Susanne Flach, BM BCh, PhD, Ludwig-Maximilians-University, Munich, Germany, discusses results of the LIONESS study on liquid biopsy for minimal residual disease (MRD) detection in head and neck squamous cell carcinoma (HNSCC). LIONESS was a single-center prospective cohort analysis investigating whether circulating tumor DNA (ctNDA) is a viable biomarker for tumor clearance and molecular-level recurrence in patients with p16-negative HNSCC who received curative-intent primary surgical treatment. A highly sensitive personalized assay was utilized to analyze pre- and post-operative plasma samples for evidence of MRD and recurrence. ctDNA was detected in 17 of 17 patients included in the study prior to surgery. ctDNA was detected in all cases of recurrence prior to progression, suggesting potential for ctDNA as biomarker for MRD detection and recurrence in HNSCC. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.