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目的 探讨血循环肿瘤DNA(ctDNA)-微小残留病灶(MRD)预测NSCLC术后早期复发风险和辅助化疗疗效的效能。方法 收集2020年1月至2022年12月在宁德师范学院附属宁德市医院接受手术的102例非小细胞肺癌(NSCLC)患者为研究对象。术前、术后(术后4周内和辅助治疗开始前)、辅助治疗后以及后续纵向监测期间(每3个月一次),采用二代测序(NGS)技术检测ctDNA-MRD情况。随访患者的无复发生存期(RFS)。结果 92例患者肿瘤组织检测到体细胞突变，其中83.70%(77/92)术前血浆样本中检测到突变。患者中位随访时间为388天(范围：123～592天),复发率30.43%(28/92)。多因素Cox风险比例回归模型结果显示，术后ctDNA-MRD是影响NSCLC术后RFS的独立因素(P<0.05)。与术后ctDNA-MRD阴性患者比较，术后ctDNA-MRD阳性患者的复发率更高(68.0%vs. 16.42%),中位RFS更短(311天vs. 401天，P<0.05)。Kaplan-Meier结果显示，接受辅助治疗的ctDNA-MRD阳性患者的中位RFS时间显著长于未接受辅助治疗者(352天vs. 140天，P=0.027)。在影像学证实复发的28例患者中，24例患者纵向ctDNA-MRD呈阳性。ctDNA-MRD阳性先于影像学复发，中位领先时间为158天。纵向ctDNA-MRD阳性患者中位RFS时间显著短于阴性患者322天vs. 422天(P<0.05)。结论 血ctDNA-MRD阳性与NSCLC的RFS有关。术后ctDNA-MRD阳性的患者接受辅助治疗后更可能获益。血ctDNA-MRD可能作为NSCLC术后早期复发风险分层以及辅助治疗决策的有用生物标志物。
Abstract：Objective To explore the efficacy of circulating tumor DNA(ctDNA)-minimal residual lesions(MRD) in predicting the risk of early recurrence after NSCLC and the efficacy of adjuvant chemotherapy.Methods One hundred and two patients with non-small cell lung cancer(NSCLC) who underwent surgery at Ningde Hospital affiliated to Ningde Normal University from January 2020 to December 2022 were collected as research subjects.Second generation sequencing(NGS) technology was used to detect ctDNA mutations before surgery, after surgery(within 4 weeks after surgery and before the start of adjuvant therapy), after adjuvant therapy, and during subsequent longitudinal monitoring(every 3 months).Patients were followed for recurrence-free survival(RFS).Results Somatic mutations were detected in tumor tissues of 92(90.20%) patients, of which 83.70%(77/92) mutations were detected in preoperative plasma samples.The median follow-up time of patients was 388 days(range: 123 to 592 days), and the recurrence rate was 30.43%(28/92).The results of multivariate Cox hazard proportion regression model showed that postoperative ctDNA-MRD was an independent factor affecting postoperative RFS of NSCLC(P<0.05).Compared with postoperative ctDNA-MRD negative patients, postoperative ctDNA-MRD positive patients had higher recurrence rate and shorter median RFS(P<0.05).Kaplan-Meier results showed that the median time to RFS was significantly longer in ctDNA-MRD-positive patients receiving adjuvant therapy than in positive patients without adjuvant therapy(352 days vs. 140 days, P=0.027).Of the 28 patients with radiographically confirmed recurrence, 85.71%(24/28) had positive longitudinal ctDNA-MRD.ctDNA-MRD positivity preceded radiographic recurrence with a median lead time of 158 days.The median RFS time of longitudinal ctDNA-MRD positive patients was significantly shorter than that of negative patients(P<0.05).Conclusion the positive blood ctDNA-MRD is related to RFS in NSCLC.Patients with positive ctDNA-MRD after surgery are more likely to benefit after receiving adjuvant therapy.Blood ctDNA-MRD may serve as a useful biomarker for risk stratification of early postoperative recurrence in NSCLC as well as adjuvant treatment decision-making.
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基本信息:
DOI：
中图分类号:R734.2
引用信息:
[1]叶辉,许涛,杨莺等.血ctDNA-MRD监测对预测NSCLC术后早期复发风险和辅助治疗疗效的临床观察[J].临床肿瘤学杂志,2025,30(03):233-238.
基金信息: