LBPO.CL02 · 临床研究 · Late-Breaking
驱动基因特异性MRD策略与接受新辅助治疗的III期驱动基因突变型NSCLC的病理反应及预测复发相关
Driver-specific MRD strategy associated with pathological response and predicted recurrence in stage III driver-mutant NSCLC receiving neoadjuvant treatment
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：术后驱动基因特异性循环肿瘤DNA（ctDNA）监测可对可切除III期驱动基因突变型NSCLC的复发风险进行分层（NCT06443684）。驱动基因特异性ctDNA MRD是否能评估新辅助反应并预测III期驱动基因突变型NSCLC的复发仍有待界定。方法：2022年至2025年，在中国14个中心前瞻性纳入203例经组织确认存在驱动基因突变的可切除III期NSCLC患者（NCT06443684）。在新辅助治疗前、术前、术后3天和1个月，以及此后每3个月直至研究者确认复发时采集外周血。使用10基因驱动panel（LC10）分析ctDNA。本分析聚焦于82例接受新辅助治疗后行手术的患者的围新辅助期ctDNA动态及临床结局。结果：在82例接受新辅助治疗的患者中，方案包括化疗-免疫治疗（57.3%）、TKI（第三代EGFR TKI/第二或第三代ALK TKI，39.0%）和单纯化疗（3.7%）。新辅助治疗后ctDNA阳性与显著更低的MPR率相关（相比ctDNA阴性，0% vs 42.3%，p=0.004），而基线ctDNA状态与MPR无关（16.7% vs 21.2%）。新辅助治疗后ctDNA分子残留水平（hGE/mL）与残留存活肿瘤细胞呈正相关（R=0.332，p=0.009）。新辅助治疗后ctDNA阳性患者的无事件生存期显著更短（中位EFS 11.4 vs 23.8个月；HR=8.82；p=0.009）。对于非MPR患者，新辅助治疗后ctDNA阴性状态也提示良好预后（中位EFS 23.8 vs 4.7个月；HR=5.80；p=0.054）。与其他方案相比，新辅助TKI与更低的治疗后ctDNA残留率相关（0% vs 15.3%；p=0.05）。持续ctDNA阳性（基线→新辅助治疗后）的患者EFS最短（中位4.7个月），其次为阴性→阳性（23.8个月），而阳性转阴性和持续阴性的ctDNA提示无病状态（log-rank p<0.001）。结论：驱动基因特异性ctDNA MRD策略为III期驱动基因突变型NSCLC患者的新辅助疗效评估和术后复发风险分层提供了一种实用工具。
查看英文原文 English abstract
Background: Postoperative driver gene-specific circulating tumor DNA (ctDNA) monitoring stratifies recurrence risk in resectable stage III driver-mutant NSCLC (NCT06443684). Whether driver-specific ctDNA MRD can evaluate neoadjuvant response and predict recurrence in stage III driver-mutant NSCLC remains to be defined. Methods: From 2022 to 2025, 203 resectable stage III NSCLC patients with tissue-confirmed driver mutations were prospectively enrolled at 14 centers in China (NCT06443684). Peripheral blood was collected before neoadjuvant therapy, preoperatively, 3 days and 1 month after surgery, and every 3 months until investigator-confirmed recurrence. ctDNA was analyzed using a 10-gene driver panel (LC10). This analysis focused on peri-neoadjuvant ctDNA dynamics and clinical outcomes among 82 patients who received neoadjuvant therapy followed by surgery. Results: Among the 82 neoadjuvant-treated patients, regimens included chemo-immunotherapy (57.3%), TKI (3 rd -EGFR TKI/2 nd or 3 rd -ALK TKI, 39.0%), and chemotherapy alone (3.7%). Post-neoadjuvant ctDNA positivity was associated with a significantly lower MPR rate versus ctDNA negativity (0% vs 42.3%, p=0.004), whereas baseline ctDNA status was not associated with MPR (16.7% vs 21.2%). Post-neoadjuvant ctDNA molecular residual level (hGE/mL) positively correlated with residual viable tumor cells (R=0.332, p=0.009). Post-neoadjuvant ctDNA-positive patients had significantly shorter event-free survival (median EFS 11.4 vs 23.8 months; HR=8.82; p=0.009). For non-MPR patients, post-neoadjuvant negative ctDNA status also indicated favorable prognosis (median EFS 23.8 vs 4.7 months; HR=5.80; p=0.054). Compared with other regimens, neoadjuvant TKI was associated with a lower post-treatment ctDNA residual rate (0% vs 15.3%; p=0.05). Patients with persistent ctDNA positivity (baseline→post-neoadjuvant) had the shortest EFS (median 4.7 months), followed by negative→positive (23.8 months), while positive to negative and persistent negative ctDNA indicated disease free status(log-rank p<0.001). Conclusions: A driver-specific ctDNA MRD strategy provides a practical tool for neoadjuvant efficacy assessment and postoperative recurrence risk stratification for stage III driver-mutant NSCLC patients.
利益披露 Disclosure
J. Hu, None..
X. Teng, None..
Z. Li, None..
Y. Qi, None..
F. Li, None..
Q. Chen, None..
C. Zhu, None..
X. Li, None..
S. Lu, None.