Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.
Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.
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DOI：
10.1056/nejmoa2200075
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发表时间：
2022-06-16
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辅助化疗在II期结肠癌中的作用仍有争议。手术后循环肿瘤DNA（ctDNA）的存在预示着非常差的无复发生存率，而其缺失预示着低复发风险。ctDNA阳性患者辅助化疗的益处尚不清楚。我们进行了一项试验，以评估ctDNA引导的方法是否可以减少辅助化疗的使用，而不影响复发风险。II期结肠癌患者以2：1的比例随机分配，根据ctDNA结果或标准临床病理学特征指导治疗决策。对于ctDNA指导的治疗，术后4周或7周的ctDNA阳性结果提示使用奥沙利铂或氟嘧啶化疗。ctDNA阴性的患者未接受治疗。主要疗效终点为2年无复发生存率。一个关键的次要终点是辅助化疗的使用。在接受随机分组的455例患者中，302例被分配到ctDNA指导管理组，153例被分配到标准管理组。中位随访时间为37个月。ctDNA指导组接受辅助化疗的患者比例低于标准管理组（15% vs. 28%;相对风险，1.82; 95%置信区间[CI]，1.25 - 2.65）。在2年无复发生存率的评估中，ctDNA指导治疗非劣效于标准治疗（分别为93.5%和92.4%;绝对差异为1.1个百分点; 95% CI为-4.1至6.2 [非劣效性界值为-8.5个百分点]）。接受辅助化疗的ctDNA阳性患者的3年无复发生存率为86.4%，未接受辅助化疗的ctDNA阴性患者为92.5%。ctDNA指导的II期结肠癌治疗方法减少了辅助化疗的使用，而不影响无复发生存率。（由澳大利亚国家健康和医学研究理事会和其他机构支持; DYNAMIC澳大利亚新西兰临床试验注册号ACTRN 12615000381583。）
The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, −4.1 to 6.2 [noninferiority margin, −8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.)