Dataset Information

[Investigation on the Possibility of EGFR Mutation Testing on DNA Extracted from Fixation Liquid of Lung Cancer Biopsy].

ABSTRACT: BACKGROUND:Epidermal growth factor receptor (EGFR) mutation is the most common gene mutation in patients with non-small cell lung cancer (NSCLC). Many international guidelines are recommended to detected the EGFR mutation before the treatment of advanced non-small cell lung cancer. To investigate the possibility of EGFR mutation testing on DNA extracted from fixation liquid of lung cancer biopsy. METHODS:Fixation liquid of lung cancer biopsy was collected and stored at -80 oC after centrifugal. DNA was extracted and EGFR gene mutation was detected by ARMS. Compared with EGFR mutation status of paraffin-embedded tissues, the consistency, the sensitivity and specificity of EGFR mutation testing were analyzed. RESULTS:Among the 28 cases of EGFR mutation positive and 20 cases of EGFR mutation negative previously tested on paraffin-embedded tissue by clinic test, 20 cases with EGFR mutation positive and 20 cases with negative were detected by matched fixation liquid of lung cancer biopsy, respectively. The sensitivity and specificity were 71.4% and 100%. Moreover, 52 paraffin-embedded tissues and matched fixation liquid of lung cancer biopsy with unknown EGFR mutation status were detected, and the EGFR mutation positive rate were 36.5% and 28.8% respectively. The sensitivity and specificity of fixation liquid of lung cancer biopsy were 78.9% and 100.0%. CONCLUSIONS:Extracting the DNA from fixation liquid of lung cancer biopsy may be a kind of feasible way to detect EGFR mutation.

SUBMITTER: Liao X

PROVIDER: S-EPMC6712265 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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[Investigation on the Possibility of EGFR Mutation Testing on DNA Extracted from Fixation Liquid of Lung Cancer Biopsy].

Liao Xuanzhi X Gu Yingying Y Jiang Juhong J

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20190701 7

<h4>Background</h4>Epidermal growth factor receptor (EGFR) mutation is the most common gene mutation in patients with non-small cell lung cancer (NSCLC). Many international guidelines are recommended to detected the EGFR mutation before the treatment of advanced non-small cell lung cancer. To investigate the possibility of EGFR mutation testing on DNA extracted from fixation liquid of lung cancer biopsy.<h4>Methods</h4>Fixation liquid of lung cancer biopsy was collected and stored at -80 oC afte ...[more]

PMID: 31315782

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Project description:15-40% of non-small cell lung cancer (NSCLC) patients harbor epidermal growth factor receptor (EGFR)-sensitizing mutations. Tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in this population, yet all patients will ultimately progress. Liquid biopsy can reliably identify somatic tumor-associated EGFR mutations in plasma. This study aimed to assess the feasibility and value of the quantitative assessment of EGFR driver mutations in plasma in EGFR-mutated NSCLC patients treated with EGFR-TKIs as a tool to evaluate therapeutic response to TKIs and monitor for disease progression. The study included 136 patients with tissue biopsy-confirmed EGFR-sensitizing, mutation-positive lung adenocarcinoma with plasma collected prior to TKI treatment and at least two post-initiation TKI treatment/follow-up blood samples. Plasma samples were tested with the cobas® EGFR Mutation Test v2 (cobas EGFR Test), and semi-quantitative index (SQI) values for each identified mutation were reported by the assay software. The most common baseline EGFR mutations detected in tissue were L858R (53.7%) and exon 19 deletion (39.7%). Plasma cell-free DNA analysis detected EGFR mutations in 74% of the baseline samples. Objective response rate by RECIST 1.1 was achieved in 72% of patients, while 93% had a molecular response (defined as disappearance of the EGFR mutation from plasma). 83% of patients had molecular progression (MP; 1.5X SQI increase or new T790M mutation), and 82% who had a clinical response had clinical progression. On average, MP occurred 42 days prior to clinical progression. Patients who progressed while on first-line TKI showed MP of the original EGFR-sensitizing mutations prior to the emergence of a T790M mutation, which was detected in 27% of the EGFR plasma-positive patients. Longitudinal monitoring of EGFR mutational load in plasma is feasible and can predict both response and clinical progression in EGFR-mutated NSCLC patients treated with EGFR-TKIs, as well as detect treatment-emergent EGFR mutations.

Project description:BackgroundAbout 15% of non-small cell lung cancers (NSCLCs) harbor epidermal growth factor receptor (EGFR) mutations. Upfront treatment with first and second generation EGFR tyrosine kinase inhibitors (1-2gen TKIs) is superior to chemotherapy. The most frequent resistance mechanism to 1-2gen TKIs is EGFR T790M mutation, which is targeted by osimertinib. T790M mutation can be revealed by liquid biopsy (LB) or by tissue rebiopsy (TB). LB is easily feasible but less sensitive than TB. We focused on repeated LBs and analyzed clinical features associated with EGFR T790M detection.MethodsThis is a retrospective multicenter observational study including EGFR-mutant NSCLC consecutive patients with disease progression (PD) after 1-2gen TKIs and with a first EGFR LB negative for T790M mutation, referred between 2016 and 2019. Aims of the study were to determine the prevalence of T790M mutation using LB in a real-life setting and the prevalence of T790M mutation by repeated LBs. We explored the association of T790M with clinical-pathological features and, through a survey, we evaluated the decision-making process behind LB request. Data on TBs were also collected.ResultsOne hundred and ten patients were included in the study, for a total of 326 LBs. Median number of LB per patient was 3.0. The T790M prevalence through LB was 34.5%. Over time, significantly more LBs were requested "at clinical and radiological PD" and "at radiological PD" compared to "arbitrarily". The probability of finding the T790M mutation for a patient across each subsequent LB did not significantly change. Liver and lymph node PD were significantly correlated to T790M positivity. Notably, "at PD" compared to "arbitrarily" LB request and liver, bone or lymph node PD were correlated to the detection of any EGFR mutation in cfDNA. TB was performed in 59.7% of patients with a T790M negative LB and 18.8% of them were T790M positive. In most cases, TB was not feasible due to anatomical reasons. In our study population, the overall T790M prevalence-detected with both LB and TB-was 42.7%.ConclusionsRepeated LB testing can be useful in a real-life scenario to detect EGFR T790M mutation.

Project description:BackgroundEGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient's follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment.Case presentationIn this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R2 = 0.447, p <0.001 EGFR activating mutations R2 = 0.301, p = 0.003 for T790M; and R2 = 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis.ConclusionTo our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management.

Dataset Information

[Investigation on the Possibility of EGFR Mutation Testing on DNA Extracted from Fixation Liquid of Lung Cancer Biopsy].

Publications

[Investigation on the Possibility of EGFR Mutation Testing on DNA Extracted from Fixation Liquid of Lung Cancer Biopsy].

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