prior to progression, with lead times ranging from 108 to 248 days. One case with two primary tumours in the floor of the mouth and larynx, respectively, showed evidence of post-operative minimal residual disease originating from the laryngeal SCC, ultimately developing clinical recurrence 108 days later.
Conclusions
This study illustrates the potential of ctDNA as a biomarker for monitoring of minimal residual disease as well as recurrence in patients with HNSCC and demonstrates the feasibility of personalised ctDNA assays for detection of disease post-treatment and with consequences for further therapy planning.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hospital of the University of Munich.
Funding
Inivata.
Disclosure
K. Howarth: Financial Interests, Personal, Full or part-time Employment, Shareholders: Inivata. S. Hackinger: Financial Interests, Personal, Full or part-time Employment, Shareholders: Inivata. C. Pipinikas: Financial Interests, Personal, Full or part-time Employment, Shareholders: Inivata. K. McLay: Financial Interests, Personal, Full or part-time Employment, Shareholders: Inivata. G. Marsico: Financial Interests, Personal, Full or part-time Employment, Shareholders: Inivata. All other authors have declared no conflicts of interest.