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转移性结直肠癌患者使用循环肿瘤 DNA 进行术后随访的意义。

Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA.

机构信息

Centre for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague CZ 161 00, Czech Republic.

Surgery Department, 2 Faculty of Medicine of Charles University Prague and Military University Hospital, Prague CZ 169 02, Czech Republic.

出版信息

World J Gastroenterol. 2019 Dec 28;25(48):6939-6948. doi: 10.3748/wjg.v25.i48.6939.

Abstract

BACKGROUND

One of the most notable applications for circulating tumor DNA (ctDNA) detection in peripheral blood of patients with metastatic colorectal cancer (mCRC) is a long-term postoperative follow-up. Sometimes referred to as a "liquid (re)biopsy" it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals (months or even weeks). The presence of the disease and the actual extent of the tumor burden (tumor mass) within the patient's body can be monitored. This is of particular importance, especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.

AIM

To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.

METHODS

A total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers. Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling. In addition to the baseline ctDNA testing prior to surgery, a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals. The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.

RESULTS

Among the monitored patients, the R0 (curative) resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures (26/28, 93%). In the remaining cases of R0 surgeries that displayed ctDNA, both patients were diagnosed with a recurrence of the disease after 6 months. In 7 patients who underwent an R1 resection, 4 ctDNA positivities (4/7, 57%) were detected after surgery and associated with the confirmation of early disease recurrence (after 3 to 7 months). All 15 patients (15/15, 100%) undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period. In 22 cases of recurrence, ctDNA positivity was detected 22 times (22/22, 100%) compared to 16 positives (16/22, 73%) by imaging methods and 15 cases (15/22, 68%) of elevated tumor markers.

CONCLUSION

ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment.

摘要

背景

循环肿瘤 DNA(ctDNA)检测在转移性结直肠癌(mCRC)患者外周血中的最显著应用之一是长期术后随访。它有时被称为“液体(再)活检”,是一种微创程序,可以在相对较短的时间间隔(数月甚至数周)内重复进行。可以监测患者体内疾病的存在和肿瘤负担(肿瘤质量)的实际程度。这一点尤其重要,特别是在评估手术治疗的根治性以及早期发现疾病进展或复发时。

目的

使用 ctDNA 确认手术的根治性,并比较检测转移性结直肠癌复发的可用方法。

方法

共有 47 名检测到 ctDNA 并符合 mCRC 切除术指征的患者参加了这项涉及三个外科中心的多中心研究。标准的术后随访包括影像学技术和肿瘤标志物的测定,并辅以 ctDNA 取样。除了手术前的基线 ctDNA 检测外,还通过评估术后一周内和随后大约每三个月的 ctDNA 存在情况进行术后观察。ctDNA 的存在与手术治疗的根治性和患者的实际临床状况相关。

结果

在监测的患者中,28 例手术中有 26 例(26/28,93%)R0(治愈性)切除与术后 ctDNA 阴性相关。在其余显示 ctDNA 的 R0 手术中,两名患者均在 6 个月后被诊断为疾病复发。在接受 R1 切除的 7 名患者中,术后检测到 4 例 ctDNA 阳性(4/7,57%),并与早期疾病复发的确认相关(3-7 个月后)。在整个随访期间,所有 15 名接受 R2 切除的患者(15/15,100%)一直持续 ctDNA 阳性。在 22 例复发中,ctDNA 阳性检测到 22 次(22/22,100%),而影像学方法检测到 16 次阳性(16/22,73%)和 15 例肿瘤标志物升高(15/22,68%)。

结论

ctDNA 检测在 mCRC 患者中是一种早期发现疾病复发以及确认手术治疗根治性的可行工具。

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