Background:Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors improve outcomes in EGFR T790M-positive non-small cell lung cancer (NSCLC), but the prognostic value of plasma-detected T790M remains uncertain. We evaluated the clinical significance of baseline plasma T790M in patients treated with lazertinib, accounting for metastatic distribution and coexisting genomic alterations. Methods:In this prospective multicenter cohort, we analyzed 117 patients with EGFR-mutant NSCLC who received lazertinib after T790M confirmation in tissue or plasma. Plasma EGFR mutations were profiled using next-generation sequencing before treatment. Progression-free survival (PFS) and overall survival (OS) were compared by plasma T790M status, metastatic sites, and co-alterations. Results:Of 117 patients, 92 were plasma T790M-positive and 25 were plasma T790M-negative. Plasma T790M positivity was associated with shorter PFS (10.0 vs. 23.0 months, P=0.03) and OS (20.0 months vs. not reached, P=0.006). All patients with liver or adrenal metastases were plasma T790M-positive, and involvement of either site predicted poorer outcomes than in patients without these metastases. Bone metastasis also portended a worse prognosis, irrespective of plasma T790M status. Among co-alterations, EGFR C797S or MYC alterations correlated with shorter PFS. Conclusions:Baseline plasma T790M, interpreted alongside metastatic distribution, provided prognostic information in EGFR-mutant NSCLC treated with lazertinib. Liver and adrenal metastases occurred exclusively in plasma T790M-positive patients and were associated with markedly worse outcomes, consistent with a ctDNA-shedding phenotype. Bone metastasis was an adverse prognostic factor independent of plasma T790M, underscoring the combined prognostic impact of molecular and metastatic features.

Patients who undergo tracheostomy and remain ventilator-dependent for over 21 days (defined as prolonged mechanical ventilation, PMV) represent a critically ill subgroup with high long-term mortality. Existing prognostic models such as the ProVent score may not fully capture the specific risk profile of these patients. This study aimed to develop and validate a novel prognostic model, the Tracheostomy-ProVent score, to predict 3-, 6-, and 12-month mortality using clinical variables measured on day 21 of mechanical ventilation. This retrospective cohort study included 213 tracheostomized adult patients who received invasive mechanical ventilation for more than 21 consecutive days in a tertiary care hospital between February 2011 and February 2023. Multivariate logistic regression was used to identify predictors of mortality and construct a scoring model. Model performance was assessed using area under the receiver operating characteristic curve and calibration analyses. The cumulative mortality rates in our patient cohort were 55.9

ABSTRACT Introduction The clinical application of lazertinib, a third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has extended to the treatment of EGFR‐mutant non‐small‐cell lung cancer (NSCLC); however, the effects of its dose modification on its efficacy and safety have not yet been adequately established. Methods This prospective, multicenter, observational cohort study aims to evaluate the clinical implications of adjusting the lazertinib dose. Patients will be categorized into two groups based on the lazertinib dose administered during the initial 12 weeks of treatment in routine clinical practice: 160 and 240 mg groups. The primary endpoints are progression‐free survival in the 160 mg group and identifying risk factors associated with dose modification during the 12‐week period. Discussion The findings from the present study will provide real‐world insights into the clinical factors leading to lazertinib dose adjustments and deepen our understanding of the efficacy and safety of lazertinib in patients with NSCLC. Our research will contribute toward optimizing medical strategies for NSCLC treatment and aid clinicians in making accurate clinical decisions regarding dose modifications in routine practice.

Background/Aims This study investigated the efficacy and safety of first-line afatinib treatment in older patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Methods This retrospective, multicenter, observational cohort study included 103 patients aged ≥ 75 years who were treated with first-line afatinib for EGFR-mutated NSCLC. The primary outcome was time-on-treatment (TOT). Results The median TOT of patients was 13.6 months (95% confidence interval 11.0–16.2). Ninety-two patients (89.3%) required dose modification. Dose reduction was significantly more frequent in the 40 mg starting dose group than in the 30 mg group (93.1% vs. 68.8%, p = 0.004). The most common grade 3 or worse adverse events (AEs) were diarrhea (n = 16, 54%), acneiform rash (n = 4, 14.3%), and stomatitis (n = 4, 14.3%). Grade 3 or worse AEs led to dose modification in 23 of 28 patients (82.1%) and permanent discontinuation of therapy in five of 28 patients (17.9%). On disease progression, tissue re-biopsy was performed in 18 of 74 patients (24.3%). Thirty-four patients (45.9%) received subsequent chemotherapy; of these, most patients (n = 21, 61.8%) received pemetrexed monotherapy. Conclusions This study demonstrated the efficacy of first-line afatinib treatment for EGFR-mutant NSCLC in older patients. However, despite similar safety profiles and frequencies of AEs reported in previous studies, the frequency of dose modifications was higher in this population. A 30 mg starting dose of afatinib and a predefined dose adjustment may be suitable strategies for this population. Post-tyrosine kinase inhibitor management, such as tissue re-biopsy and platinum-based chemotherapy, tended to be underprescribed in this age group.

Introduction: Transbronchial lung biopsy using radial probe endobronchial ultrasound (RP-EBUS) is an important modality for diagnosing peripheral lung lesions (PLLs), but unmet needs remain. This study evaluates the diagnostic yields and safety of cryobiopsy-based tri-modality sampling using an ultrathin bronchoscope (UTB) with RP-EBUS for diagnosing PLLs. METHODS:This prospective observational pilot study was conducted from November 2023 to January 2024, and included patients with PLLs ≤30 mm in diameter. Bronchoscopic procedures were performed using a UTB guided by RP-EBUS. Tri-modality sampling was sequentially conducted using cryobiopsy, forceps biopsy, and transbronchial needle aspiration (TBNA). The primary outcome was cumulative diagnostic yield, and secondary outcomes included the diagnostic yield of each modality and adverse events. RESULTS:Fifty patients with PLLs, with a median diameter of 20.3 mm, were included. A bronchus sign was present in 66% of cases, and lesions were invisible on RP-EBUS in three instances. The overall cumulative diagnostic yield was 78%. The diagnostic yields were 78.7%, 66.7%, and 54.2% for cryobiopsy, forceps biopsy, and TBNA, respectively. Adding forceps biopsy to cryobiopsy improved the diagnostic yield by 4%, from 74% to 78%, and increased sensitivity for malignancy by 5.1%, from 84.6% to 89.7%. TBNA did not provide any additional improvement in diagnostic yield or sensitivity to malignancy. Bleeding occurred in 68% of the patients, with 28% experiencing grade 3 bleeding, all managed without life-threatening complications. CONCLUSION:Cryobiopsy-based combination sampling modality using UTB is feasible and safe for diagnosing PLLs, offering high diagnostic yield and improved sensitivity for malignancy. .

PURPOSE:There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation. MATERIALS AND METHODS:A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue. RESULTS:In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation. CONCLUSION:We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

After the successful development of targeted therapy and immunotherapy for the treatment of advanced-stage non-small cell lung cancer (NSCLC), these innovative treatment options are rapidly being applied in the adjuvant setting for early-stage NSCLC. Some adjuvants that have recently been approved include osimertinib for epidermal growth factor receptor-mutated tumors and atezolizumab and pembrolizumab for selected patients with resectable NSCLC. Numerous studies on various targeted therapies and immunotherapy with or without chemotherapy are currently ongoing in the adjuvant setting. However, several questions regarding optimal strategies for adjuvant treatment remain unanswered. The present review summarizes the available literature, focusing on recent advances and ongoing trials with targeted therapy and immunotherapy in the adjuvant treatment of early-stage NSCLC.

Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74–ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib’s sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies.

Background/Objectives: The purpose of this study was to evaluate the relationship between 1-year mortality and health insurance benefit extension policy items in severe pneumonia pa-tients requiring mechanical ventilation using a South Korean nationwide cohort. Methods: A nationwide population-based retrospective study was conducted using the Korean National Health Insurance database. A total of 1,099 patients (542 patients in the health insurance benefit item group and 557 patients in the control group) were included. The primary outcome was 1-year mortality. Results: Among patients with health insurance benefit extension policy items, 203 patients (37.5%) were diagnosed with hemato-oncological disease, who were categorized as group A, and 339 patients (62.5%) were diagnosed with cerebrovascular, cardiovascular, or rare diseases, who were categorized as group B. Group B had lower 1-year mortality (50.7% vs. 62.5%, P

Background Molecular screening using next-generation sequencing (NGS) in the pathologic evaluation of lung cancer is considered the standard in clinical practice; hence, we evaluated the diagnostic yields of various sampling methods for NGS. Methods NGS data from patients with lung cancer at the Pusan National University Hospital (Busan, South Korea), admitted October, 2020-April, 2023, was obtained. The sampling methods by which NGS data was obtained were divided into surgical and nonsurgical. Surgical methods included thoracoscopic surgery, surgical biopsy from the metastatic site, and lymph node excisional biopsy, whereas nonsurgical methods included bronchoscopy procedures and medical thoracoscopic biopsy. Results In total, we obtained 319 patients' NGS data:150 (47.0%) and 169 (53.0%) was obtained using surgical and nonsurgical methods, respectively. The overall diagnostic yield of NGS analysis was 97.5% for all samples. There were no significant differences in the success rates of deoxyribonucleic acid sequencing between surgical and nonsurgical sampling methods (98.0% vs. 96.4%, p = 0.313). On the other hand, the success rate of ribonucleic acid (RNA) sequencing was significantly lower in the surgical method group (78.0% vs. 92.3%; p < 0.001). Multivariate analysis showed that surgical sampling significantly correlated with RNA sequencing failure (Odd Ratio 4.128, 95% Confidence Interval 1.681-10.133, p = 0.002). Conclusions Small samples obtained using nonsurgical procedures are suitable for NGS analysis in clinical practice. However, surgical sampling showed a relatively lower success rate for RNA sequencing than nonsurgical sampling. This information may help in the development of protocols to reduce RNA degradation during the surgical process.

Invasive mucinous adenocarcinoma (IMA) of the lungs is a rare subtype of lung adenocarcinoma with a limited understanding of its prognosis, particularly in advanced stages. This study aimed to assess the prognosis of patients with advanced IMA by focusing on treatment modalities. This single-center retrospective study evaluated 33 patients with IMAs diagnosed with advanced-stage disease or disease progression after curative treatment between 2011 and 2021. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). OS and PFS were calculated from the date of the diagnosis of advanced IMA. The study cohort included 13 patients at the initial advanced stage and 20 patients who progressed after curative treatment. Treatment modalities included conventional chemotherapy in 24 patients (72.7

Background and ObjectiveNext-generation sequencing (NGS) analysis is considered standard for lung cancer diagnosis in clinical practice. Little is known about the feasibility of NGS using tumour tissue sampled with a 1.1 mm-diameter cryoprobe. We aimed to investigate the suitability of specimens obtained by transbronchial cryobiopsy (TBC) using a 1.1 mm-diameter cryoprobe for NGS analysis.MethodsPatients with lung cancer who underwent TBC using a 1.1 mm-diameter cryoprobe for NGS testing between October 2020 and April 2023 were enrolled. A 4.0- or 3.0 mm-diameter bronchoscope with radial probe endobronchial ultrasound and virtual bronchoscopic navigation was used to detect peripheral lung lesions. All procedures were performed under fluoroscopic guidance. Data were analysed retrospectively.ResultsA total of 56 patients underwent TBC using a 1.1 mm cryoprobe for NGS testing, during the study period. Most patients (98%) were in the advanced stage of lung cancer (recurrent or inoperable disease of stages III or IV). The diagnostic yield of NGS for DNA and RNA sequencing was 95% each (53 of 56). Moderate bleeding was noted in three patients (5%) and none of the study patients developed life-threatening complications, such as pneumothorax or lung infection.ConclusionTBC using a 1.1 mm-diameter cryoprobe is a useful and safe tool for NGS analysis, for both DNA and RNA sequencing. imageConclusionTBC using a 1.1 mm-diameter cryoprobe is a useful and safe tool for NGS analysis, for both DNA and RNA sequencing. image A total of 56 patients underwent transbronchial cryobiopsy using a 1.1 mm cryoprobe for next-generation sequencing (NGS) testing. The yields of NGS using cryobiopsy was 95% in both DNA and RNA sequencing. Patients did not develop any life-threatening complications during the procedure. image

PURPOSE:Radial probe endobronchial ultrasound (RP-EBUS) accurately locates peripheral lung lesions (PLLs) during transbronchial biopsy (TBB). We performed an updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS to generate recommendations for the development of the Korean Association of Lung Cancer guidelines.MATERIALS AND METHODS:We systematically searched MEDLINE and EMBASE (from January 2013 to December 2022), and performed a meta-analysis using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total lesion number. Subgroup analysis was performed to identify related factors.RESULTS:Forty-one studies with a total of 13,133 PLLs were included. The pooled diagnostic yield of RP-EBUS was 0.72 (95% confidence interval [CI], 0.70 to 0.75). Significant heterogeneity was observed among studies (χ2=292.38, p < 0.01, I2=86.4%). In a subgroup analysis, there was a significant difference in diagnostic yield based on RP-EBUS findings (within, adjacent to, invisible), with a risk ratio of 1.45 (95% CI, 1.23 to 1.72) between within and adjacent to, 4.20 (95% CI, 1.89 to 9.32) between within and invisible, and 2.59 (95% CI, 1.32 to 5.01) between adjacent to and invisible. There was a significant difference in diagnostic yield based on lesion size, histologic diagnosis, computed tomography (CT) bronchus sign, lesion character, and location from the hilum. The overall complication rate of TBB with RP-EBUS was 6.8% (bleeding, 4.5%; pneumothorax, 1.4%).CONCLUSION:Our study showed that TBB with RP-EBUS is an accurate diagnostic tool for PLLs with good safety profiles, especially for PLLs with within orientation on RP-EBUS or positive CT bronchus sign.

Since the introduction of low-dose computed tomography (CT) screening for patients at high risk of lung cancer, the detection rate of suspicious lung cancer has increased. In addition, there have been many advances in therapeutics targeting oncogenic drivers in non-small cell lung cancer. Therefore, accurate pathological diagnosis of lung cancer, including molecular diagnosis, is increasingly important. This review examines the problems in the pathological diagnosis of suspected lung cancer. For successful pathological diagnosis of lung cancer, clinicians should determine the appropriate modality of the diagnostic procedure, considering individual patient characteristics, CT findings, and the possibility of complications. Furthermore, clinicians should make efforts to obtain a sufficient amount of tissue sample using non- or less-invasive procedures for pathological diagnosis and biomarker analysis.

Purpose Epidermal growth factor receptor (EGFR) T790M mutations have been detected in the second or third rebiopsy, even if the T790M mutation was not identified in the first rebiopsy. This meta-analysis investigated the EGFR T790M mutation detection rates and its additional advantages with repeated rebiopsies.Materials and Methods We searched through the PubMed and EMBASE databases up to June 2022. Studies reporting rebiopsy to identify the EGFR T790M mutation in case of disease progression among patients with advanced non-small cell lung cancer and multiple rebiopsies were included. The quality of the included studies was checked using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.Results Eight studies meeting the eligibility criteria, reporting 1,031 EGFR mutation–positive patients were selected. The pooled EGFR T790M mutation detection rate of the first and repeated rebiopsies were 0.442 (95% confidence interval [CI], 0.411 to 0.473; I2=84%; p < 0.01) and 0.465 (95% CI, 0.400 to 0.530; I2=69%; p < 0.01), respectively. Overall, the pooled detection rate of EGFR T790M mutation was 0.545 (95% CI, 0.513 to 0.576), which increased by 10.3% with repeated rebiopsies.Conclusion This meta-analysis identified that repeated rebiopsy increases the detection rate of EGFR T790M mutation by 10.3%, even if EGFR T790M mutation is not detected in the first rebiopsy. Our results indicate that the spatiotemporal T790M heterogeneity can be overcome with repeated rebiopsy.

Purpose The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs).Materials and Methods From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022.Results The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm2) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm2, p < 0.001) and 1.9-mm forceps (3.7 mm2, p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications.Conclusion Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

Background: The combination of radial probe endobronchial ultrasound (R-EBUS) and cryobiopsy for peripheral lung lesions (PLLs) improves the performance of transbronchial biopsy (TBB). We investigated the performance and safety of an additional cryobiopsy using a novel 1.1-mm diameter probe following conventional TBB using R-EBUS for the diagnosis of PLLs. Methods: Patients who underwent biopsy for the diagnosis of PLL ≤ 30 mm from April 2021 to November 2021 and received combined TBB using R-EBUS and sequential cryobiopsy with a 1.1-mm diameter probe were included in our study. All records were followed-up until April 2022. Results: Baseline characteristics for study patients (n = 110) are presented in Table 1. The overall diagnostic yield was 79%, which was significantly higher than 61% of TBB (P < 0.01). The diagnostic yield of subsequent cryobiopsy was 66% and cryobiopsy increased the overall diagnostic yield by 18%. There were significant differences in the surface area of the tissue between cryobiopsy (mean area, 19 mm2) and both TBB using 1.5-mm forceps (mean area, 3 mm2; P < 0.01) and 1.9-mm forceps (mean area, 4 mm2; P < 0.01). Complications were found in 10% of samples: pneumothorax (1%), infection (1%), and significant bleeding (8%). No patients developed life-threatening complications. Conclusions: Additional cryobiopsy using 1.1-mm diameter probe increased the diagnostic yield of TBB using R-EBUS by 18%. The overall diagnostic yield of combined procedures with TBB using R-EBUS and subsequent cryobiopsy was 79% for PLL ≤ 30 mm. Table 1.

Purpose Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.Materials and Methods Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.Results A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.