Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer

Abstract

Comprehensive genomic profiling (CGP) provides information regarding cancer-related genetic aberrations. However, its clinical utility in recurrent/metastatic head and neck cancer (R/M HNC) remains unknown. Additionally, predictive biomarkers for immune checkpoint inhibitors (ICIs) should be fully elucidated because of their low response rate. Here, we analyzed the clinical utility of CGP and identified predictive biomarkers that respond to ICIs in R/M HNC. We evaluated over 1100 cases of HNC using the nationwide genetic clinical database established by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and 54 cases in an institution-based study. The C-CAT database revealed that 23% of the cases were candidates for clinical trials, and 5% received biomarker-matched therapy, including NTRK fusion. Our institution-based study showed that 9% of SCC cases and 25% of salivary gland cancer cases received targeted agents. In SCC cases, the tumor mutational burden (TMB) high (≥10 Mut/Mb) group showed long-term survival (>2 years) in response to ICI therapy, whereas the PD-L1 combined positive score showed no significant difference in progression-free survival. In multivariate analysis, CCND1 amplification was associated with a lower response to ICIs. Our results indicate that CGP may be useful in identifying prognostic biomarkers for immunotherapy in patients with HNC.

Tumor mutational burden predictability in head and neck squamous cell carcinoma patients treated with immunotherapy: systematic review and meta-analysis

“…TMB was determined through NGS/WES sequencing analyses of tumor samples in all the studies, except one study [ 20 ] that also assessed peripheral blood samples (Additional file 1 : Table S3).…”

“…The muts/exome values were not available. One study defined a high TMB value of 175.0 muts/exome based on a literature review [ 21 ], and two studies used a cut-off of 10.0 and 15.0 muts/Mb [ 20 , 28 ]. Three studies established cut-off values based on the median TMB, with calculated values of 5.0 [ 18 ], 6.71 [ 22 ], and 7.6 [ 23 ].…”

The Use of Immune Regulation in Treating Head and Neck Squamous Cell Carcinoma (HNSCC)

“…The presence of infiltrating T cells in the tumor containing interferon-gamma (IFN-γ) responsive genes, a key factor for PD-L1 expression in HNSCC, may enhance the efficacy of anti-PD-1 therapies [ 139 ]. Furthermore, CCND1 amplification is mostly associated with an unfavorable response to ICIs and an unfavorable prognosis in HNSCC [ 140 ].…”

Precision Medicine in Oral Health and Diseases: A Systematic Review

“…Activating mutations or amplifications of ERBB2 and NTRK3 were discovered in 20% and 5% of cases, respectively, despite the absence of NTRK3 fusion. In contrast to forms with CCNDI1 amplification, which were less responsive and had a poor prognosis, it was found that forms with a high tumor mutational burden responded better to this type of approach [62]. According to recent studies, the human immune system can be a valuable ally in the battle against cancer.…”