Prospective multicentre study evaluating ctDNA as a biomarker of residual disease after chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: NeckTAR-IN protocol.

INTRODUCTION: The first therapeutic assessment of locally advanced (LA) head and neck squamous cell carcinomas (HNSCCs) is often performed 10-12 weeks after the end of chemoradiotherapy as a result of the delayed action of radiotherapy. Diagnostic uncertainty between persistent disease and treatment-related changes (oedema, necrosis) can delay confirmation of residual cancer. According to data in the literature, a correlation exists between the detection of circulating tumour DNA (ctDNA) at the end of chemoradiotherapy treatment and residual disease. However, additional data are required before this molecular tool can be used in routine clinical practice. The aim of this clinical trial (NeckTAR-IN) is to assess the usefulness of ctDNA to detect residual disease 3 months after the end of chemoradiotherapy among patients with LA HNSCC. METHODS AND ANALYSIS: At M3, objective response (clinical and radiological) will be set against the detection or not of ctDNA in the blood. This is an interventional, multicentre, prospective trial, ancillary to the NeckTAR study. All the patients included in the NeckTAR study are eligible for the NeckTAR-IN study. We expect to enrol 59 patients in this ancillary trial. A blood sample will be taken 1 month and 3 months after the end of chemoradiotherapy. Approval from the ethics committee was granted on 29 August 2025. ETHICS AND DISSEMINATION: The study protocol obtained approval from the French Ethics Committee (N°25.02461.000435). The results will be published in scientific journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT07178847.