Zhang Jia-Tao, Liu Si-Yang, Gao Xuan, Liu Si-Yang Maggie, Yan Bingfa, Huang Chen, Jiao Zicong, Yan Hong-Hong, Pan Yi, Dong Song, Gao Wei, Gong Yuhua, Tu Hai-Yan, Xia Xue-Feng, Zhou Qing, Zhong Wen-Zhao, Yang Xue-Ning, Yi Xin, Wu Yi-Long
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Geneplus-Beijing Institute, Beijing, China.
Clin Cancer Res. 2025 Apr 1;31(7):1305-1314. doi: 10.1158/1078-0432.CCR-24-2909.
The prognostic value of molecular residual disease (MRD) in non-small cell lung cancer (NSCLC) is well established, with treatment-guiding results anticipated. Here, we present updated analyses from our previously published cohort study of 261 patients with NSCLC undergoing complete resection.
A total of 261 patients with stage I to III lung cancer who underwent radical surgery were enrolled. Enrolled patients underwent follow-up blood draws according to the predefined time points after surgery. As of December 31, 2023, with a median follow-up of 43.4 months, 948 postoperative blood samples were collected.
Landmark and longitudinal MRD exhibited positive predictive values of 91.3% and 92.8%, respectively, with a median lead time of 5.2 months. Negative predictive values were 76.5% and 93.2%, respectively. Patients with landmark undetectable MRD could not benefit from adjuvant therapy through the updated follow-up (P = 0.529). Among the 13 patients with recurrent NSCLC and longitudinal undetectable MRD, seven (53.8%) had brain-only metastases, and four (30.8%) had no updated blood samples for over 6 months prior to recurrence. Besides, for those with longitudinal detectable MRD, higher maximum variant allele frequency (>0.55%) and ctDNA level (>13 hGE/mL) were associated with a high risk of short-term recurrence. Additionally, updated follow-up data further support that the peak time for detectable MRD was 18 months after landmark detection.
These findings suggest the significant potential of MRD in guiding personalized treatment for NSCLC. Postoperative longitudinal undetectable MRD can indicate a cured population.
分子残留病灶（MRD）在非小细胞肺癌（NSCLC）中的预后价值已得到充分证实，预期会有指导治疗的结果。在此，我们展示了我们之前发表的对261例接受完全切除的NSCLC患者队列研究的更新分析。
共纳入261例接受根治性手术的I至III期肺癌患者。纳入的患者在术后按照预定义的时间点进行随访采血。截至2023年12月31日，中位随访时间为43.4个月，共收集了948份术后血样。
标志性和纵向MRD的阳性预测值分别为91.3%和92.8%，中位提前期为5.2个月。阴性预测值分别为76.5%和93.2%。通过更新的随访，标志性MRD不可检测的患者无法从辅助治疗中获益（P = 0.529）。在13例复发性NSCLC且纵向MRD不可检测的患者中，7例（53.8%）仅有脑转移，4例（30.8%）在复发前6个月以上没有更新的血样。此外，对于纵向可检测到MRD的患者，更高的最大变异等位基因频率（>0.55%）和ctDNA水平（>13 hGE/mL）与短期复发的高风险相关。此外，更新的随访数据进一步支持可检测到MRD的峰值时间是在标志性检测后18个月。
这些发现表明MRD在指导NSCLC个性化治疗方面具有巨大潜力。术后纵向不可检测到的MRD可表明为治愈人群。
