scholarly journals Molecular Therapeutics of Non-Small Cell Lung Cancer (NSCLC) and Challenges in Repeat Tissue Biopsy

2021 ◽  
Vol 10 (03) ◽  
pp. 21-39
Author(s):  
Devanna Vasista Ganesha ◽  
Radheshyam Naik ◽  
Suhail Sayeed Mufti ◽  
Hrishi Varayathu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tissue Biopsy ◽  
Molecular Therapeutics

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.

Correlation between tissue PD-L1, TMB, and blood PD-L1, MSI biomarkers in patients with advanced-stage non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21564-e21564
Author(s):  
Sujitha Nandimandalam ◽  
Nitika Sharma
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Linear Correlation ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Response To Therapy ◽  
Small Cell Lung ◽  
Tissue Biopsy ◽  
Bivariate Correlation

e21564 Background: Tissue biomarkers like programmed cell death ligand-1 (PD-L1), microsatellite instability (MSI) and high tumor mutational burden (TMB) are surrogates in identifying patients with non-small cell lung cancer (NSCLC) for treatment with immune checkpoint blockade (ICB) therapy. Although tissue biopsy is widely used for identifying the tumor biology, the invasive nature as well as insufficiency of tissue biopsy specimens limits its application. Liquid biopsy is a minimally invasive procedure and has gained interest in recent times for profiling cancer. We sought to study the correlation in the molecular tumor profile specifically PD-L1, MSI and TMB markers between the tissue and liquid biopsies. Methods: We conducted a retrospective review of patients with Stage 3, 4 and recurrent NSCLC that underwent tissue next generation sequencing (NGS) using Caris life sciences and liquid biopsy using Circulogene molecular diagnostics from January 2018 to December 2019 at East Carolina University. A total of 524 patients were reviewed out of which 199 patients had both liquid and tissue NGS performed at the time of initial diagnosis. TMB high was defined as greater than 10 mut/Mb whereas TMB low as less than or equal to 10 mut/Mb. PD-L1 was divided into negative (0%), 1-49% and ≥50%. The blood MSI was classified as positive or negative. We used frequency table, logistic regression and Pearson bivariate correlation for statistical analysis using SPSS platform. Results: The study cohort had 60% (n = 119) male and 40% (n = 80) female patients of which 53% (n = 105) were Caucasians and 45% (n = 89) were African Americans. A total of 87 patients (44%) had negative tissue PD-L1, 59 patients (30%) had tissue PD-L1 ≥ 50%. A linear correlation was seen between negative tissue PD-L1 and negative blood PD-L1 in 92% of patients (n = 80). However, only 15.3% (n = 9) had correlating tissue PD-L1 and blood PD-L1 ≥ 50%, p = 0.024. The negative blood MSI correlated to low tissue TMB in 83% ( n = 60) whereas positive blood MSI correlated to high tissue TMB in 25% (n = 19), p = 0.023. Conclusions: Our results indicate a linear correlation between tissue PD-L1 and blood PD-L1. Similarly, a linear correlation was seen between blood MSI and tissue TMB. Further studies are needed to elucidate the efficacy of ICB therapy using blood MSI and blood PD-L1 as biomarkers for response to therapy.

scholarly journals Diagnostic and prognostic role of liquid biopsy in non-small cell lung cancer: evaluation of circulating biomarkers

2020 ◽  
Vol 1 (5) ◽  
Author(s):  
Giovanni Vicidomini ◽  
Roberto Cascone ◽  
Annalisa Carlucci ◽  
Alfonso Fiorelli ◽  
Marina Di Domenico ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Biological Fluids ◽  
Small Cell ◽  
Colorectal Cancers ◽  
Small Cell Lung ◽  
Neoplastic Tissue ◽  
Tissue Biopsy

Lung cancer is still one of the main causes of cancer-related death, together with prostate and colorectal cancers in males and breast and colorectal cancers in females. The prognosis for non-small cell lung cancer (NSCLC) is strictly dependent on feasibility of a complete surgical resection of the tumor at diagnosis. Since surgery is indicated only in early stages tumors, it is necessary to anticipate the timing of diagnosis in clinical practice. In the diagnostic and therapeutic pathway for NSCLC, sampling of neoplastic tissue is usually obtained using invasive methods that are not free from disadvantages and complications. A valid alternative to the standard biopsy is the liquid biopsy (LB), that is, the analysis of samples from peripheral blood, urine, and other biological fluids, with a simple and non-invasive collection. In particular, it is possible to detect in the blood different tumor derivatives, such as cell-free DNA (cfDNA) with its subtype circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), and circulating tumor cells (CTCs). Plasma-based testing seems to have several advantages over tumor tissue biopsy; firstly, it reduces medical costs, risk of complications related to invasive procedures, and turnaround times; moreover, the analysis of genes alteration, such as EGFR, ALK, ROS1, and BRAF is faster and safer with this method, compared to tissue biopsy. Despite all these advantages, the evidences in literatures indicate that assays performed on liquid biopsies have a low sensitivity, making them unsuitable for screening in lung cancer at the current state. This is caused by lack of standardization in sampling and preparation of specimen and by the low concentration of biomarkers in the bloodstream. Instead, routinely use of LB should be preferred in revaluation of patients with advanced NSCLC resistant to chemotherapy, due to onset of new mutations.

scholarly journals Liquid Biopsy for Biomarker Testing in Non-Small Cell Lung Cancer: A European Perspective

2021 ◽  
Vol 2 (3) ◽  
pp. 255-273
Author(s):  
Umberto Malapelle ◽  
Marcello Tiseo ◽  
Ana Vivancos ◽  
Joshua Kapp ◽  
M. Josè Serrano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Molecular Diagnosis ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Liquid Biopsy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tissue Biopsy ◽  
Biomarker Testing

The development of targeted therapies has improved survival rates for patients with advanced non-small cell lung cancer (NSCLC). However, tissue biopsy is unfeasible or inadequate in many patients, limiting biomarker testing and access to targeted therapies. The increasing numbers of established and emerging biomarkers with available targeted treatments highlights the challenges associated with sequential single-gene testing and limited tissue availability. Multiplex next-generation sequencing (NGS) offers an attractive alternative and represents a logical next step, and in cases where the tumour is inaccessible, tissue biopsy yields insufficient tumour content, or when the patient’s performance status does not allow a tissue biopsy, liquid biopsy can provide valuable material for molecular diagnosis. Here, we explore the role of liquid biopsy (i.e., circulating cell-free DNA analysis) in Europe. Liquid biopsies could be used as a complementary approach to increase rates of molecular diagnosis, with the ultimate aim of improving patient access to appropriate targeted therapies. Expert opinion is also provided on potential future applications of liquid biopsy in NSCLC, including for cancer prevention, detection of early stage and minimum residual disease, monitoring of response to therapy, selection of patients for immunotherapy, and monitoring of tumour evolution to enable optimal adaptation/combination of drug therapies.

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