Department of Medical Oncology, Institut Roi Albert II - Cliniques universitaires Saint-Luc, Brussels, Belgium; Institute for Clinical and Experimental Research (MIRO), Université catholique de Louvain, Brussels, Belgium.
Department of Medical Oncology, Institut Roi Albert II - Cliniques universitaires Saint-Luc, Brussels, Belgium; Institute for Clinical and Experimental Research (MIRO), Université catholique de Louvain, Brussels, Belgium; Laboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Oral Oncol. 2020 May;104:104631. doi: 10.1016/j.oraloncology.2020.104631. Epub 2020 Mar 10.
The molecular landscape of head and neck squamous cell carcinoma (HNSCC) harbors potentially actionable genomic alterations. We aimed to study the utility of liquid biopsy to (i) characterize the mutational landscape of recurrent/metastatic HNSCC using a comprehensive gene panel and (ii) estimate the concordance between DNA mutations identified from circulating tumor DNA (ctDNA) and matched tumor tissues.
Targeted next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) of 39 patients with locoregional recurrent (n = 19) and/or metastatic (n = 20) HNSCC. Tumor biopsy (n = 18) was sequenced using the same technique.
ctDNA was detected in 51% of patients (20/39) with a higher probability of detection in metastatic than locoregional recurrent disease (70% versus 30%, p = 0.025). 81% and 58% of the tissue tumor variants were not detected in plasma when considering all patients and only metastatic patients with detectable ctDNA, respectively. In a multivariate analysis, the likelihood of detecting the tissue tumor variant in plasma was related to metastatic status (p = 0.012), tumor variant allele frequency (p < 0.001) and ctDNA quantity (p < 0.001). 26% of the variants were detected only in liquid and not in the solid biopsy. Three patients without an available tumor sample had plasma containing three different potentially actionable PIK3CA mutations.
CtDNA detection and characterization using targeted NGS is feasible in metastatic HNSCC. Liquid biopsies do not reflect the complete mutation profile of the tumor but have the potential to identify actionable mutations when tumor biopsies are not available as well as variants not found in matched tumor tissue.
头颈部鳞状细胞癌（HNSCC）的分子图谱具有潜在的可治疗的基因组改变。我们旨在研究液体活检的应用，（i）使用综合基因面板来描述复发性/转移性 HNSCC 的突变景观，以及（ii）估计从循环肿瘤 DNA（ctDNA）中鉴定的 DNA 突变与匹配肿瘤组织之间的一致性。
对 39 例局部复发性（n=19）和/或转移性（n=20）HNSCC 患者的无细胞 DNA（cfDNA）进行靶向下一代测序（NGS）。使用相同的技术对肿瘤活检（n=18）进行测序。
ctDNA 在 51%的患者（20/39）中被检测到，在转移性疾病中比局部复发性疾病更有可能被检测到（70%对 30%，p=0.025）。当考虑所有患者和仅可检测到 ctDNA 的转移性患者时，分别有 81%和 58%的组织肿瘤变体未在血浆中检测到。在多变量分析中，在血浆中检测到组织肿瘤变体的可能性与转移状态有关（p=0.012）、肿瘤变体等位基因频率（p<0.001）和 ctDNA 量（p<0.001）。26%的变体仅在液体中检测到，而不在实体活检中检测到。3 名无可用肿瘤样本的患者的血浆中含有 3 种不同的潜在可操作 PIK3CA 突变。
使用靶向 NGS 检测和表征 ctDNA 在转移性 HNSCC 中是可行的。液体活检不能反映肿瘤的完整突变谱，但当肿瘤活检不可用时，具有识别可操作突变的潜力，以及在匹配的肿瘤组织中未发现的变体。
