scholarly journals Circulating mRNA Expression of astrocyte-Elevated Gene-1 Associated with Treatment Response and Survival in Non-Small Cell Lung Cancer Patients Treated with Pemetrexed

2021 ◽  
Author(s):  
You-Lung Chang ◽  
Yen-Fu Chen ◽  
Ying-Yin Chen ◽  
Shih-Chieh Chang ◽  
Cheng-Yu Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Treatment Response ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Nsclc Patients

Abstract Backgrounds: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumor response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed advanced NSCLC were enrolled to be treated with pemetrexed combined platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR.Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of SD (n = 13) and PD (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS) and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR v.s. SD or PD, AEG-1: 1.22 ± 0.80 v.s. 4.51 ± 15.45, p = 0.043). NSCLC patients had elevated AEG-1 (AEG-1 ≥ 2) after 2-cycle chemotherapy had shorter PFS and OS (high AEG-1 v.s. low AEG-1, median, PFS: 5.5 v.s. 11.9 months, p = 0.021; OS: 25.9 v.s. 40.8 months, p = 0.019, respectively). In Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival.Conclusion: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.

scholarly journals Circulating mRNA Expression of Astrocyte-Elevated Gene-1 Associated with Treatment Response and Survival in Non-Small Cell Lung Cancer Patients Treated with Pemetrexed

2021 ◽  
Vol 11 (23) ◽  
pp. 11334
Author(s):  
You-Lung Chang ◽  
Yen-Fu Chen ◽  
Ying-Yin Chen ◽  
Shih-Chieh Chang ◽  
Cheng-Yu Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Treatment Response ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Nsclc Patients

Background: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumour response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed with advanced NSCLC were enrolled to be treated with pemetrexed combined with platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) of treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR. Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of stable disease (SD) (n = 13) and progressive disease (PD) (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS), and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR vs. SD or PD, AEG-1: 1.22 ± 0.80 vs. 4.51 ± 15.45, p = 0.043). NSCLC patients who had elevated AEG-1 (AEG-1 ≥ 2) after two cycles of chemotherapy had shorter PFS and OS (high AEG-1 vs. low AEG-1, median, PFS: 5.5 vs. 11.9 months, p = 0.021; OS: 25.9 vs. 40.8 months, p = 0.019, respectively). In a Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival. Conclusions: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.

scholarly journals Longitudinal Change of Circulating Tumor Cells During Chemoradiation Therapy and Its Correlation with Prognosis in Advanced Non-Small Cell Lung Cancer Patients

2020 ◽  
Author(s):  
Jun Liu ◽  
Yongping Liu ◽  
Cheng Gu ◽  
Lei Zhang ◽  
Xujing Lu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Treatment Response ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background: This study aimed to investigate the association of circulating tumor cells (CTCs) change during chemoradiation with the treatment response and survival profiles in advanced non-small cell lung cancer (NSCLC) patients.Methods: 58 advanced NSCLC patients underwent concurrent chemoradiation were enrolled, then their peripheral blood samples were collected pre-chemoradiation and at 1 months post-chemoradiation to assess the CTCs using a CTC-Biopsy system. Moreover, CTCs were classified as CTCs positive and CTCs negative according to CTCs’ count, and CTCs’ change was calculated. Additionally, response of chemoradiation was evaluated at 1 months post-chemoradiation, then progression-free survival (PFS) and overall survival (OS) were assessed. Results: Pre-chemoradiation CTCs positive was associated with increased TNM stage, but not correlated with other clinicopathologic characteristics. After chemoradiation, the CTCs’ number (1.0 (0.0-3.0) vs. 4.0 (2.0-10.0)) and the percentage of CTCs positive cases (37.9% vs. 77.6%) were both decreased compared with those prior to chemoradiation. Regarding treatment response, pre-chemoradiation CTCs positive was associated with lower partial response; post-chemoradiation CTCs positive was associated with reduced disease control rate; while CTCs’ change during chemoradiation was not associated with treatment response. Kaplan–Meier curves showed that post-chemoradiation CTCs positive and increased CTCs’ number during chemoradiation were associated with reduced PFS, then multivariate Cox’s regression analysis disclosed that they independently predicted decreased PFS. However, no correlation of CTCs status or CTCs’ change with OS was observed. Conclusions: Longitudinal monitoring of CTCs may provide important reflection for the prognosis in chemoradiation treated advanced NSCLC patients.

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jianming Hu ◽  
Jiawei Hu ◽  
Xiaolan Liu ◽  
Long Li ◽  
Xue Bai
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

scholarly journals Prognostic significance of peripheral CD8+CD28+ and CD8+CD28− T cells in advanced non-small cell lung cancer patients treated with chemo(radio)therapy

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Chao Liu ◽  
Wang Jing ◽  
Ning An ◽  
Aijie Li ◽  
Weiwei Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Natural Killer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Radio Therapy ◽  
Nsclc Patients

Abstract Background Noninvasive prognostic biomarkers are needed for advanced non-small cell lung cancer (NSCLC) patients with different histological types to identify cases with poor survival. Here, we investigated the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28− T cells in advanced NSCLC patients treated with chemo(radio)therapy and the impact of histological type on them. Methods Of 232 registered advanced NSCLC patients, 101 treatment-naïve individuals were eligible and included in our study. Flow cytometry was used to evaluate CD8+CD28+ T cells, CD8+CD28− T cells, CD4+ CD25hi T cells, B cells, natural killer cells, γδT cells, and natural killer T cells in patients’ peripheral blood. Results The median follow-up time was 13.6 months. Fifty-nine (58.4%) patients died by the end of our study. Fifty-three of the 101 advanced NSCLC cases selected for our study were adenocarcinomas (ADs), and 48 were squamous cell carcinomas (SCCs). Multivariate analyses showed that increased levels of CD8+CD28+ T cells independently predicted favorable overall survival (OS) [hazard ratio (HR): 0.51, 95% confidence interval (CI) 0.30–0.89, P = 0.021] and progression-free survival (PFS) (HR: 0.66, 95% CI 0.37–0.93, P = 0.038) in ADs, but the prediction in SCCs was not statistically significant. In contrast, high levels of CD8+CD28− T cells independently predicted unfavorable OS (HR: 1.41, 95% CI 1.17–3.06, P = 0.035) and PFS (HR: 2.01, 95% CI 1.06–3.85, P = 0.029) in SCCs, but the prediction in ADs was not statistically significant. ADs had higher levels of CD4+CD25hi T cells and CD8+CD28− T cells and lower NK cells (all P < 0.05) than SCCs. Conclusions Our findings uncovered the prognostic values of peripheral CD8+CD28+ T cells and CD8+CD28− T cells in advanced NSCLC patients treated with chemo(radio)therapy, which could help to identify patients with poor outcomes and refine treatment strategies.

scholarly journals The New Immunotherapy Combinations in the Treatment of Advanced Non-Small Cell Lung Cancer: Reality and Perspectives

2020 ◽  
Vol 15 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Danilo Rocco ◽  
Luigi D. Gravara ◽  
Cesare Gridelli
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Significant Shift ◽  
Small Cell Lung ◽  
Future Directions ◽  
Therapeutic Algorithm ◽  
Nsclc Patients

Background: In the recent years, immunotherapeutics and specifically immunecheckpoints inhibitors have marked a significant shift in the diagnostic and therapeutic algorithm of Non-Small Cell Lung Cancer (NSCLC), allowing us to use immunotherapeutics alone or combined with chemotherapy for a great subset of patients. However, new interesting approaches are being presently investigated, markedly immunotherapy combinations, that is, the use of two or more immunotherapeutics combined. Methods: In particular, the combination of anti-PD-1 nivolumab and anti-CTLA-4 ipilimumab has already provided groundbreaking positive results in the advanced NSCLC and other combinations are currently under investigation. Results: Therefore, this paper aims to provide a comprehensive state-of-the-art review about immunotherapy combination, along with suggestions about future directions. A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed and ClinicalTrials.gov. Conclusion: Nivolumab plus ipilimumab represent the most promising immunotherapy combination for the treatment of advanced NSCLC patients; safety, tolerability and efficacy of new immunotherapeutics (in monotherapy and in immunotherapy combinations) must be further assessed in future studies.

scholarly journals Next Generation Sequencing-Based Profiling of Cell Free DNA in Patients with Advanced Non-Small Cell Lung Cancer: Advantages and Pitfalls

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3804
Author(s):  
Riziero Esposito Abate ◽  
Daniela Frezzetti ◽  
Monica Rosaria Maiello ◽  
Marianna Gallo ◽  
Rosa Camerlingo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Dna ◽  
Nsclc Patients ◽  
Generation Sequencing

Lung cancer (LC) is the main cause of death for cancer worldwide and non-small cell lung cancer (NSCLC) represents the most common histology. The discovery of genomic alterations in driver genes that offer the possibility of therapeutic intervention has completely changed the approach to the diagnosis and therapy of advanced NSCLC patients, and tumor molecular profiling has become mandatory for the choice of the most appropriate therapeutic strategy. However, in approximately 30% of NSCLC patients tumor tissue is inadequate for biomarker analysis. The development of highly sensitive next generation sequencing (NGS) technologies for the analysis of circulating cell-free DNA (cfDNA) is emerging as a valuable alternative to assess tumor molecular landscape in case of tissue unavailability. Additionally, cfDNA NGS testing can better recapitulate NSCLC heterogeneity as compared with tissue testing. In this review we describe the main advantages and limits of using NGS-based cfDNA analysis to guide the therapeutic decision-making process in advanced NSCLC patients, to monitor the response to therapy and to identify mechanisms of resistance early. Therefore, we provide evidence that the implementation of cfDNA NGS testing in clinical research and in the clinical practice can significantly improve precision medicine approaches in patients with advanced NSCLC.

The Presence of EGFR Mutations Predicts the Response in Chinese Non-Small Cell Lung Cancer Patients Treated with Erlotinib

2014 ◽  
Vol 29 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Rui-chao Li ◽  
Li-jun Zheng ◽  
Ming-hao Fang ◽  
Shi-ying Yu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iiib ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Nsclc Patients ◽  
Line Chemotherapy

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. The upregulation of the epidermal growth factor receptor (EGFR) due to mutations has been observed in a number of cancers, and tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, which specifically target EGFR signaling, have been used to treat NSCLC patients. The presence of EGFR mutations was previously shown to confer sensitivity to TKIs. In this study, we evaluated the correlation between EGFR mutations and response to erlotinib in Chinese NSCLC patients. We recruited 36 patients with stage IIIB/IV NSCLC who had failed first-line chemotherapy, and treated them with erlotinib. We used immunohistochemistry to determine EGFR expression, and we screened for mutations using PCR analysis. We used Cox regression analysis and Kaplan-Meier curves for survival analysis. We found that 8 patients had exon 19 mutations, while 3 patients had exon 21 mutations. An Eastern Cooperative Oncology Group (ECOG) grade of 2 was a significant negative predictor of overall survival (OS). Patients with EGFR mutations showed a significantly better OS compared to those without EGFR mutations. Additionally, multivariate analysis showed that erlotinib-treated stage IV patients had a significantly longer progression-free survival (PFS) compared to stage IIIB patients. Patients with EGFR mutations also had a significantly better PFS compared to those without EGFR mutations. The overall remission rate (22.2%) and disease control rate (75%) were significantly higher compared to the rates after second-line chemotherapy (<10%). In conclusion, the presence of EGFR mutations could be a marker to predict the therapeutic efficacy of erlotinib and the prognosis in Chinese NSCLC patients.

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