ctDNA 在 III 期结肠癌中的预后价值及其与辅助治疗时间的关系：PRODIGE-GERCOR IDEA-France 试验分析。

Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: a Analysis of the PRODIGE-GERCOR IDEA-France Trial.

机构信息

Department of Gastroenterology and Gastrointestinal Oncology, Hôpital Européen Georges-Pompidou, AP-HP, Université de Paris, Paris, France.

Centre de Recherche des Cordeliers, INSERM, CNRS, Université de Paris, Sorbonne Université, USPC, Equipe labellisée Ligue Nationale Contre le Cancer, SIRIC CARPEM, Paris, France.

出版信息

Clin Cancer Res. 2021 Oct 15;27(20):5638-5646. doi: 10.1158/1078-0432.CCR-21-0271. Epub 2021 Jun 3.

DOI:10.1158/1078-0432.CCR-21-0271

PMID:34083233

Abstract

PURPOSE

Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage-III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial.

EXPERIMENTAL DESIGN

ctDNA was tested for and by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatment duration (3/6 months) and disease stage (high/low-risk stage III).

RESULTS

Of 2,010 randomized patients, 1,345 had available ctDNA samples (1,017 collected both post-surgery and pre-chemotherapy). More Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (78% versus 69%) and T4 and/or N2 (40% versus 36%) were observed in patients studied ( = 1017) versus not analyzed ( = 993). There were 877 ctDNA-negative (86.2%) and 140 ctDNA-positive (13.8%) patients; their baseline characteristics were similar. With a median follow-up of 6.6 years, the 3-year DFS rate was 66.39% for ctDNA-positive patients and 76.71% for ctDNA-negative patients ( = 0.015). ctDNA was confirmed as an independent prognostic marker for DFS (adjusted HR = 1.55, 95% CI 1.13-2.12, = 0.006) and OS (HR = 1.65, 95% CI 1.12-2.43, = 0.011). ctDNA was prognostic in patients treated for 3 months and with T4 and/or N2 tumors, but not in those treated for 6 months and with T1-3/N1 tumors.

CONCLUSIONS

In this first ctDNA assessment of a large series of patients with stage III colon cancer enrolled in phase III trial, post-surgery ctDNA was found in 13.8% of them and was confirmed as an independent prognostic marker..

摘要

目的

循环肿瘤 DNA（ctDNA）已被认为是 III 期结肠癌切除术后的主要预后因素。我们分析了 III 期 IDEA-France 试验中随机分组患者的 ctDNA。

实验设计

采用开发和验证的用于结直肠癌的液滴数字 PCR 法检测 ctDNA 的和。在有 ctDNA 样本的患者和根据治疗持续时间（3/6 个月）和疾病阶段（高/低危 III 期）的亚组中，通过多变量分析评估无病生存（DFS）和总生存（OS）。

结果

在 2010 名随机分组的患者中，有 1345 名患者有可用的 ctDNA 样本（1017 名在手术后和化疗前采集）。研究组（=1017）中，更多的东部合作肿瘤学组表现状态（ECOG PS）为 0（78% vs 69%）和 T4 和/或 N2（40% vs 36%），而未分析组（=993）则没有。877 名 ctDNA 阴性（86.2%）和 140 名 ctDNA 阳性（13.8%）患者；他们的基线特征相似。中位随访 6.6 年后，ctDNA 阳性患者的 3 年 DFS 率为 66.39%，ctDNA 阴性患者为 76.71%（=0.015）。ctDNA 被确认为 DFS（调整 HR=1.55，95%CI 1.13-2.12，=0.006）和 OS（HR=1.65，95%CI 1.12-2.43，=0.011）的独立预后标志物。ctDNA 在治疗 3 个月和 T4 和/或 N2 肿瘤的患者中具有预后意义，但在治疗 6 个月和 T1-3/N1 肿瘤的患者中则没有。