Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China; Molecular Diagnosis and Gene Test Centre, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China; Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
Drug Resist Updat. 2024 Sep;76:101117. doi: 10.1016/j.drup.2024.101117. Epub 2024 Jul 2.
Treatment resistance commonly emerges in small cell lung cancer (SCLC), necessitating the development of novel and effective biomarkers to dynamically assess therapeutic efficacy. This study aims to evaluate the clinical utility of aneuploid circulating tumor cells (CTCs) for risk stratification and treatment response monitoring.
A total of 126 SCLC patients (two cohorts) from two independent cancer centers were recruited as the study subjects. Blood samples were collected from these patients and aneuploid CTCs were detected. Aneuploid CTC count (ACC) and aneuploid CTC score (ACS), were used to predict progression-free survival (PFS) and overall survival (OS). The performance of the ACC and the ACS was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC).
Compared to ACC, ACS exhibited superior predictive power for PFS and OS in these 126 patients. Moreover, both univariate and multivariate analyses revealed that ACS was an independent prognostic factor. Dynamic ACS changes reflected treatment response, which is more precise than ACC changes. ACS can be used to assess chemotherapy resistance and is more sensitive than radiological examination (with a median lead time of 2.8 months; P < 0.001). When patients had high ACS levels (> 1.115) at baseline, the combination of immunotherapy and chemotherapy resulted in longer PFS (median PFS, 7.7 months; P = 0.007) and OS (median OS, 16.3 months; P = 0.033) than chemotherapy alone (median PFS, 4.9 months; median OS, 13.6 months).
ACS could be used as a biomarker for risk stratification, treatment response monitoring, and individualized therapeutic intervention in SCLC patients.
小细胞肺癌（SCLC）常出现治疗抵抗，因此需要开发新的、有效的生物标志物来动态评估治疗效果。本研究旨在评估非整倍体循环肿瘤细胞（CTC）在风险分层和治疗反应监测中的临床应用价值。
本研究共纳入来自两个独立癌症中心的 126 例 SCLC 患者（两个队列）作为研究对象。采集这些患者的血液样本并检测非整倍体 CTC。采用非整倍体 CTC 计数（ACC）和非整倍体 CTC 评分（ACS）预测无进展生存期（PFS）和总生存期（OS）。通过计算接受者操作特征（ROC）曲线下面积（AUC）评估 ACC 和 ACS 的性能。
与 ACC 相比，ACS 对这 126 例患者的 PFS 和 OS 具有更好的预测能力。此外，单因素和多因素分析均表明 ACS 是独立的预后因素。ACS 的动态变化反映了治疗反应，比 ACC 变化更准确。ACS 可用于评估化疗耐药性，比影像学检查更敏感（中位领先时间为 2.8 个月；P < 0.001）。当患者基线时 ACS 水平较高（> 1.115）时，免疫治疗联合化疗的 PFS（中位 PFS，7.7 个月；P = 0.007）和 OS（中位 OS，16.3 个月；P = 0.033）均长于单独化疗（中位 PFS，4.9 个月；中位 OS，13.6 个月）。
ACS 可作为 SCLC 患者风险分层、治疗反应监测和个体化治疗干预的生物标志物。
