Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non–Small Cell Lung Cancer: Updated Analysis of the RESET Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). @*Materials and Methods@#In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. @*Results@#The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5). @*Conclusion@#This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Adverse Events in Healthcare Workers after the First Dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 Vaccination: a Single Center Experience

Coronavirus disease 2019 vaccinations for healthcare workers (HCWs) have begun in South Korea. To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital. We found that 1,301 of 1,403 ChAdOx1 nCoV-19 recipients and 38 of 80 BNT162b2 recipients reported AEs respectively (90.9% vs. 52.5%): injection-site pain (77.7% vs. 51.2%), myalgia (60.5% vs.11.2%), fatigue (50.7% vs. 7.5%), headache (47.4% vs. 7.5%), and fever (36.1% vs. 5%; P < 0.001 for all). Young HCWs reported more AEs with ChAdOx1 nCoV-19 than with BNT162b2.No incidences of anaphylaxis were observed. Only one serious AE required hospitalization for serious vomiting, and completely recovered. In conclusion, reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.

Adverse Events in Healthcare Workers after the First Dose of ChAdOx1 nCoV-19 or BNT162b2 mRNA COVID-19 Vaccination: a Single Center Experience

Coronavirus disease 2019 vaccinations for healthcare workers (HCWs) have begun in South Korea. To investigate adverse events (AEs) of the first dose of each vaccine, any symptom was collected daily for seven days after vaccination in a tertiary hospital. We found that 1,301 of 1,403 ChAdOx1 nCoV-19 recipients and 38 of 80 BNT162b2 recipients reported AEs respectively (90.9% vs. 52.5%): injection-site pain (77.7% vs. 51.2%), myalgia (60.5% vs.11.2%), fatigue (50.7% vs. 7.5%), headache (47.4% vs. 7.5%), and fever (36.1% vs. 5%; P < 0.001 for all). Young HCWs reported more AEs with ChAdOx1 nCoV-19 than with BNT162b2.No incidences of anaphylaxis were observed. Only one serious AE required hospitalization for serious vomiting, and completely recovered. In conclusion, reported AEs were more common in recipients with ChAdOx1 nCoV-19 than in those with BNT162b2. However, most of the reported AEs were mild to moderate in severity. Sufficient explanation and preparation for expected AEs required to promote widespread vaccination.

Indoor Radon and Lung Cancer: National Radon Action Plans Are Urgently Required

No abstract available.

Lung Cancer Risk and Residential Exposure to Air Pollution: A Korean Population-Based Case-Control Study

PURPOSE: To investigate the association between long-term exposure to ambient air pollution and lung cancer incidence in Koreans. MATERIALS AND METHODS: This was a population-based case-control study covering 908 lung cancer patients and 908 controls selected from a random sample of people within each Korean province and matched according to age, sex, and smoking status. We developed land-use regression models to estimate annual residential exposure to particulate matter (PM₁₀) and nitrogen dioxide (NO₂) over a 20-year exposure period. Logistic regression was used to estimate odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Increases in lung cancer incidence (expressed as adjusted OR) were 1.09 (95% CI: 0.96−1.23) with a ten-unit increase in PM₁₀ (µg/m³) and 1.10 (95% CI: 1.00−1.22) with a ten-unit increase in NO₂ (ppb). Tendencies for stronger associations between air pollution and lung cancer incidence were noted among never smokers, among those with low fruit consumption, and among those with a higher education level. Air pollution was more strongly associated with squamous cell and small cell carcinomas than with adenocarcinoma of the lung. CONCLUSION: This study provides evidence that PM₁₀ and NO₂ contribute to lung cancer incidence in Korea.

Extracellular Vesicles as a Source of Urological Biomarkers: Lessons Learned From Advances and Challenges in Clinical Applications to Major Diseases / 대한배뇨장애요실금학회지

Extracellular vesicles (EVs) not only eliminate unwanted molecular components, but also carry molecular cargo essential for specific intercellular communication mechanisms. As the molecular characteristics and biogenetical mechanisms of heterogeneous EVs are different, many studies have attempted to purify and characterize EVs. In particular, exosomal molecules, including proteins, lipids, and nucleic acids, have been suggested as disease biomarkers or therapeutic targets in various diseases. However, several unresolved issues and challenges remain despite these promising results, including source variability before the isolation of exosomes from body fluids, the contamination of proteins during isolation, and methodological issues related to the purification of exosomes. This paper reviews the general characteristics of EVs, particularly microvesicles and exosomes, along with their physiological roles and contribution to the pathogenesis of major diseases, several widely used methods to isolate exosomes, and challenges in the development of disease biomarkers using the molecular contents of EVs isolated from body fluids.

Alveolar Hemorrhage after Polyacrylamide Injection for Breast Augmentation / 대한내과학회지

Polyacrylamide hydrogel is used widely in plastic surgery due to its nontoxic, nonabsorbent nature. There have been reports of silicone leading to pulmonary embolism and acute respiratory distress syndrome with systemic adverse effects. However, there have been case reports only of local reactions involving polyacrylamide; systemic reactions appear to be rare. Furthermore, there has been no report of alveolar hemorrhage after polyacrylamide injection for breast augmentation. We treated a 53-year-old female with an alveolar hemorrhage that occurred 2 days after a polyacrylamide injection. On the day of admission, the patient had a fever with chills and dyspnea. The chest X-ray showed multiple infiltrations and chest computed tomography showed consolidation and a ground-glass appearance in both lung fields. The alveolar hemorrhage was confirmed at fiber-optic bronchoscopy and bronchoalveolar lavage. The symptoms and radiology findings improved after corticosteroid administration and conservative treatment. We report the first case of alveolar hemorrhage after a polyacrylamide injection for breast augmentation.

Multiple Hypercoagulability Disorders at Presentation of Non-Small-Cell Lung Cancer / 결핵및호흡기질환

Hypercoagulability disorders are commonly encountered in clinical situations in patients with a variety of cancers. However, several hypercoagulability disorders presenting as first symptoms or signs in cancer patients have rarely been reported. We herein described a case of a woman with adenocarcinoma of the lung presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis, recurrent cerebral embolic infarction, and heart failure.

Multiple Hypercoagulability Disorders at Presentation of Non-Small-Cell Lung Cancer / 결핵및호흡기질환

Hypercoagulability disorders are commonly encountered in clinical situations in patients with a variety of cancers. However, several hypercoagulability disorders presenting as first symptoms or signs in cancer patients have rarely been reported. We herein described a case of a woman with adenocarcinoma of the lung presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis, recurrent cerebral embolic infarction, and heart failure.

Pancreaticothoracic Fistula Presenting with Hemoptysis and Pneumothorax in a Chronic Alcoholic Patient / 결핵및호흡기질환

Pancreaticothoracic fistula is a rare complication of acute or chronic alcoholic pancreatitis. It may present with various symptoms, like dyspnea, abdominal pain, cough, chest pain, fever, back pain, hemoptysis, fatigue, or orthopnea. Pancreaticothoracic fistula can be detected by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or computed tomography. MRCP has high sensitivity and fewer side effects, and thus it has recently been recommended as the first choice for the detection of pancreaticothoracic fistula. On the other hand, ERCP enables the detection and treatment of pancreaticothoracic fistula and allows for stent insertion; for this reason it is a commonly used modality in pancreaticothoracic fistula cases. Herein, the authors describe a case of pancreaticothoracic fistula detected by ERCP and MRCP that manifested only respiratory symptoms, namely hemoptysis and pneumothorax without abdominal pain, which commonly accompanies pancreatitis.

A Case of Diaphragmatic Hernia Mimicking Acute Pleural Effusion / 대한내과학회지

Diaphragmatic hernia may be either congenital or acquired. Acquired cases may be secondary to trauma, infection, pregnancy, or surgery. In adults, diaphragmatic hernia causes chronic and variable symptoms such as abdominal discomfort, dyspepsia, and chronic dyspnea; in infants, however, it frequently causes acute respiratory failure. We report herein a case of diaphragmatic hernia in an adult patient who presented with left chest pain. Left pleural effusion was revealed on a plain chest radiograph. Computed tomography confirmed the presence of a diaphragmatic defect and a shift of the omentum to the thoracic cavity. The patient underwent omental resection and primary repair of the diaphragmatic muscle defect via exploratory thoracotomy.

Erlotinib Induced Trichomegaly of the Eyelashes / 결핵및호흡기질환

Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for non-small-cell lung cancer patients. Its untoward cutaneous effects are largely well known and developed in many patients treated with EGFR TKIs. However trichomegaly of eyelash is rarely reported. Although trichomegaly is not a drug-limiting side effect, it could be troublesome of continuing the treatment because of cosmetic issue or eyeball irritation by long eyelashes. Therefore clinicians are needed to pay attention to this uncommon effect. We herein describe erlotinib induced trichomegaly of eyelashes in a woman with adenocarcinoma of the lung.

Late-Onset Distant Metastatic Upper Urinary Tract Urothelial Carcinoma Mimicking Lung Adenocarcinoma / 결핵및호흡기질환

Urothelial carcinomas (UCs) can occur in the upper urinary tract or lower urinary tract. Upper urinary tract urothelial carcinoma (UUT-UC) is relatively a rare disease and accounts for only about 5% of UC cases. Sporadic cases of late-onset metastasis, associated with UC of the bladder, have occasionally been reported. In contrast, no late-onset distant metastatic UUT-UC without local recurrence has, to the best of our knowledge, been reported in the English literature. We report an extremely rare case of distant metastatic UC, mimicking lung adenocarcinoma that originated from UUT-UC 12 years previously.

Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE) / 결핵및호흡기질환

BACKGROUND: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). METHODS: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. RESULTS: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). CONCLUSION: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

Clinicopathologic and Molecular Characteristics of Lung Adenocarcinoma Arising in Young Patients

Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.

A Case of Common Variable Immune Deficiency Presenting as Recurrent Pneumococcal Pneumonia / 결핵및호흡기질환

Common variable immune deficiency (CVID) is the most common primary immune deficiency, which is manifested as chronic recurrent respiratory infections and hypoglobulinemia. CVID usually presents in the second or third decade of life. A 33-year-old woman was admitted with recurrent pneumococcal pneumonia with bacteremia and had very low levels of serum immunoglobulin G, M and A. This case emphasized a high index of suspiciousness for diagnosis of CVID in a mid-adulthood patient presenting with recurrent pneumonia with hypoglobulinemia.

Gender Differences in Susceptibility to Smoking among Patients with Lung Cancer

BACKGROUND/AIMS: To determine whether female smokers are more or less susceptible to the detrimental pulmonary-function effects of smoking when compared to male smokers among patients with lung cancer. METHODS: Pack-years and pulmonary function indices were compared between 1,594 men and women with lung cancer ifferences in individual susceptibility to smoking were estimated using a susceptibility index formula. RESULTS: Of the patients, 959 (92.8%) men and 74 (7.2%) women were current smokers. Common histological types of lung cancer were squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, among others. Women had a lower number of pack-years, forced expiratory volume in 1 second (FEV1, liters), forced vital capacity (FVC, liters), and total lung capacity (TLC, liters) compared to those of men (25.0 +/- 19.2 vs. 42.9 +/- 21.7 for pack-years; 1.4 +/- 0.5 vs. 2.0 +/- 0.6 for FEV1; 3.0 +/- 0.7 vs. 2.0 +/- 0.6 for FVC; 4.5 +/- 0.8 vs. 5.7 +/- 1.0 for TLC; all p < 0.001). The susceptibility index for women was significantly higher compared to that of men (1.1 +/- 4.1 vs. 0.7 +/- 1.1; p = 0.001). A significant inverse association was shown between the susceptibility index and TLC and FVC (r = -0.200 for TLC, -0.273 for FVC; all p < 0.001). CONCLUSIONS: The results suggest that the detrimental effects of smoking on pulmonary function are greater in women, as compared to those in men, among patients with lung cancer.

Diagnosis and Management of Malignant Pleural Effusion / 대한내과학회지

Malignant pleural effusions (MPEs) are an important clinical problem in patients with neoplastic disease. They can occur as the initial presentation of cancer, a delayed complication in patients with previously diagnosed malignancies, or the first manifestation of cancer recurrence after therapy. Common cancer types causing MPEs include lymphomas, mesotheliomas, and carcinomas of the breast, lung, and ovaries. However, almost all tumor types have been reported to cause MPEs. Regardless of the etiology, the median survival from clinical recognition is 4 months. New imaging modalities assist the evaluation of patients with a suspected MPE. However cytologic or tissue confirmation of malignant cells is necessary to establish a diagnosis. Management of an MPE remains palliative. Managements are directed toward removing pleural fluids and when appropriate, performing pleurodesis or initiating long-term drainage to prevent fluid reaccumulation. Talc pleurodesis is still the choice of treatment although concerns about its safety remain. Several factors such as performance status, expected survival, lung re-expansion following pleural fluid drainage and co-morbidities should be considered before the treatment.

Pulmonary Cryptococcosis Presenting Solitary Pulmonary Nodule in an Immunocompetence: A Case Report and Review of the Korean Literatures

In immunocompetent individuals, pulmonary cryptococcosis is a rarely diagnosed fungal infection. It's common radiological findings are multiple pulmonary nodules. We report a case of pulmonary cryptococcosis in a 67-year-old woman who presented with solitary pulmonary nodule (SPN) on chest computed tomography (CT). She complained of intermittent blood tinged sputum for 10 days. She was a non-smoker and had no clinical evidence of immonosuppression. Pathological examination of the lung tissue core via percutaneous fine needle biopsy revealed chronic granulomatous inflammation compatible with cryptococcosis on the special stain. She received 6 months of antifungal therapy with fluconazole and the SPN was disappeared on the CT after antifungal therapy. We also reviewed that the features of pulmonary cryptococcosis presenting SPN in immnocompetent patients reported in the Korean literatures.

An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population. MATERIALS AND METHODS: A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk. RESULTS: Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer. CONCLUSION: JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.