Comprehensive circulating tumor DNA profiling of driver genes in Chinese NSCLC patients.

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.

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Genotyping of circulating tumor DNA in cholangiocarcinoma reveals diagnostic and prognostic information

Scientific Reports ◽

10.1038/s41598-019-49860-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 9

Author(s):

T. J. Ettrich ◽

D. Schwerdel ◽

A. Dolnik ◽

F. Beuter ◽

T. J. Blätte ◽

...

Keyword(s):

Deep Sequencing ◽

Tumor Tissue ◽

Circulating Tumor Dna ◽

Therapeutic Strategies ◽

Variant Allele Frequency ◽

Prognostic Information ◽

Driver Genes ◽

Tumor Load ◽

Molecular Landscape ◽

Tumor Dna

Abstract Diagnosis of Cholangiocarcinoma (CCA) is difficult, thus a noninvasive approach towards (i) assessing and (ii) monitoring the tumor-specific mutational profile is desirable to improve diagnosis and tailor treatment. Tumor tissue and corresponding ctDNA samples were collected from patients with CCA prior to and during chemotherapy and were subjected to deep sequencing of 15 genes frequently mutated in CCA. A set of ctDNA samples was also submitted for 710 gene oncopanel sequencing to identify progression signatures. The blood/tissue concordance was 74% overall and 92% for intrahepatic tumors only. Variant allele frequency (VAF) in ctDNA correlated with tumor load and in the group of intrahepatic CCA with PFS. 63% of therapy naive patients had their mutational profile changed during chemotherapy. A set of 76 potential progression driver genes was identified among 710 candidates. The molecular landscape of CCA is accessible via ctDNA. This could be helpful to facilitate diagnosis and personalize and adapt therapeutic strategies.

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Abstract 2997: Longitudinal circulating tumor DNA (ctDNA) analysis predicts response and reveals the resistance mechanisms of ensartinib in ALK+ NSCLC patients (pts) progressed on crizotinib: Updated analysis of a phase II clinical trial

10.1158/1538-7445.am2020-2997 ◽

2020 ◽

Author(s):

Yunpeng Yang ◽

Jie Huang ◽

Tao Wang ◽

Jianya Zhou ◽

Jing Zheng ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Circulating Tumor Dna ◽

Resistance Mechanisms ◽

Phase Ii Clinical Trial ◽

Ctdna Analysis ◽

Nsclc Patients ◽

Tumor Dna

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Abstract 1349: Personalized circulating tumor DNA profiling in malignant pleural mesothelioma

10.1158/1538-7445.sabcs18-1349 ◽

2019 ◽

Author(s):

Luke J. Martinson ◽

Annabel J. Sharkey ◽

Alan G. Dawson ◽

Robert K. Hastings ◽

Gareth Wilson ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Circulating Tumor Dna ◽

Dna Profiling ◽

Pleural Mesothelioma ◽

Tumor Dna

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Assessment of EGFR mutation status in matched plasma and tumor tissue of NSCLC patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20032 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20032-e20032

Author(s):

Qin Feng

Keyword(s):

Tumor Tissue ◽

Egfr Mutation ◽

Circulating Tumor Dna ◽

Egfr Mutations ◽

Amplification Refractory Mutation System ◽

Circulating Dna ◽

Mutation Status ◽

Nsclc Patients ◽

Tumor Dna ◽

Egfr Tkis

e20032 Background: Tumor tissue is currently used for EGFR testing non-small cell lung cancer (NSCLC) patients, but the detection of circulating tumor DNA (ctDNA) is being actively investigated as a new method for the detection and longitudinal monitoring of actionable mutations in plasma samples. Around 30% patients with EGFR mutation presented inconsistent status of EGFR mutation between in tissues and plasma. We compared EGFR mutation detection in circulating tumor DNA from blood to that in matched tissue. Methods: EGFR mutation status were assessed by the Human EGFR Gene Mutations Detection Kit (Beijing ACCB Biotech Ltd.) both in tissue and plasma. Retrospective analysis to evaluate the concordance of tissue and plasma EGFR determination for assessing eligibility for EGFR-TKIs therapy in NSCLC patients. 10 mL tubes of blood were collected from patients who never had been treated by EGFR TKI, and plasma circulating tumor DNA were extracted from plasma by Biomark Circulating DNA Kit. Qubit2.0 Fluorometer was used to make plasma circulating DNA tumor quantitation. The concentration of final DNA sample is ≦2ng/μl. Results: A total of 224 NSCLC patients were detected by Amplification Refractory Mutation System (ARMS), with 92 tissue positive and 49 blood positive. Results showed 53.3% sensitivity in overall samples, but 81.4% sensitivity in ⅢB~Ⅲ patients. The specificity is 100%. Conclusions: The high sensitivity and specificity between tissue and plasma EGFR determination supports the blood-based EGFR mutation testing to determinate the eligibility of NSCLC patients for EGFR-TKIs treatment, especialy in ⅢB~Ⅲ NSCLC patients. Blood, in particular plasma, is a good screening substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the blood negativity should be confirmed with other sample, biopsy tissue, pleural effusion, etc..

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