澳大利亚沃尔特伊丽莎霍尔医学研究所Jeanne Tie团队研究了循环肿瘤DNA分析指导II期结肠癌辅助治疗的效果。相关论文于2022年6月4日发表在《新英格兰医学杂志》上。

辅助化疗在II期结肠癌中的作用仍有争议。循环肿瘤DNA（ctDNA）的存在预示着术后无复发生存率非常低，而缺乏ctDNA预示着低复发风险。ctDNA阳性患者辅助化疗的益处尚不清楚。

研究组进行了一项试验，以评估ctDNA引导的方法是否可以在不增加复发风险的情况下减少辅助化疗的使用。将II期结肠癌患者按2:1的比例随机分配，根据ctDNA结果或标准临床病理特征进行治疗决策。对于ctDNA引导的治疗，术后4周或7周的ctDNA阳性结果提示以奥沙利铂或氟嘧啶为基础的化疗。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。次要关键终点是辅助化疗的使用。

在455名接受随机分组的患者中，302名接受ctDNA引导管理，153名接受标准管理。中位随访时间为37个月。ctDNA引导组接受辅助化疗的患者比例为15%，显著低于标准管理组的28%，相对风险为1.82。ctDNA引导组的2年无复发生存率为93.5%，不劣于标准治疗（92.4%；绝对差异为1.1个百分点）。接受辅助化疗的ctDNA阳性患者三年无复发生存率为86.4%，未接受辅助化疗的ctDNA阴性患者三年无复发生存率为92.5%。

研究结果表明，ctDNA引导的II期结肠癌治疗方法减少了辅助化疗的使用，且不影响无复发生存率。

附：英文原文

Title: Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer | NEJM

Author: Jeanne Tie, M.D.,, Joshua D. Cohen, M.Phil.,, Kamel Lahouel, Ph.D.,, Serigne N. Lo, Ph.D.,, Yuxuan Wang, M.D., Ph.D.,, Suzanne Kosmider, M.B., B.S.,, Rachel Wong, M.B., B.S.,, Jeremy Shapiro, M.B., B.S.,, Margaret Lee, M.B., B.S.,, Sam Harris, M.B., B.S.,, Adnan Khattak, M.B., B.S.,, Matthew Burge, M.B., B.S.,, Marion Harris, M.B., B.S.,, James Lynam, M.B., B.S.,, Louise Nott, M.B., B.S.,, Fiona Day, Ph.D.,, Theresa Hayes, M.B., B.S.,, Sue-Anne McLachlan, M.B., B.S.,, Belinda Lee, M.B., B.S.,, Janine Ptak, M.S.,, Natalie Silliman, B.S.,, Lisa Dobbyn, B.A.,, Maria Popoli, M.S.,, Ralph Hruban, M.D.,, Anne Marie Lennon, M.D., Ph.D.,, Nicholas Papadopoulos, Ph.D.,, Kenneth W. Kinzler, Ph.D.,, Bert Vogelstein, M.D.,, Cristian Tomasetti, Ph.D.,, and Peter Gibbs, M.D.

Issue&Volume: 2022-06-04

Abstract:

Background

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.

Methods

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.

Results

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.

Conclusions

A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival.

DOI: 10.1056/NEJMoa2200075

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2200075