Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: the randomized phase 2/3 DYNAMIC-III trial.

Circulating tumor DNA (ctDNA) may help refine risk-adjusted treatment selection.

循环肿瘤DNA（ctDNA）可能有助于优化风险调整后的治疗选择。

In this multicenter, randomized, phase 2/3 trial, patients with stage III colon cancer underwent ctDNA testing 5-6 weeks after surgery and were assigned (1:1) to ctDNA-guided or standard management.

在这项多中心、随机、2/3期试验中，III期结肠癌患者在手术后5-6周进行了ctDNA检测，并按1:1的比例被分配到ctDNA指导或标准管理组。

In the ctDNA-guided arm, patients negative for ctDNA received de-escalated therapy, whereas ctDNA-positive patients received escalated therapy.

在ctDNA指导组中，ctDNA阴性的患者接受了降阶治疗，而ctDNA阳性的患者接受了升级治疗。

Clinicians prespecified the standard regimen.

临床医生预先规定了标准治疗方案。

Primary endpoints were 3-year recurrence-free survival (RFS) for ctDNA-negative patients and 2-year RFS for ctDNA-positive patients.

主要终点是ctDNA阴性患者的3年无复发生存期（RFS）和ctDNA阳性患者的2年无复发生存期（RFS）。

Secondary endpoints included treatment-related hospitalization and ctDNA clearance.

次要终点包括治疗相关的住院和循环肿瘤DNA（ctDNA）清除。

Among 968 evaluable patients, 702 (72.5%) were ctDNA negative.

在968名可评估的患者中，有702名（72.5%）ctDNA检测结果为阴性。

With a median follow-up of 47 months, ctDNA-negative patients experienced significantly fewer recurrences than ctDNA-positive patients (3-year RFS 87% versus 49%; P < 0.001).

中位随访时间为47个月，ctDNA阴性患者的复发率显著低于ctDNA阳性患者（3年无复发生存率87%对比49%；P < 0.001）。

In ctDNA-negative patients, de-escalation reduced oxaliplatin use (34.8% versus 88.6%) and hospitalizations (8.5% versus 13.2%) but yielded slightly lower RFS than standard management (85.3% versus 88.1%), not meeting the non-inferiority margin.

在ctDNA阴性患者中，降级治疗减少了奥沙利铂的使用（34.8%对比88.6%）和住院率（8.5%对比13.2%），但其无复发生存率略低于标准治疗（85.3%对比88.1%），未达到非劣效性标准。

In ctDNA-positive patients, higher ctDNA burden correlated with recurrence risk (3-year RFS 77% to 23% across quartiles; P < 0.001).

在ctDNA阳性患者中，较高的ctDNA负荷与复发风险相关（四分位数间3年无复发生存率从77%降至23%；P < 0.001）。

Escalated therapy did not improve outcomes over standard management (2-year RFS 51% versus 61%).

强化治疗并未改善标准管理的预后（2年无复发生存率为51%对比61%）。

There was no unexpected toxicity.

未出现意外的毒性反应。

Persistent ctDNA after treatment predicted markedly worse prognosis (3-year RFS 14% versus 79%). ctDNA is validated as a strong prognostic classifier. ctDNA-guided de-escalation reduced oxaliplatin exposure and adverse events with outcomes approaching standard of care, whereas exploratory chemotherapy intensification conferred no RFS benefit, suggesting a need for novel strategies in ctDNA-positive disease.Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617001566325 .

治疗后持续存在的循环肿瘤DNA（ctDNA）预示着预后明显较差（3年无复发生存期为14%对比79%）。ctDNA被验证为一个强效的预后分类器。基于ctDNA的降阶梯治疗减少了奥沙利铂的暴露和不良事件，结果接近标准治疗，而探索性的化疗加强并未带来无复发生存期（RFS）的益处，这表明在ctDNA阳性疾病中需要新的治疗策略。