Purpose: We performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response.
Methods: Patients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC were divided into two groups: good responders and poor responders by tumor response and progression-free survival. Targeted gene sequencing for 2404 somatic mutations of 44 genes was performed on HNSCC tissues. Mutations with total coverage of <500 were excluded, and the cutoff for altered allele frequency was >10 %.
Results: Of the 71 patients, 45 were treated upfront with IC. Mean total coverage was 1941 per locus, and 42.2 % of tumors had TP53 mutations. Thirty-three mutations in TP53, NOTCH3, FGFR2, FGFR3, ATM, EGFR, MET, PTEN, FBXW7, SYNE1, and SUFU were frequently altered in poor responders. Among the patients who were treated with IC, those with unfavorable genomic profiles had significantly poorer overall survival than those without unfavorable genomic profiles (hazard ratio 6.45, 95 % confidence interval 2.07-20.10, P < 0.001).
Conclusions: Comprehensive analysis of mutation frequencies identified unfavorable genomic profiles, and the patients without unfavorable genomic profiles can obtain clinical benefits from IC in patients with HNSCC.
Keywords: Concurrent chemoradiotherapy; Head and neck cancer; Induction chemotherapy; Survival; Targeted gene sequencing.