Dynamic ctDNA Monitoring Guides Early Treatment Intensification in Locally Advanced Rectal Cancer Undergoing Neoadjuvant Chemotherapy.

However, many patients experience poor pathologic response, necessitating early-prediction tools.

然而，许多患者经历了较差的病理反应，需要早期预测工具。

We investigated dynamic circulating tumor DNA (ctDNA) analysis for early response monitoring in patients with LARC undergoing NCT.

我们研究了动态循环肿瘤DNA（ctDNA）分析在进行新辅助化疗（NCT）的局部晚期直肠癌（LARC）患者早期反应监测中的应用。

experimental_design

In this biomarker substudy of the multicenter randomized COPEC trial, 153 patients with low-/intermediate-risk LARC were enrolled.

在这项多中心随机COPEC试验的生物标志物子研究中，共有153名低/中危局部晚期直肠癌（LARC）患者被纳入。

Plasma samples (n = 526) were collected at baseline and after each cycle of NCT. ctDNA was analyzed via tumor-informed sequencing.

收集了基线时以及每个新辅助化疗(NCT)周期后的血浆样本(n = 526)。通过肿瘤知情测序分析了循环肿瘤DNA(ctDNA)。

Patients were classified by dynamic status into high-risk (delayed/no clearance and recurred positive) and low-risk (early clearance and persistent negative) groups.

根据动态状态将患者分类为高风险组(延迟/未清除和复发阳性)和低风险组(早期清除和持续阴性)。

Poor response was defined as pathologic tumor regression grade (pTRG) 3 or distant metastasis.

差的反应被定义为病理肿瘤退缩分级（pTRG）3或远处转移。

The association between ctDNA status and responses was analyzed.

分析了循环肿瘤DNA（ctDNA）状态与反应之间的关联。

Results

No patient with high-risk ctDNA dynamics achieved a major pathologic response (pTRG 0-1).

没有一个高风险ctDNA动态的患者实现了主要的病理反应（pTRG 0-1）。

The poor response rate was 59.4% in the high-risk group versus 12.4% in the low-risk group (P < 0.001).

高风险组的不良反应率为59.4%，而低风险组为12.4%（P < 0.001）。

High-risk dynamic ctDNA status was a strong independent predictor of poor response (OR = 11.69; 95% confidence interval, 5-27.25; P < 0.001).

高风险动态循环肿瘤DNA（ctDNA）状态是不良反应的强烈独立预测因子（比值比=11.69；95%置信区间，5-27.25；P < 0.001）。

Both delayed/no clearance (OR = 12.64; P < 0.001) and recurred positivity (OR = 8.91; P < 0.001) were significant risk factors.

延迟/未清除（比值比=12.64；P < 0.001）和复发阳性（比值比=8.91；P < 0.001）都是显著的风险因素。

A single preoperative ctDNA-positive result also predicted poor response (OR = 11.27; P < 0.001).

术前单次循环肿瘤DNA（ctDNA）阳性结果也预示着较差的治疗反应（比值比=11.27；P<0.001）

Conclusions

Dynamic ctDNA monitoring identifies patients with LARC at high risk for NCT failure as early as two cycles into treatment, which can form the basis for an adaptive trial design and eventual personalization of therapy selection.

动态循环肿瘤DNA监测能够在治疗开始两个周期后就识别出局部晚期直肠癌（LARC）患者中对新辅助化疗（NCT）高风险失败的病例，这可以作为自适应试验设计的基础，并最终实现治疗选择的个性化。