scholarly journals Mutated circulating tumor DNA as a liquid biopsy in lung cancer detection and treatment

2021 ◽  
Author(s):  
Martyna Filipska ◽  
Rafael Rosell
Keyword(s):  
Lung Cancer ◽  
Cancer Detection ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Lung Cancer Detection ◽  
Tumor Dna

scholarly journals Liquid biopsy in NSCLC: a new challenge in radiation therapy

2021 ◽  
Author(s):  
Annarita Perillo ◽  
Mohamed Vincenzo Agbaje Olufemi ◽  
Jacopo De Robbio ◽  
Rossella Margherita Mancuso ◽  
Anna Roscigno ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Biological Fluids ◽  
Circulating Tumor Dna ◽  
Minimum Residual ◽  
Nsclc Patients ◽  
Choice Of Therapy ◽  
Tumor Dna

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. To date, tissue biopsy has been the gold standard for the diagnosis and the identification of specific molecular mutations, to guide choice of therapy. However, this procedure has several limitations. Liquid biopsy could represent a solution to the intrinsic limits of traditional biopsy. It can detect cancer markers such as circulating tumor DNA or RNA (ctDNA, ctRNA), and circulating tumor cells, in plasma, serum or other biological fluids. This procedure is minimally invasive, reproducible and can be used repeatedly. The main clinical applications of liquid biopsy in non-small cell lung cancer (NSCLC) patients are the early diagnosis, stratification of the risk of relapse, identification of mutations to guide application of targeted therapy and the evaluation of the minimum residual disease. In this review, the current role of liquid biopsy and associated markers in the management of NSCLC patients was analyzed, with emphasis on ctDNA and CTCs, and radiotherapy.

Concordance of next-generation sequencing between tissue and liquid biopsies in non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21547-e21547
Author(s):  
Fahmin Basher ◽  
Diana Saravia ◽  
Dino Fanfan ◽  
Jared Addison Cotta ◽  
Gilberto Lopes
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Liquid Biopsy ◽  
Median Number ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Dna ◽  
Generation Sequencing ◽  
Gene Alterations

e21547 Background: While genetic profiling has become standard of care for patients diagnosed with non-small cell lung cancer (NSCLC), next-generation sequencing (NGS) provides a wealth of information about targetable mutations. Advances in genetic testing have led to sequencing platforms that utilize tissue itself or extracellular circulating tumor DNA in the blood, known as a “liquid biopsy.” Methods: We identified 55 patients with NSCLC who had undergone both tissue and liquid biopsy, using Foundation One and Guardant 360 at the University of Miami / Sylvester Comprehensive Cancer Center between January 2016 and December 2018, and performed retrospective analysis to determine patient characteristics as well concordance between different NGS platforms. Results: In our patient population, 34% of patients had never smoked prior to diagnosis, while 22% had more than a 30 pack-year smoking history. 64% of patients had no treatment prior to initial NGS. 40% of patients had both testing done essentially simultaneously, while 60% of patients had one test done after disease progression. Of these patients, therapy was changed as a result in 73%. Median number of days between tests was 21 days, with 56% of testing done within 90 days of the previous testing. Nine patients had an additional Foundation One tissue NGS performed. Concordance across all genes tested in both platforms was 98 ± 0.2%. Concordance with consideration of genetic alterations detected in both assays was 24.5 ± 3.0%. The median number of gene alterations determined by Foundation One testing was 4 (range 1-9), while the median for gene alterations detected by Guardant 360 was 3 (range 1-13). The median number of variants of unknown significance (VUS) was 10 (range 5-25). Conclusions: Our analysis indicates a role for both tissue-based and circulating tumor DNA-based NGS for determination of targetable mutations and thus appropriate treatment regimens. Low levels of concordance are potentially related to post-treatment changes in the tumor genetic profile as well as evolution in the testing itself.

NGS to reveal heterogeneity between cerebrospinal fluid and plasma ctDNA among non-small cell lung cancer patients with leptomeningeal carcinomatosis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9022-9022 ◽  
Author(s):  
Ben-Yuan Jiang ◽  
Yangsi LI ◽  
Shaokun Chuai ◽  
Zhou Zhang ◽  
Jin-Ji Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cerebrospinal Fluid ◽  
Small Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Leptomeningeal Carcinomatosis ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Tumor Dna

9022 Background: In current clinical setting, NSCLC patients harboring specific driver mutation were usually treated guiding by prior profiling of the primary tumor when developed to brain metastasis. Some studies have shown that circulating tumor DNA (ctDNA) derived from cerebrospinal fluid (CSF) can reveal unique genomic alterations present in brain malignancies. We assessed CSF as a liquid biopsy media and compared to matched plasma. Methods: We performed capture-based ultra deep sequencing on ctDNA derived from matched CSF, plasma of 40 non-small cell lung cancer (NSCLC) patients with suspected leptomeningeal carcinomatosis (LC) using a panel consisting of 168 genes. Results: Among the 40 suspected LC cases, 35 were confirmed to have LC, ctDNA in CSF from the 5 non-LC cases are all undetectable. Circulating tumor DNA was detected in 93.8% of CSF and 66.7% of plasma. We compared mutation profiles and identified 86 and 46 SNVs from CSF and plasma, respectively, with 42 SNVs overlapping. Furthermore, ctDNA from CSF revealed many copy number variations (CNVs) that were not detected from plasma (189 CNVs vs. 3 CNVs). The average maximum allelic fraction (AF) of CSF ctDNA is significantly higher than in plasma (56.7% vs. 4.4% p < 10^-6). Twenty-eight patients were pre-treated with EGFR-TKIs and developed subsequent resistance. EGFR T790M and MET amplification were detected in 21% and 39% in CSF, respectively, showing a unique resistance profile among leptomeningeal metastases patients compared to the general population. Interestingly, 60% of CSF samples harbor TP53 loss of heterozygosity, only 11% of which were detected in the matched plasma samples. Such heterogeneity may reflect unique biological themes for brain metastatic tumor sub-clones. Furthermore, 26 patients received molecular targeted therapy based on the results from CSF, and 23 reported alleviation of symptoms at subsequent evaluations. Conclusions: Collectively, our data reveal that ctDNA derived from CSF provides a unique and more comprehensive characterization of genomic alterations of leptomeningeal carcinomatosis than plasma, supporting the importance of CSF as a liquid biopsy media.

scholarly journals Emerging Role of microRNAs as Liquid Biopsy Biomarkers in Lung Cancer: A Review

2021 ◽  
Author(s):  
Moslem Bahadori ◽  
Shahriar Dabiri ◽  
Mohammad Hossein Azizi ◽  
Neda Bahadori
Keyword(s):  
Lung Cancer ◽  
Cancer Detection ◽  
Liquid Biopsy ◽  
Poor Prognosis ◽  
Circulating Micrornas ◽  
Lung Cancers ◽  
Disease Outcomes ◽  
Cancerous Cells ◽  
Lung Cancer Detection

The emergence of patient-tailored medicine has changed all measurable disease outcomes. Among human diseases, cancers appear to be the most dangerous. Furthermore, lung cancers rank the first among human cancers in both morbidity and mortality. When lung cancer is clinically diagnosed, it is often too late for therapy. The absence of accurate and specific tools for early detection results in a poor prognosis for lung cancer. The discovery of microRNAs and their function in lung cancer offers a new mechanism for the detection of lung cancer cells. These molecules, derived from cancerous cells, circulate in the patient's blood. Recently, a revolutionary technique, i.e., liquid biopsy has shown promise in discovering these circulating microRNAs molecules in body fluids, namely peripheral blood. A liquid biopsy allows the detection and isolation of circulating tumor cells, circulating nucleotides, and cellular exosome as a source of genomic and proteomic information in cancerous patients, especially in the early stages of cancer cell development. In this review, by searching various databases, including PubMed, Google Scholar, and Scopus, we explore liquid biopsy as a novel tool and the application of miRNAs in lung cancer detection in diagnostic pathology.  

scholarly journals Application of Circulating Tumor DNA as a Biomarker for Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jialiang Yang ◽  
Yan Hui ◽  
Yanxiang Zhang ◽  
Minghui Zhang ◽  
Binbin Ji ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Clinical Applications ◽  
Small Cell ◽  
Molecular Testing ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Tumor Dna

BackgroundNon-small cell lung cancer (NSCLC) is one of the most prevalent causes of cancer-related death worldwide. Recently, there are many important medical advancements on NSCLC, such as therapies based on tyrosine kinase inhibitors and immune checkpoint inhibitors. Most of these therapies require tumor molecular testing for selecting patients who would benefit most from them. As invasive biopsy is highly risky, NSCLC molecular testing based on liquid biopsy has received more and more attention recently.ObjectiveWe aimed to introduce liquid biopsy and its potential clinical applications in NSCLC patients, including cancer diagnosis, treatment plan prioritization, minimal residual disease detection, and dynamic monitoring on the response to cancer treatment.MethodWe reviewed recent studies on circulating tumor DNA (ctDNA) testing, which is a minimally invasive approach to identify the presence of tumor-related mutations. In addition, we evaluated potential clinical applications of ctDNA as blood biomarkers for advanced NSCLC patients.ResultsMost studies have indicated that ctDNA testing is critical in diagnosing NSCLC, predicting clinical outcomes, monitoring response to targeted therapies and immunotherapies, and detecting cancer recurrence. Moreover, the changes of ctDNA levels are associated with tumor mutation burden and cancer progression.ConclusionThe ctDNA testing is promising in guiding the therapies on NSCLC patients.

scholarly journals Plasma circulating tumor DNA-based genetic profiling of lung cancer patients in Vietnam using ultra-deep massive parallel sequencing with unique identifier tagging.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 58-58
Author(s):  
Huy Phuoc Do ◽  
Thao Thanh Tran Nguyen ◽  
Uyen Vu Tran ◽  
Thanh-Truong Tran ◽  
Anh-Thu Huynh Dang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Circulating Tumor Dna ◽  
Massive Parallel Sequencing ◽  
Driver Mutations ◽  
Unique Identifier ◽  
Parallel Sequencing ◽  
Cancer Driver ◽  
Lung Cancer Patients ◽  
Tumor Dna

58 Background: Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Genotype-directed therapy becomes a promising method for cancer treatment beside surgery and chemo-radiotherapy. Liquid biopsy using massive parallel sequencing has emerged as a non-invasive alternative procedure in profiling cancer driver mutations. In this study, we report the spectrum of clinically actionable mutations in plasma circulating tumor DNA of 299 non-small cell lung cancer patients using ultra-deep massive parallel sequencing with unique identifier tagging. Methods: Plasma circulating tumor DNA was extracted, ligated with unique identifier (Swift Bioscience), enriched of the target coding regions of EGFR, KRAS, NRAS, BRAF and the breakpoints of ALK, ROS1 (IDT) and sequenced using NextSeq 550 (Illumina) at mean coverage depth of 20,000X. Results: Out of 299 patients tested, 128 (42,8%) carried driver mutations. Genetic alterations were identified in EGFR (79 samples, 26,4%), KRAS (30 samples, 10%), ALK (7 samples, 2,34%), ROS1 (6 samples, 2%), BRAF (3 samples, 1%). There was no sample with NRAS mutation. In 79 EGFR-cases, there were 23 carry two pathogenic variants. 28 mutation types of EGFR were found including 19 indels and 9 missense variants L858R and T790M were the major ones. One case was found with concomitant EGFR and BRAF. Our study showed the spectrum and frequency of the cancer driver mutations detected in liquid biopsy was correlated to those detected in tissue biopsy samples. Conclusions: For the first time the spectrum of mutation types in liquid biopsy of Vietnamese NSCLC patients were investigated and showed the correlation with those detected in tissue biopsy samples.

Detection of low abundant mutants from circulating tumor DNA of plasma, pleural effusion, and cerebrospinal fluid of lung cancer patients using a novel mutant-capture enrichment approach.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14520-e14520
Author(s):  
Rui Lin ◽  
Yue Pu ◽  
Li Mao
Keyword(s):  
Lung Cancer ◽  
Cerebrospinal Fluid ◽  
Pleural Effusion ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
High Sensitivity ◽  
Circulating Tumor Dna ◽  
Lung Cancer Patients ◽  
Egfr Tki ◽  
Tumor Dna

e14520 Background: In the era of precision medicine, liquid biopsy analysis is well accepted based on advantages including availability, non-invasiveness, and non-heterogeneity. However, the circulating tumor DNA (ctDNA) in liquid biopsy is diluted by a large excess of wild-type alleles, which necessitates high sensitivity approach for ctDNA detection. In addition, ctDNA analysis from different liquid biopsy samples need to be evaluated. Methods: We have developed a novel mutant-capture based method, termed PErsonalized Analysis of Cancer (PEAC), for high sensitivity detection of cancer driver mutants at abundance as low as 0.01-0.1% for circulating free DNA (cfDNA) standards. ctDNA samples were extracted from body fluids of lung cancer patients including plasma, pleural effusion and cerebrospinal fluid. EGFR mutants predictive of EGFR tyrosine kinase activity were enriched using PEAC technology, and analyzed using Sanger sequencing. Results: Plasma ctDNA samples B7110003, B7110010, and B7112012 had no or barely detectable L858R mutation, which was enriched to 50-90% after PEAC and readily detected by Sanger. T790M was undetectable before PEAC in plasma sample B7112052 and became 50% after PEAC enrichment. Pleural effusion samples E8106029 and E8111305 had dominated L858R and T790M peaks, respectively, in Sanger chromatograms after PEAC, which was almost to the background levels prior to PEAC. Interestingly, both EGFR L858R and T790M mutants were detected in pleural effusion sample E8106029 after PEAC; the sample was from a patient who had previously treated with an EGFR tyrosine kinase inhibitor (TKI), suggestive of resistance developed after target therapy and the utility of PEAC in monitoring patient’s response to EGFR TKI. In addition to enriching point mutations, we also established enrichment of the most frequently occurred EGFR 19 deletion, E746_A750del (c. 2235_2249 del15), which were dominant after PEAC enrichment of ctDNA from plasma samples (B8101186 and B8101241), pleural effusion (E8108088) and cerebrospinal fluid (C8108095); the mutants were undetectable without PEAC enrichment. Conclusions: PEAC technology can enrich ctDNA from body fluids in lung cancer patients and allow detection of low abundant mutants predictive for EGFR TKI therapy. With further validation, the technology may improve current detection methods used in clinical practice.

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