Simultaneous in Situ Detection of Protein Expression of Multiple Tumor Markers of CTC and Heteroploid of Chromosome 8 in Primary Lung Cancer

2021 ◽  
Author(s):  
Hanqing Yao ◽  
Zhengdong Wang ◽  
Junjun Yang ◽  
Xingxiang Xu ◽  
Yong Song
Keyword(s):  
Lung Cancer ◽  
Peripheral Blood ◽  
Primary Lung Cancer ◽  
Small Cell ◽  
Chromosome 8 ◽  
Clinical Staging ◽  
Advanced Lung Cancer ◽  
Multiple Tumor ◽  
Positive Rate

Abstract Background Past studies have shown that circulating tumor cells (CTCs) play an important role in the clinical staging, efficacy monitoring and prognosis evaluation of lung cancer. Methods In this study we investigated the expression of CK18 and Vimentin on the surface of CTC and the aneuploidy of chromosome 8 in peripheral blood of 24 patients with metastatic primary lung cancer which were detected by subtraction enrichment and immunofluorescence in situ hybridization (SE-iFISH), and their correlation with clinicopathological features, curative effect and prognosis was analyzed. Results The positive rate of CTC was 95.83% (23/24). There was a certain correlation between the positive rate of CTC and smoking and a correlation between the number of CTC and the histopathological type of patients. The number of monoploid, diploid, triploid and polyploid CTC had no statistical correlation with progression-free survival (PFS) or overall survival (OS). However, a tetraploid CTC count of two or more was an unfavorable predictor of response and a tetraploid CTC count ≥ 1 is an unfavorable prognostic predictor of poor OS. The positive rate of CK18 + CTC in all 24 patients was 4.35% (1/23). Meanwhile, 7 out of these 24 patients were also tested for Vimentin, and the positive rate of Vimentin + CTC was 85.71% (6/7). Small-cell (≤ 5µm) CTC was found in 6 of these 7 patients and it accounted for 11.83% (11/93) of the total CTC. The tumor marker phenotype of small-cell CTC was CK18 - Vimentin +. In addition, circulating tumor microthrombi (CTM) were found in 2 of these 7 patients (28.57%). Conclusion SE-iFISH has a high detection rate of CTC in peripheral blood of patients with metastatic primary lung cancer, and it can identify small-cell CTC. Tetraploid CTC count ≥ 2 can predict poor PFS in patients with advanced lung cancer. Tetraploid CTC count ≥ 1 may predict poor OS in patients with advanced lung cancer. CTM can predict poor prognosis in patients with lung cancer.

scholarly journals Vimentin expression in circulating tumor cells (CTCs) associated with liver metastases predicts poor progression-free survival in patients with advanced lung cancer

2019 ◽  
Vol 145 (12) ◽  
pp. 2911-2920 ◽  
Author(s):  
Ying Wang ◽  
Yanxia Liu ◽  
Lina Zhang ◽  
Li Tong ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liver Metastases ◽  
Cell Size ◽  
Progression Free Survival ◽  
Small Cell ◽  
Chromosome 8 ◽  
Advanced Lung Cancer ◽  
Vimentin Expression ◽  
Free Survival ◽  
Lung Cancer Patients

Abstract Objective To investigate the presence of vimentin expression in CTCs and its clinical relevance in patients with advanced lung cancer. Methods Peripheral blood was obtained from 61 treatment-naive patients with advanced lung cancer. Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform was applied to identify, enumerate and characterize CTCs based on cell size, aneuploidy of chromosome 8 (Chr8) and vimentin expression. Quantification and analysis of CTCs were performed on patients before chemotherapy administration and after two cycles of therapy. Results Before treatment, CTCs were detected in 60 (98.4%) patients, small cell CTCs (≤ 5 µm of WBCs) accounted for 52.8% of the absolute CTCs number, while 12 (19.7%) of the included patients had detectable vimentin-positive CTCs (vim+ CTCs). Liver metastases were reported in 7 (11.5%) patients and were significantly correlated to the presence of Vim+ CTCs (p = 0.002), with a high positivity rate of 71.4% (5/7). Vim+ CTCs were mostly in small cell size and Chr8 aneuploidy (77.0% and 82.05%, respectively). Baseline small cell CTCs ≥ 2/6 ml, triploid CTCs ≥ 2/6 ml, Vim+ CTCs ≥ 1/6 ml were found to significantly correlate with poor progression-free survival (PFS) (p = 0.017, p = 0.009 and p = 0.001, respectively). After adjusting for clinically significant factors, baseline Vim+ CTCs ≥ 1/6 ml was the only independent predictor of poor PFS [hazard ratio (HR):2.756, 95% confidence interval (CI): 1.239–6.131; p = 0.013]. Conclusions This study demonstrates an important morphologic, karyotypic and phenotypic CTCs heterogeneity in advanced lung cancer patients. The majority of Vim+ CTCs are in small size and Chr8 aneuploidy. Baseline presence of Vim+ CTCs is correlated with liver metastases and may help predict poor PFS.

scholarly journals Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study

2020 ◽  
Vol 8 (2) ◽  
pp. e001302
Author(s):  
Suchita Pakkala ◽  
Kristin Higgins ◽  
Zhengjia Chen ◽  
Gabriel Sica ◽  
Conor Steuer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Radiation Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Peripheral Blood ◽  
Stereotactic Body Radiation Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stereotactic Body Radiation

BackgroundImmune checkpoint blockade (ICB) targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein 4 has achieved modest clinical activity as salvage therapy in relapsed small cell lung cancer (SCLC). We conducted this signal-finding study to assess the efficacy of ICB with or without radiation in relapsed SCLC.MethodsPatients with relapsed SCLC and ≤2 previous lines of therapy were randomized to (1) arm A: durvalumab (D) 1500 mg/tremelimumab (T) 75 mg (intravenously every 4 weeks without stereotactic body radiation therapy (SBRT)) or (2) arm B: immune-sensitizing SBRT to one selected tumor site (9 Gy × 3 fractions) followed by D/T. Treatment continued until progression or a maximum of 12 months. The co-primary endpoints of the study were overall response rate (ORR) and progression-free survival (PFS). We evaluated circulating lymphocyte repertoire in serial peripheral blood samples and tumor infiltrating lymphocytes (TILs) from on-treatment biopsies as pharmacodynamic markers.ResultsEighteen patients were randomized to arms A and B (n=9 each): median age 70 years; 41.2% women. The median PFS and ORR were 2.1 months and 0% in arm A and 3.3 months and 28.6% in arm B. The median overall survival (OS) was 2.8 months in arm A and 5.7 months in arm B (p=0.3772). Pooled efficacy of D/T±SBRT in 15 Response evaluation criteria in solid tumors (RECIST) evaluable patients across both arms showed the best ORR in terms of partial response in 13.3%, stable disease in 26.6% and progressive disease in 60.0%; the overall median PFS and OS were 2.76 and 3.9 months. The most common adverse events were grade 1 fatigue (66%) and grade 1 elevated amylase (56%) in arm A, and grade 1 fatigue (56%) and pain (44%) in arm B. There was a significant increase in activated CD8(+)ICOS+ T cells (p=0.048) and a reduction in naïve T cells (p=0.0454) in peripheral blood following treatment, along with a significant amount of activated CD8+ICOS+ T cells in TILs from responders.ConclusionsThe D/T combination with and without SBRT was safe but did not show sufficient efficacy signal in relapsed SCLC. Changes in peripheral blood lymphocyte and TILs were consistent with an immunologic response.Trial registration numberNCT02701400.

scholarly journals Mediterranean Diet Implementation to Protect against Advanced Lung Cancer Index (ALI) Rise: Study Design and Preliminary Results of a Randomised Controlled Trial

2021 ◽  
Vol 18 (7) ◽  
pp. 3700
Author(s):  
Aristea Gioxari ◽  
Dimitrios Tzanos ◽  
Christina Kostara ◽  
Panos Papandreou ◽  
Giannis Mountzios ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Randomised Controlled Trial ◽  
Nutritional Status ◽  
Mediterranean Diet ◽  
Controlled Trial ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Study Endpoint ◽  
Preliminary Results ◽  
Randomised Controlled

The Mediterranean diet (MD) has been inversely associated with lung cancer (LC) risk. Hereby we show the preliminary results of our prospective randomised controlled trial in inflammatory and nutritional status of LC patients after 3-month implementation of MD. In total, 30 patients with small-cell or non-small-cell LC (stages III–IV) were enrolled. They were randomly assigned either to Control group, receiving general nutritional guidelines, or the MD group, in which a personalised MD plan was provided. Medical and dietary history, anthropometrics, blood biomarkers, and circulating antioxidant vitamins were assessed. The main outcome was a significantly higher advanced lung cancer inflammation index (ALI) in patients of the control arm than those following MD (p = 0.003). In the MD group, platelets were significantly reduced at the study endpoint (p = 0.044). BMI and body fat mass remained unchanged in both arms, but serum glucose was significantly higher in control compared to MD group (p = 0.017). In conclusion, we showed for the first time that implementing a personalised MD for 3 months is promising to regulate prognostic biomarkers in advanced LC. The final results of our on-going trial will shed a light on the inflammatory, antioxidant and nutritional status of LC patients following MD.

Circulating tumor cell proportion scoring (CTPS) based PD-L1 assessment and clinical application of circulating tumor cells (CTCs) on stage IV non-small cell lung cancer (NSCLC) through liquid biopsy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15031-e15031
Author(s):  
Mi Young Choi ◽  
Da Hye Moon ◽  
Jong-min Jo ◽  
Hae Ung Lee ◽  
Seri Park ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
False Positive ◽  
Stage Iv ◽  
Small Cell ◽  
Advanced Lung Cancer ◽  
Diagnostic Strategy ◽  
Small Cell Lung ◽  
Tissue Biopsy

e15031 Background: Stage IV lung cancer is the most advanced lung cancer state accompanied by metastasized to the area around the lungs or distant major organs. The most common type of lung cancer is non-small cell lung cancer, which is more aggressive and may spread quickly due to organ-specific complex networks such as lymph and major blood vessels. Thus, only precise diagnostic strategy approaches will determine the effectiveness of the actual and successful clinical treatment. Until a recent date, Immunohistochemistry (IHC) for programmed death-ligand 1(PD-L1) test is the only available biomarker test that purpose diagnostics (CDx) and guide the treatment with immune checkpoint inhibitors in NSCLC. Methods: Given that CDx strategy, tissue biopsy has inevitable limitations, including patient risk, repetitive examination, sample preparation, sensitivity, and accuracy. For this reason, our research team contrived the best strategy for biomarker, PD-L1-specific CTCs in stage IV NSCLC group (N = 30) compared to pulmonary inflammatory patient groups (N = 30) CytoGen Smart biopsy platform. Herein, we removed false-positive cells for the first strategy of distinguishing between lymphoid/myeloid cells and the enriched-CTCs. And the second strategic approach is to calculate the pure CTCs (without false-positive cells) and then CTPS) as measured by the PD-L1 expression among pure-CTCs. That application is the percentage of viable CTCs showing partial or complete stained cells at the deducted cut-off value in each fluorescence, respectively. Results: Consequently, we demonstrated over 80% of the concordance rate between VENTANA PD-L1(SP263) and DAKO PD-L1(SP263) assay tested by the PD-L1 expression on stage IV NSCLC in tissue and pure-CTCs based CTPS from the blood. In contrast, pure-CTCs based CTPS in the pulmonary inflammatory group were all negative (recorded as zero). Conclusions: Conclusively, this study implicates that pure-CTCs based CTPS could be deployed for innovative diagnosis strategies as alternatives for tissue biopsy. Our clinical study's data suggested that the possibility for prompt decision for diagnosis and gain powerful insights to guide the personalized treatment in NSCLCs. Clinical trial information: 2020-0553.

Worldwide Overview of the Current Status of Lung Cancer Diagnosis and Treatment

2012 ◽  
Vol 136 (12) ◽  
pp. 1478-1481 ◽  
Author(s):  
Paul A. Bunn
Keyword(s):  
Lung Cancer ◽  
Cancer Mortality ◽  
Kinase Inhibitors ◽  
False Positive Rate ◽  
Lung Cancer Mortality ◽  
Current Status ◽  
Advanced Lung Cancer ◽  
Lung Cancer Diagnosis ◽  
Positive Rate ◽  
Inhaled Prostacyclin

Lung cancer is the leading worldwide cause of cancer deaths. Smoking is the dominant cause of lung cancer and smoking cessation is the established method to reduce lung cancer mortality. While lung cancer risk is reduced in former smokers, they have a lifelong increase in risk, compared to never-smokers. Novel chemoprevention strategies, such as oral or inhaled prostacyclin analogs, hold promise for these subjects. Low-dose spiral computed tomography screening reduced lung cancer mortality by 20% in high-risk heavy smokers older than 50 years. However, the high false-positive rate (96%) means that screened patients required controlled follow-up in experienced centers. An increasing percentage of patients with advanced lung cancer have molecular drivers in genes for which oral tyrosine kinase inhibitors have been developed.

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