研究动态
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使用下一代测序和表观遗传修饰进行序贯循环肿瘤 DNA 分析用于指导结直肠癌转移热消融的临床价值:一项前瞻性研究。

Clinical value of sequential circulating tumor DNA analysis using next-generation sequencing and epigenetic modifications for guiding thermal ablation for colorectal cancer metastases: a prospective study.

发表日期:2024 Aug 25
作者: Tom Boeken, Olivier Pellerin, Camille Bourreau, Juliette Palle, Claire Gallois, Aziz Zaanan, Julien Taieb, Widad Lahlou, Alessandro Di Gaeta, Marc Al Ahmar, Xavier Guerra, Carole Dean, Pierre Laurent Puig, Marc Sapoval, Helena Pereira, Hélène Blons
来源: Epigenetics & Chromatin

摘要:

虽然热消融现在是寡转移结直肠癌患者的标准治疗选择,但选择那些将从局部治疗中受益最大的患者仍然具有挑战性。这项概念验证研究首次评估了具有治疗目的的热消融前后 ctDNA 常规测试的可行性,并通过下一代测序 (NGS) 和甲基化特异性数字液滴 PCR (ddPCR) 进行分析。我们的前瞻性研究的主要目的是评估热消融前 ctDNA 的预后价值。这项于 2021 年 11 月至 2022 年 6 月进行的单中心前瞻性研究纳入了转诊接受治疗性热消融的结直肠癌患者。通过新一代测序在不同时间点测试游离 DNA,并使用 ddPCR 检测 WIF1 和 NPY 基因高甲基化。如果检测到肿瘤突变或高甲基化,则 ctDNA 被视为阳性;无复发生存期作为主要终点。该研究招募了 15 名患者,总共分析了 60 个样本。消融后的中位随访时间为 316 天,中位无复发生存期为 250 天。前 24 小时内收集的样本中有 33% 的 CtDNA 呈阳性。根据基线循环肿瘤 DNA 的存在情况,进展的风险比估计为 0.14(CI 95%:0.03-0.65,p = 0.019)。提供了动态,并且没有复发的患者在 H24 时 ctDNA 均为阴性。这项研究表明了热消融前后 ctDNA 常规检测的可行性,以达到治疗目的。我们报告使用两种技术可在低肿瘤负荷患者中检测到循环肿瘤 DNA。这项研究强调了 ctDNA 对于有洞察力的患者的潜力,这些患者可能会从热消融中受益,而那些可能不会受益的患者,这可能会影响未来的转诊。消融前后 ctDNA 的动态揭示了进一步研究和更大规模研究的必要性。© 2024。意大利医学放射学会。
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.© 2024. Italian Society of Medical Radiology.