Noji Rika, Tohyama Kohki, Nakamura Shin, Naito Takahiro, Oikawa Yu, Kuroshima Takeshi, Tomioka Hirofumi, Michi Yasuyuki, Ikeda Sadakatsu, Asakage Takahiro, Miura Masahiko, Hamamoto Yasuo, Harada Hiroyuki, Kano Yoshihito
Department of Oral and Maxillofacial Surgical Oncology, Division of Health Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8510, Japan.
Department of Medical Oncology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8510, Japan.
Int J Mol Sci. 2024 Dec 30;26(1):235. doi: 10.3390/ijms26010235.
Immune checkpoint inhibitors (ICIs) are effective in treating recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but only 20% of patients achieve durable responses. This study evaluated circulating tumor DNA (ctDNA) as a real-time biomarker for monitoring treatment response in HNSCC. The SHIZUKU-HN study prospectively collected and analyzed serial plasma samples (n = 27) from HNSCC patients undergoing ICIs, using Guardant360 to assess ctDNA variant allele frequency (VAF) and genetic mutations. Tumor volumes were quantified using 3D reconstruction of CT scans, and data from Japan's C-CAT database (n = 2255) provided insights into ctDNA testing in HNSCC. C-CAT data showed that ctDNA testing was underutilized, performed in only 7% of head and neck cancer cases. In SHIZUKU-HN, mean VAF significantly correlated with tumor volume (Spearman's ρ = 0.70, = 0.001), often preceding radiographic progression. BRAF and APC mutations disappeared in partial responders, while GNAS mutations varied. EGFR and PIK3CA amplifications, detectable via ctDNA but missed in tissue biopsies, indicated emerging resistance mechanisms. The SHIZUKU-HN study demonstrates the potential of ctDNA as a dynamic biomarker in HNSCC, offering early insights into treatment efficacy and informing personalized ICI therapy.
免疫检查点抑制剂（ICIs）在治疗复发/转移性头颈部鳞状细胞癌（HNSCC）方面有效，但只有20%的患者能实现持久缓解。本研究评估了循环肿瘤DNA（ctDNA）作为监测HNSCC治疗反应的实时生物标志物。SHIZUKU-HN研究前瞻性收集并分析了接受ICIs治疗的HNSCC患者的系列血浆样本（n = 27），使用Guardant360评估ctDNA变异等位基因频率（VAF）和基因突变。利用CT扫描的三维重建对肿瘤体积进行量化，来自日本C-CAT数据库（n = 2255）的数据为HNSCC中ctDNA检测提供了见解。C-CAT数据显示ctDNA检测未得到充分利用，仅在7%的头颈癌病例中进行。在SHIZUKU-HN研究中，平均VAF与肿瘤体积显著相关（Spearman氏ρ = 0.70，P = 0.001），通常先于影像学进展。BRAF和APC突变在部分缓解者中消失，而GNAS突变则有所不同。通过ctDNA可检测到但在组织活检中未发现的EGFR和PIK3CA扩增表明出现了新的耐药机制。SHIZUKU-HN研究证明了ctDNA作为HNSCC动态生物标志物的潜力，可为治疗疗效提供早期见解并为ICI个性化治疗提供依据。
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