Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery

A Moreira; A Poulet; J Masliah-Planchon; C Lecerf; S Vacher; L Larbi Chérif; C Dupain; G Marret; E Girard; L Syx; C Hoffmann; E Jeannot; J Klijanienko; I Guillou; O Mariani; A Dubray-Vautrin; N Badois; M Lesnik; O Choussy; V Calugaru; E Borcoman; S Baulande; P Legoix; B Albaud; N Servant; I Bieche; C Le Tourneau; M Kamal

doi:10.1016/j.esmoop.2021.100178

Prognostic value of tumor mutational burden in patients with oral cavity squamous cell carcinoma treated with upfront surgery

ESMO Open. 2021 Aug;6(4):100178. doi: 10.1016/j.esmoop.2021.100178. Epub 2021 Jun 9.

Authors

A Moreira¹, A Poulet¹, J Masliah-Planchon², C Lecerf¹, S Vacher², L Larbi Chérif¹, C Dupain¹, G Marret¹, E Girard³, L Syx³, C Hoffmann⁴, E Jeannot⁵, J Klijanienko⁶, I Guillou¹, O Mariani⁶, A Dubray-Vautrin⁷, N Badois⁷, M Lesnik⁷, O Choussy⁷, V Calugaru⁸, E Borcoman¹, S Baulande⁹, P Legoix⁹, B Albaud⁹, N Servant³, I Bieche¹⁰, C Le Tourneau¹¹, M Kamal¹²

Affiliations

¹ Department of Drug Development and Innovation (D3i), Institut Curie, Paris and Saint-Cloud, France.
² Department of Genetics, Institut Curie, PSL Research University, Paris, France.
³ INSERM U900 Research Unit, Institut Curie, Paris and Saint-Cloud, France.
⁴ INSERM U932 Research Unit, Institut Curie, PSL Research University, Paris, France; Department of Oncologic Surgery, Institut Curie, PSL Research University, Paris, France.
⁵ Department of Genetics, Institut Curie, PSL Research University, Paris, France; Department of Pathology, Institut Curie, PSL Research University, Paris, France.
⁶ Department of Pathology, Institut Curie, PSL Research University, Paris, France.
⁷ Department of Oncologic Surgery, Institut Curie, PSL Research University, Paris, France.
⁸ Department of Oncologic Radiotherapy, Institut Curie, PSL Research University, Paris, France.
⁹ Institut Curie Genomics of Excellence (ICGex) Platform, PSL Research University, Paris, France.
¹⁰ Department of Genetics, Institut Curie, PSL Research University, Paris, France; INSERM U1016, Paris Descartes University, Faculty of Pharmaceutical and Biological Sciences, Paris, France.
¹¹ Department of Drug Development and Innovation (D3i), Institut Curie, Paris and Saint-Cloud, France; INSERM U900 Research Unit, Institut Curie, Paris and Saint-Cloud, France; Paris-Saclay University, Paris, France.
¹² Department of Drug Development and Innovation (D3i), Institut Curie, Paris and Saint-Cloud, France. Electronic address: maud.kamal@curie.fr.

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.

Keywords: next-generation sequencing; oral cavity squamous cell carcinoma; prognostic marker; tumor mutational burden.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell* / genetics
Carcinoma, Squamous Cell* / surgery
Head and Neck Neoplasms*
Humans
Mouth Neoplasms* / genetics
Mouth Neoplasms* / surgery
Prognosis
Squamous Cell Carcinoma of Head and Neck / genetics
Squamous Cell Carcinoma of Head and Neck / surgery