Li Yaqi, Mo Shaobo, Zhang Long, Ma Xiaoji, Hu Xiang, Huang Dan, Lu Binbin, Luo Chonglin, Peng Haixiang, Cai Sanjun, Sheng Weiqi, Peng Junjie
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Eur J Cancer. 2022 Jul;169:198-209. doi: 10.1016/j.ejca.2022.04.010. Epub 2022 May 27.
Precise methods for risk stratification to guide adjuvant chemotherapy for stage III colon cancers are needed. Here, we combined circulating tumor DNA (ctDNA) with consensus molecular subtype (CMS) to improve risk stratification in stage III colon cancers.
We conducted a prospective, observational cohort study of 165 patients with stage III colon cancers. Somatic variants in tumor tissues and plasmas collected pre- and post-chemo were detected via a targeted sequencing panel of 197 cancer-related genes. CMSs classification was characterized using a targeted RNA sequencing panel of 788 genes.
We analyzed 151 pre-chemo and 124 post-chemo plasmas, while 130 patients were CMSs classified. ctDNA was detectable in 15.9% pre-chemo and 8.9% post-chemo samples. Significantly worse recurrence-free survival (RFS) was seen if ctDNA was detectable in pre-chemo samples (hazard ratio [HR], 3.585; P < 0.001) or in post-chemo samples (HR, 3.337; P = 0.005). Pre-chemo ctDNA (HR, 5.538; P < 0.001) and post-chemo ctDNA status (HR, 3.272; P = 0.037) remained independently associated with RFS in multivariate analysis. According to the redefined recurrence risk stratification, mid-risk patients (ctDNA-negative with CMS4/T4 or N2 tumors) were 5.3 times (HR, 5.269; P = 0.025) more likely to relapse than low-risk patients (ctDNA-negative with CMS1-3/T3N1 tumors), while high-risk patients (ctDNA-positive) were 14.6 times (HR, 14.590; P < 0.001) more likely to relapse.
Postoperative ctDNA indicating residual disease, combined with CMSs classification and clinical risk reflecting the intrinsic characteristics of tumors, can redefine risk stratification of stage III colon cancers and better predict relapse.
需要精确的风险分层方法来指导III期结肠癌的辅助化疗。在此，我们将循环肿瘤DNA（ctDNA）与共识分子亚型（CMS）相结合，以改善III期结肠癌的风险分层。
我们对165例III期结肠癌患者进行了一项前瞻性观察队列研究。通过一个包含197个癌症相关基因的靶向测序面板，检测化疗前和化疗后收集的肿瘤组织和血浆中的体细胞变异。使用一个包含788个基因的靶向RNA测序面板对CMS进行分类。
我们分析了151份化疗前和124份化疗后的血浆，同时对130例患者进行了CMS分类。化疗前样本中ctDNA的可检测率为15.9%，化疗后样本中为8.9%。如果化疗前样本中可检测到ctDNA（风险比[HR]，3.585；P < 0.001）或化疗后样本中可检测到ctDNA（HR，3.337；P = 0.005），则无复发生存期（RFS）显著更差。在多变量分析中，化疗前ctDNA（HR，5.538；P < 0.001）和化疗后ctDNA状态（HR，3.272；P = 0.037）仍然与RFS独立相关。根据重新定义的复发风险分层，中风险患者（ctDNA阴性且为CMS4/T4或N2肿瘤）复发的可能性比低风险患者（ctDNA阴性且为CMS1-3/T3N1肿瘤）高5.3倍（HR，5.269；P = 0.025），而高风险患者（ctDNA阳性）复发的可能性高14.6倍（HR，14.590；P < 0.001）。
术后提示残留疾病的ctDNA，结合CMS分类和反映肿瘤内在特征的临床风险，可以重新定义III期结肠癌的风险分层，并更好地预测复发。
