Pre-treatment Circulating Tumor Cell Associated White Blood Cell Clusters Independently Predict Poor Survival in
Ying Wang1, Minghang Zhang2, Cen Chen3
1Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, China.
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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