Feasibility of re‐biopsy and <i>EGFR</i> mutation analysis in patients with non‐small cell lung cancer

Kim, Tae-Ok; Oh, In Jae; Kho, Bo Gun; Park, Ha Young; Chang, Jane; Park, Cheol‐Kyu; Shin, Hyeonsook; Lim, Jung Hwan; Kwon, Yong Soo; Kim, Yu-Il; Lim, Sung‐Chul; Kim, Young‐Chul; Choi, Yoo‐Duk

doi:10.1111/1759-7714.12762

Cited by 23 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…afatinib, erlotinib, geftinib, and osimertinib) will be greater than the total number who received EGFR-TKI c Of the 47 patients who received osimertinib as subsequent therapies, 24 were tested T790M positive, seven were not positive for T790M, and 16 were not tested for EGFR mutations d Other targeted therapeutic agents are listed in Table 1 therapy (including EGFR-TKIs) [20]. Furthermore, the 30% rate of EGFR testing before subsequent therapy is consistent with previous estimates (30-48%) [21][22][23] and emphasizes that, during the study period, a substantial proportion of patients initiated a subsequent therapy without updated information on the molecular profile of the tumor.…”

Section: Discussionsupporting

confidence: 80%

EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors

et al. 2020

View full text Add to dashboard Cite

Background: The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first−/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received. Methods: Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first−/second-generation EGFR-TKI from 11/2015-09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first−/second-generation EGFR-TKI were described. Results: Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib. Conclusions: A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFRmutated NSCLC.

show abstract

Section: Discussionsupporting

confidence: 80%

EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors

et al. 2020

View full text Add to dashboard Cite

show abstract

“…12,13 Notwithstanding re-biopsy is feasible in clinical practice, it is an invasive operation and faces the same challenges voiced by previous studies. 14,15 These defects enormously limit the practicability of precision medicine at scale.…”

Section: Introductionmentioning

confidence: 99%

“…Besides, the poor DNA quality, intratumoral heterogeneity and long turnaround time raise much concern on the balance of costs and benefits . Notwithstanding re‐biopsy is feasible in clinical practice, it is an invasive operation and faces the same challenges voiced by previous studies . These defects enormously limit the practicability of precision medicine at scale.…”

Section: Introductionmentioning

confidence: 99%

Toward automatic prediction of EGFR mutation status in pulmonary adenocarcinoma with 3D deep learning

Zhao

Yang

et al. 2019

Cancer Medicine

View full text Add to dashboard Cite

To develop a deep learning system based on 3D convolutional neural networks (CNNs), and to automatically predict EGFR‐mutant pulmonary adenocarcinoma in CT images. A dataset of 579 nodules with EGFR mutation status labels of mutant (Mut) or wild‐type (WT) was retrospectively analyzed. A deep learning system, namely 3D DenseNets, was developed to process 3D patches of nodules from CT data, and learn strong representations with supervised end‐to‐end training. The 3D DenseNets were trained with a training subset of 348 nodules and tuned with a development subset of 116 nodules. A strong data augmentation technique, mixup , was used for better generalization. We evaluated our model on a holdout subset of 115 nodules. An independent public dataset of 37 nodules from the cancer imaging archive (TCIA) was also used to test the generalization of our method. Conventional radiomics analysis was also performed for comparison. Our method achieved promising performance on predicting EGFR mutation status, with AUCs of 75.8% and 75.0% for our holdout test set and public test set, respectively. Moreover, strong relations were found between deep learning feature and conventional radiomics, while deep learning worked through an enhanced radiomics manner, that is, deep learned radiomics (DLR), in terms of robustness, compactness and expressiveness. The proposed deep learning system predicts EGFR‐mutant of lung adenocarcinomas in CT images noninvasively and automatically, indicating its potential to help clinical decision‐making by identifying eligible patients of pulmonary adenocarcinoma for EGFR‐targeted therapy.

show abstract

“…The continuous treatment using EGFR-TKI for EGFR-mutant NSCLC develops resistance to EGFR-TKIs, due to the acquired secondary EGFR mutations such as T790M on exon 20 of the EGFR gene [19,[24][25][26]. Re-biopsy is desirable for the early detection of tumor recurrence and proliferative reactivation of carcinoma by acquired drug resistance [19,27,28]. However, this is not practical because of the high invasiveness involved.…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Liquid-Based Cytological Specimen Using Virtually Positive Sputum with Adenocarcinoma Cells

et al. 2020

View full text Add to dashboard Cite

Liquid-based cytology (LBC) analysis of sputum is a useful diagnostic and prognostic tool for detecting lung cancer. DNA and RNA derived from lung cancer cells can be used for this diagnosis. However, the quality of cytological material is not always adequate for molecular analysis due to the effect of formalin in the commercially available fixation kits. In this study, we examined DNA and RNA extraction methods for LBC analysis with formalin fixation, using lung carcinoma cell lines and sputum. The human non-small cell lung cancer cell lines were fixed with LBC fixation reagents, such as CytoRich red preservative. Quantification of thyroid transcription factor-1 (TTF-1) and actin mRNA, epidermal growth factor receptor (EGFR) DNA in HCC827, H1975, and H1299 cells, and mutation analysis of EGFR in HCC827 and H1975 cells were performed by quantitative PCR (qPCR) and fluorescence resonance energy transfer (FRET)-based preferential homoduplex formation assay (F-PHFA) method, respectively. mRNA and DNA extracted from cell lines using RNA and/or DNA extraction kits for formalin-fixed paraffin-embedded (FFPE) fixed with various LBC solutions were efficiently detected by qPCR. The detection limit of EGFR mutations was at a rate of 5% mutated positive cells in LBC. The detection limit of the EGFR exon 19 deletion in HCC827 was detected in more than 1.5% of the positive cells in sputum. In contrast, the detection limit of the T790M/L858R mutation in H1975 was detected in more than 13% of the positive cells. We also detected EGFR mutations using next generation sequencing (NGS). The detection limit of NGS for EGFR mutation was lower than that of the F-PHFA method. Furthermore, more than 0.1% of positive cells could be cytomorphologically detected. Our results demonstrate that LBC systems are powerful tools for cytopathological and genetic analyses. However, careful attention should be paid to the incidence of false negative results in the genetic analysis of EGFR mutations detected by LBC.

show abstract

Feasibility of re‐biopsy and EGFR mutation analysis in patients with non‐small cell lung cancer

Cited by 23 publications

References 36 publications

EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors

EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors

Toward automatic prediction of EGFR mutation status in pulmonary adenocarcinoma with 3D deep learning

Molecular Analysis of Liquid-Based Cytological Specimen Using Virtually Positive Sputum with Adenocarcinoma Cells

Contact Info

Product

Resources

About