围手术期游离 DNA 趋势比 CEA 趋势更早地预测非转移性结直肠癌的复发，在 II 期和 III 期结肠癌患者术后 2 年内尤其显著。
Perioperative cell-free DNA trends predict recurrence of non-metastatic colorectal cancer significantly earlier than CEA trends over the first 2 years post-operatively in stage II and stage III colon cancer.
机构信息
Department of Colorectal Surgery, Cork University Hospital, Cork, Ireland.
Cork Breast Research Centre, University College Cork, Cork, Ireland.
出版信息
Int J Colorectal Dis. 2022 May;37(5):1119-1126. doi: 10.1007/s00384-022-04133-7. Epub 2022 Apr 20.
PURPOSE
We aimed to compare the diagnostic accuracy of perioperative ΔcfDNA to ΔCEA (over the first 2 years post-operatively) for identifying disease recurrence in colon cancer.
METHODS
Patients presenting for elective resection for colon cancer with curative intent were screened for inclusion. Perioperative cfDNA levels were measured at seven different times points(pre-operative and post-operative at 3 h, 6 h, 24 h, 48 h, POD3 and POD5). CEA levels were measured on the same patients up to 2 years post-operatively. Change in trend (Δ) was defined as the β coefficient using a logistic regression model. Statistical analysis was performed using SPSS, version 23.
RESULTS
Longitudinal data on twenty-two patients were analysed (n = 16 male, n = 6 female) for a median of 29 months (IQR 23 months) during which time three patients developed (distant) recurrence. Perioperative ΔcfDNA at 48Hrs, POD3 and POD5 were significantly associated with early recurrence. ΔCEA was significantly associated with early recurrence at 6 months, 1 year and 2 years post-operatively, only when disease recurrence was macroscopically established. ΔcfDNA was associated with an area under the curve (AUC) of 0.947 (95% CI 0.88-1.0, p < 0.001) and ΔCEA was associated with an AUC of 0.9382 (95%CI 0.88-0.99, p < 0.0001). This translated into a specificity of 97% (95%CI 86.51-99.87%) for ΔcfDNA and 77.5% sensitivity (95%CI 62.5-87.7%) in the immediate perioperative period and an 88.9% specificity (95%CI 56.5-99.4%) and 76.5% sensitivity (95%CI 63.24-86%) for ΔCEA over the first 2 years post-operatively.
CONCLUSIONS
In this pilot study, following curative resection for colon cancer changing trends in perioperative cfDNA (ΔcfDNA) identify those at risk of recurrent disease before recurrence develops which is at least 6 months earlier than CEA changes (ΔCEA) which are only observed when recurrence is established.
目的
本研究旨在比较围手术期 cfDNA （术后前 2 年）的变化（Δ cfDNA）与 ΔCEA（术后前 2 年）对结直肠癌患者术后疾病复发的诊断准确性。
方法
本研究纳入了接受择期结直肠癌根治术且具有治愈倾向的患者。在七个不同时间点（术前及术后 3h、6h、24h、48h、术后第 3 天和第 5 天）测量患者围手术期 cfDNA 水平。同时检测相同患者的 CEA 水平，直至术后 2 年。使用逻辑回归模型定义趋势变化（Δ）为β系数。采用 SPSS 版本 23 进行统计学分析。
结果
对 22 例患者的纵向数据进行了分析（n=16 例男性，n=6 例女性），中位随访时间为 29 个月（IQR 23 个月），在此期间 3 例患者出现（远处）复发。术后 48 小时、术后第 3 天和第 5 天的围手术期Δ cfDNA 与早期复发显著相关。仅当疾病复发已被宏观证实时，CEA 才与术后 6 个月、1 年和 2 年的早期复发显著相关。Δ cfDNA 的曲线下面积（AUC）为 0.947（95%CI 0.88-1.0，p<0.001），而 ΔCEA 的 AUC 为 0.9382（95%CI 0.88-0.99，p<0.0001）。这意味着Δ cfDNA 的特异性为 97%（95%CI 86.51-99.87%），在围手术期的即刻阶段具有 77.5%的敏感性（95%CI 62.5-87.7%），而术后前 2 年的 ΔCEA 特异性为 88.9%（95%CI 56.5-99.4%）和 76.5%的敏感性（95%CI 63.24-86%）。
结论
在本试点研究中，结直肠癌根治性切除术后 cfDNA（Δ cfDNA）的变化趋势可在疾病复发前识别出具有复发风险的患者，这至少比仅在复发已确立时才观察到的 CEA 变化（Δ CEA）早 6 个月。
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