Dataset Information

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

ABSTRACT:

Background

Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC.

Objectives

We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy.

Design

Chemotherapy is administered and blood specimens are collected at four time points from baseline to disease progression for CTC detection.

Methods

This multicenter prospective study enrolled patients with previously untreated stage III or IV NSCLC fit for standard platinum-based chemotherapy. Bloods were sampled as per standard operating procedures at baseline, cycle 1 and cycle 4 of chemotherapy, and at disease progression for CTC analysis using the CellSearch system.

Results

Among 150 patients enrolled, median overall survival (OS) was 13.8, 8.4, and 7.9 months in patients with CTC^-, KIT^-CTC, and KIT⁺CTC at baseline (p = 0.002). Patients with persistent negative CTC (46.0%) had longer progression-free survival [5.7 months, 95% confidence interval (CI): 5.0-6.5 versus 3.0 months, 0.6-5.4; hazard ratio (HR): 0.34, 95% CI: 0.18-0.67) and OS (13.1 months, 10.9-15.3 versus 5.6 months, 4.1-7.1; HR: 0.17, 0.08-0.36) compared with patients with persistent positive CTC (10.7%), which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% (54/150) to 13.7% (13/95).

Conclusions

CTC persistent presence during treatment represents poor prognosis and resistance to chemotherapy in advanced NSCLC. Chemotherapy could effectively eliminate CTCs. Molecular characterization and the functionalization of CTC will be warranted for further intensive investigation.

Trial registration

NCT01740804.

SUBMITTER: Wang Z

PROVIDER: S-EPMC10126699 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

Wang Zhen Z Zhang Xu-Chao XC Feng Wei-Neng WN Zhang Li L Liu Xiao-Qing XQ Guo Wei-Bang WB Deng Yan-Ming YM Zou Qing-Feng QF Yang Jin-Ji JJ Zhou Qing Q Wang Bin-Chao BC Chen Hua-Jun HJ Tu Hai-Yan HY Yan Hong-Hong HH Wu Yi-Long YL

Therapeutic advances in medical oncology 20230422

<h4>Background</h4>Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC.<h4>Objectives</h4>We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy.<h4>Design</h4>Chemotherapy is administered and blood specimens are collected at four time poi ...[more]

PMID: 37113733

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Project description:Purpose This study aimed to investigate the clinical utility of diverse aneuploid circulating tumor cell (CTC) subtypes and particularly CTC-associated white blood cell (CTC-WBC) clusters in predicting treatment response, prognosis and real-time monitoring disease progression in advanced driver gene-negative non-small lung cancer (NSCLC) patients. Materials and methods A total of 74 eligible patients were prospectively enrolled and serial blood samples were collected at pre-treatment(t0), after two cycles of therapy (t1) and at post-four-to-six treatment cycles (t2). Co-detection of diverse subtypes of aneuploid CTCs and CTC-WBC clusters was conducted in advanced NSCLC patients receiving first-line treatment. Results At baseline, CTCs were detected in 69 (93.24%) patients and CTC-WBC clusters were detected in 23 (31.08%) patients. Patients with CTCs < 5/6ml or with CTC-WBC clusters undetectable exhibited a better treatment response than patients with pre-therapeutic aneuploid CTCs ≥ 5/6ml or harboring CTC-WBC clusters (p = 0.034 and p = 0.012, respectively). Before treatment, patients bearing tetraploid CTCs ≥ 1/6ml showed significantly inferior progression-free survival (PFS) [hazard ratio (HR):2.420, 95% confidence interval (CI): 1.426–4.106; p = 0.001] and overall survival (OS) compared to patients with tetraploid CTCs < 1/6ml (HR:1.907, 95%CI: 1.119–3.251; p = 0.018). A longitudinal study demonstrated that post-therapeutic patients harboring CTC-WBC clusters displayed the reduced PFS and OS compared with those without CTC-WBC clusters, and subgroup analysis showed that the presence of CTC-WBC clusters indicated a worse prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. After adjusting for multiple significant factors, post-therapeutic CTC-WBC clusters were the only independent predictor of both PFS (HR:2.872, 95% CI: 1.539–5.368; p = 0.001) and OS (HR:2.162, 95% CI: 1.168–4.003; p = 0.014). Conclusions In addition to CTCs, longitudinal detection of CTC-WBC clusters provided a feasible tool to indicate initial treatment response, dynamically monitor disease progression and predict survival in driver gene-negative advanced NSCLC patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-023-10985-1.

Dataset Information

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

Background

Objectives

Design

Methods

Results

Conclusions

Trial registration

Publications

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

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