Cell-free DNA from cerebrospinal fluid can be used to detect the EGFR mutation status of lung adenocarcinoma patients with central nervous system metastasis

Purpose Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue. Materials and Methods We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer. Results We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. Conclusion The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.

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P2.01-66 Comparison of EGFR Mutation Status in Tissue and Plasma Cell-Free DNA Detected by ARMS in Advanced Lung Adenocarcinoma Patients

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.1120 ◽

2018 ◽

Vol 13 (10) ◽

pp. S690-S691

Author(s):

Y. Li ◽

H. Xu ◽

S. Su ◽

J. Ye ◽

C. Chen

Keyword(s):

Lung Adenocarcinoma ◽

Plasma Cell ◽

Egfr Mutation ◽

Cell Free Dna ◽

Mutation Status ◽

Free Dna

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A comparison of EGFR mutation status in tissue and plasma cell-free DNA detected by ADx-ARMS in advanced lung adenocarcinoma patients

Translational Lung Cancer Research ◽

10.21037/tlcr.2019.03.10 ◽

2019 ◽

Vol 8 (2) ◽

pp. 135-143 ◽

Cited By ~ 4

Author(s):

Hanyan Xu ◽

◽

Adam Abdul Hakeem Baidoo ◽

Shanshan Su ◽

Junru Ye ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Plasma Cell ◽

Egfr Mutation ◽

Cell Free Dna ◽

Mutation Status ◽

Free Dna

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PATH-27. MUTATION DETECTION USING PLASMA CELL-FREE DNA IN CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.662 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii430-iii430

Author(s):

Ross Mangum ◽

Jacquelyn Reuther ◽

Koel Sen Baksi ◽

Ryan C Zabriskie ◽

Ilavarasi Gandhi ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Plasma Cell ◽

Pediatric Patients ◽

Cns Tumors ◽

Cell Free Dna ◽

Pilot Studies ◽

Dna And Rna ◽

Free Dna ◽

Initial Cohort

Abstract BACKGROUND The role of plasma cell-free DNA (cfDNA) as a cancer biomarker for tracking treatment response and detecting early relapse has been well described for solid tumors outside the central nervous system (CNS). However, the presence of a blood-brain barrier complicates the application of plasma cfDNA analysis for patients with CNS malignancies. METHODS cfDNA was extracted from plasma of pediatric patients with CNS tumors utilizing a QIAmp® MinElute® kit and quantitated with Qubit 2.0 Fluorometer. Extensive genomic testing, including targeted DNA and RNA solid tumor panels, exome and transcriptome sequencing, as well as copy number array, was performed on matched tumor samples as part of the Texas KidsCanSeq study. An Archer® Reveal ctDNA28 NGS kit was then used for assaying the sensitivity of detecting tumor-specific mutations in the plasma of these patients. RESULTS A median of 10.7ng cfDNA/mL plasma (Interquartile range: 6.4 – 15.3) was extracted from 78 patients at time of study enrollment. Longitudinal samples from 24 patients exhibited a median yield of 7.7ng cfDNA/mL plasma (IQR: 5.9 – 9.1). An initial cohort of 6 patients was identified with 7 somatic variants covered by the Archer® Reveal kit. Four of seven mutations identified in matched tumor specimens were detected in patient plasma at variant allele frequencies ranging from 0.2–1%. CONCLUSIONS While challenging, detection of cfDNA in the plasma of pediatric patients with CNS tumors is possible and is being explored in a larger patient cohort along with pilot studies investigating cerebrospinal fluid as an additional source for tumor-specific cfDNA.

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EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6

British Journal of Cancer ◽

10.1038/bjc.2016.420 ◽

2016 ◽

Vol 116 (2) ◽

pp. 175-185 ◽

Cited By ~ 37

Author(s):

Yi-Long Wu ◽

Lecia V Sequist ◽

Cheng-Ping Hu ◽

Jifeng Feng ◽

Shun Lu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Mutation Detection ◽

Egfr Mutation ◽

Cell Free Dna ◽

Free Dna ◽

Circulating Cell Free Dna

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Cerebrospinal fluid as a medium of liquid biopsy in the management of patients with non-small-cell lung cancer having central nervous system metastasis

Frontiers in Bioscience-Landmark ◽

10.52586/5060 ◽

2021 ◽

Vol 26 (12) ◽

pp. 1679-1688

Author(s):

Chi-Lu Chiang ◽

Hsu-Ching Huang ◽

Yung-Hung Luo ◽

Chao-Hua Chiu

Keyword(s):

Lung Cancer ◽

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Small Cell ◽

Central Nervous System Metastasis ◽

Small Cell Lung

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CONCORDANCE study: An observational, multicenter, prospective study to evaluate concordance of detecting EGFR mutations by circulating tumor-free DNA versus tissues biopsy in NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21615 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21615-e21615

Author(s):

Kumar Prabhash ◽

Bivas Biswas ◽

Sachin Khurana ◽

Ullas Batra ◽

Ghanashyam Biswas ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Real World ◽

Egfr Mutation ◽

Tissue Sample ◽

Primary Objective ◽

Egfr Mutations ◽

Newly Diagnosed ◽

Mutation Status ◽

Free Dna ◽

Sample Testing

e21615 Background: Epidermal growth factor receptor (EGFR) mutations on circulating tumour free DNA (ctDNA) by liquid biopsy is suitable option in those with difficulty in obtaining tissue samples. Correlation in tissue and plasma results of EFGRm has not been established in the Indian population. 1,2,3 This study was done to investigate the utility of ctDNA for EGFRm testing with Next-Generation Sequencing (NGS) in a real-world diagnostic setting. Methods: This is a multicentre, prospective, diagnostic observational study in 245 newly diagnosed treatment naïve, histologically confirmed, advanced lung adenocarcinoma patients. This was a single visit study. The primary objective of the study was to determine the level of concordance between EGFR mutation status obtained by tissue and ctDNA from blood (plasma) based testing in terms of overall concordance, sensitivity & specificity. Study was registered at Clinicaltrials.gov NCT03562819 & CTRI/2018/08/015290. Results: Seventy-five (30.6%) and eighty-four (34.3%) subjects showed positive mutation status by plasma & tissue testing respectively. The overall concordance of 82.9% was observed between tissue and ctDNA (Plasma) based testing. Sensitivity of EGFR mutation status between ctDNA and tissue was observed for EGFR mutation subtypes was observed to be 100% while specificity was observed to be 90.1%. Plasma and tissue sample testing detected 1.2% (n = 3) and 2.4% (n = 6) positive in exon 20 T790M EGFR mutation, respectively. In terms of secondary outcomes, plasma sample testing detected 16.7% (n = 41) positive for Exon 19 deletions type EGFR mutation followed Exon 21 L858R [11.4% (n = 28)]. Conclusions: CONCORDANCE, a real-world study in Indian patients suggest that ctDNA testing for EGFR mutation analysis is a diagnostic option in newly diagnosed lung adenocarcinoma patients. EGFR Mutation testing in ctDNA, being non-invasive and especially in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies. [Table: see text]

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