PDF(Pubmed)
Abstract：
Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next-generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7-27.0 months). ctDNA-positive or -negative patients with tumors of any stage had similar disease-free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non-tissue derived. Patients with detectable postoperative ctDNA with tissue-derived mutations had comparable DFS with those with non-tissue-derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test.
摘要：
循环肿瘤DNA（ctDNA）具有作为肺癌分子残留病检测的潜在生物标志物的潜力。随着用于ctDNA检测的下一代测序标准化小组的出现，其临床效用需要验证。我们从四个医疗中心前瞻性招募了184名可切除的肺癌患者。通过标准化小组分析连续的术后ctDNA。总共纳入了来自177名合格患者的427份术后血浆样品。手术后ctDNA阳性是疾病复发的独立预测因子，中位时间为6.6个月（范围，0.7-27.0个月）。任何阶段的ctDNA阳性或阴性患者的无病生存率（DFS）相似。与未接受辅助治疗或化疗的患者相比，接受靶向治疗的患者DFS明显改善，无论基线/前佐剂ctDNA状态。根据是否在其匹配的组织中检测到ctDNA变体，它们分为组织来源和非组织来源。具有组织衍生突变的术后可检测到的ctDNA的患者的DFS与非组织衍生突变的患者相当。总的来说，我们证明，在可切除的肺癌中，术后ctDNA具有分层预后和优化肿瘤分期的潜力。在分子残留疾病测试中，应考虑组织样本中未发现的ctDNA变体。
