Abstract：
OBJECTIVE: To assess the efficacy of ctDNA measurement at different time intervals in predicting response and prognosis in patients diagnosed with locally advanced rectal cancer (LARC) who underwent neoadjuvant treatment prior to curative resection.
METHODS: English language randomized controlled trials and observational studies, published from 1946 to January 2024, comparing outcomes between ctDNA-positive and ctDNA-negative patients with LARC undergoing neoadjuvant treatment prior to curative surgical resection were included in the search. The search included Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR).
RESULTS: Data for 1022 patients were analysed. Patients with positive ctDNA in the preoperative period had more than five times the risk of developing distant metastasis (RR [95% CI] 5.03 [3.31-7.65], p < 0.001), while those with positive ctDNA in the postoperative period had more than six times the risk (RR [95% CI] 6.17 [2.38-15.95], p < 0.001). There was no significant relationship between ctDNA status at baseline, pre-, or postoperative periods and achievement of pCR (RR [95% CI] 1.21 [0.86-1.7], 1.82 [0.94-3.55], 1.48 [0.78-2.82], p = 0.27, 0.08, and 0.23, respectively). However, patients with positive ctDNA in the pre- and postoperative periods had more than 13 and 12 times the risk of overall disease relapse after curative-intent treatment (RR [95% CI] 13.55 [7.12-25.81], 12.14 [3.19-46.14], p < 0.001), respectively.
CONCLUSIONS: ctDNA could potentially guide treatment and follow-up in LARC, predicting high-risk patients for disease relapse, allowing individualized surveillance and treatment strategies. Prospective studies are needed for standardization.
METHODS: English language randomized controlled trials and observational studies, published from 1946 to January 2024, comparing outcomes between ctDNA-positive and ctDNA-negative patients with LARC undergoing neoadjuvant treatment prior to curative surgical resection were included in the search. The search included Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR).
RESULTS: Data for 1022 patients were analysed. Patients with positive ctDNA in the preoperative period had more than five times the risk of developing distant metastasis (RR [95% CI] 5.03 [3.31-7.65], p < 0.001), while those with positive ctDNA in the postoperative period had more than six times the risk (RR [95% CI] 6.17 [2.38-15.95], p < 0.001). There was no significant relationship between ctDNA status at baseline, pre-, or postoperative periods and achievement of pCR (RR [95% CI] 1.21 [0.86-1.7], 1.82 [0.94-3.55], 1.48 [0.78-2.82], p = 0.27, 0.08, and 0.23, respectively). However, patients with positive ctDNA in the pre- and postoperative periods had more than 13 and 12 times the risk of overall disease relapse after curative-intent treatment (RR [95% CI] 13.55 [7.12-25.81], 12.14 [3.19-46.14], p < 0.001), respectively.
CONCLUSIONS: ctDNA could potentially guide treatment and follow-up in LARC, predicting high-risk patients for disease relapse, allowing individualized surveillance and treatment strategies. Prospective studies are needed for standardization.
摘要：
目的：评估ctDNA测量在不同时间间隔预测局部晚期直肠癌（LARC）患者在根治性切除前接受新辅助治疗的疗效和预后。
方法：英语随机对照试验和观察性研究，在1946年至2024年1月发表的研究中,本研究纳入了ctDNA阳性和ctDNA阴性LARC患者在根治性手术切除前接受新辅助治疗的比较结果.搜索包括OvidMEDLINE,Embase,Cochrane中央对照试验登记册（中央），和Cochrane系统评价数据库(CDSR)。
结果：分析了1022例患者的数据。术前ctDNA阳性的患者发生远处转移的风险是其5倍以上(RR[95%CI]5.03[3.31-7.65],p<0.001)，而术后ctDNA阳性的患者的风险是其6倍以上（RR[95%CI]6.17[2.38-15.95]，p<0.001)。基线时ctDNA状态之间没有显著关系，pre,或术后时期和pCR的实现(RR[95%CI]1.21[0.86-1.7]，1.82[0.94-3.55],1.48[0.78-2.82],p分别=0.27、0.08和0.23)。然而,术前和术后ctDNA阳性的患者在治愈性治疗后总疾病复发的风险超过13和12倍(RR[95%CI]13.55[7.12-25.81],12.14[3.19-46.14],p<0.001)，分别。
结论：ctDNA可能指导LARC的治疗和随访，预测高危患者的疾病复发，允许个性化监测和治疗策略。标准化需要前瞻性研究。
方法：英语随机对照试验和观察性研究，在1946年至2024年1月发表的研究中,本研究纳入了ctDNA阳性和ctDNA阴性LARC患者在根治性手术切除前接受新辅助治疗的比较结果.搜索包括OvidMEDLINE,Embase,Cochrane中央对照试验登记册（中央），和Cochrane系统评价数据库(CDSR)。
结果：分析了1022例患者的数据。术前ctDNA阳性的患者发生远处转移的风险是其5倍以上(RR[95%CI]5.03[3.31-7.65],p<0.001)，而术后ctDNA阳性的患者的风险是其6倍以上（RR[95%CI]6.17[2.38-15.95]，p<0.001)。基线时ctDNA状态之间没有显著关系，pre,或术后时期和pCR的实现(RR[95%CI]1.21[0.86-1.7]，1.82[0.94-3.55],1.48[0.78-2.82],p分别=0.27、0.08和0.23)。然而,术前和术后ctDNA阳性的患者在治愈性治疗后总疾病复发的风险超过13和12倍(RR[95%CI]13.55[7.12-25.81],12.14[3.19-46.14],p<0.001)，分别。
结论：ctDNA可能指导LARC的治疗和随访，预测高危患者的疾病复发，允许个性化监测和治疗策略。标准化需要前瞻性研究。
