《动力试验》研究了循环肿瘤DNA（ctDNA）在II期结肠癌辅助治疗决策中的应用。尽管《动力试验》声称以ctDNA为导向的方法可以减少辅助治疗的使用，而不影响无复发生存 (RFS)，但我们在一篇辩论文章中对该试验的方法论和实际结果提出了关切。在这里，我们继续回应《动力试验》作者的来信，并扩展对这些关切的阐述。我们对《动力试验》中选择了相当大的非劣效边界提出质疑，仅仅因为8.5个百分点的复发生存率降低可能对患者造成重大伤害。我们对作者将《动力试验》结果与观察研究进行比较表示怀疑。这样的比较容易受到选择偏倚和随时间变化的限制，从而降低了其相关性。我们强调，ctDNA的预后作用并不自动意味着在ctDNA阳性患者中增加治疗就会改善结果。在实际临床环境中，我们预计由于临床医生将ctDNA与现有临床病理因素结合使用，而不是完全替代，可能会导致化疗的潜在增加。最后，《动力试验》中一个关键关切是ctDNA组奥沙利铂的使用率比标准处理组高出350％（分别为9.5％和2.7％），这存在长期神经病变的风险。我们期待在辅助治疗中改进患者选择，但对《动力试验》及其结果在实际应用中仍持有保留意见。作为与大幅边界的非劣效试验相比的替代方案，我们提出在II期患者中进行优越性试验可能是一种更有效的策略。© 2023. BioMed Central Ltd., part of Springer Nature.

The DYNAMIC trial investigated the use of circulating tumor DNA (ctDNA) to guide adjuvant treatment decisions in stage II colon cancer. Despite the DYNAMIC trial's assertion that a ctDNA-guided approach could minimize the use of adjuvant treatment without compromising recurrence-free survival (RFS), we raised concerns regarding the trial's methodology and the practical implications of its findings in a Debate article. Here, we expand upon these concerns in a response to a correspondence by the authors of the DYNAMIC trial.We dispute the choice of a large non-inferiority margin in the DYNAMIC trial, simply because an 8.5 percentage points decrease in recurrence-free survival could result in significant harm to patients. We challenge the authors' comparisons of the DYNAMIC trial outcomes with observational studies. Such comparison is subject to selection bias and changes over time that limit their relevance. The prognostic role of ctDNA do not automatically imply that more treatment in patients with ctDNA positivity would improve outcomes, which we highlight. In real-world settings, we anticipate a potential rise in chemotherapy use due to clinicians utilizing ctDNA alongside existing clinicopathologic factors, rather than using ctDNA as an entire replacement. Lastly, a key concern in DYNAMIC was an 350% higher use of oxaliplatin in the ctDNA arm compared with standard management (9.5% versus 2.7%, respectively), which poses a risk for long-term neuropathy.We look forward improvements in patient selection in the adjuvant setting, but we maintain our reservations about the DYNAMIC trial and the real-life implementation of its results. As an alternative to exploring de-escalation strategies with large margins non-inferiority trials, we propose that superiority trials in stage II patients could be a more effective strategy.© 2023. BioMed Central Ltd., part of Springer Nature.