Circulating Tumor DNA in Non–Small-Cell Lung Cancer: A Primer for the Clinician

2017 ◽  
pp. 1-13 ◽  
Author(s):  
Aditi P. Singh ◽  
Haiying Cheng ◽  
Xiaoling Guo ◽  
Benjamin Levy ◽  
Balazs Halmos
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) consists of short, double-stranded DNA fragments that are released into the circulation by tumor cells. With the advent of newer molecular platforms, ctDNA can be detected with high sensitivity and specificity in plasma. The assay’s noninvasive nature, ability to reflect intratumoral heterogeneity, short turnaround time, and ability to obtain serial samples make it an attractive option compared with traditional tissue biopsy tumor sequencing. Currently, this technology is mostly being used for the detection of EGFR mutations in patients with advanced non–small-cell lung cancer where tissue is inadequate to detect EGFR mutations that drive acquired resistance, most notably EGFR T790M. Emerging uses include the incorporation of ctDNA testing into primary diagnosis, treatment monitoring, detection of minimal residual disease, and detection of early-stage disease in screening populations. This review summarizes both validated and evolving uses of ctDNA testing in non–small-cell lung cancer in the context of oncologists’ daily practice and some of its potential challenges in the era of targeted therapy and immunotherapy.

scholarly journals An Improved Detection of Circulating Tumor DNA in Extracellular Vesicles-Depleted Plasma

2021 ◽  
Vol 11 ◽  
Author(s):  
Li Sun ◽  
Meijun Du ◽  
Manish Kohli ◽  
Chiang-Ching Huang ◽  
Xiaoxiang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Extracellular Vesicles ◽  
Cell Lung Cancer ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Small Cell Lung ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) in plasma has been used as a biomarker for cancer detection and outcome prediction. In this study, we collected the five precipitates (fractions 1–5) and leftover supernatant plasma component (fraction 6) by a sequential centrifugation in plasma samples from nine small cell lung cancer (SCLC) patients. The fractions 3, 5 and 6 were large vesicles, exosomes and extracellular vesicles (EVs)-depleted plasma, respectively. Fragment size analysis using DNAs from these fractions showed dramatical differences from a peak of 7–10 kb in fraction 1 to 140–160 bp in fraction 6. To determine ctDNA content, we performed whole genome sequencing and applied copy number-based algorithm to calculate ctDNA percentage. This analysis showed the highest ctDNA content in EV-depleted plasma (average = 27.22%), followed by exosomes (average = 22.09%) and large vesicles (average = 19.70%). Comparatively, whole plasma, which has been used in most ctDNA studies, showed an average of 23.84% ctDNA content in the same group of patients. To further demonstrate higher ctDNA content in fraction 6, we performed mutational analysis in the plasma samples from 22 non-small cell lung cancer (NSCLC) patients with known EGFR mutations. This analysis confirmed higher mutation detection rates in fraction 6 (14/22) than whole plasma (10/22). This study provides a new insight into potential application of using fractionated plasma for an improved ctDNA detection.

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

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.

Circulating Tumor DNA Minimal Residual Disease Detection of Non–Small-Cell Lung Cancer Treated With Curative Intent

2022 ◽  
Author(s):  
Bruna Pellini ◽  
Aadel A. Chaudhuri
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Post Treatment ◽  
Small Cell Lung ◽  
Curative Intent ◽  
Tumor Dna ◽  
Minimal Residual

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) is a powerful biomarker with the potential to improve survival outcomes for non–small-cell lung cancer (NSCLC). Multiple groups have shown the ability to detect MRD following curative-intent NSCLC treatment using next-generation sequencing–based assays of plasma cell-free DNA. These studies have been modest in size, largely retrospective, and without thorough prospective clinical validation. Still, when restricting measurement to the first post-treatment timepoint to assess the clinical performance of ctDNA MRD detection, they have demonstrated sensitivity for predicting disease relapse ranging between 36% and 100%, and specificity ranging between 71% and 100%. When considering all post-treatment follow-up timepoints (surveillance), including those beyond the initial post-treatment measurement, these assays' performances improve with sensitivity and specificity for identifying relapse ranging from 82% to 100% and 70% to 100%, respectively. In this manuscript, we review the evidence available to date regarding ctDNA MRD detection in patients with NSCLC undergoing curative-intent treatment and the ongoing prospective studies involving ctDNA MRD detection in this patient population.

scholarly journals P3.04-11 The Influence of Circulating Tumor DNA Analysis on Response to Immunotherapy in Non-Small Cell Lung Cancer (NSCLC)

2018 ◽  
Vol 13 (10) ◽  
pp. S925-S926
Author(s):  
R. Grinberg ◽  
L. Roisman ◽  
S. Geva ◽  
M. Lefterova ◽  
K. Quinn ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Dna Analysis ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Dna
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