Circulating tumor DNA as a marker of minimal residual disease following local treatment of metastases from colorectal cancer
Circulating tumor DNA as a marker of minimal residual disease following local treatment of metastases from colorectal cancer
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DOI：
10.1080/0284186x.2020.1806357
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发表时间：
2020-08-12
期刊：
影响因子：
3.1
通讯作者：
Spindler, Karen-Lise G.
中科院分区：
文献类型：
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作者：
Boysen, Anders K.;Pallisgaard, Niels;Spindler, Karen-Lise G.
背景 结直肠癌（CRC）肝和/或肺转移的局部治疗越来越多地用于日常实践，包括切除、射频消融（RFA）和立体定向放射治疗（SBRT）。目前尚未满足接受此类治疗的患者对预后标志物的需求。我们研究了治疗后循环肿瘤特异性 DNA (ctDNA) 分析，并在一项试点研究中探讨了可能的预后价值。材料 2015 年 7 月至 2017 年 9 月，接受肝和/或肺转移标准护理局部治疗的患者被纳入一项前瞻性转化研究。局部治疗后两周和随访期间抽取血样。 CtDNA 通过 ddPCR 和基于质谱的平台 MassARRAY(R) 进行检测。结果 35 名患者获得了治疗后血液样本，其中 5 名患者通过 ddPCR 可检测到 ctDNA（KRAS 突变，n = 2；NRAS 突变，n = 2；BRAF 突变，n = 1）。在 ctDNA 阳性的患者中，35 名患者中有 17 名 (49%) 在中位 273 天内出现复发 (95%CI 95-NA)，而 ctDNA 阴性的患者组未达到中位复发时间 (p = .03)。结论 转移性 CRC 局部治疗后 ctDNA 的存在与复发风险增加和失败时间短相关。
Background Local treatment of liver and/or lung metastases from colorectal cancer (CRC) is increasingly used in daily practice and comprises resection, radiofrequency ablation (RFA) and stereotactic radiotherapy (SBRT). The need for prognostic markers for patients undergoing such treatment is currently unmet. We investigated post-treatment circulating tumor-specific DNA (ctDNA) analysis and address a possible prognostic value in a pilot study. Materials From July 2015 to September 2017, patients undergoing standard of care local treatment of liver and/or lung metastases were included in a prospective translational study. Blood samples were drawn 2 weeks after local treatment and during follow-up. CtDNA was detected by ddPCR and a mass spectrometry-based platform MassARRAY(R). Results Post treatment blood samples were available for 35 patients including five with detectable ctDNA (KRAS mutation,n = 2; NRAS mutation,n = 2; BRAF mutation,n = 1) by ddPCR. 17 out of 35 patients (49%) developed recurrence within a median of 273 days (95%CI 95-NA) among patients positive for ctDNA, while the median time to recurrence was not reached for the group of patients negative for ctDNA (p = .03). Conclusion The presence of ctDNA following local treatment of metastatic CRC is associated with an increased risk of recurrence and a short time to failure.