循环血浆无细胞DNA（cfDNA）作为头颈癌放疗预测生物标志物：前瞻性试验结果。
Circulating Plasma Cell-free DNA (cfDNA) as a Predictive Biomarker for Radiotherapy: Results from a Prospective Trial in Head and Neck Cancer.
发表日期：2023
作者：
Michael I Koukourakis, Erasmia Xanthopoulou, Ioannis M Koukourakis, Sotirios P Fortis, Nikolaos Kesesidis, Ioannis Karakasiliotis, Constantin N Baxevanis
来源：
Cell Death & Disease
摘要：
癌症患者的细胞游离DNA（cfDNA）浆液水平因快速癌细胞增殖和死亡而增加。因此，cfDNA可用于研究特定的肿瘤-DNA特征。此外，非特异性的cfDNA浓度可能是癌症预后的重要生物标志物。我们前瞻性地研究了cfDNA水平和动力学在47例局部晚期鳞状细胞头颈癌（SCHNC）接受确定性化疗放疗（CRT）治疗的患者队列中的预测作用。治疗完成后（治疗前/后比率；A/B比率>1），26/47例患者（55.3%）发现cfDNA水平升高。T4期局部晚期与CRT后cfDNA水平显著相关（T4期为3.3ng/μl，T1-3期为1.3ng/μl，p=0.007）。对CRT有反应（部分/完全反应）的患者治疗前cfDNA水平显著较低（平均值1.2ng/μl vs. 2.7ng/μl，p=0.03）。A/B比率>1的患者局部区域进展无进展生存率显著较差（p=0.01；风险比3.5，95%CI=1.2-9.7）。这在多变量分析中也得到证实，其中A/B比率是局部复发的独立预测变量（p=0.03，风险比3.9，95%CI=1.2-13）。CRT后cfDNA水平升高可能是将SCHNC患者立即纳入巩固化疗免疫疗法方案的早期生物标志物。
版权所有©2023，国际抗癌研究所。
The plasma levels of cell-free DNA (cfDNA) in cancer patients increase due to rapid cancer cell proliferation and death. Therefore, cfDNA can be used to study specific tumor-DNA features. In addition, the non-specific cfDNA concentration may be an important biomarker of cancer prognosis.We prospectively examined the predictive role of cfDNA levels and the kinetics in the outcome of chemo-radiotherapy (CRT) in a cohort of 47 patients with locally advanced squamous cell head-neck cancer (SCHNC) treated with definitive chemo-radiotherapy.Increased cfDNA levels after therapy completion (after/before treatment ratio; A/B-ratio >1) were found in 26/47 patients (55.3%). Locally advanced T4-stage was significantly associated with higher cfDNA levels after CRT (3.3 ng/μl in T4-stage vs. 1.3 ng/μl in T1-3 stages, p=0.007). Patients who responded to CRT (partial/complete response) had significantly lower cfDNA levels before therapy (mean values 1.2 ng/μl vs. 2.7 ng/μl, p=0.03). A significantly worse locoregional progression-free survival in patients with an A/B-ratio >1 was documented (p=0.01; hazard ratio 3.5, 95%CI=1.2-9.7). This was also confirmed in multivariate analysis, where the A/B-ratio was an independent predictive variable of locoregional relapse (p=0.03, hazard ratio 3.9, 95%CI=1.2-13).High post-CRT cfDNA levels could be an early biomarker for the immediate recruitment of patients with SCHNC in consolidation chemo-immunotherapy protocols.Copyright 2023, International Institute of Anticancer Research.