Li Zhao, Xu Ke, Tartarone Alfredo, Santarpia Mariacarmela, Zhu Yuming, Jiang Gening
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Transl Lung Cancer Res. 2021 Feb;10(2):995-1006. doi: 10.21037/tlcr-21-149.
The development of metastasis is the primary cause of death in patients with non-small cell lung cancer (NSCLC). However, identifying those NSCLC patients who will have loco-regional or distant disease recurrence after surgery is still challenging. Circulating tumor cells (CTCs) can accurately reflect the impact of micro-metastasis of tumor cells in circulating blood on patients' treatment and prognosis. The aim of the present study was to explore the value of preoperative CTC concentration in predicting postoperative metastasis and recurrence risk in patients with NSCLC.
This study enrolled 347 patients with stage I-IIIA NSCLC. The CTCs were isolated using folate receptor (FR) positivity from peripheral blood samples before surgery, and then enriched and analyzed. Patients were divided into two groups for retrospective survival analysis based on the geometric mean of CTC concentration. The primary study endpoint was recurrence-free survival. Spearman's correlation was used to evaluate the relationship between CTC concentration and clinical characteristics of NSCLC patients. A nomogram based on the multivariate Cox regression model was developed to predict recurrence and metastasis in the NSCLC patients. The performance of the nomogram was evaluated using the concordance index, calibration curve, and Hosmer-Lemeshow test.
The median follow-up time was 38 months. Preoperative CTC concentration was not significantly related to tumor-node-metastasis staging (P>0.05) and was an independent prognostic factor for NSCLC patients [hazard ratio (HR), 5.489; 95% confidence interval (CI): 2.660-11.326, P<0.001]. The nomogram based on preoperative CTC concentration had a concordance index value of 0.82. Validation revealed that the nomogram possessed excellent predictive ability and calibration.
Preoperative CTC concentration is an independent and sensitive biomarker of prognosis in patients with NSCLC. Our nomogram based on preoperative CTC concentration is an effective and non-invasive tool for predicting the recurrence and metastasis of NSCLC.
转移的发生是非小细胞肺癌（NSCLC）患者死亡的主要原因。然而，识别那些术后将发生局部区域或远处疾病复发的NSCLC患者仍然具有挑战性。循环肿瘤细胞（CTC）能够准确反映肿瘤细胞微转移对循环血液中患者治疗和预后的影响。本研究的目的是探讨术前CTC浓度在预测NSCLC患者术后转移和复发风险中的价值。
本研究纳入了347例I-IIIA期NSCLC患者。术前从外周血样本中利用叶酸受体（FR）阳性分离出CTC，然后进行富集和分析。根据CTC浓度的几何平均值将患者分为两组进行回顾性生存分析。主要研究终点是无复发生存期。采用Spearman相关性分析评估CTC浓度与NSCLC患者临床特征之间的关系。基于多变量Cox回归模型构建列线图，以预测NSCLC患者的复发和转移。使用一致性指数、校准曲线和Hosmer-Lemeshow检验评估列线图的性能。
中位随访时间为38个月。术前CTC浓度与肿瘤-淋巴结-转移分期无显著相关性（P>0.05），是NSCLC患者的独立预后因素[风险比（HR），5.489；95%置信区间（CI）：2.660-11.326，P<0.001]。基于术前CTC浓度的列线图一致性指数值为0.82。验证显示该列线图具有出色的预测能力和校准性。
术前CTC浓度是NSCLC患者预后的独立且敏感的生物标志物。我们基于术前CTC浓度的列线图是预测NSCLC复发和转移的有效且非侵入性工具。
