Performance evaluation of a fully closed real-time PCR platform for the detection of KRAS p.G12C mutations in liquid biopsy of patients with non-small cell lung cancer

Whenever tissue sample is not available, non-small cell lung cancer (NSCLC) biomarker testing is performed with liquid biopsy. The Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is a novel target in patients with NSCLC. In this study, 33 NSCLC frozen plasma samples, previously characterised for KRAS mutational status by next generation sequencing (NGS), were processed by the fully automated Idylla KRAS assay. In 30/33 cases, archival matched cell-free DNA (cfDNA) was also directly pipetted in the cartridge. Overall, 30/33 plasma and 28/30 cfDNA samples yielded valid results. In 29/30 of KRAS p.G12C mutant plasma samples and 26/28 of cfDNA, Idylla confirmed the NGS results. In conclusion, the Idylla NSCLC KRAS liquid biopsy assay may represent a reliable tool to assess KRAS p.G12C mutation.

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Role of liquid biopsy for thoracic cancers immunotherapy

Exploration of Targeted Anti-tumor Therapy ◽

10.37349/etat.2020.00012 ◽

2020 ◽

Vol 1 (3) ◽

pp. 183-199

Author(s):

Raimondo Di Liello ◽

Flora Cimmino ◽

Soraya Simón ◽

Emilio Francesco Giunta ◽

Vincenzo De Falco ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Residual Disease ◽

Tissue Sample ◽

Small Cell ◽

Response To Treatment ◽

Small Cell Lung ◽

Cancer Breast

Immunotherapy has shifted the therapeutic landscape in thoracic cancers. However, assessment of biomarkers for patient selection and disease monitoring remain challenging, especially considering the lack of tissue sample availability for clinical and research purposes. In this scenario, liquid biopsy (LB), defined as the study and characterization of biomarkers in body fluids, represents a useful alternative strategy. In other malignancies such as colorectal cancer, breast cancer or melanoma, the potential of LB has been more extensively explored for monitoring minimal residual disease or response to treatment, and to investigate mechanisms of resistance to targeted agents. Even if various experiences have already been published about the applications of LB in immunotherapy in thoracic cancers, the standardization of methodology and assessment of its clinical utility is still pending. In this review, the authors will focus on the applications of LB in immunotherapy in non-small cell lung cancer, small cell lung cancer, and malignant pleural mesothelioma, describing available data and future perspectives.

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Landmark Studies of Targeted Therapies for Advanced Non-Small Cell Lung Cancer: A Guide for Pulmonologists

Current Respiratory Medicine Reviews ◽

10.2174/1573398x16666200319134739 ◽

2020 ◽

Vol 16 (1) ◽

pp. 5-10

Author(s):

Adrien Costantini ◽

Theodoros Katsikas ◽

Clementine Bostantzoglou

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Standard Of Care ◽

Genetic Alterations ◽

Small Cell ◽

Extensive Literature ◽

Small Cell Lung ◽

Anaplastic Lymphoma ◽

Mutational Status

Over the past decade, major breakthroughs in the understanding of lung cancer histology and mutational pathways have radically changed diagnosis and management. More specifically, in non-small cell lung cancer (NSCLC), tumour characterisation has shifted from differentiating based solely on histology to characterisation that includes genetic profiling and mutational status of Epidermal Growth Factor (EGFR), Anaplastic Lymphoma Kinase (ALK), c-ros oncogene 1 (ROS1) and BRAF. These genetic alterations can be targeted by specific drugs that result in improved progression-free survival, as well as higher response rates and are currently standard of care for NSCLC patients harbouring these mutations. In this a narrative, non-systematic review we aim to handpick through the extensive literature and critically present the ground-breaking studies that lead to the institution of tailored treatment options as the standard of care for the main targetable genetic alterations.

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Liquid Biopsy for Small Cell Lung Cancer either De Novo or Transformed: Systematic Review of Different Applications and Meta-Analysis

Cancers ◽

10.3390/cancers13092265 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2265

Author(s):

Elio Gregory Pizzutilo ◽

Martino Pedrani ◽

Alessio Amatu ◽

Lorenzo Ruggieri ◽

Calogero Lauricella ◽

...

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

De Novo ◽

Meta Analysis ◽

Small Cell ◽

Genomic Profiling ◽

Small Cell Lung

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

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Use of Liquid Biopsy in the Care of Patients with Non-Small Cell Lung Cancer

Current Treatment Options in Oncology ◽

10.1007/s11864-021-00882-9 ◽

2021 ◽

Vol 22 (10) ◽

Cited By ~ 1

Author(s):

Atocha Romero ◽

Roberto Serna-Blasco ◽

Virginia Calvo ◽

Mariano Provencio

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Small Cell ◽

Small Cell Lung

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Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

Biomedicines ◽

10.3390/biomedicines9010048 ◽

2021 ◽

Vol 9 (1) ◽

pp. 48

Author(s):

Patricia Mondelo-Macía ◽

Jorge García-González ◽

Luis León-Mateos ◽

Adrián Castillo-García ◽

Rafael López-López ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Small Cell ◽

New Drugs ◽

Current Status ◽

Small Cell Lung ◽

Tumor Biopsy ◽

Future Utility

Approximately 19% of all cancer-related deaths are due to lung cancer, which is the leading cause of mortality worldwide. Small cell lung cancer (SCLC) affects approximately 15% of patients diagnosed with lung cancer. SCLC is characterized by aggressiveness; the majority of SCLC patients present with metastatic disease, and less than 5% of patients are alive at 5 years. The gold standard of SCLC treatment is platinum and etoposide-based chemotherapy; however, its effects are short. In recent years, treatment for SCLC has changed; new drugs have been approved, and new biomarkers are needed for treatment selection. Liquid biopsy is a non-invasive, rapid, repeated and alternative tool to the traditional tumor biopsy that could allow the most personalized medicine into the management of SCLC patients. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the most commonly used liquid biopsy biomarkers. Some studies have reported the prognostic factors of CTCs and cfDNA in SCLC patients, independent of the stage. In this review, we summarize the recent SCLC studies of CTCs, cfDNA and other liquid biopsy biomarkers, and we discuss the future utility of liquid biopsy in the clinical management of SCLC.

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Pan-cancer circulating tumor DNA detection in over 10,000 Chinese patients

Nature Communications ◽

10.1038/s41467-020-20162-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yongliang Zhang ◽

Yu Yao ◽

Yaping Xu ◽

Lifeng Li ◽

Yan Gong ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Circulating Tumor Dna ◽

Small Cell ◽

Chinese Patients ◽

Plasma Samples ◽

Small Cell Lung ◽

Pan Cancer ◽

Tumor Dna

AbstractCirculating tumor DNA (ctDNA) provides a noninvasive approach to elucidate a patient’s genomic landscape and actionable information. Here, we design a ctDNA-based study of over 10,000 pan-cancer Chinese patients. Using parallel sequencing between plasma and white blood cells, 14% of plasma cell-free DNA samples contain clonal hematopoiesis (CH) variants, for which detectability increases with age. After eliminating CH variants, ctDNA is detected in 73.5% of plasma samples, with small cell lung cancer (91.1%) and prostate cancer (87.9%) showing the highest detectability. The landscape of putative driver genes revealed by ctDNA profiling is similar to that in a tissue-based database (R2 = 0.87, p < 0.001) but also shows some discrepancies, such as higher EGFR (44.8% versus 25.2%) and lower KRAS (6.8% versus 27.2%) frequencies in non-small cell lung cancer, and a higher TP53 frequency in hepatocellular carcinoma (53.1% versus 28.6%). Up to 41.2% of plasma samples harbor drug-sensitive alterations. These findings may be helpful for identifying therapeutic targets and combined treatment strategies.

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

Cancers ◽

10.3390/cancers13081794 ◽

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.

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