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脑癌免疫治疗期间循环瘤DNA的动态变化:SHIZUKU-HN研究

Rika Noji^1,2, Kohki Tohyama³, Shin Nakamura³

¹Department 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.

International journal of molecular sciences

|January 11, 2025

概括

循环瘤DNA (ctDNA) 显示出作为实时生物标志物的承诺,用于监测头部和部状细胞癌 (HNSCC) 对免疫检查点抑制剂 (ICI) 的治疗反应. ctDNA分析,特别是变异性等位基因频率 (VAF),与瘤体积相关,可以在放射性进展之前进行,有助于个性化治疗.

科学领域:

在瘤学瘤学.
分子诊断学分子诊断
生物标志物研究生物标志物研究

背景情况:

免疫检查点抑制剂 (ICI) 在复发性/转移性头支状细胞癌 (HNSCC) 中显示出有限的持久反应率 (20%).
循环瘤DNA (ctDNA) 已成为癌症监测的潜在非侵入性生物标志物.
目前在HNSCC中使用ctDNA测试的比例很低 (在日本的C-CAT数据库中为7%).

研究的目的:

评估ctDNA作为实时生物标志物,用于监测接受ICI的HNSCC患者的治疗反应.
为了将ctDNA动态与瘤体积和X光学变化相关联.
通过ctDNA识别可能表明治疗耐药性的遗传突变.

主要方法:

来自27名接受ICI的HNSCC患者的连续血样本的前性分析 (SHIZUKU-HN研究).
用于评估ctDNA变体等位基因频率 (VAF) 和遗传突变的Guardant360测定.
使用3DCT重建量化瘤体积;与日本C-CAT数据库进行比较 (n=2255).

主要成果:

平均ctDNA VAF与瘤体积显著相关 (斯皮尔曼的 ρ = 0.70,p = 0.001).
ctDNA变化往往先于放射性进展,表明早期治疗反应或耐药性.
在部分响应者中消失的BRAF/APC突变,并通过ctDNA检测EGFR/PIK3CA放大,表明了耐药性机制.

结论:

ctDNA作为一个动态和敏感的生物标志物,用于实时监测HNSCC对ICI的治疗反应.
ctDNA分析提供了对治疗疗效的早期见解,并可以识别新出现的耐药性机制.
这种方法支持针对HNSCC患者的个性化ICI治疗策略.

关键词:

癌症基因组学和先进治疗中心 (C-CAT)循环瘤DNA (ctDNA) 的发生.动态监控动态监控动态监控头部和部状细胞癌 (HNSCC)免疫检查点抑制剂 (ICI)液体活检活检液体活检变异的等位基因频率 (VAF)

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