ctDNA as an Adjunct to Posttreatment PET for Head and Neck Cancer Recurrence Risk Assessment

Abstract Objective Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as an adjunct method to help overcome the limitations of positron emission tomography (PET) and select patients who are at high risk for recurrence. Study Design Retrospective Single Institutional Study. Setting University Hospital Setting. Methods Twenty‐nine patients who underwent definitive treatment for squamous cell carcinoma of the head and neck (HNSCC) from 8/2021 to 01/2023 had ctDNA levels analyzed at 1 to 3, 6, 9, and 12 months after definitive treatment. A personalized, tumor‐informed, multiplex polymerase chain reaction (PCR) next‐generation sequencing (NGS) assay was used to detect the ctDNA levels. The primary outcome was recurrence‐free probability (RFP), and the secondary outcomes were overall survival (OS), sensitivity, specificity, and the test's negative (NPV) and positive predictive values (PPV). Results The median age of patients was 65 years (interquartile range: 56‐69), with majority being males (n = 22, 76%). The primary sites were larynx (n = 12), oropharynx (n = 10), and oral cavity (n = 6). Posttreatment ctDNA was detected in 7 patients, all of whom had disease recurrence. ctDNA detection after definitive treatment was associated with a higher risk of disease recurrence (hazard ratio: 9.94, 95% confidence interval: 1.56‐63.3, P = .015). ctDNA identified recurrence with 100% specificity and 78% sensitivity. The NPV and PPV were 91% and 100%. PET had 78% sensitivity but only 68% specificity with 86% NPV, and 54% PPV. Conclusion Based on our data, ctDNA can be an excellent adjunct test for posttreatment PET and can help guide physicians in cases where PET results are inconclusive and difficult to interpret.