Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.
Cancer Research UK Lung Cancer Centre of Excellence, The University of Manchester, Manchester, UK.
Nat Med. 2019 Oct;25(10):1534-1539. doi: 10.1038/s41591-019-0593-1. Epub 2019 Oct 7.
Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.
约 50%接受根治性手术治疗的早期非小细胞肺癌（NSCLC）患者在 5 年内会复发。手术时检测循环肿瘤细胞（CTCs）可能代表一种识别复发风险较高患者的工具，建议对这些患者进行更频繁的监测。在这里，我们询问了早期 NSCLC 手术切除时检测到的肺静脉 CTC（PV-CTCs）是否代表了随后疾病复发的亚克隆。在 TRACERx 研究中纳入的 100 名患者中，有 48%检测到了 PV-CTCs，它们与肺癌特异性复发相关，并且在调整肿瘤分期的多变量分析中仍然是复发的独立预测因素。在一项病例研究中，对手术时收集的单个 PV-CTC 进行的基因组分析显示，与 10 个月后检测到的转移灶（91%）相比，与原发性肿瘤（79%）的突变重叠更高，提示早期播散的 PV-CTCs 是疾病复发的原因。总之，PV-CTC 计数和基因组分析突出了 PV-CTCs 作为 NSCLC 手术后复发的早期预测因子的潜力。然而，PV-CTCs 预测复发的敏感性有限，因此需要使用更大的、独立的队列进行进一步研究，以确认和更好地定义 PV-CTCs 在早期 NSCLC 中的潜在临床应用。
