PDF(Pubmed)
Abstract：
UNASSIGNED: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC.
UNASSIGNED: To define potentially cured CRC patients through ctDNA monitoring following surgery.
UNASSIGNED: A prospective, multicenter, observational study.
UNASSIGNED: We enrolled 309 patients with stages I-IV CRC who underwent definitive surgery. Tumor tissues were sequenced by a custom-designed next-generation sequencing panel to identify somatic mutations. Plasma was analyzed using a ctDNA-based molecular residual disease (MRD) assay which integrated tumor-genotype-informed and tumor-genotype-naïve ctDNA analysis. The turnaround time of the assay was 10-14 days.
UNASSIGNED: Postoperative ctDNA was detected in 5.4%, 13.8%, 15%, and 30% of patients with stage I, II, III, and IV disease, respectively, and in 17.5% of all longitudinal samples. Patients with positive postsurgery MRD had a higher recurrence rate than those with negative postsurgery MRD [hazard ratio (HR), 13.17; p < 0.0001], producing a sensitivity of 64.6%, a specificity of 94.8%, a positive predictive value (PPV) of 75.6%, and a negative predictive value (NPV) of 91.5%. Furthermore, patients with positive longitudinal MRD also had a significantly higher recurrence rate (HR, 14.44; p < 0.0001), with increased sensitivity (75.0%), specificity (94.9%), PPV (79.6%), and NPV (93.4%). Subgroup analyses revealed that adjuvant therapy did not confer superior survival for patients with undetectable or detectable MRD. In addition, MRD detection was less effective in identifying lung-only and peritoneal metastases.
UNASSIGNED: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and microsatellite instability status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.
UNASSIGNED: To define potentially cured CRC patients through ctDNA monitoring following surgery.
UNASSIGNED: A prospective, multicenter, observational study.
UNASSIGNED: We enrolled 309 patients with stages I-IV CRC who underwent definitive surgery. Tumor tissues were sequenced by a custom-designed next-generation sequencing panel to identify somatic mutations. Plasma was analyzed using a ctDNA-based molecular residual disease (MRD) assay which integrated tumor-genotype-informed and tumor-genotype-naïve ctDNA analysis. The turnaround time of the assay was 10-14 days.
UNASSIGNED: Postoperative ctDNA was detected in 5.4%, 13.8%, 15%, and 30% of patients with stage I, II, III, and IV disease, respectively, and in 17.5% of all longitudinal samples. Patients with positive postsurgery MRD had a higher recurrence rate than those with negative postsurgery MRD [hazard ratio (HR), 13.17; p < 0.0001], producing a sensitivity of 64.6%, a specificity of 94.8%, a positive predictive value (PPV) of 75.6%, and a negative predictive value (NPV) of 91.5%. Furthermore, patients with positive longitudinal MRD also had a significantly higher recurrence rate (HR, 14.44; p < 0.0001), with increased sensitivity (75.0%), specificity (94.9%), PPV (79.6%), and NPV (93.4%). Subgroup analyses revealed that adjuvant therapy did not confer superior survival for patients with undetectable or detectable MRD. In addition, MRD detection was less effective in identifying lung-only and peritoneal metastases.
UNASSIGNED: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and microsatellite instability status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.
摘要：
■循环肿瘤DNA（ctDNA）已成为一种生物标志物，可以定义结直肠癌（CRC）患者根治性手术后复发的风险。然而,超出了术后ctDNA检测的预测能力，ctDNA检测的有效性和潜在局限性迫切需要在大量CRC队列中得到充分阐明.
■通过ctDNA监测确定手术后可能治愈的CRC患者。
■预期，多中心，观察性研究。
■我们招募了309名I-IV期CRC患者，他们接受了明确的手术。通过定制设计的下一代测序面板对肿瘤组织进行测序以鉴定体细胞突变。使用基于ctDNA的分子残留病（MRD）测定分析血浆，该测定整合了肿瘤基因型信息和肿瘤基因型初始ctDNA分析。测定的周转时间为10-14天。
■术后检测到5.4%的ctDNA，13.8%,15%,30%的I期患者,II,III,和IV疾病，分别,在所有纵向样本中占17.5%。术后MRD阳性患者的复发率高于术后MRD阴性患者[风险比(HR),13.17；p<0.0001]，产生64.6%的灵敏度，特异性为94.8%，阳性预测值(PPV)为75.6%，阴性预测值(NPV)为91.5%。此外，纵向MRD阳性的患者也有明显更高的复发率(HR，14.44；p<0.0001)，灵敏度提高（75.0%），特异性（94.9%），PPV（79.6%），和净现值（93.4%）。亚组分析显示，辅助治疗不能为检测不到或检测到MRD的患者提供优越的生存率。此外,MRD检测在识别仅肺和腹膜转移方面效果较差。
■术后ctDNA状态是独立于分期和微卫星不稳定状态的复发的强预测因子。纵向不可检测的MRD可用于定义接受治愈性手术的CRC患者的潜在治愈人群。
■通过ctDNA监测确定手术后可能治愈的CRC患者。
■预期，多中心，观察性研究。
■我们招募了309名I-IV期CRC患者，他们接受了明确的手术。通过定制设计的下一代测序面板对肿瘤组织进行测序以鉴定体细胞突变。使用基于ctDNA的分子残留病（MRD）测定分析血浆，该测定整合了肿瘤基因型信息和肿瘤基因型初始ctDNA分析。测定的周转时间为10-14天。
■术后检测到5.4%的ctDNA，13.8%,15%,30%的I期患者,II,III,和IV疾病，分别,在所有纵向样本中占17.5%。术后MRD阳性患者的复发率高于术后MRD阴性患者[风险比(HR),13.17；p<0.0001]，产生64.6%的灵敏度，特异性为94.8%，阳性预测值(PPV)为75.6%，阴性预测值(NPV)为91.5%。此外，纵向MRD阳性的患者也有明显更高的复发率(HR，14.44；p<0.0001)，灵敏度提高（75.0%），特异性（94.9%），PPV（79.6%），和净现值（93.4%）。亚组分析显示，辅助治疗不能为检测不到或检测到MRD的患者提供优越的生存率。此外,MRD检测在识别仅肺和腹膜转移方面效果较差。
■术后ctDNA状态是独立于分期和微卫星不稳定状态的复发的强预测因子。纵向不可检测的MRD可用于定义接受治愈性手术的CRC患者的潜在治愈人群。
