Predictive Role of Circulating Tumor DNA in Stage III Colon Cancer Treated With Celecoxib: A Post Hoc Analysis of the CALGB (Alliance)/SWOG 80702 Phase 3 Randomized Clinical Trial.

While randomized clinical trials have not shown benefit across all patients, these findings suggest that select subgroups may benefit from their use.

尽管随机临床试验并未显示所有患者均受益，但这些发现表明，特定的亚组患者可能会从其使用中受益。

Despite the well-established prognostic value of circulating tumor DNA (ctDNA), its role in guiding treatment remains unclear.

尽管循环肿瘤DNA（ctDNA）的预后价值已经得到充分证实，但其在指导治疗中的作用仍不明确。

Background

To investigate the predictive value of postoperative ctDNA for survival outcomes with adjuvant celecoxib alongside conventional chemotherapy in patients with stage III colon cancer.

本研究旨在探讨在III期结肠癌患者中，术后ctDNA对于辅助性塞来昔布与常规化疗相结合的生存结果的预测价值。

DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the phase 3 Cancer and Leukemia Group B (now Alliance)/Southwest Oncology Group 80702 randomized clinical trial (2010-2015) assessing adjuvant celecoxib vs placebo and 3 vs 6 months of adjuvant 5-fluorouracil, leucovorin, and oxaliplatin for stage III colon cancer.

这是一项对癌症和白血病研究组B（现为联盟）/西南肿瘤研究组80702第三阶段随机临床试验（2010-2015年）的事后分析，该试验评估了辅助性塞来昔布与安慰剂以及3个月与6个月的辅助性5-氟尿嘧啶、亚叶酸和奥沙利铂治疗III期结肠癌的效果。

Patients consented to biospecimen collection and had ctDNA analysis performed.

患者同意进行生物样本采集，并进行了循环肿瘤DNA（ctDNA）分析。

Data analysis was performed from September 2024 to June 2025.

数据分析从2024年9月进行至2025年6月。

exposures

Postoperative ctDNA positivity was determined using a clinically validated, tumor-informed 16-plex-polymerase chain reaction-next-generation sequencing assay (Signatera; Natera Inc) performed between surgery and initiation of adjuvant therapy.

术后循环肿瘤DNA（ctDNA）阳性是通过在手术和辅助治疗开始之间进行的临床验证的肿瘤信息型16重聚合酶链反应-下一代测序检测（Signatera; Natera Inc）来确定的。

main_outcomes_and_measures

Disease-free survival (DFS) and overall survival(OS).

无病生存期（DFS）和总生存期（OS）。

Survival by ctDNA status and adjuvant celecoxib use were assessed as part of a post hoc companion study with prespecified statistical analysis plan.

通过ctDNA状态和辅助使用塞来昔布评估生存情况，这是作为预先设定统计分析计划的事后伴随研究的一部分。

Results

Among 940 patients (mean [SD] age, 60.9 [10.8] years; 426 female [45.3%] and 515 male [54.7%] individuals; 222 [23.6%] with prior low-dose aspirin use; and median follow-up of 6.0 [95% CI, 6.0-6.0] years), 767 (81.6%) were ctDNA negative and 173 (18.4%) were ctDNA positive. ctDNA positivity was highly prognostic of worse DFS (reference, ctDNA negativity; adjusted hazard ratio[aHR], 6.12; 95% CI, 4.66-8.03) and OS (aHR, 5.86; 95% CI, 4.19-8.19).

在940名患者中（平均年龄[标准差]为60.9[10.8]岁；426名女性[45.3%]和515名男性[54.7%]；222名[23.6%]有先前使用低剂量阿司匹林的历史；中位随访时间为6.0年[95%置信区间，6.0-6.0]），767名（81.6%）患者ctDNA阴性，173名（18.4%）患者ctDNA阳性。ctDNA阳性高度预示着较差的无病生存期（DFS）（参考，ctDNA阴性；调整后风险比[aHR]，6.12；95%置信区间，4.66-8.03）和总生存期（OS）（aHR，5.86；95%置信区间，4.19-8.19）。

In patients with ctDNA positivity, celecoxib was associated with improved DFS (aHR, 0.61; 95% CI, 0.42-0.89) and OS (aHR, 0.62; 95% CI, 0.40-0.96) compared to placebo.

在ctDNA阳性的患者中，与安慰剂相比，塞来昔布与改善的无病生存期（DFS）（aHR，0.61；95%置信区间，0.42-0.89）和总生存期（OS）（aHR，0.62；95%置信区间，0.40-0.96）相关。

Among patients with ctDNA negativity, celecoxib did not provide survival benefit (DFS: aHR, 0.76; 95% CI, 0.53-1.09; OS: aHR, 0.85; 95% CI, 0.54-1.36), although the interaction was not significant (P for interaction, .41 and .33 for DFS and OS, respectively).

在 ctDNA 阴性的患者中，塞来昔布并未提供生存益处（无病生存期：调整后的风险比 aHR, 0.76; 95% 置信区间, 0.53-1.09; 总生存期：aHR, 0.85; 95% 置信区间, 0.54-1.36），尽管交互作用不显著（无病生存期和总生存期的交互作用 P 值分别为 .41 和 .33）。

These findings persisted when stratifying patients by microsatellite instability status and PIK3CA mutational status.

当根据微卫星不稳定性状态和 PIK3CA 突变状态对患者进行分层时，这些发现仍然存在。

conclusion_and_relevance

The findings of this post hoc analysis suggest that ctDNA status has the potential to inform clinical decision-making among patients with stage III colon cancer who should consider adjuvant celecoxib in addition to conventional chemotherapy.

这项事后分析的结果表明，循环肿瘤DNA（ctDNA）状态有可能为临床决策提供信息，帮助III期结肠癌患者决定是否除了常规化疗外，还应考虑使用辅助性塞来昔布治疗。

trial_registration

ClinicalTrials.gov Identifier: NCT01150045.

ClinicalTrials.gov 注册号：NCT01150045。