Abstract 684P
Background
Head and neck squamous cell carcinoma (HNSCC) remains a substantial health burden. Early relapse and recurrent metastasis are some of the primary reasons for the poor prognosis. The recent advent of personalised assays capable to detect circulating tumour DNA (ctDNA) has enabled detection of molecular residual disease and recurrence following curative therapy.
Methods
We conducted LIONESS, a single-centre prospective cohort study to assess ctDNA in plasma and saliva from HNSCC patients (Stage I-IVb) receiving primary surgery with curative intent. Samples were collected pre- and postoperatively and during clinical follow-up. Whole exome sequencing was performed on formalin-fixed paraffin-embedded tumour tissue to a median depth of 250x. Tumour-specific variants for personalised assay design (RaDaR, Inivata) were selected to analyse serial samples for evidence of molecular residual disease. Based on staging computer tomography images, tumour volumes were correlated to ctDNA and clinical parameters.
Results
In 348 longitudinal plasma samples from 46 patients analysed to date, ctDNA was detected to levels ranging from 10.8% variant allele fraction (eVAF) to as low as 0.0005%. ctDNA was detected in 10/10 cases with confirmed clinical recurrences with lead times up to 265 days. ctDNA was also detected in baseline saliva samples from patients with tumours of various anatomical locations. This included a case with two synchronous tumours, one pT4a laryngeal tumour and a second pT1 tumour of the floor of the mouth. Postoperative plasma ctDNA detection originating from the laryngeal tumour was observed 108 days ahead of clinical recurrence. Plasma ctDNA from the small pT1 tumour was not detected preoperatively and remained undetected throughout the patient’s course of management, however, ctDNA was detected at a baseline saliva sample. Work is ongoing for analysis of the full cohort of plasma and saliva samples, which will be presented at the congress.
Conclusions
The use of ctDNA measurements in this HNSCC patient cohort has significant potential to guide treatment decisions and improve disease outcome. In future, ctDNA analysis with subsequent ctDNA-guided treatment may reduce morbidity for HNSCC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K. Howarth, S. Hackinger, C. Pipinikas, P. Ellis, K. McLay, G. Marsico: Financial Interests, Institutional, Full or part-time Employment: Inivata. All other authors have declared no conflicts of interest.