eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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6/2020
vol. 16
 
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Pulmonology
abstract:
Letter to the Editor

Assessment of EGFR gene mutations in circulating free DNA in monitoring of response to EGFR tyrosine kinase inhibitors in patients with lung adenocarcinoma

Marcin Nicoś
1, 2
,
Kamila Wojas-Krawczyk
1, 3
,
Paweł Krawczyk
1, 4
,
Izabela Chmielewska
1
,
Magdalena Wojcik-Superczyńska
1
,
Katarzyna Reszka
3, 5
,
Robert Kieszko
1
,
Anna Góra-Florek
6
,
Małgorzata Dudek
6
,
Daria Świniuch
7
,
Wojciech Papiewski
8
,
Paulina Całka
9
,
Marzanna Ciesielka
9
,
Rodryg Ramlau
7
,
Janusz Milanowski
1

1.
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Poland
2.
Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
3.
Lublin Foundation for Cancer Patients “JestemnaTak”, Poland
4.
Polish Society of Clinical Oncology, Warsaw, Poland
5.
GENIM LCC, Institute of Genetics and Immunology, Lublin, Poland
6.
Independent Public Provincial Hospital named Jan Boży in Lublin, Poland
7.
Department of Oncology, Poznan University of Medical Science, Poznan, Poland
8.
Department of Pulmonology and Pulmonary Oncology of Mazovian Specialist Hospital in Radom, Radom, Poland
9.
Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland
Arch Med Sci 2020; 16 (6): 1496–1500
Online publish date: 2019/11/03
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The presence of EGFR mutations in non-small cell lung cancer (NSCLC) patients is commonly evaluated in tissue material (surgery/biopsy) that may not be both representative of the overall genetic profile, especially for patients with heterogeneous cancer or distant metastases, and sufficient to perform a reliable genetic test (e.g. low tumor cell content). Therefore, a promising alternative in the analysis of EGFR profile is circulating free DNA (cf-DNA) that is released into peripheral blood from both normal and tumor cells that have undergone apoptosis or necrosis [1–5]. Molecular analysis of cf-DNA enables detection and monitoring of EGFR mutations, as well as detection of the acquired resistance for 1st and 2nd generation EGFR-tyrosine kinase inhibitors (TKIs) (erlotinib, gefitinib, afatinib and dacomitinib) caused by Thr790Met substitution that sensitizes NSCLC cells for 3rd generation EGFR-TKIs (osimertinib, rociletinib) [1–3]. EGFR status in plasma or serum is highly concordant with the tumor cells and can be alternatively used in molecular analysis when material from tumor lesions cannot be obtained [1, 4, 5].
In the current study we analyzed the sensitivity of EGFR gene examination in liquid biopsy and utility of this material in monitoring changes in EGFR status during the EGFR-TKI therapy. The studied group included 23 Caucasian patients (8 male and 15 female, median age 71 ±9 years) with lung adenocarcinoma and known status of activating EGFR mutations (analyzed in formalin-fixed paraffin-embedded (FFPE) and cell blocks). The plasma samples were collected prior to the first EGFR-TKI administration and in 10 patients were re-obtained every 2 months until disease progression. Detailed characteristic of the studied group is presented in Table I and on Figure 1.
The sensitivity of the ctEGFR Mutation Analysis Kit (Entrogen, USA) was 81.2% (9/11) for deletions in exon 19 and 83.33% (10/12) for substitution Leu858Arg in exon 21. Moreover, we did not observe false positive results in control materials. The concordance between plasma and tissue samples reached 82.61% (19/23), which was lower than the concordance demonstrated by Xiong et al. (93.3%), Reck et al. (89%), Douillard et al. (94.3%) and Mok et al. (88%) [1, 2, 4, 5]. On the other hand, Yao et al. observed lower concordance (78.21%) between plasma and tissue samples in next generation sequencing (NGS) analysis [6]. However, nowadays digital droplet PCR (dd-PCR), BEAMing...


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