{"title":"Pre-treatment Circulating Tumor Cell Associated White Blood Cell Clusters Independently Predict Poor Survival in Patients with Extensive-disease Small Cell Lung Cancer.","authors":"Ying Wang, Minghang Zhang, Cen Chen, Yanxia Liu, Yuan Gao, Hongxia Li, Baohua Lu, Mingming Hu, Hongmei Zhang, Peter Ping Lin, Zhanliang Ren, Tongmei Zhang, Shaofa Xu","doi":"10.1177/11772719251338620","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Patients with extensive disease (ED)-small cell lung cancer (SCLC) commonly suffer a more inferior prognosis than those with limited disease (LD)-SCLC.</p><p><strong>Objectives: </strong>This study aims to investigate the heterogeneity and prognostic significance of various aneuploid circulating tumor cells (CTCs) subtypes and CTC-associated white blood cell (CTC-WBC) clusters in patients with LD-and ED-SCLC respectively.</p><p><strong>Design: </strong>This prospective, non-interventional, single-center study included 48 patients with LD-SCLC and 47 patients with ED-SCLC.</p><p><strong>Methods: </strong>A total of 95 SCLC patients were prospectively enrolled and serial blood samples were obtained before chemotherapy administration (t<sub>0</sub>) and after 2 cycles of chemotherapy (t<sub>1</sub>). Comprehensive in situ co-detection of CTCs and CTC-WBC clusters were performed in all enrolled patients.</p><p><strong>Results: </strong>The analysis revealed no significant difference in CTCs quantity between LD-SCLC and ED-SCLC patients (<i>P</i> = .610). However, significant morphologic heterogeneity in CTCs, including cell size and chromosome 8 (Chr8) ploidy in CTCs was observed between the 2 groups (<i>P</i> < .001 and <i>P</i> < .001). Patients with post-therapeutic small cell CTCs ⩾ 2/6 ml or triploid CTCs ⩾ 2/6 ml exhibited reduced overall survival (OS) compared to those with small cell CTCs < 2/6 ml or triploid CTCs < 2/6 ml in the ED-SCLC (<i>P</i> = .011 and <i>P</i> = .018). Additionally, the positive detection of post-therapeutic tetraploid CTCs was associated with inferior survival in both LD-and ED-SCLC (<i>P</i> = .041 and <i>P</i> = .049). The presence of CTC-WBC clusters at baseline and after treatment significantly correlated with inferior OS in ED-SCLC (<i>P</i> = .016 and <i>P</i> = .028) but not in LD-SCLC (<i>P</i> = .355 and <i>P</i> = .621). Multivariate analysis identified brain metastasis and pre-treatment CTC-WBC clusters as independent prognostic factors for OS in ED-SCLC patients (<i>P</i> = .004 and <i>P</i> = .013).</p><p><strong>Conclusion: </strong>Ideal biomarkers should be more specific for survival prediction in patients with different disease stages. Pre-treatment CTC-WBC clusters can independently predict inferior OS in ED-SCLC but not LD-SCLC.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251338620"},"PeriodicalIF":2.6000,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335652/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomarker Insights","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/11772719251338620","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Patients with extensive disease (ED)-small cell lung cancer (SCLC) commonly suffer a more inferior prognosis than those with limited disease (LD)-SCLC.
Objectives: This study aims to investigate the heterogeneity and prognostic significance of various aneuploid circulating tumor cells (CTCs) subtypes and CTC-associated white blood cell (CTC-WBC) clusters in patients with LD-and ED-SCLC respectively.
Design: This prospective, non-interventional, single-center study included 48 patients with LD-SCLC and 47 patients with ED-SCLC.
Methods: A total of 95 SCLC patients were prospectively enrolled and serial blood samples were obtained before chemotherapy administration (t0) and after 2 cycles of chemotherapy (t1). Comprehensive in situ co-detection of CTCs and CTC-WBC clusters were performed in all enrolled patients.
Results: The analysis revealed no significant difference in CTCs quantity between LD-SCLC and ED-SCLC patients (P = .610). However, significant morphologic heterogeneity in CTCs, including cell size and chromosome 8 (Chr8) ploidy in CTCs was observed between the 2 groups (P < .001 and P < .001). Patients with post-therapeutic small cell CTCs ⩾ 2/6 ml or triploid CTCs ⩾ 2/6 ml exhibited reduced overall survival (OS) compared to those with small cell CTCs < 2/6 ml or triploid CTCs < 2/6 ml in the ED-SCLC (P = .011 and P = .018). Additionally, the positive detection of post-therapeutic tetraploid CTCs was associated with inferior survival in both LD-and ED-SCLC (P = .041 and P = .049). The presence of CTC-WBC clusters at baseline and after treatment significantly correlated with inferior OS in ED-SCLC (P = .016 and P = .028) but not in LD-SCLC (P = .355 and P = .621). Multivariate analysis identified brain metastasis and pre-treatment CTC-WBC clusters as independent prognostic factors for OS in ED-SCLC patients (P = .004 and P = .013).
Conclusion: Ideal biomarkers should be more specific for survival prediction in patients with different disease stages. Pre-treatment CTC-WBC clusters can independently predict inferior OS in ED-SCLC but not LD-SCLC.
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