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; = 0.007) and OS (median OS, 16.3 months; = 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.

中文翻译：

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非整倍性增加的循环肿瘤细胞预示着小细胞肺癌的较差预后和治疗耐药性


小细胞肺癌（SCLC）通常出现治疗耐药，因此需要开发新型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效用。来自两个独立癌症中心的总共 126 名 SCLC 患者（两个队列）被招募为研究对象。从这些患者身上采集血样并检测非整倍体 CTC。非整倍体 CTC 计数 (ACC) 和非整倍体 CTC 评分 (ACS) 用于预测无进展生存期 (PFS) 和总生存期 (OS)。通过计算受试者工作特征（ROC）曲线下面积（AUC）来评估 ACC 和 ACS 的性能。与 ACC 相比，ACS 对这 126 名患者的 PFS 和 OS 表现出卓越的预测能力。此外，单变量和多变量分析均显示 ACS 是一个独立的预后因素。动态 ACS 变化反映了治疗反应，比 ACC 变化更精确。 ACS可用于评估化疗耐药性，比放射学检查更敏感（中位提前期为2.8个月；P < 0.001）。当患者基线时 ACS 水平较高 (> 1.115) 时，免疫治疗和化疗相结合可导致比单独化疗（中位 PFS，7.7 个月；= 0.007）和 OS（中位 OS，16.3 个月；= 0.033）更长的 PFS（中位 PFS，7.7 个月；= 0.007）和 OS（中位 OS，16.3 个月；= 0.033） PFS，4.9 个月；中位 OS，13.6 个月）。 ACS 可用作 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。