Susanne Flach (München), Karen Howarth (Lund, SE), Sophie Hackinger (Cambridge, GB), Christodoulos Pipinikas (Cambridge, GB), Patricia Rojas (Cambridge, GB), Pete Ellis (Cambridge, GB), Kirsten McLay (Cambridge, GB), Giovanni Marsico (Cambridge, GB), Christoph Walz (München), Axel Lechner (München), Tom Huberty (München), Lukas Käsmann (München), Christoph Reichel (München), Olivier Gires (München), Martin Canis (München), Philipp Baumeister (München)
Introduction
The recent advent of personalised assays capable of detecting circulating cell-free tumour DNA (ctDNA) has enabled detection of molecular residual disease (MRD) and recurrence following curative-intent therapy. We conducted LIONESS, a single-centre prospective cohort study to assess ctDNA in patients with HNSCC receiving primary surgery with curative intent to determine whether post-operative ctDNA detection can act as a biomarker for surgical tumour clearance and to evaluate the potential of personalised ctDNA analysis for early molecular-level detection of relapse or prior to clinically confirmed recurrence.
Material and methods
Samples from 77 HNSCC patients were collected pre- and postoperatively and during clinical follow-up. Whole exome sequencing was performed on FFPE tumour tissue to an average coverage of 250x. Tumour-specific variants for personalised assay design were selected and used in the analysis of serial samples for evidence of MRD.
Results
In 531 longitudinal plasma and 94 saliva samples collected preoperatively and during clinical follow-up, ctDNA was detected at levels ranging from 18.4% estimated variant allele fraction (eVAF) to as low as 0.0005% eVAF. Increased plasma ctDNA levels were detected postoperatively in 18/20 cases with confirmed clinical recurrences with lead times up to 500 days. ctDNA was also detected in baseline saliva samples. RNA sequencing and IHC for immune profiling has been performed on primary tumours.
Conclusion
The use of ctDNA measurements in this HNSCC patient cohort has significant potential to guide treatment decisions, improve disease outcome and potentially spare patients unnecessary, partially invasive interventions during clinical follow-up.
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