Circulating Tumor Cells as a Predictive Biomarker in Resectable Lung Cancer: A Systematic Review and Meta-Analysis

Wankhede, Durgesh; Grover, Sandeep; Hofman, Paul

doi:10.3390/cancers14246112

Cited by 19 publications

(12 citation statements)

References 84 publications

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“…Recently, CTC has been recognized as a biomarker for postoperative recurrence. [17][18][19] Additionally, the activation of EMT is associated with an increased number of CTC and poor prognosis. 8,9,20 Therefore, it is reasonable to think that the upfront vein division may contribute to a better prognosis because the upfront vein division could prevent CTC from spreading during the surgery; however, upfront vein division was beneficial to the patients without EMT activation in our study and the patients with early-stage in the previous reports.…”

Section: Discussionmentioning

confidence: 99%

The impact of vascular division sequence and epithelial–mesenchymal transition status on postoperative recurrence in lung adenocarcinoma

Nishikawa,

Menju,

Takahashi

et al. 2024

Asian Cardiovasc Thorac Ann

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Background The vascular division sequence in video-assisted thoracic surgery (VATS) lung resection is usually determined by the handling difficulty due to the limited surgical view through the scope. However, upfront pulmonary vein division is theoretically desirable to avoid tumor cells spreading by surgical manipulation. Epithelial–mesenchymal transition (EMT) is associated with poor prognosis and an increased number of circulating tumor cells. The purpose of this study is to evaluate the effect of vascular division sequence and EMT on postoperative recurrence. Methods We retrospectively investigated tissue microarrays of 282 lung adenocarcinomas surgically resected between 2001 and 2007. We excluded the cases with segmentectomy, wedge resection, dissemination, insufficient material for staining, or lack of medical records. The effect of vascular division sequence and clinicopathologic factors on recurrence was evaluated in 195 cases. Results The upfront pulmonary vein division (V-first) was performed in 60 patients, and the upfront pulmonary artery division (A-first) was performed in 135 patients. The recurrence was observed in 67 patients (13 in V-first and 54 in A-first). Epithelial–mesenchymal transition activation was observed in 104 patients. Multivariable analysis with 195 patients revealed that lymph node metastasis and pleural invasion were risk factors for the recurrence. The stratified multivariable analysis showed that vascular division sequence (A-first) was a risk factor only in the EMT-negative group (91 patients). In the EMT-negative subset, the 5-year relapse-free survival rate was significantly lower in the A-first group than the V-first group (72.6% vs. 92.2%, p = 0.0136). Conclusions The upfront pulmonary artery division might be a risk factor in patients without EMT activation.

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Section: Discussionmentioning

confidence: 99%

The impact of vascular division sequence and epithelial–mesenchymal transition status on postoperative recurrence in lung adenocarcinoma

Nishikawa,

Menju,

Takahashi

et al. 2024

Asian Cardiovasc Thorac Ann

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“…In addition to cf-DNA, blood components such as CTC, circulating free non-coding RNA and even plasmatic proteins could be of interest in assessing MRD, particularly in association with assays targeting cf-DNA. [35][36][37] Many studies have shown that perioperative detection of CTCs can be integrated into the evaluation of the risk of tumour progression in resected early stage NSCLC. [38][39][40][41][42] However, as there are multiple approaches to CTC detection and the risk of false-negative and false-positive results varies depending on the method used, it is currently difficult to integrate this biomarker into daily practice.…”

Section: Integration Of Multiple Circulating Blood Biomarkers Into Mr...mentioning

confidence: 99%

“…In addition to cf‐DNA, blood components such as CTC, circulating free non‐coding RNA and even plasmatic proteins could be of interest in assessing MRD, particularly in association with assays targeting cf‐DNA 35–37 . Many studies have shown that perioperative detection of CTCs can be integrated into the evaluation of the risk of tumour progression in resected early stage NSCLC 38–42 .…”

Section: Recommendations To Close the Gap Between The Use Of Minimal ...mentioning

confidence: 99%

The use of minimal residual disease in thoracic oncology: Gaps between promises and the on‐the‐ground reality of daily practice

Hofman

Denis

2023

Cytopathology

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The assessment of minimal residual disease (MRD) from blood samples of patients with resected non‐small cell lung carcinoma (NSCLC) is promising and opens up many opportunities for the optimisation of patient care in daily practice. Notably, this includes the potential for escalation or de‐escalation of adjuvant therapies. Thus, the evaluation of MRD status can directly contribute to an increase in the overall survival of early stage NSCLC patients and/or limit therapeutic but also “financial” toxicity. Therefore, several clinical trials recently evaluated MRD in early stage NSCLC by integrating and retrospectively comparing the results of MRD assessments. In this context, there is an urgent need to close the gap between clinical research and the use of the evaluation of MRD in routine daily practice. Further action needs to be taken, particularly in evaluating the pertinence of the detection of MRD in prospective interventional clinical studies. This may be done in part by comparing different parameters, such as the techniques used, the different time points and the cutoffs of MRD assessments. This article investigates the assessment of MRD in non‐small cell lung cancers, with a special focus on the issues associated with the various assays and the limitations of using circulating free DNA analyses for MRD assessment in early stage lung cancer. Recommendations and tips for the optimisation of MRD evaluation in non‐small cell lung cancers are provided.

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“… 4 – 11 CTCs might also be a promising predictive biomarker of mortality and recurrence in early-stage NSCLC, and CTC detection can potentially serve as a tool for minimal residual disease detection in resectable lung cancer after curative surgery. 12 , 13 …”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8][9][10][11] CTCs might also be a promising predictive biomarker of mortality and recurrence in early-stage NSCLC, and CTC detection can potentially serve as a tool for minimal residual disease detection in resectable lung cancer after curative surgery. 12,13 CTC was used in molecular detection of human epidermal growth factor receptor 2 (HER2), KRAS, and EGFR mutation in breast, colon, and lung cancer. 14 CTC could be detected long before radiological diagnosis of lung cancer, 15 and therefore was applied in lung cancer screening in highrisk patients in a prospective study but failed to be used as biomarker.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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Circulating Tumor Cells as a Predictive Biomarker in Resectable Lung Cancer: A Systematic Review and Meta-Analysis

Cited by 19 publications

References 84 publications

The impact of vascular division sequence and epithelial–mesenchymal transition status on postoperative recurrence in lung adenocarcinoma

The impact of vascular division sequence and epithelial–mesenchymal transition status on postoperative recurrence in lung adenocarcinoma

The use of minimal residual disease in thoracic oncology: Gaps between promises and the on‐the‐ground reality of daily practice

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

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