Department of Vascular and Oncological Interventional Radiology, AP-HP, INSERM PARCC U 970, Hôpital Européen Georges Pompidou, HEKA INRIA, Université de Paris Cité, Paris, France.
INSERM 1138 Centre de Recherche des Cordeliers, Paris, France.
Radiol Med. 2024 Oct;129(10):1530-1542. doi: 10.1007/s11547-024-01865-0. Epub 2024 Aug 25.
While thermal ablation is now a standard treatment option for oligometastatic colorectal cancer patients, selecting those who will benefit most from locoregional therapies remains challenging. This proof-of-concept study is the first to assess the feasibility of routine testing of ctDNA before and after thermal ablation with curative intent, analyzed by next-generation sequencing (NGS) and methylation specific digital droplet PCR (ddPCR). Our prospective study primary objective was to assess the prognostic value of ctDNA before thermal ablation.
This single-center prospective study from November 2021 to June 2022 included colorectal cancer patients referred for curative-intent thermal ablation. Cell-free DNA was tested at different time points by next-generation sequencing and detection of WIF1 and NPY genes hypermethylation using ddPCR. The ctDNA was considered positive if either a tumor mutation or hypermethylation was detected; recurrence-free survival was used as the primary endpoint.
The study enrolled 15 patients, and a total of 60 samples were analyzed. The median follow-up after ablation was 316 days, and median recurrence-free survival was 250 days. CtDNA was positive for 33% of the samples collected during the first 24 h. The hazard ratio for progression according to the presence of baseline circulating tumor DNA was estimated at 0.14 (CI 95%: 0.03-0.65, p = 0.019). The dynamics are provided, and patients with no recurrence were all negative at H24 for ctDNA.
This study shows the feasibility of routine testing of ctDNA before and after thermal ablation with curative intent. We report that circulating tumor DNA is detectable in patients with low tumor burden using 2 techniques. This study emphasizes the potential of ctDNA for discerning patients who are likely to benefit from thermal ablation from those who may not, which could shape future referrals. The dynamics of ctDNA before and after ablation shed light on the need for further research and larger studies.
虽然热消融术现在是寡转移性结直肠癌患者的标准治疗选择，但选择最能从局部区域治疗中获益的患者仍然具有挑战性。这项验证概念的研究首次评估了在有治愈意向的热消融术前后，通过下一代测序（NGS）和甲基化特异性数字液滴 PCR（ddPCR）常规检测 ctDNA 的可行性。我们的前瞻性研究主要目的是评估热消融术前 ctDNA 的预后价值。
这项从 2021 年 11 月至 2022 年 6 月进行的单中心前瞻性研究纳入了因有治愈意向的热消融术而转诊的结直肠癌患者。通过下一代测序和 ddPCR 检测 WIF1 和 NPY 基因的超甲基化，在不同时间点检测无细胞 DNA。如果检测到肿瘤突变或超甲基化，则认为 ctDNA 为阳性；无复发生存率被用作主要终点。
该研究纳入了 15 名患者，共分析了 60 个样本。消融后中位随访时间为 316 天，中位无复发生存时间为 250 天。在第 24 小时内采集的样本中，ctDNA 阳性率为 33%。根据基线循环肿瘤 DNA 存在情况，进展的风险比估计为 0.14（95%CI：0.03-0.65，p=0.019）。提供了动态信息，且在 H24 时无复发的患者 ctDNA 均为阴性。
本研究表明，有治愈意向的热消融术前后常规检测 ctDNA 是可行的。我们报告使用 2 种技术，在低肿瘤负荷的患者中可以检测到循环肿瘤 DNA。本研究强调了 ctDNA 用于区分可能从热消融术获益的患者和可能无法获益的患者的潜力，这可能会影响未来的转诊。消融术前后 ctDNA 的动态变化表明需要进一步研究和更大规模的研究。
