The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy

• Published in: Experimental & molecular medicine Vol. 55; no. 5; pp. 926 - 938
• Main Authors: Wang, Hui-Ching, Moi, Sin-Hua, Chan, Leong-Perng, Wu, Chun-Chieh, Du, Jeng-Shiun, Liu, Pei-Lin, Chou, Meng-Chun, Wu, Che-Wei, Huang, Chih-Jen, Hsiao, Hui-Hua, Pan, Mei-Ren, Chen, Li-Tzong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 38/39; 45/43; 45/47; 631/208/205/2138; 631/67/1536/1665; Biomedical and Life Sciences; Biomedicine; Cancer; Chemoradiotherapy; Chemotherapy; Chromatin remodeling; Genetic screening; Head & neck cancer; Head and neck carcinoma; Medical Biochemistry; Medical personnel; Molecular Medicine; Mutation; Next-generation sequencing; Nomograms; Patients; Radiation therapy; Squamous cell carcinoma; Stem Cells; Tumors
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-00984-4

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively ( p  < 0.001 and p  = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT. Head and neck cancer: genetic profiling improves predictions of relapse Including personalized genetic profiling data greatly improves calculations of the risk of relapse in head and neck squamous cell cancer (HNSCC) after treatment. HNSCC, which develops in the nose, mouth and throat, has a 5-year overall survival rate of ~50% due to recurrence. Mei-Ren Pan and Li-Tzong Chen at Kaohsiung Medical University in Taiwan and co-workers analyzed genetic, clinical and survival data from 120 HNSCC patients who had received a course of concurrent radiotherapy and chemotherapy. The researchers developed a computational model that revealed key genetic risk predictors, such as the tumor mutation burden, the total number of mutations in the cancer cell DNA. The model showed much better performance in predicting relapse-free survival than one based solely on clinical and laboratory data, indicating the huge potential benefits of including genetic profiles in prognostic models.