Real-world study of lazertinib as second-line or greater treatment in advanced non-small cell lung cancer.

BACKGROUND: Lazertinib is an oral, third-generation EGFR-TKI, which specifically targets the EGFR T790M mutation along with activating mutations Ex19del and L858R. More real-world data are needed to evaluate its efficacy and safety in treating locally advanced and metastatic non-small cell lung cancer (NSCLC) following prior EGFR TKI treatment. METHODS: This multicenter retrospective study was conducted at seven university hospitals affiliated to the Catholic Medical Center (CMC) in Korea. A clinical data warehouse (CDW) platform was used to access and extract information. RESULTS: A total of 48 patients were assessed. The majority were female (75%) and diagnosed with adenocarcinoma (95.8%). All patients had the EGFR mutation at diagnosis, 27 (56.3%) had the exon 19 deletion, 20 (41.7%) had the L858R mutation, and one (2.0%) had the exon 18 mutation. The median progression-free survival (PFS) was 15.4 months. At 6, 12, and 18 months, PFS rates were 79.1%, 53.6%, and 27.3%, respectively. When PFS was analyzed by prior TKI duration (<18 months vs. >18 months), significant differences were noted at the 6 and 9-month mark (p = 0.013 and p = 0.010, respectively). In multivariate analysis for PFS, only prior TKI duration and ECOG score showed statistical significance (p = 0.026 and p = 0.049, respectively). In the multivariate analysis for OS, ECOG score showed statistical significance (p = 0.006). Among 48 patients, 34 (70.8%) experienced adverse events (AEs) related to lazertinib. The most frequent AEs were skin reaction (29.8%), diarrhea (21.3%), and peripheral neuropathy (20.8%). CONCLUSIONS: The results suggest that lazertinib is effective in second or more line settings, with tolerable safety profile. More patient data are necessary to find possible prognostic markers associated with patient outcome.

Endobronchial valves for emphysema and persistent air-leak: 10-year experience in an Asian country.

BACKGROUND: Endobronchial valve (EBV) therapy, a validated method for bronchoscopic lung volume reduction (BLVR) in severe emphysema, has been explored for persistent air-leak (PAL) management. However, its effectiveness and safety in the Asian population require further real-world evaluation. In this study, we assessed the outcomes of treatment with EBV within this demographic. METHODS: We conducted a retrospective analysis of medical records from 11 Korean centers. For the emphysema cohort, inclusion criteria were patients diagnosed with emphysema who underwent bronchoscopy intended for BLVR. We assessed these patients for clinical outcomes of chronic obstructive pulmonary disease. All patients with PAL who underwent treatment with EBV were included. We identified the underlying causes of PAL and evaluated clinical outcomes after the procedure. RESULTS: The severe emphysema cohort comprised 192 patients with an average age of 70.3 years, and 95.8% of them were men. Ultimately, 137 underwent treatment with EBV. Three months after the procedure, the BLVR group demonstrated a significant improvement in forced expiratory volume in 1 s (+160 mL vs. +30 mL; P = 0.009). Radiographic evidence of lung volume reduction 6 months after BLVR was significantly associated with improved survival (adjusted hazard ratio 0.020; 95% confidence interval 0.038-0.650; P = 0.010). Although pneumothorax was more common in the BLVR group (18.9% vs. 3.8%; P = 0.018), death was higher in the no-BLVR group (38.5% vs. 54.5%, P = 0.001), whereas other adverse events were comparable between the groups. Within the subset of 18 patients with PAL, the predominant causes of air-leak included spontaneous secondary pneumothorax (44.0%), parapneumonic effusion/empyema (22.2%), and post-lung resection surgery (16.7%). Following the treatment, the majority (77.8%) successfully had their chest tubes removed. Post-procedural complications were minimal, with two incidences of hemoptysis and one of empyema, all of which were effectively managed. CONCLUSIONS: Treatment with EBV provides substantial clinical benefits in the management of emphysema and PAL in the Asian population, suggesting a favorable outcome for this therapeutic approach.

Smoking Status at Time of Diagnosis Affects the Efficacy of Anti-PD-1/L1 Therapy in Patients With Advanced NSCLC.

BACKGROUND/AIM: Programmed death ligand-1 (PD-L1) expression is known to be a predictive biomarker for response to immunotherapy in non-small cell lung cancer (NSCLC). However, PD-L1 is not always a reliable predictive biomarker. In the present study, we aimed to compare responses to immunotherapy according to smoking status in NSCLC patients receiving immunotherapy in second line or further line treatment. PATIENTS AND METHODS: The lung cancer registry database of the Catholic Medical Center, Seoul, Republic of Korea was used. Patients were eligible for this study if they were diagnosed with histologically confirmed NSCLC and received immune checkpoint inhibitors (ICIs) as second-line or further line therapy from January 2017 to December 2021. RESULTS: Overall, 220 patients with NSCLC treated with ICIs were enrolled. There were 40 never smokers, 73 former smokers, and 107 current smokers. In multivariate analysis, smoking status, pathologic type, and PD-L1 expression were significant factors affecting PFS. Sex, ECOG performance status, pathologic type, and PD-L1 expression were significant factors affecting OS. CONCLUSION: Smoking status at diagnosis of lung cancer could be a predictive biomarker for response to ICIs in patients with advanced NSCLC.

Identification of predictive factors for early relapse in patients with unresectable stage III non-small cell lung cancer receiving consolidation durvalumab after concurrent chemoradiation therapy.

BACKGROUND: Patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) receiving definitive concurrent chemoradiation therapy (CCRT) benefit from durvalumab consolidation therapy. However, predictive factors for early relapse during durvalumab maintenance have not yet been identified. METHODS: The present study included the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from January 2018 to December 2021. A total of 51 NSCLC patients treated with durvalumab consolidation therapy after definitive CCRT were included in the analysis. Early relapse was defined as patients experiencing relapse within 6 months of starting initial durvalumab therapy. RESULTS: Among the 51 patients, 15 (29.4%) relapsed during the study period. Median time from initial therapy of durvalumab to progression was 451.00 ± 220.87 days (95% confidence interval [CI]: 18.10-883.90) in overall patients. In multivariate analysis, younger age (adjusted odds ratio [aOR], 0.792; 95% CI: 0.642-0.977; p = 0.030), higher pack-years (aOR, 1.315; 95% CI: 1.058-1.635; p = 0.014), non-COPD (aOR, 0.004; 95% CI: 0.000-0.828; p = 0.004) and anemia (aOR, 234.30; 95% CI: 1.212-45280.24; p = 0.042), were independent predictive factors for early relapse during durvalumab consolidation therapy. CONCLUSION: Younger age, higher number of pack-years, non-COPD, and anemia were independent predictive factors for early relapse during durvalumab consolidation therapy in patients with unresectable stage III NSCLC after definitive CCRT. Careful patient selection and clinical attention are needed for high-risk individuals.

Association Between Quality of Life Questionnaire at Diagnosis and Survival in Patients With Lung Cancer.

BACKGROUND: Patients with lung cancer experience considerable symptom burden, which can decrease patients' QOL. Our aim was to investigate the association between QOL questionnaire at diagnosis and survival of lung cancer. PATIENTS AND METHODS: This was a multicenter study of lung cancer patients at 7 medical centers of the Catholic University of Korea that responded to a quality of life questionnaire between December 1, 2017 and December 31, 2020. We analyzed 5 functional (physical, role, emotional, cognitive, and social functioning) and nine symptom (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) scales and examined their associations with survival. A Cox proportional hazards model was used to evaluate the prognostic value. RESULTS: In total, 1297 lung cancer patients were enrolled. The results of multivariable analysis showed that female, younger age, never smoker, stage I or II cancer, higher physical functioning, and emotional functioning were statistically significant favorable predictors for survival. On subgroup analysis according to early (stage I and II) or advanced (stage III or IV) stage, higher physical functioning and emotional functioning were each found to be favorable prognostic factors for survival. Meanwhile, fatigue, pain, insomnia, and financial difficulties were found to be associated with low scores on the emotional functioning scale; fatigue, pain, dyspnea, and financial difficulties were associated with low scores on the physical functioning scale. CONCLUSION: Assessing the physical functioning and emotional functioning scales of QOL questionnaire items at diagnosis can help clinicians predict the survival of patients with lung cancer.

Prediction of Postoperative Lung Function in Lung Cancer Patients Using Machine Learning Models.

BACKGROUND: Surgical resection is the standard treatment for early-stage lung cancer. Since postoperative lung function is related to mortality, predicted postoperative lung function is used to determine the treatment modality. The aim of this study was to evaluate the predictive performance of linear regression and machine learning models. METHODS: We extracted data from the Clinical Data Warehouse and developed three sets: set I, the linear regression model; set II, machine learning models omitting the missing data: and set III, machine learning models imputing the missing data. Six machine learning models, the least absolute shrinkage and selection operator (LASSO), Ridge regression, ElasticNet, Random Forest, eXtreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM) were implemented. The forced expiratory volume in 1 second measured 6 months after surgery was defined as the outcome. Five-fold cross-validation was performed for hyperparameter tuning of the machine learning models. The dataset was split into training and test datasets at a 70:30 ratio. Implementation was done after dataset splitting in set III. Predictive performance was evaluated by R2 and mean squared error (MSE) in the three sets. RESULTS: A total of 1,487 patients were included in sets I and III and 896 patients were included in set II. In set I, the R2 value was 0.27 and in set II, LightGBM was the best model with the highest R2 value of 0.5 and the lowest MSE of 154.95. In set III, LightGBM was the best model with the highest R2 value of 0.56 and the lowest MSE of 174.07. CONCLUSION: The LightGBM model showed the best performance in predicting postoperative lung function.

The association between clinical parameters and resectability in stage III non-small cell lung cancer, and a combination of N2 lymph node burden and lung immune prognostic index score as a potential biomarker.

Background: Surgery is important treatment option for stage III non-small cell lung cancer (NSCLC) because of its curative potential. We investigated the characteristics of resectable patients, and compared the outcomes according to treatment modalities. Methods: Among 1,092 patients with NSCLC diagnosed between 2008 to 2020 from 7 university hospitals of Catholic Medical Center, we retrospectively analyzed 252 patients with clinical or pathological stage III. We compared survival outcomes among the groups according to resectability, first-line treatments, and the lung immune prognostic index (LIPI) score. Clinical N2 subgroup was analyzed using multi-parameter scoring system. Results: The resectable group consisted of less smokers, showed better pulmonary function and lower inflammatory markers, and tended to be diagnosed as earlier cancer stage than the unresectable group. The resectable group showed better progression-free survival (PFS) and overall survival (OS) than the unresectable group (P<0.001 and P<0.001, respectively). Regarding the first-line treatment, surgery showed the longest median PFS (33.70 months) and the highest 12-month OS rate (91.6%) than the other treatment modalities. OS was significantly different depending on the LIPI score in whole population, as well as in the unresectable group (P=0.004 and P=0.003, respectively). LIPI 0 group exhibited better OS than LIPI 1 and 2 in both populations. Eastern Cooperative Oncology Group (ECOG) 2-4, LIPI 1-2, and first-line treatment were independent prognostic factors for OS. Smoking, forced expiratory volume in the first second (FEV1) and more advanced cancer stage were associated with unresectability. In subgroup analysis of N2 disease, we attempted to create new scoring system combining lymph node (LN) status and LIPI score. This scoring system showed significant association with OS. Conclusions: The patients with resectable stage III NSCLC showed better PFS and OS than the patients with unresectable tumor. LIPI score exhibited possibility to be used as potential biomarker in stage III NSCLC. The multi-parameter scoring system using LN status and LIPI score was predictive of OS in the N2 subgroup.

Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide-platinum-atezolizumab treatment.

BACKGROUND: The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free-survival (PFS) when compared to the placebo group in treatment-naïve extensive stage (ES) small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy have become mainstay treatment modalities as first-line treatment in ES-SCLC. Nevertheless, real-world data are still lacking and the search for potential biomarkers is essential. This study aimed to evaluate potential predictive biomarkers applicable in ES-SCLC under combination therapy. METHODS: Patients with ES-SCLC under etoposide-platinum-atezolizumab enrolled from seven university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. p-values below 0.05 were considered statistically significant. RESULTS: A total of 41 patients were evaluated. Six-month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, nine (22.0%) showed stable disease, and four (9.8%) showed progressive disease. During the induction phase, grade I-II AEs occurred in 22 (53.7%) patients, and grade III-IV AEs occurred in 26 (63.4%) patients. During the maintenance phase, nine out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase (LDH), c-reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant. CONCLUSION: In ES-SCLC under etoposide-platinum-atezolizumab, pretreatment CRP, LDH and FVC (%) were independent predictive factors.

Association of weight change following smoking cessation with the risk of tuberculosis development: A nationwide population-based cohort study.

BACKGROUND: Smoking or weight loss is a risk of tuberculosis (TB) development. However, the impact of weight change after smoking cessation on the occurrence of TB remains elusive. We aimed to determine the relationship between weight change after smoking cessation and the risk of TB development. METHODS: We conducted a population-based cohort study using the national database in Republic of Korea. Of the 10,490,491 subjects who underwent health check-up in 2009, we enrolled 9,953,124 subjects without a previous TB history and followed them until 2017. We divided all study participants into the following three groups: never, former, and current smokers. The primary endpoint was newly developed TB. RESULTS: Among 9,953,124 subjects analyzed, 5,922,845 (59.5%) were never smokers, 1,428,209 (14.4%) were former smokers, and 2,602,080 (26.1%) were current smokers. The risk of TB development was significantly higher in current smokers than in never smokers (adjusted hazard ratio (aHR) 1.158; 95% confidence interval [CI] 1.131-1.186). Among current smokers, individuals who stopped smoking and maintained weight after baseline evaluation had a significantly lower risk of TB development compared with those who continued to smoke (aHR 0.771; 95% CI 0.741-0.892). However, even after smoking cessation, individuals who lost weight were at a significantly higher risk of TB development compared with those who continued to smoke (aHR 1.327; 95% CI 1.119-1.715). CONCLUSIONS: Our findings suggest that smoking is a risk factor for TB and weight maintenance (neither gaining or losing) after quitting smoking might reduce the risk of TB development.

Impaired Lung Function and Lung Cancer Incidence: A Nationwide Population-Based Cohort Study.

BACKGROUND: It is unclear whether the presence of minimal lung function impairment is an independent risk factor for the development of lung cancer in general populations. METHODS: We conducted a population-based cohort study using nationally representative data from the Korean National Health and Nutrition Examination Survey and the Korean National Health Insurance Service. RESULTS: Of 20,553 participants, 169 were diagnosed with lung cancer during follow-up (median, 6.5 years). Participants with obstructive lung function impairment had increased risk of lung cancer (aHR: 2.51; 95% CI: 1.729-3.629) compared with those with normal lung function. The lower was the quartile or decile of forced expiratory volume in one second (FEV1) or the FEV1/forced vital capacity (FVC) ratio, the significantly higher was the incidence rate of lung cancer (p for trend < 0.0001). With FEV1 values in the lowest quartile (Q4), the incidence of lung cancer was significantly increased regardless of FVC (FEV1 Q4 and FVC values in the higher three quartiles Q1-3: aHR 1.754; 95% CI 1.084-2.847, FEV1 Q4 and FVC Q4: aHR 1.889; 95% CI 1.331-2.681). CONCLUSION: Our findings suggest that minimal lung function impairment, as expressed by lower FEV1 or FEV1/FVC value, may be associated with increased risk of lung cancer.

Integrative analysis of lung molecular signatures reveals key drivers of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease with a high clinical burden. The molecular signatures of IPF were analyzed to distinguish molecular subgroups and identify key driver genes and therapeutic targets. METHODS: Thirteen datasets of lung tissue transcriptomics including 585 IPF patients and 362 normal controls were obtained from the databases and subjected to filtration of differentially expressed genes (DEGs). A functional enrichment analysis, agglomerative hierarchical clustering, network-based key driver analysis, and diffusion scoring were performed, and the association of enriched pathways and clinical parameters was evaluated. RESULTS: A total of 2,967 upregulated DEGs was filtered during the comparison of gene expression profiles of lung tissues between IPF patients and healthy controls. The core molecular network of IPF featured p53 signaling pathway and cellular senescence. IPF patients were classified into two molecular subgroups (C1, C2) via unsupervised clustering. C1 was more enriched in the p53 signaling pathway and ciliated cells and presented a worse prognostic score, while C2 was more enriched for cellular senescence, profibrosing pathways, and alveolar epithelial cells. The p53 signaling pathway was closely correlated with a decline in forced vital capacity and carbon monoxide diffusion capacity and with the activation of cellular senescence. CDK1/2, CKDNA1A, CSNK1A1, HDAC1/2, FN1, VCAM1, and ITGA4 were the key regulators as evidence by high diffusion scores in the disease module. Currently available and investigational drugs showed differential diffusion scores in terms of their target molecules. CONCLUSIONS: An integrative molecular analysis of IPF lungs identified two molecular subgroups with distinct pathobiological characteristics and clinical prognostic scores. Inhibition against CDKs or HDACs showed great promise for controlling lung fibrosis. This approach provided molecular insights to support the prediction of clinical outcomes and the selection of therapeutic targets in IPF patients.

Significance of Glasgow Prognostic Scores in NSCLC Patients Treated With Immunotherapy After Platinum-based Cytotoxic Chemotherapy.

BACKGROUND/AIM: Little is known about the prognostic role of the Glasgow prognostic score (GPS) in non-small cell lung cancer (NSCLC) patients treated with immunotherapy after platinum-based cytotoxic chemotherapy. PATIENTS AND METHODS: This study used a lung cancer cohort of the Catholic Medical Center of Korea between January 2018 and September 2020. RESULTS: A total of 78 patients with NSCLC treated with immunotherapy as second or further-line therapy were included. Higher GPS values were significant predictors of shorter immune-related progression-free survival (irPFS) and overall survival (OS). The hazard ratios for irPFS were 0.249 for programmed death-ligand 1 (PD-L1) expression ≥50% and 9.73 for a GPS of 2. Older age, lower PD-L1 expression and higher GPS values were independently associated with shorter OS. CONCLUSION: Higher GPS values were identified as a poor prognostic factor for OS and irPFS in NSCLC patients who received immunotherapy as second or further-line therapy.

The Value of Residual Volume/Total Lung Capacity as an Indicator for Predicting Postoperative Lung Function in Non-Small Lung Cancer.

Chronic obstructive pulmonary disease (COPD) is one of the most frequently occurring concomitant diseases in patients with non-small cell lung cancer (NSCLC). It is characterized by small airways and the hyperinflation of the lung. Patients with hyperinflated lung tend to have more reserved lung function than conventionally predicted after lung cancer surgery. The aim of this study was to identify other indicators in predicting postoperative lung function after lung resection for lung cancer. Patients with NSCLC who underwent curative lobectomy with mediastinal lymph node dissection from 2017 to 2019 were included. Predicted postoperative FEV1 (ppoFEV1) was calculated using the formula: preoperative FEV1 × (19 segments-the number of segments to be removed) ÷ 19. The difference between the measured postoperative FEV1 and ppoFEV1 was defined as an outcome. Patients were categorized into two groups: preserved FEV1 if the difference was positive and non-preserved FEV1, if otherwise. In total, 238 patients were included: 74 (31.1%) in the FEV1 non-preserved group and 164 (68.9%) in the FEV1 preserved group. The proportion of preoperative residual volume (RV)/total lung capacity (TLC) ≥ 40% in the FEV1 non-preserved group (21.4%) was lower than in the preserved group (36.1%) (p = 0.03). In logistic regression analysis, preoperative RV/TLC ≥ 40% was related to postoperative FEV1 preservation. (adjusted OR, 2.02, p = 0.041). Linear regression analysis suggested that preoperative RV/TLC was positively correlated with a significant difference. (p = 0.004) Preoperative RV/TLC ≥ 40% was an independent predictor of preserved lung function in patients undergoing curative lobectomy with mediastinal lymph node dissection. Preoperative RV/TLC is positively correlated with postoperative lung function.

Predictive Role of Prior Radiotherapy and Immunotherapy-Related Adverse Effects in Advanced NSCLC Patients Receiving Anti-PD-1/L1 Therapy.

The present study evaluated the impact of prior radiotherapy (RT) on patients with advanced non-small cell lung cancer (NSCLC) receiving therapy with immune checkpoint inhibitors (ICIs) and further assessed the prognostic factors in patients receiving both RT and ICI. Patients diagnosed with NSCLC at the Catholic Medical Center and Asan Medical Center between January 2016 and October 2020 and who received immunotherapy were retrospectively reviewed. Among 240 patients, poor Eastern Cooperative Oncology Group (ECOG) score, high PD-L1 expression, and ICI-related adverse events (AE) were significantly associated with progression-free survival (PFS) (HR, 2.654; 95% CI, 1.484-4.749; p = 0.001; HR, 0.645; 95% CI, 0.449-0.926, p = 0.017; HR, 0.430; 95% CI, 0.229-0.808; p = 0.009, respectively). Among patients who received both RT and immunotherapy, poor ECOG status, squamous cell carcinoma, and ICI-related AE were significant factors associated with poor PFS (HR, 2.430; 95% CI, 1.464-4.034; p = 0.001; HR, 0.667; 95% CI, 0.455-0.978, p = 0.038; HR, 0.520; 95% CI, 0.284-0.953, p = 0.034, respectively). The present study showed that prior RT showed no significant independent association with primary outcomes in patients with advanced NSCLC receiving immunotherapy. In patients who received both RT and immunotherapy, clinical parameters, including ICI-related AEs, were independently predictive of PFS.

Revised Korean Cough Guidelines, 2020: Recommendations and Summary Statements.

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient's quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Impact of smoking amount on clinicopathological features and survival in non-small cell lung cancer.

BACKGROUND: Screening for early detection of lung cancer has been performed in high-risk individuals with smoking history. However, researches on the distribution, clinical characteristics, and prognosis of these high-risk individuals in an actual cohort are lacking. Thus, the objective of this study was to retrospectively review characteristics and prognosis of patients with smoking history in an actual lung cancer cohort. METHODS: The present study used the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from 2014 to 2017. Patients with non-small cell lung cancer were enrolled. They were categorized into high and low-risk groups based on their smoking history using the national lung screening trial guideline. Distribution, clinical characteristics, and survival data of each group were estimated. RESULTS: Of 439 patients, 223 (50.8%) patients were in the high-risk group. Patients in the high-risk group had unfavorable clinical characteristics and tumor biologic features. Overall survival of the high-risk group was significantly shorter than that of the low-risk group with both early (I, II) and advanced stages (III, IV). In multivariate analysis, heavy smoking remained one of the most important poor clinical prognostic factors in patients with lung cancer. It showed a dose-dependent relationship with patients' survival. CONCLUSIONS: High-risk individuals had poor clinical outcomes. Patients' prognosis seemed to be deteriorated as smoking amount increased. Therefore, active screening and clinical attention are needed for high-risk individuals.

Regional emphysema score is associated with tumor location and poor prognosis in completely resected NSCLC patients.

BACKGROUND: Lung cancer is a frequent comorbidity of chronic obstructive pulmonary disease (COPD). However, the local risk of developing lung cancer related to regional emphysema distribution and clinical outcome has not been investigated. Our aim was to evaluate the impact of regional emphysema score (RES) on tumor location and prognosis in non-small cell lung cancer (NSCLC) patients. METHODS: We enrolled 457 patients who underwent curative surgery for NSCLC at seven hospitals at The Catholic University of Korea from 2014 to 2018. Emphysema was visually assessed for each lobe, with the lingula as a separate lobe. Semi-quantitative emphysema scoring was classified as follows: 0 = none, 0.5 = 1 to 10%, 1 = 11 to 25%, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. An RES was given to each of the six lung zone: the upper, middle, and lower lobes in the right and left lungs. RESULTS: There were 145 patients in the high RES (≥ 3) group and 312 in the low RES (< 3) group. The mean RES in each lobe with cancer was significantly higher than that in other lobes without cancer (0.51 vs. 0.37, P <  0.001). This group showed significantly shorter disease-free survival (P <  0.001), in addition, presence of COPD, low diffusing capacity of the lung for carbon monoxide (< 80), smoking status, and poor differentiation were more frequent in this group. Also, cancer in a lobe with a higher RES (odds ratio (OR) = 1.56; 95% confidence interval (CI:1.01-2.42; P = 0.04), pathologic stage ≥ III (OR = 2.23; 95% CI: 1.28-3.89; P <  0.001), and poor differentiation (OR = 1.99; 95% CI: 1.22-3.21; P <  0.001) were independent factors for tumor recurrence. CONCLUSIONS: The regional severity of emphysema by visual qualification was associated with the location of lung cancer, and was an independently poor prognostic factor for tumor recurrence in completely resected NSCLC patients.

Clinical significance of anemia as a prognostic factor in non-small cell lung cancer carcinoma with activating epidermal growth factor receptor mutations.

BACKGROUND: Anemia is a frequent finding in cancer patients. Pre-treatment anemia is known to be associated with poor survival after surgery or stereotactic body radiation therapy of non-small cell lung cancer (NSCLC). However, little study was conducted in NSCLC with activating epidermal growth factor receptor (EGFR) mutations. METHODS: This was a multicenter retrospective study conducted in seven university teaching hospitals in the Republic of Korea from January 2009 to February 2016. A total of 290 patients were diagnosed with NSCLC harboring sensitizing EGFR mutations and treated with EGFR-tyrosine kinase inhibitor (TKI) as 1st line. Of these patients, 104 met the exclusion criteria. Pre-treatment anemia was defined according to World Health Organization criteria (Hb concentration <13 g/dL for men and <12 g/dL for women). RESULTS: A total of 186 patients were finally included for analysis. Of these patients, 86 (46.2%) and 100 (53.8%) patients were classified into anemia and non-anemia groups, respectively. The anemia group had shorter median overall survival (OS) than the non-anemia group [24.83 (95% CI, 17.49-32.17) months vs. 42.10 (95% CI, 31.87-52.34) months, P=0.031]. In multivariate analysis, anemia (aHR, 2.573; 95% CI, 1.122-5.901; P=0.026) was only independent factors for poor OS. CONCLUSIONS: Our study suggests that pre-treatment anemia is a significant poor prognostic factor for OS of NSCLC patients with EGFR mutations treated with EGFR-TKI.

Smoking is associated with pneumonia development in lung cancer patients.

BACKGROUND: Various host factors can promote pneumonia susceptibility of lung cancer patients. However, data about risk factors for pneumonia in lung cancer patients receiving active treatments such as chemotherapy, radiotherapy, and surgical intervention are limited. Thus, the purpose of this study was to identify risk factors for pneumonia development in lung cancer patients. METHODS: The present study used a lung cancer cohort of the Catholic Medical Center at the Catholic University of Korea from January 2015 to December 2018. Pneumonia was defined by the presence of a new or progressive infiltration on chest imaging together with any of the following: new onset purulent sputum, change in character of chronic sputum, and fever. We ruled out noninfectious infiltration such as drug or radiation toxicity and hydrostatic pulmonary edema. We especially excluded those if computed tomography revealed sharp demarcation consolidation or ground glass opacity limited radiation field. RESULTS: A total of 413 patients were enrolled in this study. Pneumonia occurred in 118 (28.6%) patients. The pneumonia group had significantly worse overall survival (OS) than the non-pneumonia group (456.7 ± 35.0 days vs. 813.4 ± 36.1 days, log rank p < 0.001). In patients with pneumonia, OS was shorter in ex-smokers and current smokers than in never smokers (592.0 ± 101.0 days vs. 737.0 ± 102.8 days vs. 1357.0 days, log rank p < 0.001). Age (hazard ratio [HR]: 1.046; 95% confidence interval [CI]: 1.019-1.074; p = 0.001), clinical stage IV (HR: 1.759; 95% CI: 1.004-3.083; p = 0.048), neutropenia (HR: 2.620; 95% CI: 1.562-4.396; p < 0.001], and smoking (HR: 2.040; 95% CI: 1.100-3.784; p = 0.024) were independent risk factors of pneumonia development in lung cancer patients in multivariate analysis. In subgroup analysis for patients treated with chemotherapy, age (HR: 1.043; 95% CI: 1.012-1.074; p = 0.006), neutropenia (HR: 3.199; 95% CI: 1.826-5.605; p < 0.001), and smoking (HR: 2.125; 95% CI: 1.071-4.216; p = 0.031) were independent risk factors of pneumonia development. CONCLUSIONS: Smoking and neutropenia were risk factors affecting pneumonia development in the total group and subgroup of patients with lung cancer.

Factors Related to the Diagnostic Yield of Flexible Bronchoscopy without Guidance in Bronchoscopically Invisible Peripheral Lung Lesions.

BACKGROUND: We aimed to analyze the factors predicting the diagnostic performance of flexible bronchoscopy without guidance in peripheral lung lesions that are endoscopically invisible. METHODS: This was a retrospective study conducted in St. Paul's Hospital, The Catholic University of Korea, between January 2007 and March 2013. We included all patients who received bronchoscopy during this period. The analyzed variables were age, sex, the etiology of the lesion, lesion size, distance from the pleura, and presence of the bronchus sign. We used multiple logistic regression analysis to identify the significant independent factors associated with diagnostic yield. RESULTS: We included 151 patients in this study. The overall diagnostic yield was 58.3%. The sensitivity was 43.2% for malignant disease and 78.1% for benign disease. The benign lung lesions (p<0.001), lesion size (p=0.015), presence of the exposed type of bronchus sign (p<0.001), and presence of cavitary lung lesions (p=0.005) were factors influencing the yield of flexible bronchoscopy by univariate analysis. In a multivariate logistic regression analysis, the exposed type of bronchus sign and benign lung lesions were independent predicting factors (odds ratio [OR]: 27.95; 95% confidence interval [CI], 7.56-103.32; p<0.001 and OR, 4.91; 95% CI, 1.76-13.72; p=0.002). CONCLUSION: The presence of the exposed type of bronchus sign and benign lung lesions are determining factors of the diagnostic yield in flexible bronchoscopy in evaluating peripheral lesions that are not endoscopically visible.