scholarly journals Application of Multigroup Technology in Non-Small-Cell Lung Cancer with Qi Stagnation and Blood Stasis Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guan-Jun Ma ◽  
Xiang Qian ◽  
Zhuo Chen ◽  
Sha-Sha Chen ◽  
Ai-Qin Zhang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Blood Stasis ◽  
Intestinal Flora ◽  
Small Cell ◽  
Blood Stasis Syndrome ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Qi Stagnation ◽  
Nsclc Patients

Objective. To explore the basic characteristics of intestinal flora, metabolomics, and proteomics of non-small cell lung cancer (NSCLC) in patients with Qi stagnation and blood stasis syndrome. Methods. Twelve NSCLC patients with Qi stagnation and blood stasis syndrome were selected for the QZXY group and 15 healthy volunteers were selected for the control group. Fecal samples from the two groups were collected to evaluate intestinal microecology using the 16s rDNA technique. Serum samples were collected to compare the differences in metabolomics and proteomics between the two groups using liquid chromatography-mass spectrometry (LC-MS). Another 34 NSCLC patients with other syndromes were selected for the nQZXY group and their serum samples were collected. Metabolomics differences between the QZXY and nQZXY groups were compared using LC-MS, and four metabolites with the most obvious differences were selected for receiver operation characteristic curve representation. Finally, multigroup results were analyzed using the WGCNA software. Results. There were two significantly different types of bacteria (Aerococcaceae and Abiotrophia), 11 different proteins (six upregulated and five downregulated), and 38 different metabolites (nine upregulated, 29 downregulated) between the QZXY and control groups. There was a correlation between differential bacteria, proteins, and metabolites. The conjoint analysis found that the different substances were related to MAPK, PI3K/Akt, Ras signaling pathway, cancer pathways, and cytokine-cytokine receptor interaction. There were four significant differences in metabolites (Pseudouridine, phenlacetyl-C0A, L-glutamic, and phospho-anandamide) between the QZXY and nQZXY groups. Conclusions. NSCLC with Qi stagnation and blood stasis syndrome had specific intestinal flora and protein and metabolites, which were closely related to the occurrence and development of tumors.

Retrospective validation of a pretreatment serum protein profile in metastatic non-small cell lung cancer patients treated with a pembrolizumab containing regime as first line of treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21135-e21135
Author(s):  
Wouter W. Mellema ◽  
Edwin A. Basak ◽  
Heinrich Roder ◽  
Joanna Roder ◽  
Robert W. Georgantas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Serum Samples ◽  
Resistant Group ◽  
Nsclc Patients ◽  
Pretreatment Serum

e21135 Background: There is an unmet need for reliable biomarkers predictive of treatment outcome with immunotherapy in patients with non-small cell lung cancer (NSCLC). The aim of our study is to examine, in front-line patients, the potential utility of a proteomic signature, PIR (primary immune response), developed and validated in 2nd line patients (M. Muller Clin Cancer Res. 2020 Oct 1;26(19):5188-5197. doi: 10.1158/1078-0432.CCR-20-0538. Epub 2020 Jul 6) as a predictive biomarker of response to treatment with pembrolizumab in a first-line setting. Methods: Pretreatment serum samples were collected from stage IV NSCLC patients treated with a pembrolizumab-containing regimen in first-line at the Netherlands Cancer Institute and Erasmus Medical Center between 2016 and 2020. Data on demographics, ECOG performance status (PS), PD-L1 expression, treatment, progression free survival (PFS) and overall survival (OS) were collected. The PIR test was performed and classified in two groups: resistant vs. intermediate/sensitive (not-resistant). Results: Serum samples of 119 patients were available for analysis. Median age was 65 (36-82) years; 49% female; PS 0-1 80%. 45 samples failed QC and were excluded allowing for the analysis of 74 patients: 24 receiving pembrolizumab monotherapy, and 50 receiving a combination of chemotherapy and pembrolizumab. Overall, median PFS was 5.3 months in the resistant group vs. 9.0 months in the not-resistant group (HR 0.60 (95%CI 0.33-1.08; p = 0.09). In patients receiving pembrolizumab monotherapy, the resistant group had a trend toward shorter PFS (median PFS 3.4 months vs. 10.3 months) then the non-resistant group, (HR 0.42 (95% CI 0.15-1.21; p = 0.11))). No difference was observed in patients treated with a combination of chemotherapy and pembrolizumab (median PFS 5.8 months vs. 9.0 months, respectively; HR = 0.65 (95% CI 0.31-1.36; p = 0.25). Median OS was not reached vs 17.0 months, respectively (HR 0.90 (95% CI 0.34-2.36; p = 0.83)). We did not observe any significant association between performance score and PD-L1 expression, and the PIR test. Conclusions: These data encourage further study of PIR as a predictive biomarker for first-line treatment with pembrolizumab in NSCLC patients.

scholarly journals Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3828
Author(s):  
Anello Marcello Poma ◽  
Rossella Bruno ◽  
Iacopo Pietrini ◽  
Greta Alì ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Durable Response ◽  
Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

scholarly journals Metabolic Changes in Early-Stage Non–Small Cell Lung Cancer Patients after Surgical Resection

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3012
Author(s):  
Naseer Ahmed ◽  
Biniam Kidane ◽  
Le Wang ◽  
Zoann Nugent ◽  
Nataliya Moldovan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Surgical Resection ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Resonance Spectroscopy ◽  
Small Cell Lung ◽  
Serum Samples ◽  
Post Surgery

Metabolic alterations in malignant cells play a vital role in tumor initiation, proliferation, and metastasis. Biofluids from patients with non–small cell lung cancer (NSCLC) harbor metabolic biomarkers with potential clinical applications. In this study, we assessed the changes in the metabolic profile of patients with early-stage NSCLC using mass spectrometry and nuclear magnetic resonance spectroscopy before and after surgical resection. A single cohort of 35 patients provided a total of 29 and 32 pairs of urine and serum samples, respectively, pre-and post-surgery. We identified a profile of 48 metabolites that were significantly different pre- and post-surgery: 17 in urine and 31 in serum. A higher proportion of metabolites were upregulated than downregulated post-surgery (p < 0.01); however, the median fold change (FC) was higher for downregulated than upregulated metabolites (p < 0.05). Purines/pyrimidines and proteins had a larger dysregulation than other classes of metabolites (p < 0.05 for each class). Several of the dysregulated metabolites have been previously associated with cancer, including leucyl proline, asymmetric dimethylarginine, isopentenyladenine, fumaric acid (all downregulated post-surgery), as well as N6-methyladenosine and several deoxycholic acid moieties, which were upregulated post-surgery. This study establishes metabolomic analysis of biofluids as a path to non-invasive diagnostics, screening, and monitoring in NSCLC.

scholarly journals Circulating Biomarkers of Response and Toxicity of Immunotherapy in Advanced Non-Small Cell Lung Cancer (NSCLC): A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1794
Author(s):  
Alice Indini ◽  
Erika Rijavec ◽  
Francesco Grossi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Circulating Biomarkers ◽  
Small Cell Lung ◽  
Nsclc Patients

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.

scholarly journals Feasibility and effectiveness of afatinib for poor performance status patients with EGFR-mutation-positive non-small-cell lung cancer: a retrospective cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chiao-En Wu ◽  
Ching-Fu Chang ◽  
Chen-Yang Huang ◽  
Cheng-Ta Yang ◽  
Chih-Hsi Scott Kuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Disease Control ◽  
Performance Status ◽  
Poor Performance ◽  
Small Cell ◽  
Poor Performance Status ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Afatinib is one of the standard treatments for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). However, data on the use of afatinib in patients with poor performance status (PS ≥ 2) are limited. This study aimed to retrospectively review the clinical outcomes and safety of afatinib treatment in EGFR-mutation-positive (EGFRm+) NSCLC patients with PS ≥ 2. Methods The data for 62 patients who were treated at Linkou Chang Gung Memorial Hospital from January 2010 to August 2019 were retrospectively reviewed. Patients’ clinicopathological features were obtained, and univariate and multivariate analyses were performed to identify possible prognostic factors. Data on adverse events were collected to evaluate general tolerance for afatinib therapy. Results Until February 2020, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 58.1% (36/62), 69.4% (43/62), 8.8 months, and 12.9 months, respectively. The absence of liver metastasis (PFS: p = 0.044; OS: p = 0.061) and good disease control (p < 0.001 for PFS and OS) were independent favorable prognostic factors for PFS and OS. Bone metastasis (p = 0.036) and dose modification (reduction/interruption, p = 0.021) were predictors of disease control. Conclusion Afatinib demonstrated acceptable efficacy and safety in the current cohort. This study provided evidence to support the use of afatinib as a first-line treatment in EGFRm+ NSCLC patients with poor PS.

scholarly journals 1318P Association between soluble PD-L1 and prognosis of non-small cell lung cancer (NSCLC) patients treated with immunotherapy

2020 ◽  
Vol 31 ◽  
pp. S851
Author(s):  
C. Dellepiane ◽  
S. Coco ◽  
M.G. Dal Bello ◽  
G. Rossi ◽  
E. Rijavec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients
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