## 1 Introduction  
One of the main public health concerns impacting populations globally is lung cancer, which is responsible for the highest number of deaths related to cancer and accounts for 12.4% of patients receiving a new cancer diagnosis [1]. Approximately 85% of patients diagnosed with lung cancer have non-small-cell lung carcinoma (NSCLC); adenocarcinoma constitutes the histological subtype of this heterogeneous entity that occurs most frequently [2]. However, it encompasses a spectrum of unique molecular subtypes, all of which are characterized by specific oncogenic genetic alterations, rather than a single disease entity. The identification of these molecular changes driving malignancy has resulted in new therapies targeting these pathways being developed, ushering in an era of targeted therapy in cancer management. Gene mutations, rearrangements, and amplifications can initiate NSCLC carcinogenesis. The detection of specific driver mutations has led to significant enhancements in terms of NSCLC treatments, particularly for patients whose cancer has metastasized. Targeted therapies for NSCLC are associated with an increased response rate and extended progression-free survival (PFS) and overall survival (OS), making them the preferred treatments for cases involving specific driver mutations, including the mutations that affect the epidermal growth factor receptor (_EGFR_), _ALK_, _BRAF_, and _ROS1_ genes [3]. _EGFR_ is one of the leading molecular targets in NSCLC patients. For cases involving patients exhibiting advanced NSCLC with _EGFR_ mutations (_EGFR_), it has been demonstrated that a correlation exists between oral _EGFR_-tyrosine kinase inhibitor treatment and extended PFS and OS, as well as higher objective radiographic response rates in comparison to conventional first-line chemotherapy. In such cases, treatment with osimetinib, a third-generation oral _EGFR_-tyrosine kinase inhibitor, has been linked with PFS > 18 months [4] and OS > 3 years [5]. According to the recommendations in current guidelines, such as those published by the National Comprehensive Cancer Network (NCCN), molecular testing for _EGFR_ mutations in individuals with metastatic pulmonary adenocarcinoma, large-cell carcinoma, and NSCLC--not otherwise specified (NOS) is recommended [3]. Furthermore, for patients with metastatic pulmonary squamous cell carcinoma, such testing is also a potential option. In addition to the recommendation for metastatic patients, _EGFR_ mutation testing is currently recommended for patients with completely resected stage IB-IIIA NSCLC [3], because the addition of osimetinib after adjuvant chemotherapy for such patients leads to the significant prolongation of both PFS [6] and OS [7]. Hence, when developing treatment plans for NSCLC patients, it is critical that _EGFR_ mutations are identified. When _EGFR_ mutation status is being assessed, next-generation sequencing (NGS), real-time polymerase chain reaction, or Sanger sequencing is generally performed [3]. NGS is a revolutionary technique for the biomolecular characterization of NSCLC. In efforts to identify _EGFR_ mutations, tissue and/or cytologic specimens are the gold standard materials for molecular analyses such as NGS. Nevertheless, the acquisition of sufficient tumor samples remains challenging, particularly among patients with advanced-stage NSCLC. Although NGS is effective for the identification of _EGFR_ mutations, it is hindered by the limited availability of tumor tissues and technical factors [8]. The most commonly encountered problems include inadequate tumor sample quantity or quality [9; 10; 11]. Invasive tissue biopsy is associated with several challenges, including inadequate tumor retrieval, an inability to access suitable tissues, and risks of bleeding and pneumothorax [12; 13]. Therefore, tissue biopsy is not performed in approximately 7-15% of patients with NSCLC [9; 14]. For around 20% of patients, the feasibility of biopsy may be questionable [10; 13; 15; 16].