Ludivine Beaussire‐Trouvay, Franchel‐Raïs Obongo‐Anga, Émilie Lévêque, Anca Berghian, Arnaud François, Nicolas Bon‐Mardion, E. Meret, Sophie Deneuve, Élodie Bohers, Mathieu Viennot, Lucie Burel, Julie Libraire, Louise Libert, Nasrin Sarafan‐Vasseur, Frédéric Di Fiore, F. Clatot
ctDNA is a promising tool to optimize therapeutic strategies in patients treated for locally advanced head and neck cancer that is negative for Human Papilloma Virus (LAHNSCC/HPV-). The objective was to evaluate pre and postoperative detection of circulating tumor DNA (ctDNA) using a customized Next-Generation Sequencing (NGS) tumor-informed assay. We conducted a prospective study including patients treated with initial surgery for a LAHNSCC/HPV-. We developed an NGS assay covering the exons of 11 genes for tumor and ctDNA analysis. DNA alterations were interpreted according to two classes of variants: "pathogenic variants" classified as class 4 or 5 in public databases and "tumor specific variants" corresponding to alterations detected exclusively in tumor DNA after paired analysis of normal cell DNA using the same NGS panel. A total of 40 patients were included, 45% with T4 and 62.5% with N+ disease. Regarding tumor profiles, 41 "pathogenic variants" were detected corresponding to 30/36 (83.3%) of informative tumors with at least one alteration. In contrast, 354 "tumor specific variants" were identified with at least one alteration in 35/35 (100%) informative tumors. For ctDNA, the NGS panel was associated with a positivity rate of 74.3% and 37.1% pre and postoperative, respectively, using tumor specific variants; compared with 20% and 2.5% using interpretation of pathogenic variant. Pretreatment ctDNA positivity according to pathogenic variant was associated with lower specific progression-free survival (p = 0.025). Our customized 11-genes NGS panel tumor-informed assay provides high rates of ctDNA detection and may be used to evaluate new strategies in LA HNSCC/HPV- patients.