Background: The detection of circulating tumor DNA (ctDNA) with next-generation sequencing (NGS) in venous blood is a promising tool for the genomic profiling of head and neck squamous cell carcinoma (HNSCC). The association between ctDNA findings and metabolic tumor burden detected with FDG-PET/CT imaging is of particular interest for developing prognostic and predictive algorithms in HNSCC. Methods: Twenty-six prospectively enrolled HNSCC patients were eligible for further analysis. All patients underwent tumor tissue and venous liquid biopsy sampling and FDG-PET/CT before definitive oncologic treatment. An NGS-based commercial panel was used for a genomic analysis of the samples. Results: Maximum variant allele frequency (VAF) in blood correlated positively with whole-body (WB) metabolic tumor volume (MTV) and total lesion glycolysis (TLG) (r = 0.510,p= 0.008 and r = 0.584,p= 0.002, respectively). A positive liquid biopsy was associated with high WB-TLG using VAF ≥ 1.00% or ≥5.00% as a cut-off value (p= 0.006 orp= 0.003, respectively). Additionally, ctDNA detection was associated with WB-TLG when only concordant variants detected in both ctDNA and tissue samples were considered. Conclusions: A high metabolic tumor burden based on FDG imaging is associated with a positive liquid biopsy and high maximum VAF. Our findings suggest a complementary role of metabolic and genomic signatures in the pre-treatment evaluation of HNSCC.
背景：利用下一代测序（NGS）检测静脉血中的循环肿瘤DNA（ctDNA），是一种对头颈部鳞状细胞癌（HNSCC）进行基因组分析的有前景的工具。ctDNA检测结果与FDG-PET/CT成像所显示的代谢肿瘤负荷之间的关联，对于开发HNSCC的预后和预测算法具有重要意义。方法：26例前瞻性入组的HNSCC患者符合进一步分析条件。所有患者在确定性肿瘤治疗前均接受了肿瘤组织与静脉液体活检采样以及FDG-PET/CT检查。使用基于NGS的商业化panel对样本进行基因组分析。结果：血液中的最大变异等位基因频率（VAF）与全身（WB）代谢肿瘤体积（MTV）及总病灶糖酵解（TLG）呈正相关（分别为 r = 0.510，p = 0.008 和 r = 0.584，p = 0.002）。以VAF ≥ 1.00% 或 ≥5.00% 作为临界值时，液体活检阳性与高WB-TLG相关（分别为 p = 0.006 和 p = 0.003）。此外，当仅考虑在ctDNA和组织样本中均检测到的一致变异时，ctDNA的检出也与WB-TLG相关。结论：基于FDG成像的高代谢肿瘤负荷与液体活检阳性及高最大VAF相关。我们的研究结果表明，在HNSCC的治疗前评估中，代谢特征与基因组特征具有互补作用。
肿瘤(癌症)患者之家