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+.

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.

Background: Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea. Methods: A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement). Results: The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers. Conclusion Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. Conclusion CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. Conclusion CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

PURPOSE: The extension of endocrine therapy beyond 5 years for recurrence-free survivors of breast cancer improves survival; however, the issue on how to clinically identify appropriate candidates remains controversial. This study aimed to identify prognostic factors for breast-cancer-specific mortality in patients who have had 5 years of tamoxifen treatment and categorize subgroups based on the risk of death using combinations of these prognostic factors to assist in the clinical decision to perform further endocrine therapy. METHODS: In total, 3,158 patients with breast cancer were enrolled. Breast cancer-specific survival rates after 5 years of tamoxifen treatment were calculated, and associated prognostic factors were analyzed using a Cox proportional-hazards model. RESULTS: An age extreme at diagnosis (i.e., < 40 or ≥ 60 years), tumor size > 2 cm, and positive lymphovascular invasion were robust independent prognostic factors for late breast cancer-specific death in tamoxifen-treated patients (hazard ratio [HR] = 2.162, 1.739, and 1.993; p = 0.001, 0.047, and 0.011, respectively). Lymph node metastasis and progesterone receptor negativity had borderline significance in this regard (HR = 1.741 and 1.638, p = 0.099 and 0.061). The study patients were classified into four groups according to the number of prognostic indicators, i.e., low, intermediate, high, and extremely high risk. The additional 5- and 10-year cumulative risks of breast cancer-specific death were 0.8% and 1.5% in the low-risk group, 0.9% and 3.9% in the intermediate-risk group, 1.3% and 7.3% in the high-risk group, and 4.8% and 13.8% in the extremely high-risk group, respectively. CONCLUSION: This new risk stratification system for late mortality in breast cancer can be used to identify the right candidates for extended endocrine therapy after 5 years of tamoxifen treatment.
Breast Neoplasms ; Breast ; Diagnosis ; Humans ; Lymph Nodes ; Mortality ; Neoplasm Metastasis ; Prognosis ; Receptors, Progesterone ; Survival Rate ; Survivors ; Tamoxifen

PURPOSE: We aimed to assess prognostic value of metastatic pelvic lymph node (mPLN) in early-stage cervical cancer treated with radical surgery followed by postoperative chemoradiotherapy. Also, we sought to define a high-risk group using prognosticators for recurrence. MATERIALS AND METHODS: A multicenter retrospective study was conducted using the data from 13 Korean institutions from 2000 to 2010. A total of 249 IB-IIA patients with high-risk factors were included. We evaluated distant metastasis-free survival (DMFS) and disease-free survival (DFS) in relation to clinicopathologic factors including pNstage, number of mPLN, lymph node (LN)ratio (number of positive LN/number of harvested LN), and log odds of mPLNs (log(number of positive LN+0.5/number of negative LN+0.5)). RESULTS: In univariate analysis, histology (squamous cell carcinoma [SqCC] vs. others), lymphovascular invasion (LVI), number of mPLNs (≤ 3 vs. > 3), LN ratio (≤ 17% vs. > 17%), and log odds of mPLNs (≤ -0.58 vs. > -0.58) were significant prognosticators for DMFS and DFS. Resection margin involvement only affected DFS. No significant survival difference was observed between pN0 patients and patients with 1-3 mPLNs. Multivariate analysis revealed that mPLN > 3, LVI, and non-SqCC were unfavorable index for both DMFS (p < 0.001, p=0.020, and p=0.031, respectively) and DFS (p < 0.001, p=0.017, and p=0.001, respectively). A scoring system using these three factors predicts risk of recurrence with relatively high concordance index (DMFS, 0.69; DFS, 0.71). CONCLUSION: mPLN > 3 in early-stage cervical cancer affects DMFS and DFS. A scoring system using mPLNs > 3, LVI, and non-SqCC could stratify risk groups of recurrence in surgically resected early-stage cervix cancer with high-risk factors.
Chemoradiotherapy ; Cohort Studies* ; Combined Modality Therapy ; Disease-Free Survival ; Humans ; Lymph Nodes* ; Lymphatic Metastasis ; Multivariate Analysis ; Recurrence* ; Retrospective Studies ; Risk Factors* ; Uterine Cervical Neoplasms*

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to develop clinical practice guidelines for the surgical treatment of laryngeal cancer. This Task Force conducted a systematic search of the EMBASE, MEDLINE, Cochrane Library, and KoreaMed databases to identify relevant articles, using search terms selected according to the key questions. Evidence-based recommendations were then created on the basis of these articles. An external expert review and Delphi questionnaire were applied to reach consensus regarding the recommendations. The resulting guidelines focus on the surgical treatment of laryngeal cancer with the assumption that surgery is the selected treatment modality after a multidisciplinary discussion in any context. These guidelines do not, therefore, address non-surgical treatment such as radiation therapy or chemotherapy. The committee developed 62 evidence-based recommendations in 32 categories intended to assist clinicians during management of patients with laryngeal cancer and patients with laryngeal cancer, and counselors and health policy-makers.
Advisory Committees ; Consensus ; Counseling ; Drug Therapy ; Glottis ; Humans ; Laryngeal Neoplasms* ; Neck*

BACKGROUND/AIMS: The smoking rates and patterns in the North Korean population are not well known. More than 20,000 North Korean defectors have settled in South Korea; thus, we can estimate the current North Korean smoking situation using this group. METHODS: All North Korean defectors spend their first 3 months in a South Korean facility learning to adapt to their new home. We retrospectively analyzed the results from a questionnaire conducted among North Korean male defectors in this facility from August 2012 to February 2014. RESULTS: Of 272 men, 84.2% were current smokers, 12.5% were ex-smokers, and 3.3% were non-smokers. The mean age of this group was 35.9 ± 11.3 years, and smoking initiation occurred at a mean age of 18.2 ± 4.7 years. Among the subjects, 78.1% had a family member who smoked. Of the 221 current smokers, 67.4% responded that they intended to quit smoking. Fagerström test and Kano test for social nicotine dependence (KTSND) results for current smokers were 3.35 ± 2.26 and 13.76 ± 4.87, respectively. Question 9 on the KTSND (doctors exaggerate the ill effects of smoking) earned a significantly higher score relative to the other questions and a significantly higher score in current smokers compared with non-smokers. CONCLUSIONS: The smoking rate in North Korean male defectors was higher than that indicated previously. However, interest in smoking cessation was high and nicotine dependence was less severe than expected. Further investigation is needed to identify an efficient method for North Korean smokers to stop smoking.
Humans ; Korea ; Learning ; Male* ; Methods ; Nicotine* ; Retrospective Studies ; Smoke* ; Smoking Cessation ; Smoking* ; Tobacco Use Disorder*

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the primitive hematopoietic stem cells. CML is characterized by the overproduction of myeloid cells, which results in marked splenomegaly and leukocytosis. CML presented by multiple chloromas is extremely rare. Multiple chloromas in the skin and brain are quite rare as the initial presentation of CML. These rare manifestation should alert clinicians to include CML in the differential diagnosis of patients presenting with multiple non-pruritic skin nodules or neurologic symptoms. Dasatinib has promising therapeutic potential for managing intracranial leukemic disease. Here, we report the case of a patient who visited the hospital with multiple chloroma which is unusual presentation of CML, and treated with dasatinib successfully.
Brain ; Diagnosis, Differential ; Hematopoietic Stem Cells ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Leukocytosis ; Myeloid Cells ; Myeloproliferative Disorders ; Neurologic Manifestations ; Sarcoma, Myeloid* ; Skin ; Splenomegaly ; Dasatinib