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. 2023 Jul 31;12(7):1425-1435.
doi: 10.21037/tlcr-22-892. Epub 2023 Jun 19.

A prospective phase 2 study of expeditious EGFR genotyping and immediate therapeutic initiation through extracellular vesicles (EV)-based bronchoalveolar lavage fluid (BALF) liquid biopsy in advanced NSCLC patients

In Ae Kim  1 , Jae Young Hur  1   2 , Hee Joung Kim  1   3 , Wan Seop Kim  1   2 , Kye Young Lee  1   3
Affiliations

A prospective phase 2 study of expeditious EGFR genotyping and immediate therapeutic initiation through extracellular vesicles (EV)-based bronchoalveolar lavage fluid (BALF) liquid biopsy in advanced NSCLC patients

In Ae Kim et al. Transl Lung Cancer Res. .

Abstract

Background: In our previous study, epidermal growth factor receptor (EGFR) genotyping using extracellular vesicles (EV)-derived DNA isolated from bronchoalveolar lavage fluid (BALF) was proven to be highly concordant with conventional tissue-based genotyping and its turn-around-time (TAT) was only 1-2 days. On this background, we prospectively validated the performance of EV-based BALF liquid biopsy for EGFR genotyping in the real practice of advanced non-small cell lung cancer (NSCLC) patients.

Methods: After screening 120 newly diagnosed stage III-IV NSCLC patients, 51 cases were detected as EGFR-mutated by EV-based BALF EGFR genotyping and 40 patients were enrolled for gefitinib treatment. BALF EV were isolated by ultracentrifuge method and EGFR genotyping was performed with PCR-based PNA-clamping assisted fluorescence melting curve analysis. The objective response rate, progression-free survival (PFS), TAT, time to treatment initiation (TTI), and concordance rate were analyzed with clinical parameters.

Results: There was only one false positive case among the 120 screened patients and the overall concordance rate between tissue biopsy and EV-based BALF liquid biopsy was 99.2% including the subtype of EGFR mutations. TAT for EV-based BALF EGFR genotyping was 1.9±1.1 days, while tissue-based TAT was 12.1±7.2 days (P<0.001). EGFR genotyping was determined even before obtaining histopathologic report in most cases. TTI in BALF EGFR genotyping was faster than tissue genotyping (7.8±6.5 vs. 13.8±12.9 days). Therapeutic outcomes of response rate and PFS were almost similar to tissue-based results.

Conclusions: We demonstrated, for the first time, that EV-based BALF liquid biopsy should be an excellent platform for expeditious EGFR genotyping and rapid therapeutic intervention even before obtaining the result of histopathology in advanced NSCLC patients.

Keywords: Extracellular vesicles (EV); epidermal growth factor receptor mutation (EGFR mutation); gefitinib; liquid biopsy; non-small cell lung cancer (NSCLC).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-892/coif). KYL reports that this study received funding from Chong Kun Dang Pharm. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The study flow diagram of rapid diagnosis and EGFR-TKI initiation by EV-based BALF liquid biopsy in advanced NSCLC patients. EV, extracellular vesicle; BALF, bronchoalveolar lavage fluid; EGFR, epidermal growth factor receptor; SCLC, small cell lung cancer; TKI, tyrosine kinase inhibitor; NSCLC, non-small cell lung cancer.
Figure 2
Figure 2
Concordance rate of EV-based BALF liquid biopsy for EGFR genotyping to tissue genotyping and plasma liquid biopsy (n=51). EV, extracellular vesicle; BALF, bronchoalveolar lavage fluid; EGFR, epidermal growth factor receptor.
Figure 3
Figure 3
Kaplan-Meier curve of PFS in patients treated by gefitinib based on BALF liquid biopsy (n=38). CI, confidence interval; mPFS, median progression-free survival; PFS, progression-free survival; BALF, bronchoalveolar lavage fluid.
See this image and copyright information in PMC

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