Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery
Aurélie Moreira, A. Poulet, Julien Masliah‐Planchon, Charlotte Lecerf, Sophie Vacher, Linda Larbi Chérif, Célia Dupain, Grégoire Marret, Elodie Girard, Laurène Syx, Caroline Hoffmann, Emmanuelle Jeannot, Jerzy Klijanienko, Isabelle Guillou, Odette Mariani, Antoine Dubray‐Vautrin, Nathalie Badois, Maria Lesnik, Olivier Choussy, Valentin Calugaru, Édith Borcoman, Sylvain Baulande, Patricia Legoix, Benoît Albaud, Nicolas Servant, Ivan Bièche, Christophe Le Tourneau, Maud Kamal
Abstract
BACKGROUND: Oral cavity is the most prevalent site of head and neck squamous cell carcinomas (HNSCCs). Most often diagnosed at a locally advanced stage, treatment is multimodal with surgery as the cornerstone. The aim of this study was to explore the molecular landscape of a homogenous cohort of oral cavity squamous cell carcinomas (OCSCCs), and to assess the prognostic value of tumor mutational burden (TMB), along with classical molecular and clinical parameters. PATIENTS AND METHODS: One hundred and fifty-one consecutive patients with OCSCC treated with upfront surgery at the Institut Curie were analyzed. Sequencing of tumor DNA from frozen specimens was carried out using an in-house targeted next-generation sequencing panel (571 genes). The impact of molecular alterations and TMB on disease-free survival (DFS) and overall survival (OS) was evaluated in univariate and multivariate analyses. RESULTS: Pathological tumor stage, extranodal spread, vascular emboli, and perineural invasion were associated with both DFS and OS. TP53 was the most mutated gene (71%). Other frequent molecular alterations included the TERT promoter (50%), CDKN2A (25%), FAT1 (17%), PIK3CA (14%), and NOTCH1 (15%) genes. Transforming growth factor-β pathway alterations (4%) were associated with poor OS (P = 0.01) and DFS (P = 0.02) in univariate and multivariate analyses. High TMB was associated with prolonged OS (P = 0.01 and P = 0.02, in the highest 10% and 20% TMB values, respectively), but not with DFS. Correlation of TMB with OS remained significant in multivariate analysis (P = 0.01 and P = 0.005 in the highest 10% and 20% TMB values, respectively). Pathological tumor stage combined with high TMB was associated with good prognosis. CONCLUSION: Our results suggest that a high TMB is associated with a favorable prognosis in patients with OCSCC treated with upfront surgery.