摘要
目的分析循环肿瘤DNA(circulating tumor DNA,ctDNA)对非小细胞肺癌(non-small cell lung cancer,NSCLC)根治性手术后早期复发风险的预测意义。方法选择2020年2月至2023年12月我院收治的81例NSCLC患者,完成根治性切除术,收集肿瘤标本,采集血液样本,采用基于液体活检的循环单分子扩增和重测序技术(circulating single-molecule amplification and resequencing technology,cSMART)进行ctDNA分析,记录无复发生存期(relapse-free survival,RFS)和总生存期(overall survival,OS),分析ctDNA与RFS、OS关系。结果81例平均基因突变(1.73±0.65)个,50例(61.73%)术前ctDNA阳性,76例中33例(43.42%)术后至少1个检测点ctDNA阳性。50例术前ctDNA阳性者中26例术后ctDNA阳性。中位随访44.0个月,81例NSCLC患者生存55例(67.90%),其中复发者37例(45.68%),死亡者26例(32.10%)。术前ctDNA阳性者中位RFS期19.0个月(log rank=12.531,P<0.001)和OS期34.89个月(log rank=11.028,P=0.001)短于ctDNA阴性者RFS期42.0个月、OS期46.65个月。术后33例ctDNA阳性者中复发21例(63.64%),死亡15例(45.45%)。术后ctDNA阳性者中位RFS期25.79个月(log rank=10.796,P=0.001)和OS期34.21个月(log rank=7.384,P=0.007)短于术后ctDNA阴性者RFS期39.0个月、OS期43.15个月。43例术后ctDNA阴性者影像学结果显示病灶完全切除,其中21例术前ctDNA阳性,ctDNA转阴者中位RFS期38.05个月(log rank=5.139,P=0.023)长于ctDNA未转阴者25.92个月。术前ctDNA阴性31例中7例(22.58%)术后ctDNA转阳。33例术后ctDNA阳性者中21例术后ctDNA阳性比影像学或临床症状结果平均早(11.12±5.21)个月,其中17例术后2周内ctDNA呈阳性。多因素分析显示,临床分期和术前ctDNA状态对RFS和OS具有统计学意义(P<0.05)。高分期(Ⅲ期)较低分期(Ⅰ/Ⅱ期)NSCLC复发或死亡风险分别是3.082倍或3.577倍。术前ctDNA阳性较ctDNA阴性NSCLC复发或死亡风险增加3.889倍或3.139倍。术后ctDNA阳性是影响RFS的因素(P<0.05),复发风险增加3.333倍。结论晚期和术前ctDNA阳性是经根治性切除NSCLC患者RFS和OS的影响因素。术后检测ctDNA有助于早期发现复发具有意义。
Objective To analyze the predictive significance of circulating tumor DNA(ctDNA)in the risk of early recurrence of non-small cell lung cancer(NSCLC)after radical surgery.Methods All of 81 patients with NSCLC admitted to our hospital from February 2020 to December 2023 were selected.Radical resection was completed,tumor specimens and blood samples were collected.ctDNA analysis was performed using circulating single-molecule amplification and resequencing technology(cSMART)based on liquid biopsy.Relapse-free survival(RFS)and overall survival(OS)were recorded,and the relationship between ctDNA and RFS and OS was analyzed.Results 81 cases had an average of(1.73±0.65)gene mutations,50 cases(61.73%)were positive ctDNA before surgery,and 33 of 76 cases(43.42%)were positive ctDNA at least one point after surgery.Among the 50 patients with positive ctDNA before surgery,26 patients had positive ctDNA after surgery.During a median follow-up of 44.0 months,Among the 81 NSCLC patients,55 survived(67.90%),37 cases(45.68%)relapsed and 26 cases(32.10%)died.The median RFS stage was 19.0 months(log rank=12.531,P<0.001)and OS stage was 34.89 months(log rank=11.028,P=0.001)in ctDNA-positive patients before surgery,and the median RFS stage was 42.0 months and OS stage was 46.65 months in ctDNA-negative patients.Among the 33 ctDNA positive patients,21 casses(63.64%)relapsed and 15 cases(45.45%)died.The median RFS duration of 25.79 months(log rank=10.796,P=0.001)and OS duration of 34.21 months(log rank=7.384,P=0.007)in ctDNA-positive patients were shorter than those in ctDNA-negative patients(39.0 months of RFS and 43.15 months of OS).The imaging results of 43 patients with negative ctDNA after surgery showed complete resection of the lesions,and 21 cases of them were positive ctDNA before surgery.The median RFS duration of those with negative ctDNA was 38.05 months(log rank=5.139,P=0.023),which was longer than that of those without negative ctDNA.31 patients with negative ctDNA before surgery,7 cases(22.58%)had positive ctDNA conversion after surgery.Among the 33 ctDNA positive cases,21 cases had positive ctDNA after surgery(11.12±5.21)months earlier than the average results of imaging or clinical symptoms,and 17 cases had positive ctDNA within 2 weeks after surgery.Multifactor analysis showed that clinical stage and preoperative ctDNA status had statistical significance for RFS and OS(P<0.05).The risk of recurrence or death from high stage(stageⅢ)and low stage(stageⅠ/Ⅱ)NSCLC was 3.082 times or 3.577 times,respectively.Preoperative ctDNA-positive NSCLC had 3.889 times or 3.139 times increased risk of recurrence or death compared with ctDNA-negative NSCLC.Positive ctDNA was a factor affecting RFS after operation(P<0.05),and the risk of recurrence was increased by 3.333 times.Conclusion Advanced stage and preoperative ctDNA positive are the factors affecting RFS and OS in patients with radical resection of NSCLC.The detection of ctDNA after surgery can help to detect recurrence in time.
作者
乔鲜丽
田向阳
周文雅
秦泽敏
郭姗姗
于俊岩
Qiao Xianli;Tian Xiangyang;Zhou Wenya;Qin Zemin;Guo Shanshan;Yu Junyan(Department of Oncology,Changzhi Medical College Affiliated Peace Hospital,Changzhi 046000,China;Department of General Practice,PLA Rocket Army Characteristic Medical Center,Beijing 100088,China)
出处
《中华肺部疾病杂志(电子版)》
2025年第3期395-400,共6页
Chinese Journal of Lung Diseases(Electronic Edition)
基金
2022年度军队后勤科研面上项目(20221107)。
关键词
非小细胞肺癌
循环肿瘤DNA
微小残留病灶
复发
根治性切除
Non-small cell lung cancer
Circulating tumor DNA
Minimal residual disease
Recurrence
Radical resection
