循环肿瘤DNA作为结直肠癌转移灶局部治疗后微小残留病的标志物。

Circulating tumor DNA as a marker of minimal residual disease following local treatment of metastases from colorectal cancer.

作者信息

Boysen Anders K, Pallisgaard Niels, Andersen Christina S A, Spindler Karen-Lise G

机构信息

Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.

Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.

出版信息

Acta Oncol. 2020 Dec;59(12):1424-1429. doi: 10.1080/0284186X.2020.1806357. Epub 2020 Aug 13.

DOI:10.1080/0284186X.2020.1806357

PMID:32790489

Abstract

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.

RESULTS

Post treatment blood samples were available for 35 patients including five with detectable ctDNA (KRAS mutation, = 2; NRAS mutation, = 2; BRAF mutation, = 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 ( = .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.

摘要

背景

结直肠癌（CRC）肝和/或肺转移的局部治疗在日常实践中应用越来越广泛，包括手术切除、射频消融（RFA）和立体定向放疗（SBRT）。目前，接受此类治疗的患者对预后标志物的需求尚未得到满足。我们在一项前瞻性研究中调查了治疗后循环肿瘤特异性DNA（ctDNA）分析，并探讨了其可能的预后价值。

材料

2015年7月至2017年9月，接受肝和/或肺转移标准局部治疗的患者被纳入一项前瞻性转化研究。在局部治疗后2周及随访期间采集血样。通过数字滴液PCR（ddPCR）和基于质谱的MassARRAY平台检测ctDNA。

结果

35例患者治疗后的血样可供分析，其中5例通过ddPCR检测到ctDNA（KRAS突变，2例；NRAS突变，2例；BRAF突变，1例）。在ctDNA阳性的患者中，35例患者中有17例（49%）在中位273天（95%CI 95-NA）内复发，而ctDNA阴性患者组的中位复发时间未达到（P = 0.03）。