仍然缺乏精确的术后风险分层方法来指导局部结直肠癌(CRC)的辅助化疗(ACT)的给药。这里,我们进行了一个前瞻性的,观察,和多中心研究,以探讨循环肿瘤DNA(ctDNA)在预测复发风险中的实用性。
从2017年9月至2020年3月,本研究前瞻性招募了276名II/III期CRC患者,并保留了240名可评估患者进行分析。其中收集了1290份系列血浆样本。通过425个癌症相关基因的靶向测序组来检测原发性肿瘤和血浆中的体细胞变体。根据护理标准对患者进行治疗和随访。
术前,240例患者中有154例(64.2%)检测到ctDNA。术后第3-7天,ctDNA阳性与极高的复发风险相关(风险比[HR],10.98;95CI,5.31-22.72;P<0.001)。在接受ACT治疗的17例ctDNA阳性患者中,有5例获得了ctDNA清除和无复发状态。同样,在ACT之后的第一个采样点,ctDNA阳性患者复发的可能性是其12倍(HR,12.76;95CI,5.39-30.19;P<0.001)。在明确治疗后的监测期间,ctDNA阳性也与极高的复发风险(HR,32.02;95CI,10.79-95.08;P<0.001)。在所有多变量分析中,在校正已知的临床病理危险因素后,ctDNA阳性仍然是无复发生存的最显著和独立的预测因子。连续ctDNA分析以92.0%的总体准确率确定复发,并且可以在放射成像之前检测疾病复发,平均提前期为5.01个月。
在II/III期CRC患者中,术后系列ctDNA检测可预测高复发风险,并在放射学成像之前确定疾病复发。ctDNA可用于指导术后管理的决策。
Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.
From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.
Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3-7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31-22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39-30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79-95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.
Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.