Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

Sonn, Chung-Hee; Cho, Jong Ho; Kim, Jae-Won; Kang, Moon Sung; Lee, Jinseon; Kim, Young Tae

doi:10.3892/ol.2017.5772

Cited by 12 publications

(8 citation statements)

References 27 publications

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“…We observed that a favourable therapy resulted in loose cluster formation while the tight cluster suggested therapy resistance. In addition, these clusters show different phenotypes across 4 cancer types that could be correlated with the number of CTCs reported in each cancer type 20,29,30 . We have enumerated CTCs using pan-CK positive, CD45 negative and DAPI-positive cells in clusters observed on day14 (Supplementary Table S2).…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor Cell cluster phenotype allows monitoring response to treatment and predicts survival

Balakrishnan

Koppaka

Anand

et al. 2019

Sci Rep

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Circulating tumor cells (CTCs) are putative markers of tumor prognosis and may serve to evaluate patient’s response to chemotherapy. CTCs are often detected as single cells but infrequently as clusters and are indicative of worse prognosis. In this study, we developed a short-term culture of nucleated blood cells which was applied to blood samples from breast, lung, esophageal and bladder cancer patients. Clusters of different degrees of compactness, classified as very tight, tight and loose were observed across various cancer types. These clusters show variable expression of cytokeratins. Cluster formation from blood samples obtained during the course of chemotherapy was found to be associated with disease progression and shorter overall survival. The short-term cultures offer a robust and highly reliable method for early prediction of treatment response in different cancer types.

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Section: Discussionmentioning

confidence: 99%

Circulating Tumor Cell cluster phenotype allows monitoring response to treatment and predicts survival

Balakrishnan

Koppaka

Anand

et al. 2019

Sci Rep

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“…Our results from the present study provide technical feasibility that the EGFR p.T790M mutation can be detected in CTCs using both the OncoBEAM™‐ EGFR or NGS‐56G assay technologies. Soon et al have also shown that the number of CTCs might differ considerably depending on the disease stage; for instance, they found a mean number of 1.48 ± 1.71 CTCs in stage I‐III patients (in 5 mL of total blood) and a mean of 8 ± 9.95 CTCs in stage IV‐V patients using the CellSearch platform . Given the considerable body of existing knowledge clearly indicating that the numbers of CTCs capable of being isolated from a clinical blood sample is likely to be a significant limitation to bringing CTCs into routine use in clinical diagnostics, our findings justify the use of highly sensitive assays such as BEAMing to detect mutations in combinatorial analyses with CTCs (p.T790M assay; 10 tumor cells per 7.5 mL of total blood required to detect EGFR p.T790M following enrichment with ClearCell FX) (Figure B).…”

Section: Resultsmentioning

confidence: 99%

Profiling of circulating tumor DNA in plasma of non‐small cell lung cancer patients, monitoring of epidermal growth factor receptor p.T790M mutated allelic fraction using beads, emulsion, amplification, and magnetics companion assay and evaluation in future application in mimicking circulating tumor cells

et al. 2019

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Cell‐free plasma DNA (cfDNA) and mimicking circulating tumor cells (mCTCs) have demonstrated tremendous potential for molecular diagnosis of cancer and have been rapidly implemented in specific settings. However, widespread clinical adoption still faces some obstacles. The purpose was to compare the performance of a BEAMing (beads, emulsion, amplification, and magnetics) assay (OncoBEAM™‐epidermal growth factor receptor [EGFR] [Sysmex Inostics]) and a next‐generation sequencing assay (NGS; 56G Oncology panel kit, Swift Bioscience) to detect the p.T790M EGFR mutation in cfDNA of non‐small cell lung cancer (NSCLC) patients. CfDNA samples (n = 183) were collected within our hospital from patients having a known EGFR sensitizing mutation, and presenting disease progression while under first‐line therapy. EGFR mutations were detected using NGS in 42.1% of samples during progression in cfDNA. Testing using the OncoBEAM™‐EGFR assay enabled detection of the p.T790M EGFR mutation in 40/183 NSCLC patients (21.8%) versus 20/183 (10.9%), using the NGS assay. Samples that were only positive with the OncoBEAM™‐EGFR assay had lower mutant allelic fractions (Mean = 0.1304%; SD ± 0.1463%). In addition, we investigated the detection of p.T790M in mCTCs using H1975 cells. These cells spiked into whole blood were enriched using the ClearCellFX1 microfluidic device. Using the OncoBEAM™‐EGFR assay, p.T790M was detected in as few as 1.33 tumoral cells/mL. Overall, these findings highlight the value of using the OncoBEAM™‐EGFR to optimize detection of the p.T790M mutation, as well as the complementary clinical value that each of the mutation detection assay offers: NGS enabled the detection of mutations in other oncogenes that may be relevant to secondary resistance mechanisms, whereas the OncoBEAM™‐EGFR assay achieved higher sensitivity for detection of clinically actionable mutations.

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“…CTC counting has been proven to be associated with some disease characteristics. Sonn et al [21], described a study with 82 patients with lung cancer, where they found an association of CTC counts with stage disease, as patients with stage IV had more CTCs, compared to stages I-III of TNM system (p = 0,009). Therefore, one of our findings was the correlation of CTC counts with pretreatment status, where we observed that patients with pre-treatment had more CTCs per mL.…”

Section: Discussionmentioning

confidence: 98%

Circulating tumor cells as marker of poor prognosis in metastatic lung cancer: a pilot study

et al. 2018

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Background: Circulating tumor cells (CTCs) play an important role in progression and metastasis, particularly in form of cluster, which is called circulating tumor microemboli (CTM), and can be found in the peripheral blood of cancer patients. The aim of this study was to evaluate the presence of CTCs and CTM, and its influence on tumor progression in lung cancer patients. Methods: CTCs were isolated by Isolation by Size of Epithelial Tumor cells (ISET®) Technology. The samples of metastatic lung cancer patients were collected before the beginning of systemic chemotherapy. CTCs and CTM were identified according to their morphological features. Results: Fifteen patients were analyzed. Patients who had CTM in blood previously the beginning of systemic therapy had poor progression-free survival (PFS) compared to those with absence of CTM, although without statistical significance (median PFS 3.1 months × 6.7 months, p = 0.29). Moreover, patients without any prior treatment had less than 3 CTCs/mL compared to patients previously exposed to chemotherapy, who had 3 CTCs/mL or more (p = 0.31). Additionally, these patients, with prior treatment, showed poor PFS, compared to chemo-naive patients, although without statistical significance (mean PFS: 4.6 months × 7.3 months, p = 0.47). Conclusions: We identified, even in a limited number of samples, that an elevated baseline levels of CTCs and the presence of CTM were associated with poor prognosis in patients with metastatic lung cancer. In addition, we showed that an increase of CTCs counts could indicate a pre-existing resistance. However, further studies with a large cohort are needed to support this information.

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Detection of circulating tumor cells in patients with non-small cell lung cancer using a size-based platform

Cited by 12 publications

References 27 publications

Circulating Tumor Cell cluster phenotype allows monitoring response to treatment and predicts survival

Circulating Tumor Cell cluster phenotype allows monitoring response to treatment and predicts survival

Circulating tumor cells as marker of poor prognosis in metastatic lung cancer: a pilot study

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