UNIROUEN, Inserm 1245, IRON group, Normandie Univ, Rouen, France.
Department of Hepatogastroenterology, Rouen University Hospital, Rouen, France.
Int J Cancer. 2022 Feb 1;150(3):532-541. doi: 10.1002/ijc.33829. Epub 2021 Nov 1.
Transarterial chemoembolization (TACE) is used to treat patients with unresectable hepatocellular carcinoma (HCC). We evaluated the clinical impact of a-fetoprotein (AFP) and circulating cell-free and tumor DNA (cfDNA and ctDNA) changes around the TACE procedure. Our prospective monocentric study enrolled consecutive patients treated with TACE, with samples collected at baseline (D - 1), Day 2 (D + 2) and 1 month (M + 1) after TACE. cfDNA was quantified by the fluorometric method, and ctDNA was quantified by digital polymerase chain reaction designed for two hotspot TERT mutations. Computerized tomography scans or magnetic resonance imaging were performed at M + 1 every 3 months following TACE and independently reviewed. The objective was to identify thresholds of cfDNA, ctDNA and AFP changes associated with progressive disease (PD) using receiver operating characteristic curves. Thirty-eight patients were included from March 2018 to March 2019. All markers significantly increased from D - 1 to D + 2 (P < .005), and cfDNA and ctDNA significantly decreased from D + 2 to M + 1 (P < .0001). The analysis of changes from D - 1 to M + 1 identified thresholds at +31.4% for cfDNA and 0% for ctDNA that were significantly associated with PD at M + 1 (44.4% [>+31.4%] vs 3.8% [≤+31.4%] and 50.0% [>0%] vs 5.0% [≤0%], respectively). No significant threshold was identified for AFP. Using a score combining cfDNA and ctDNA, the patients were classified into high- or low-risk PD groups at M + 1, with PD rates of 80.0% vs 4.3% (P = .001) and median progression-free survival times of 1.3 vs 10.3 months (P = .002). Our study suggests that cfDNA and ctDNA increases around the TACE procedure and are associated with therapeutic failure.
经动脉化疗栓塞术（TACE）用于治疗不可切除的肝细胞癌（HCC）患者。我们评估了 TACE 手术前后甲胎蛋白（AFP）和循环游离及肿瘤 DNA（cfDNA 和 ctDNA）变化对临床的影响。我们前瞻性的单中心研究纳入了连续接受 TACE 治疗的患者，在基线（D-1）、TACE 后第 2 天（D+2）和第 1 个月（M+1）采集样本。通过荧光法定量 cfDNA，通过针对两个热点 TERT 突变设计的数字聚合酶链反应定量 ctDNA。TACE 后每 3 个月进行 M+1 计算机断层扫描或磁共振成像，并进行独立评估。目的是通过受试者工作特征曲线确定与进展性疾病（PD）相关的 cfDNA、ctDNA 和 AFP 变化的阈值。2018 年 3 月至 2019 年 3 月，共纳入 38 例患者。所有标志物均从 D-1 到 D+2 显著增加（P<0.005），cfDNA 和 ctDNA 从 D+2 到 M+1 显著降低（P<0.0001）。从 D-1 到 M+1 的变化分析确定了 cfDNA 的+31.4%和 ctDNA 的 0%的阈值，这与 M+1 的 PD 显著相关（44.4%[+31.4%] vs 3.8%[≤+31.4%]和 50.0%[>0%] vs 5.0%[≤0%]）。未发现 AFP 的显著阈值。使用结合 cfDNA 和 ctDNA 的评分，将患者在 M+1 时分为高或低风险 PD 组，PD 发生率分别为 80.0%和 4.3%（P=0.001），中位无进展生存期分别为 1.3 个月和 10.3 个月（P=0.002）。我们的研究表明，TACE 手术前后 cfDNA 和 ctDNA 增加，并与治疗失败相关。
