scholarly journals Pathological Signature and Therapeutic Status of NSCLC Patients with Common or Rare Driver Gene Alterations in North China：A real world retrospective study

2020 ◽  
Author(s):  
Hui Zhang ◽  
Xinjie Yang ◽  
Xiaodie Qu ◽  
Kun Li ◽  
Jinghui Wang ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Gene Mutations ◽  
Stage Iv ◽  
Population Based ◽  
Driver Gene ◽  
Common Mutation ◽  
Driver Genes ◽  
Rare Mutation ◽  
Nsclc Patients ◽  
Gene Alterations

Abstract Background: Although guidelines recommended to test EGFR/ALK/ROS-1 gene alterations in advanced non-small cell lung cancer (NSCLC) patients before treatment, there is now growing evidence that rare driver genes and mutations also can inform targeted therapy and improve outcomes for this traditionally underrepresented population. This study aimed to describe mutational patterns and linked clinical parameters in a Chinese population-based NSCLC cohort.Methods: This study included patients with pathologically confirmed NSCLC, who were routinely screened for EGFR, KRAS, BRAF, ALK, ROS1, RET, MET, HER2, and PIK3CA mutations by the NMPA approved multi-gene detection kit. The demographic and clinicopathological data, treatment information, clinical outcomes after first-line treatment, as well as nine driver gene mutation statuses and PD-L1 expression level of these patients were retrospectively collected.Results: Finally, 431 patients were enrolled, most patients were male (55.9%), with adenocarcinoma or adenosquamous carcinoma (80.7%) and in stage IV (50.6%). Among all the 431 patients, 61.5% patients were identified with gene mutation including 101 with rare mutation, 164 with 19del or with L858R mutation. Adenocarcinoma patients have a higher mutation rate (73.6%), and the mutations mainly occur in EGFR, KRAS, ALK and HER2. While, the gene mutation characteristics in squamous cell carcinoma patients with were relatively simple, only 2 patients with EGFR 19del and 2 patients with PIK3CA mutation. More PD-L1 expression could detected in patients with rare mutation. The median PFS1 of patients with common mutation (13 months, 95% CI: 9.9-16) was longer than the patients with rare mutation (5 months, 95 % CI: 0-10.5). Conclusions: The clinicopathologic features and clinical treatment status among NSCLC patients with common or rare driver gene mutations were different. The survival of patients with rare mutation was worse than that of patients with common mutation. Therefore, more attention should be paid to the treatment strategy and survival status of patients with rare mutations in clinical practice.

A prospective data analysis of targeted therapy combined with concurrent radiation therapy for brain metastasis from NSCLC with driver gene mutation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14006-e14006
Author(s):  
Xiaotong Duan ◽  
Xiaoxia Zhu ◽  
Lijuan Wang
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Gene Mutation ◽  
Progression Free Survival ◽  
Driver Gene ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Concurrent Radiotherapy ◽  
Nsclc Patients

e14006 Background: Previous studies have shown that brain metastases of non-small cell lung cancer (NSCLC) with positive driver genes have poor prognosis. There is still lack of prospective studies on the efficacy and safety of targeted therapy combined with concurrent radiotherapy for brain metastases(BM). Methods: NSCLC patients, with ECOG score 0-2, having MRI confirmed brain or meningeal metastases were eligible. Patients must have driver gene mutation and received corresponding targeted therapy. The intracranial radiotherapy regimen was SRS or whole brain radiotherapy. The primary objective was iPFS (intracranial progression-free survival); Secondary objectives were: iORR (intracranial objective response rate), PFS (progression-free survival), OS (overall survival). MMSE (Mini Mental State Examination) and FACT-Br was carried out before/after weekly radiotherapy and during systematic treatment. Treatment-related toxicities were assessed according RTOG/EORTC criteria. Tumor responses were evaluated using RECIST V1.1 criteria. Survival analysis was performed using the Graphprism version 6.0 by Kaplan-Meier method and log-rank test. Results: 23 NSCLC with BM was included. Among them, 10 patients were newly diagnosed with NSCLC BM. 2 patients’ BM progressed after targeted therapy. 11 NSCLC patients were newly diagnosed with BM after targeted therapy. 91.3% of patients presented an EGFR mutation, including primarily EGFR 19-exon deletion, EGFR 21-L8585R. 11.5% presented with c-MET mutation. Median age was 58.34 yrs(44-71yrs). Patients were mostly treated with Erolotinib and Gefitinib. All patients were adenocarcinoma. At last follow-up, for patients newly diagnosed with NSCLC BM, 8 patients had achieved intracranial progression, and 7 patients had reached OS, of which 1 died before completing WBRT. The median iPFS was 9.3m(95%CI:0.571-4.055) and the median OS was 11.9m (95%CI:0.2752 -2.732). As for patients who progressed after targeted therapy, one patient’s OS was 4.4m, iPFS of the other patient was 3.9m. Among NSCLC patients who were newly diagnosed with BM after targeted therapy, 8 patients had achieved intracranial progression and 5 patients had reached OS. The median iPFS was 6.13m (95%CI:0.247-1.751) and the mOS was 13.8m (95%CI:0.3660-3.634). Common adverse effects include dry skin, fatigue, dizziness, headache, anorexia, and grade I myelosuppression and no serious adverse events (SAEs); MMSE and FACT-Br scores were no significant differences at baseline and follow-up. Conclusions: In stage IV brain metastatic NSCLC with driver gene mutation, targeted therapy combined with concurrent radiotherapy for BM is tolerable, and there is no significant impact on the quality of life and cognitive function after radiotherapy. The evaluation of efficacy requires further follow-up. Support:LC2019ZD009,81972853 and 81572279.

scholarly journals PATH-50. ROUTINE MOLECULAR DIAGNOSIS OF GLIOMA PATIENTS USING A GLIOMA-SPECIFIC NGS PANEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi154-vi155
Author(s):  
Koji Yoshimoto ◽  
Nayuta Higa ◽  
Hajime Yonezawa ◽  
Hiroyuki Uchida ◽  
Toshiaki Akahane ◽  
...  
Keyword(s):  
Molecular Diagnosis ◽  
Gene Mutations ◽  
Chromosome 1 ◽  
Clinical Samples ◽  
Driver Gene ◽  
Driver Genes ◽  
Chromosome 1P ◽  
Ffpe Tumor ◽  
Grade Ii ◽  
Key Driver

Abstract AIM The 2016 WHO classification requires molecular diagnosis in routine glioma diagnostics. However, analysis of key driver gene mutations and chromosome 1p/19q co-deletions cannot be performed in a single platform. In this study, we evaluated the feasibility of a glioma-specific NGS panel for molecular diagnosis of glioma patients. MATERIALS AND METHODS We developed a glioma-specific NGS panel consisting of 48 genes, including glioma-relevant key driver genes and 21 genes mapped to chromosome 1 and 19. DNA was extracted from formaldehyde fixed-paraffin embedded (FFPE) tumor tissues histologically identified by a pathologist, and from patient-derived blood as a control. In this system, we implemented a molecular barcodes method to enhance confidence in clinical samples and analyzed 80 glioma patients (Grade II: 17 cases, Grade III: 16 cases, Grade IV: 47 cases). RESULTS From these 80 cases, IDH1 and H3F3A mutations were detected in 23 cases (29%) and 2 cases (5%), respectively. The 1p/19q co-deletion was detected in 15 cases (19%), with all cases also containing IDH1 mutations. In Grade IV cases, EGFR, PDGFR, and FGFR mutations were detected in 6% (amp 19%), 9%, and 4% (amp 17%) of cases, respectively. PTEN, TP53, NF1, RB1, and CDKN2A mutations were detected in 37% (del 72%), 45% (del 13%), 21% (del 23%), 15% (del 60%), and 2% (del 53%) of cases, respectively. CONCLUSION Diagnosis of glioma patients with this glioma-specific NGS panel is feasible.

scholarly journals Clonal haematopoiesis in chronic ischaemic heart failure: prognostic role of clone size for DNMT3A- and TET2-driver gene mutations

2020 ◽  
Author(s):  
Birgit Assmus ◽  
Sebastian Cremer ◽  
Klara Kirschbaum ◽  
David Culmann ◽  
Katharina Kiefer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Somatic Mutations ◽  
Prognostic Significance ◽  
Gene Mutations ◽  
Amplicon Sequencing ◽  
Driver Mutations ◽  
Driver Gene ◽  
Roc Curve Analysis ◽  
Driver Genes ◽  
Clone Size

Abstract Aims Somatic mutations of the epigenetic regulators DNMT3A and TET2 causing clonal expansion of haematopoietic cells (clonal haematopoiesis; CH) were shown to be associated with poor prognosis in chronic ischaemic heart failure (CHF). The aim of our analysis was to define a threshold of variant allele frequency (VAF) for the prognostic significance of CH in CHF. Methods and results We analysed bone marrow and peripheral blood-derived cells from 419 patients with CHF by error-corrected amplicon sequencing. Cut-off VAFs were optimized by maximizing sensitivity plus specificity from a time-dependent receiver operating characteristic (ROC) curve analysis from censored data. 56.2% of patients were carriers of a DNMT3A- (N = 173) or a TET2- (N = 113) mutation with a VAF >0.5%, with 59 patients harbouring mutations in both genes. Survival ROC analyses revealed an optimized cut-off value of 0.73% for TET2- and 1.15% for DNMT3A-CH-driver mutations. Five-year-mortality was 18% in patients without any detected DNMT3A- or TET2 mutation (VAF < 0.5%), 29% with only one DNMT3A- or TET2-CH-driver mutations above the respective cut-off level and 42% in patients harbouring both DNMT3A- and TET2-CH-driver mutations above the respective cut-off levels. In carriers of a DNMT3A mutation with VAF ≥ 1.15%, 5-year mortality was 31%, compared with 18% mortality in those with VAF < 1.15% (P = 0.048). Likewise, in patients with TET2 mutations, 5-year mortality was 32% with VAF ≥ 0.73%, compared with 19% mortality with VAF < 0.73% (P = 0.029). Conclusion The present study defines novel threshold levels for clone size caused by acquired somatic mutations in the CH-driver genes DNMT3A and TET2 that are associated with worse outcome in patients with CHF.

scholarly journals Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Haiqiong Wang ◽  
Yongbo Guo ◽  
Zhenkun Dong ◽  
Tao Li ◽  
Xinsheng Xie ◽  
...  
Keyword(s):  
Survival Rate ◽  
Myelodysplastic Syndrome ◽  
Gene Mutation ◽  
Poor Prognosis ◽  
Gene Mutations ◽  
Chromosome 8 ◽  
Common Mutation ◽  
Mutation Load ◽  
Mutation Site ◽  
Increased Risk

Abstract To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1, RUNX1, SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation (p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities (p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations (p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis.

Somatic Mutational Landscape of AML with Inv(16) and t(8;21) Identifies Two Distinct Patterns in Relapse Tumors

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2362-2362
Author(s):  
Raman B. Sood ◽  
Nancy F Hansen ◽  
Frank X Donovan ◽  
Blake Carrington ◽  
Baishali Maskeri ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Clonal Evolution ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Driver Gene ◽  
Intrinsic Resistance ◽  
Driver Genes ◽  
In Vivo Models

Abstract Acute myeloid leukemia (AML) is a heterogeneous disease with a wide prognostic spectrum ranging from poor to good depending upon the underlying mutations and/or cytogenetic abnormalities. Although AMLs with inv(16)/t(16:16) or t(8,21), collectively referred to as core binding factor leukemias (CBF-AMLs), are classified as prognostically favorable, such patients often succumb to their disease following relapse after an initial response to cytarabine/anthracyclin-based treatment regimens. Thus, to develop successful treatment strategies, it is critical to understand the mechanisms leading to disease relapse and target them with novel therapeutic approaches. To pursue this goal, we applied genomic approaches (whole exome sequencing and single nucleotide polymorphism arrays) on DNA from samples collected at sequential time points (i.e., diagnosis, complete remission and relapse) in seven patients with inv(16) and six patients with t(8;21). We identified mutations in several previously identified AML driver genes, such as KIT, FLT3, DNMT3A, EZH2, SMC1A, SMC3, WT1 and NRAS. Three relapse samples showed mosaicism for monosomy/disomy of the region of chromosome 3 containing GATA2. Overall, our data revealed two distinct profiles that support different mechanisms of relapse: 1) diagnosis and relapse blasts harbor the same driver gene mutations, indicating the intrinsic resistance of the major clones present at diagnosis to treatment regimen used; 2) diagnosis and relapse tumors have different driver gene mutations, indicating disease clonal evolution possibly through treatment selective pressure. Furthermore, our data has identified previously unreported putative driver genes for AML. Among these, we identified same somatic variant (R222G) in DHX15, an RNA helicase involved in splicing, in two patients at diagnosis. The variant was also detected at relapse in one of these patients. Functional validation of the mechanistic roles of wild type and mutated DHX15 in hematopoiesis and leukemogenesis, respectively, is ongoing in in vitro and in vivo models. Disclosures No relevant conflicts of interest to declare.

scholarly journals Novel Putative Driver Gene Mutations in Chronic Lymphocytic Leukemia (CLL): Results from a Combined Analysis of Whole-Exome Sequencing of 262 Primary CLL Samples

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1952-1952 ◽  
Author(s):  
Dan A. Landau ◽  
Chip Stewart ◽  
Johannes G. Reiter ◽  
Michael Lawrence ◽  
Carrie Sougnez ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Exome Sequencing ◽  
Gene Mutations ◽  
Clinical Impact ◽  
Lymphocytic Leukemia ◽  
Driver Mutations ◽  
Driver Gene ◽  
Discovery Process ◽  
Driver Genes ◽  
Whole Exome

Abstract Unbiased high-throughput massively parallel sequencing methods have transformed the process of discovery of novel putative driver gene mutations in cancer. In chronic lymphocytic leukemia (CLL), these methods have yielded several unexpected findings, including the driver genes SF3B1, NOTCH1 and POT1. Recent analysis, utilizing down-sampling of existing datasets, has shown that the discovery process of putative drivers is far from complete across cancer. In CLL, while driver gene mutations affecting >10% of patients were efficiently discovered with previously published CLL cohorts of up to 160 samples subjected to whole exome sequencing (WES), this sample size has only 0.78 power to detect drivers affecting 5% of patients, and only 0.12 power for drivers affecting 2% of patients. These calculations emphasize the need to apply unbiased WES to larger patient cohorts. To this end, we performed a combined analysis of CLL WES data joining together our previously published cohort of 159 CLLs with data from 103 CLLs collected by the International Cancer Genome Consortium (ICGC). The raw sequencing reads from these 262 primary tumor samples (102 CLL with unmutated IGHV, 147 with mutated IGHV, 13 with unknown IGHV status) were processed together and aligned to the hg19 reference genome. Somatic single nucleotide variations (sSNVs) and indels were detected using MuTect. Subsequently, inference of recurrently mutated genes was performed using the MutSig algorithm. This method combined several characteristics such as the overall mutation rate per sample, the gene specific background mutation rate, non-synonymous/synonymous ratio and mutation clustering to detect genes that are affected by mutations more than expected by chance. This analysis identified 40 recurrently mutated genes in this cohort. This included 22 of 25 previously identified recurrently mutated genes in CLL. In addition, 18 novel candidate CLL drivers were identified, mostly affecting 1-2% of patients. The novel candidates included two histone proteins HIST1H1D and HIST1H1C, in addition to the previously identified HIST1H1E. Another was IKZF3, affected by a recurrent sSNV resulting in a p.L162R change in its DNA binding domain, in close proximity to a region recently identified as critical for lenalidomide resistance in multiple myeloma (MM). An additional recurrently mutated gene was nuclear RNA export factor 1 (NXF1), which along with previously known recurrently mutated genes (SF3B1, XPO1, DDX3X), highlights the importance of RNA processing to CLL biology. Finally, this search for putative CLL driver genes also identified ASXL1 and TRAF3, already characterized as drivers in acute myeloid leukemia and MM, respectively. Of the 59 of 262 samples for which RNA-seq data were available, 76% of the identified driver mutations were detected and thereby validated. Validation using RNAseq detection of driver mutations and targeted sequencing within the entire cohort are ongoing. The larger size of our cohort enabled the separate application of the somatic mutation discovery process to samples with mutated or unmutated IGHV. Among the 147 samples with mutated IGHV, only 5 driver genes (TP53, SF3B1, MYD88, CHD2, RANBP2) retained significance. In contrast, analysis of the 102 IGHV unmutated samples revealed a distinct and more diverse pattern of recurrently mutated genes (lacking MYD88 and CHD2, and including NOTCH1, RPS15, POT1, NRAS, EGR2, BRAF, MED12, XPO1, BCOR, IKZF3, MAP2K1, FBXW7 and KRAS). This extended cohort also allowed for better resolution of the clinical impact of those genetic variants with greater than 4% prevalence in the cohort. For example, samples with POT1 mutations were found to be associated with shorter time from sample to therapy compared with those with wild-type POT1 (P= 0.02). Our study demonstrates that with larger cohort size, we can effectively detect putative driver genes with lower prevalence, but which may nonetheless have important biological and clinical impact. Moreover, our interrogation shows that subset analysis can reveal distinct driver patterns in different disease subsets. In particular, the marked clinical difference between CLLs with mutated and unmutated IGHV may reflect the higher likelihood of the latter group to harbor a broader spectrum of driver mutations with a more complex pattern of co-occurrence. Disclosures Brown: Sanofi, Onyx, Vertex, Novartis, Boehringer, GSK, Roche/Genentech, Emergent, Morphosys, Celgene, Janssen, Pharmacyclics, Gilead: Consultancy.

scholarly journals Case Report: Abscopal Effect of Microwave Ablation in a Patient With Advanced Squamous NSCLC and Resistance to Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuchu Shao ◽  
Menghang Yang ◽  
Yingying Pan ◽  
Dacheng Xie ◽  
Bin Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Microwave Ablation ◽  
Checkpoint Inhibitors ◽  
Acquired Resistance ◽  
Gene Mutations ◽  
Initial Response ◽  
Driver Gene ◽  
Abscopal Effect ◽  
Squamous Lung Cancer ◽  
Nsclc Patients

Currently, immunotherapy has been a backbone in the treatment of advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, only a small proportion of NSCLC patients respond to immune checkpoint inhibitors, and majority of patients with initial response will develop acquired resistance at 5 years, which usually manifests as oligo-progression or oligo-metastases. Evidence from multiple clinical trials indicates that local consolidative therapies could improve the prognosis of oligometastatic NSCLC patients. Herein, we reported a case of advanced squamous lung cancer which showed a durable abscopal effect from microwave ablation after acquired resistance of immunotherapy.

scholarly journals Cancer-specific associations of driver genes with immunotherapy outcome

2020 ◽  
Author(s):  
Tomi Jun ◽  
Tao Qing ◽  
Guanlan Dong ◽  
Maxim Signaevski ◽  
Julia F Hopkins ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Gene Mutations ◽  
Driver Gene ◽  
Oncogenic Signaling ◽  
Multiple Cancer ◽  
Driver Genes ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Cancer Types ◽  
Oncogenic Signaling Pathways

AbstractGenomic features such as microsatellite instability (MSI) and tumor mutation burden (TMB) are predictive of immune checkpoint inhibitor (ICI) response. However, they do not account for the functional effects of specific driver gene mutations, which may alter the immune microenvironment and influence immunotherapy outcomes. By analyzing a multi-cancer cohort of 1,525 ICI-treated patients, we identified 12 driver genes in 6 cancer types associated with treatment outcomes, including genes involved in oncogenic signaling pathways (NOTCH, WNT, FGFR) and chromatin remodeling. Mutations of PIK3CA, PBRM1, SMARCA4, and KMT2D were associated with worse outcomes across multiple cancer types. In comparison, genes showing cancer-specific associations—such as KEAP1, BRAF, and RNF43—harbored distinct variant types and variants, some of which were individually associated with outcomes. In colorectal cancer, a common RNF43 indel was a putative neoantigen associated with higher immune infiltration and favorable ICI outcomes. Finally, we showed that selected mutations were associated with PD-L1 status and could further stratify patient outcomes beyond MSI or TMB, highlighting their potential as biomarkers for immunotherapy.

Interim analysis of the data of non-interventional study to determine the prevalence of EGFR mutations in advanced NSCLC Russian patients (ORTUS).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13109-e13109
Author(s):  
Konstantin K. Laktionov ◽  
Irina Demidova ◽  
Aleksandr Ageev ◽  
Valeriy Vladimirovich Breder ◽  
Pavel Grigoriev ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Advanced Nsclc ◽  
Gene Mutations ◽  
Stage Iv ◽  
Tumor Burden ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Stage Iv Disease ◽  
Treatment Naïve ◽  
Nsclc Patients

e13109 Background: There is a little information of correlation between EGFRm rate in cytology and plasma samples in Russian NSCLC population. The interim analysis of the study aimed to evaluate the prevalence and types of EGFR mutations in paired cytology and plasma samples in treatment-naive patients with advanced NSCLC. Methods: ORTUS is a multicenter, non-interventional, prospective study to determine EGFR mutations rate in treatmentnaive Russian patients with advanced NSCLC. ClinicalTrials.gov identifier: NCT02321046. The study enrolled 426 patients in stage IIIB / IV of NSCLC. Interim analysis covered the data of 214 cytology verified patients (mean age - 62.6 (range 32-86) years, 58,4% of men) with EGFRm test results in paired cytology and ctDNA samples. 99.5% cases were adenocarcinoma. The proportion of non-smokers/smokers/exsmokers was 46.3%/36%/17.8% respectively. Stage IV disease was in 81% of cases; 84.1% of patients had symptoms. DNA isolation performed using QIAamp DNA FFPE Tissue Kit for cytology and Qiagen Circulating Nucleic Acid Kit for ctDNA according to the manufacturer’s instructions. EGFR gene mutations were analyzed using THerascreen RGQ EGFR PCR Kit in cytology samples and RGQ Plasma EGFR PCR kit in plasma (Qiagen). Results: EGFRm was identified in 17,8% cytology samples (38/214) that is close to 20,2% (1759/8716) in Russian tissue EGFRm study (Imyanitov et al., 2016). 10,3% of paired ctDNA samples were EGFRm positive. Sensitivity and specificity for ctDNA were 42.1%, and 97.1% respectively. The EGFRm rate was 3,9% and 2,6% in smokers, 5,3% and 0% in ex-smokers and 33,3% and 21,2% in nonsmokers in cytology and plasma samples respectively. EGFRm rate and concordance between cytology and ctDNA are presented in a table. EGFRm in ctDNA were detected more frequently in M1a/b groups (p = 0,028). Conclusions: Cytology samples are appropriate for EGFRm testing in NSCLC patients in comparison with tumor tissue ones. High tumor burden (positive metastatic status) is an important factor for successful mutation analysis in ctDNA. [Table: see text]

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