scholarly journals Chemotherapy Resistance in Remutation of Epidermal Growth Factor Receptor Wild Type Becomes a Positive Type and Back Becomes a Wild Type in A Patient with Lung Adenocarcinoma

2021 ◽  
Vol 3 (1) ◽  
pp. 119-127
Author(s):  
Kristo Kurniawan ◽  
◽  
Yani Jane Sugiri ◽  
Ngakan Putu Parsama Putra ◽  
Hendy Setyo Yudhanto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Chemotherapy Resistance ◽  
Pulmonary Adenocarcinoma ◽  
Egfr Mutations ◽  
Chemotherapy Treatment ◽  
Wild Type ◽  
Conventional Chemotherapy ◽  
Tissue Biopsy ◽  
The Status

Introduction: Lung cancer is the most common type of cancer worldwide (11.6%) and the leading cause of death due to cancer throughout the world. One type of lung cancer that is often found is Adenocarcinoma, 35-40%. Mutations in EGFR often occur in patients with pulmonary Adenocarcinoma, especially in Asia. Chemotherapy selection for pulmonary adenocarcinoma patients based on the status of their EGFR mutations. Positive EGFR mutations can get treatment with Tyrosine Kinase Inhibitors. Giving chemotherapy can affect changes in EGFR mutation status. Patients with chemotherapy treatment can experience resistance to chemotherapy either primary or acquired resistance through a variety of mechanisms. Case Description: we reported one case of a 56-year-old man with pulmonary adenocarcinoma who had a positive change in EGFR-type from wild type mutations and then returned to a wild type. Patients were initially diagnosed with wild-type pulmonary adenocarcinoma from EGFR examination of tissue biopsy and given conventional chemotherapy. During the evaluation, progression occurred so that the status of the EGFR mutation was examined using ct-DNA and the result was mutation deletion exon 19 so that the patient obtained Gefitinib. Due to progressive return, the patient again examined EGFR status from tissue biopsy obtained using pleuroscopy and obtained an EGFR wild type. Patients again get conventional chemotherapy. Discussion Changes in the status of EGFR mutation in pulmonary adenocarcinoma patients and chemotherapy resistance can occur in patients with chemotherapy treatment.

Relative Abundance of EGFR Mutations Predicts Benefit From Gefitinib Treatment for Advanced Non–Small-Cell Lung Cancer

2011 ◽  
Vol 29 (24) ◽  
pp. 3316-3321 ◽  
Author(s):  
Qing Zhou ◽  
Xu-Chao Zhang ◽  
Zhi-Hong Chen ◽  
Xiao-Lu Yin ◽  
Jin-Ji Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Sequencing ◽  
Small Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
Direct Dna Sequencing ◽  
Gefitinib Treatment

Purpose Our aim was to determine whether abundance of epidermal growth factor receptor (EGFR) mutations in tumors predicts benefit from treatment with EGFR–tyrosine kinase inhibitors (TKIs) for advanced non–small-cell lung cancer (NSCLC). Patients and Methods We detected EGFR mutations in 100 lung cancer samples using direct DNA sequencing and amplification refractory mutation system (ARMS). Mutation-positive tumors by both methods carried high abundance of EGFR mutations. Tumors that were mutation positive by ARMS but mutation negative by direct DNA sequencing harbored low abundance of EGFR mutations. Mutation-negative tumors by both methods carried wild-type EGFR. All patients received gefitinib treatment. The correlation between EGFR mutation abundance and clinical benefit from gefitinib treatment was analyzed. Results Of 100 samples, 51 and 18 harbored high and low abundances of EGFR mutations, respectively; 31 carried wild-type EGFR. Median progression-free survival (PFS) was 11.3 (95% CI, 7.4 to 15.2) and 6.9 months (95% CI, 5.5 to 8.4) in patients with high and low abundances of EGFR mutations, respectively (P = .014). Median PFS of patients with low abundance of EGFR mutations was significantly longer than that of those with wild-type tumors (2.1 months; 95% CI, 1.0 to 3.2; P = .010). Objective response rates (ORRs) were 62.7%, 44.4%, and 16.1%, and overall survival (OS) rates were 15.9 (95% CI, 13.4 to 18.3), 10.9 (95% CI, 2.7 to 19.1), and 8.7 months (95% CI, 4.6 to 12.7) for patients with high abundance of EGFR mutations, low abundance of EGFR mutations, and wild-type EGFR, respectively. The difference between patients with high and low abundances of EGFR mutations was not significant regarding ORR and OS. Conclusion The relative EGFR mutation abundance could predict benefit from EGFR-TKI treatment for advanced NSCLC.

Epidermal Growth Factor Receptor Mutations in Plasma DNA Samples Predict Tumor Response in Chinese Patients With Stages IIIB to IV Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2653-2659 ◽  
Author(s):  
Hua Bai ◽  
Li Mao ◽  
hang Shu Wang ◽  
Jun Zhao ◽  
Lu Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Tumor Response ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Plasma Samples ◽  
Plasma Dna ◽  
Small Cell Lung ◽  
Epidermal Growth

Purpose Mutations in the epidermal growth factor receptor (EGFR) kinase domain can predict tumor response to tyrosine kinase inhibitors (TKIs) in non–small-cell lung cancer (NSCLC). However, obtaining tumor tissues for mutation analysis is challenging. We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC. Patients and Methods Plasma DNA samples and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography. We compared the mutations in the plasma samples and the matched tumors and determined an association between EGFR mutation status and the patients' clinical outcomes prospectively. Results In 230 patients, we detected 81 EGFR mutations in 79 (34.3%) of the patients' plasma samples. We detected the same mutations in 63 (79.7%) of the matched tumors. Sixteen plasma (7.0%) and fourteen tumor (6.1%) samples showed unique mutations. The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas (P = .012 and P = .009, respectively). In the 102 patients who failed platinum-based treatment and who were treated with gefitinib, 22 (59.5%) of the 37 with EGFR mutations in the plasma samples, whereas only 15 (23.1%) of the 65 without EGFR mutations, achieved an objective response (P = .002). Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations (P = .044) in plasma. Conclusion EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs.

scholarly journals Tissue or blood: which is more suitable for detection of EGFR mutations in non-small cell lung cancer?

2018 ◽  
Vol 33 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Rong Biaoxue ◽  
Yang Shuanying
Keyword(s):  
Lung Cancer ◽  
Receiver Operating Characteristic Curve ◽  
Receiver Operating Characteristic ◽  
Operating Characteristic ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
Egfr Mutations ◽  
Mutation Status ◽  
Operating Characteristic Curve

Background: Many studies have evaluated the accuracy of EGFR mutation status in blood against that in tumor tissues as the reference. We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations. Methods: Investigations that provided data on EGFR mutation status in blood were searched in the databases of Medline, Embase, Ovid Technologies and Web of Science. The detect efficiency of EGFR mutations in paired blood and tissues was compared using a random-effects model of meta-analysis. Pooled sensitivity and specificity and diagnostic accuracy were calculated by receiver operating characteristic curve. Results: A total of 19 studies with 2,922 individuals were involved in this meta-analysis. The pooled results showed the positive detection rate of EGFR mutations in lung cancer tissues was remarkably higher than that of paired blood samples (odds ratio [OR] = 1.47, p<0.001). The pooled sensitivity and specificity of blood were 0.65 and 0.91, respectively, and the area under the receiver operating characteristic curve was 0.89. Conclusions: Although blood had a better specificity for detecting EGFR mutations, the absence of blood positivity should not necessarily be construed as confirmed negativity. Patients with negative results for blood should decidedly undergo further biopsies to ascertain EGFR mutations.

Investigation of immune microenvironment in EGFR mutant NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20517-e20517
Author(s):  
Yi Hu ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Yuezong Bai ◽  
Fan Zhang
Keyword(s):  
T Cells ◽  
Egfr Mutation ◽  
Tumor Stroma ◽  
Median Number ◽  
Egfr Mutations ◽  
Wild Type ◽  
Immune Microenvironment ◽  
Regulatory Pathways ◽  
Significant Difference ◽  
Egfr Mutant

e20517 Background: Immune checkpoint inhibitor therapy has made great achievements in NSCLC, but patients with EGFR mutations have poor efficacy with immunotherapy. Previous studies have explored the expression of PD-L1, neo-antigen, co-mutation and regulatory pathways in EGFR mutate NSCLC. This work compared the immune microenvironment of EGFR mutant and wild-type NSCLC. Methods: Patients: NSCLC. Using multi-color immunohistochemistry (multi-IHC) to evaluate the expression of 2 indicators in tumors and tumor stroma, namely CD8+ T cell and macrophage. Shapiro-Wilk was used for normality test, and t-test or Mann-Whitney U test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 119 NSCLC patients, including 59 women (49.6%) and 60 men (50.4%), with a median age of 57. There were 68 patients (57.1%) with EGFR mutations, 19 patients (16%) with KRAS mutations, and 58 patients (48.7%) with TP53 mutations. multi-IHC results showed that, EGFR mutation Vs EGFR wild type samples, (1) the number and proportion of CD8+ T cells in tumor were not statistically different. The median number of CD8+ T cells in tumor stroma was 231.5 vs 359, p = 0.05 and the proportion of CD8+ T cells was 3.92% vs 5.64%, p = 0.02; (2) The median number of macrophage in tumors was 1522 vs 110, p < 0.01, and the proportion of macrophage cells was 24.93% Vs 1.38%, p < 0.01. The median value of macrophages in tumor stroma was 617.5 Vs 208, p < 0.01, and the proportion of macrophages cells was 10.88% vs 3.03%, p < 0.01. Conclusions: Compared with EGFR wild-type patients, EGFR mutation patients have a lower proportion of CD8+ T cells and a higher proportion of macrophages in the immune microenvironment.

scholarly journals Targeted Assessment of the EGFR Status as Reflex Testing in Treatment-Naive Non-Squamous Cell Lung Carcinoma Patients: A Single Laboratory Experience (LPCE, Nice, France)

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 955 ◽  
Author(s):  
Sandra Lassalle ◽  
Véronique Hofman ◽  
Simon Heeke ◽  
Jonathan Benzaquen ◽  
Elodie Long ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Wild Type ◽  
Pcr Assay ◽  
Cell Lung Carcinoma ◽  
Specific Pcr ◽  
Treatment Naïve ◽  
Reflex Testing ◽  
Single Laboratory

Background: Assessment of actionable EGFR mutations is mandatory for treatment-naïve advanced or metastatic non-squamous lung carcinoma (NSLC), but the results need to be obtained in less than 10 working days. For rapid EGFR testing, an EGFR-specific polymerase chain reaction (PCR) assay is an alternative and simple approach compared to next generation sequencing (NGS). Here, we describe how a rapid EGFR-specific PCR assay can be implemented in a single laboratory center (LPCE, Nice, France) as reflex testing in treatment-naïve NSLC. Methods: A total of 901 biopsies from NSLC with more than 10% of tumor cells were prospectively and consecutively evaluated for EGFR mutation status between November 2017 and December 2019 using the Idylla system (Biocartis NV, Mechelen, Belgium). NGS was performed for nonsmokers with NSLC wild type for EGFR, ALK, ROS1, and BRAF and with less than 50% PD-L1 positive cells using the Hotspot panel (Thermo Fisher Scientific, Waltham, MA, USA). Results: Results were obtained from 889/901 (97%) biopsies with detection of EGFR mutations in 114/889 (13%) cases using the Idylla system. Among the 562 EGFR wild type tumors identified with Idylla, NGS detected one actionable and one nonactionable EGFR mutation. Conclusions: Rapid and targeted assessment of EGFR mutations in treatment-naïve NSLC can be implemented in routine clinical practice. However, it is mandatory to integrate this approach into a molecular algorithm that allows evaluation of potentially actionable genomic alterations other than EGFR mutations.

scholarly journals Detection of EGFR Mutations Using Bronchial Washing-Derived Extracellular Vesicles in Patients with Non-Small-Cell Lung Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2822
Author(s):  
Juhee Park ◽  
Chaeeun Lee ◽  
Jung Seop Eom ◽  
Mi-Hyun Kim ◽  
Yoon-Kyoung Cho
Keyword(s):  
Lung Cancer ◽  
Extracellular Vesicles ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Resistance Mutation ◽  
Detection Sensitivity ◽  
Egfr Mutations ◽  
Tissue Samples ◽  
Cell Lung Carcinoma ◽  
Bronchial Washing

The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer.

scholarly journals Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 803 ◽  
Author(s):  
Ming-Szu Hung ◽  
Jr-Hau Lung ◽  
Yu-Ching Lin ◽  
Yu-Hung Fang ◽  
Shu-Yi Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Egfr Mutation ◽  
Circulating Tumor Dna ◽  
Egfr Mutations ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
First Line ◽  
Mutation Status ◽  
Egfr Tki ◽  
Tumor Dna

Mutations in the epidermal growth factor receptor (EGFR) are associated with various solid tumors. This study aimed to compare two methods for the detection of EGFR mutations in circulating tumor DNA (ctDNA) from lung adenocarcinoma (LUAD) patients and to evaluate the clinical significance of EGFR mutations in ctDNA. In this prospective cohort study, the EGFR mutation status of 77 patients with stage IIIB or IV LUAD was first determined using lung cancer tissue. The amplification refractory mutation system (ARMS) and single allele base extension reaction combined with mass spectroscopy (SABER/MassARRAY) methods were also used to detect EGFR mutations in plasma ctDNA from these patients and then compared using the EGFR mutation status in lung cancer tissue as a standard. Furthermore, the relationship between the presence of EGFR mutations in ctDNA after receiving first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and survival was evaluated. The overall sensitivity and specificity for the detection of EGFR mutations in plasma ctDNA by ARMS and SABER/MassARRAY were 49.1% vs. 56% and 90% vs. 95%, respectively. The agreement level between these methods was very high, with a kappa-value of 0.88 (95% CI 0.77–0.99). Moreover, 43 of the patients who carried EGFR mutations also received first-line EGFR-TKI therapy. Notably, patients with EGFR mutations in plasma ctDNA had significantly shorter progression-free survival (9.0 months, 95% CI 7.0–11.8, vs. 15.0 months, 95% CI 11.7–28.2; p = 0.02) and overall survival (30.6 months, 95% CI 12.4–37.2, vs. 55.6 months, 95% CI 25.8–61.8; p = 0.03) compared to those without detectable EGFR mutations. The detection of EGFR mutations in plasma ctDNA is a promising, minimally invasive, and reliable alternative to tumor biopsy, and the presence of EGFR mutations in plasma ctDNA after first-line EGFR-TKI therapy is associated with poor prognosis.

EGFR mutation analysis in histologic and cytologic specimens of non-small cell lung cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7176-7176 ◽  
Author(s):  
H. Sakai ◽  
K. Akagi ◽  
J. Sudoh ◽  
S. Yoneda ◽  
H. Komagata ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mutation Analysis ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Polymorphism Analysis ◽  
Small Cell Lung

7176 Background: Recent studies have suggested that EGFR mutations can be used to predict tumor sensitivity to gefitinib (epidermal growth factor receptor tyrosine kinase inhibitor) in patients with non-small-cell lung cancer (NSCLC). Most previous studies of EGFR mutations have used direct sequencing to analyze surgically resected specimens. More rapid, accurate, and simple techniques for analysis of EGFR mutations in histologic or cytologic specimens (i.e., transbronchial biopsy, bronchial washing, pleural effusion, lymph node aspiration) are needed to improve outcomes. Methods: DNA was extracted from histologic or cytologic specimens of NSCLC obtained from March through October 2005. The major mutations of the EGFR gene (exons 18–21) were analyzed by our original technique for fragment analysis and polymerase-chain-reaction-restriction-fragment-length polymorphism analysis. Results: About 2 days were required for mutation analysis. Pathological analysis indicated that 64 (5 histologic and 59 cytologic specimens) of 90 specimens (11 histologic and 79 cytologic specimens) were adenocarcinomas. EGFR mutations were found in 22 of these specimens (2 histologic and 20 cytologic specimens; ex19:del 13, ex19:ins 2, ex21:L858R 7). An EGFR mutation (ex19:del) was also found in a patient with large cell carcinoma. Conclusions: Our method can efficiently detect EGFR mutations in small samples of lung cancer cells obtained from histologic or cytologic specimens. This method is useful for the identification of EGFR mutations in patients with unresectable NSCLC in whom sufficient tissue specimens are difficult to obtain. No significant financial relationships to disclose.

Validation study of direct sequencing and PCR-invader for detecting EGFR mutations in non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8094-8094
Author(s):  
Y. Naito ◽  
K. Goto ◽  
H. Kenmotsu ◽  
Y. Nishiwaki ◽  
K. Kubota ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Direct Sequencing ◽  
Pcr Amplification ◽  
The Other ◽  
Egfr Mutations ◽  
Wild Type ◽  
Highly Sensitive ◽  
Formalin Fixed Paraffin Embedded ◽  
Exon 19 Deletion ◽  
Exon 19

8094 Background: EGFR mutation is both a predictive and prognostic factor for NSCLC treated with EGFR-TKI. Although new, highly sensitive methods for detecting EGFR mutations are currently available, these methods have not been validated. Methods: To validate direct sequencing and PCR-invader for detecting EGFR mutation, we analyzed 124 NSCLC by both methods concomitantly. Tumor tissues were obtained by surgical resection. Formalin-fixed paraffin-embedded specimens were prepared to analyze EGFR mutation. In direct sequencing, Exon 18, 19, and 21 of the EGFR gene were amplified, and PCR amplification products were sequenced directly (Mitsubishi Chemical Medience Corporation). PCR-invader was performed using the invasive cleavage of probe oligonucleotides to detect 10 mutations including Exon 18, 19, 20, 21 (BML incorporation). Results: EGFR mutations were detected in 51 patients (41%) by direct sequencing and 56 (45%) by PCR-invader. Discordance between two methods was found in 12 patients (10%). Exon 19 deletion was detected in 18 and 22 patients respectively. Exon 21 L858R was detected in 30 and 32 patients respectively. Each mutation in exon 19 deletions or L858R detected by direct sequencing could also be identified by PCR-invader. Overall 45 mutations were concordant by both methods. In two patients who received gefitinib, one patient with wild type by both methods did not respond to gefitinib. On the other hand, the other patient expressing Exon 19 deletion by PCR-invader but regarded as wild type by direct sequencing responded to gefitinib monotherapy. Conclusions: Discrepancy between two methods for detecting EGFR mutation was demonstrated and PCR-invader seems to be more sensitive. Further investigation including other highly sensitive methods is currently underway. No significant financial relationships to disclose.

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