Correlation between epidermal growth factor receptor tyrosine kinase inhibitor efficacy and circulating tumor cell levels in patients with advanced non-small cell lung cancer

He, Wenjie; Li, Wenhui; Jiang, Bo; Li, Chang; Jin, Congguo; Tu, Changlin; Li, Yunfen

doi:10.2147/ott.s115221

Cited by 20 publications

(17 citation statements)

References 15 publications

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“…He et al . reported that a higher baseline CTC count was significantly associated with inferior PFS (5.6 vs. 11.5 months; P = 0.005) and OS (18.3 vs. 22.8 months; P = 0.010) rates in advanced NSCLC patients with EGFR mutations . These findings in EGFR ‐mutated NSCLC patients correspond to the results of our study.…”

Section: Discussionsupporting

confidence: 90%

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Prognostic role of circulating tumor cells in patients with EGFR‐mutated or ALK‐rearranged non‐small cell lung cancer

Tong

Zhao

et al. 2018

Thoracic Cancer

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BackgroundCirculating tumor cell (CTC) counts at baseline and follow‐up are an independent prognostic factor in patients receiving standard chemotherapy for non‐small cell lung cancer (NSCLC). This study further explored the role of CTCs in EGFR‐mutated and ALK‐rearranged NSCLC patients administered targeted therapies as first‐line treatment.MethodsCTCs were enumerated with a novel high‐efficiency detection method from the blood of 43 patients with EGFR‐mutated or ALK‐rearranged NSCLC at baseline and at disease‐progression. Patients were stratified into favorable and unfavorable groups with baseline CTC counts of < 8 or ≥ 8 CTCs/3.2 mL, respectively.ResultsA total of 76.7% of the patients were positive for ≥ 2 CTCs /3.2 ml blood at baseline. The median progression‐free survival (PFS) and overall survival (OS) rates of the favorable compared to the unfavorable group were longer (11.6 vs. 8.5 months, P = 0.004 for PFS; 21.00 vs. 17.7 months, P = 0.013 for OS). Multivariate analysis demonstrated that baseline CTC count was a strong predictor of PFS (hazard ratio 2.835; 95% confidence interval 1.240–6.483; P = 0.014) and OS (hazard ratio 3.317; 95% confidence interval 1.360–8.092; P = 0.008).ConclusionBaseline CTC count could be a predictive biomarker for EGFR‐mutated and ALK‐rearranged NSCLCs, which allows for better guidance and monitoring of patients over the course of molecular targeted therapies.

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Section: Discussionsupporting

confidence: 90%

“…To our knowledge, this study provides the first complete evidence of the prognostic value of baseline CTC counts for predicting PFS and OS rates in patients with positive EGFR / ALK. To date few reports have investigated the prognostic significance of CTCs in EGFR ‐mutated or ALK ‐rearranged NSCLCs . Yang et al .…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of circulating tumor cells in patients with EGFR‐mutated or ALK‐rearranged non‐small cell lung cancer

Tong

Zhao

et al. 2018

Thoracic Cancer

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“…CTC were assessed by flow cytometry in 66 EGFR mutant advanced NSCLC patients (46). Patients were divided in two groups (high CTC count vs. low CTC count) based on the median CTC count of 68.5.…”

Section: Prognostic and Predictive Value Of Ctc In Advanced Nsclcmentioning

confidence: 99%

Clinical utility of circulating tumor cells in patients with non-small-cell lung cancer

Gallo

Luca

Maiello

et al. 2017

Transl. Lung Cancer Res.

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Several different studies have addressed the role of the circulating tumor cells (CTC) in nonsmall-cell lung cancer (NSCLC). In particular, the potential of CTC analysis in the early diagnosis of NSCLC and in the prediction of the outcome of patients with early and advanced NSCLC have been explored. A major limit of these studies is that they used different techniques for CTC isolation and enumeration, they employed different thresholds to discriminate between high-and low-risk patients, and they enrolled heterogeneous and often small cohort of patients. Nevertheless, the results of many studies are concordant in indicating a correlation between high CTC count and poor prognosis in both early and advanced NSCLC. The reduction of CTC number following treatment might also represent an important indicator of sensitivity to therapy in patients with metastatic disease. Preliminary data also suggest the potential for CTC analysis in the early diagnosis of NSCLC in high-risk individuals. However, these findings need to be confirmed in large prospective trials in order to be transferred to the clinical practice.The molecular profiling of single CTC in NSCLC might provide important information on tumor biology and on the mechanisms involved in tumor dissemination and in acquired resistance to targeted therapies. In this respect, xenografts derived from CTC might represent a valuable tool to investigate these phenomena and to develop novel therapeutic strategies.

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“…CTCs are thought to be metastatic cells from the solid tumor site and are one of the avenues for metastasis from the primary tumor site to distant tissues, thus CTCs are associated with tumor progression and patient prognosis . Moreover, because it is thought that CTCs reflect characteristics of the primary solid tumor such as genetic alterations and expression of therapeutic targets, CTCs may be useful for estimating established biomarkers that can monitor response to treatment and the presence or lack of tumor‐specific therapeutic targets . Therefore, the detection and analysis of CTCs could be a minimally invasive diagnostic procedure for repetitive monitoring and deciding on therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Moreover, because it is thought that CTCs reflect characteristics of the primary solid tumor such as genetic alterations and expression of therapeutic targets, 8,9 CTCs may be useful for estimating established biomarkers that can monitor response to treatment and the presence or lack of tumor-specific therapeutic targets. [10][11][12] Therefore, the detection and analysis of CTCs could be a minimally invasive diagnostic procedure for repetitive monitoring and deciding on therapeutic strategy. CellSearch is the only FDA-approved CTC enumeration platform and has demonstrated the clinical utility of CTCs in a several cancers, 7,13,14 however, their utility in non-small cell lung cancer (NSCLC) has been limited by the low expression of EpCAM in CTCs derived from NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Detection of AXL expression in circulating tumor cells of lung cancer patients using an automated microcavity array system

et al. 2020

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Noninvasive diagnostics using circulating tumor cells (CTCs) are expected to be useful for decision making in precision cancer therapy. AXL, a receptor tyrosine kinase is associated with tumor progression, epithelial‐to‐mesenchymal transition (EMT), and drug resistance, and is a potential therapeutic target. However, the epithelial markers generally used for CTC detection may be not enough to detect AXL‐expressing CTCs due to EMT. Here, we evaluated the detection of AXL‐expressing CTCs using the mesenchymal marker vimentin with a microcavity array system. To evaluate the recovery of cancer cells, spike‐in experiments were performed using cell lines with varying cytokeratin (CK) or vimentin (VM) expression levels. With high CK and low VM‐expressing cell lines, PC‐9 and HCC827, the recovery rate of AXL‐expressing cancer cells was 1%‐17% using either CK or VM as markers. Whereas, with low CK and high VM‐expressing cell lines, MDA‐MB231 and H1299, it was 52%‐75% using CK and 72%‐88% using VM as a marker. For clinical evaluation, peripheral blood was collected from 20 non–small cell lung cancer patients and CTCs were detected using CK or VM as markers in parallel. Significantly more AXL‐expressing single CTCs were detected in VM‐positive than CK‐positive CTCs (P < .001). Furthermore, CTC clusters were identified only among VM‐positive CTCs in 20% of patients. Patients with one or more prior treatments harbored significantly more VM‐positive AXL‐expressing CTCs, suggesting the involvement of these CTCs in drug resistance. These results indicate the necessity of integrating mesenchymal markers with CTC detection and this should be further evaluated clinically.

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Correlation between epidermal growth factor receptor tyrosine kinase inhibitor efficacy and circulating tumor cell levels in patients with advanced non-small cell lung cancer

Cited by 20 publications

References 15 publications

Prognostic role of circulating tumor cells in patients with EGFR‐mutated or ALK‐rearranged non‐small cell lung cancer

Prognostic role of circulating tumor cells in patients with EGFR‐mutated or ALK‐rearranged non‐small cell lung cancer

Clinical utility of circulating tumor cells in patients with non-small-cell lung cancer

Detection of AXL expression in circulating tumor cells of lung cancer patients using an automated microcavity array system

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