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: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

OBJECTIVETo examinie the synergistic effects of Banxia Xiexin Decoction (, Known as Banhasasim-tang in Korean) extract (BXDE) on cisplatin-induced cytotoxicity in the A549 human lung cancer cell lines.

METHODSA549 cells were treated with varying concentrations (50-200 μg/mL) of cisplatin and BXDE alone or in combination for 96 h. We used 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively.

RESULTSThe exposure of cells to cisplatin and BXDE alone or in combination decreased cell viability dose- and time-dependently (P<0.05), which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V/propidium iodide- stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-FMK).

CONCLUSIONSBXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.

A549 Cells ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Caspase Inhibitors ; pharmacology ; Cisplatin ; pharmacology ; DNA Fragmentation ; drug effects ; Humans ; Plant Extracts ; pharmacology

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.
Biphasic Insulins ; Body Weight ; Diabetes Mellitus, Type 2 ; Drug Toxicity ; Fasting ; Glucose ; Hemoglobins ; Humans ; Incidence ; Insulin ; Insulin Aspart ; Insulin, Isophane ; Insulin, Long-Acting ; Patient Selection ; Plasma ; Quality of Life ; Republic of Korea ; Treatment Outcome ; Insulin Detemir

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.
Adolescent ; Body Height ; *Body Mass Index ; Body Weight ; Child ; Child, Preschool ; Clonidine/therapeutic use ; Dopamine/therapeutic use ; Dwarfism/drug therapy ; Female ; Human Growth Hormone/*analysis ; Humans ; Insulin-Like Growth Factor I/analysis ; Male ; Regression Analysis ; Retrospective Studies

Previous studies have shown that hematopoietic stem cell transplantation (HSCT) may result in growth impairment. The purpose of this study was to evaluate the growth during 5 yr after HSCT and to determine factors that influence final adult height (FAH). We retrospectively reviewed the medical records of acute myeloid leukemia (AML) patients who received HSCT. Among a total of 37 eligible patients, we selected 24 patients who began puberty at 5 yr after HSCT (Group 1) and 19 patients who reached FAH without relapse (Group 2). In Group 1, with younger age at HSCT, sex, steroid treatment, hypogonadism and hypothyroidism were not significantly associated with growth impairment 5 yr after HSCT. History of radiotherapy (RT) significantly impaired the 5 yr growth after HSCT. Chronic graft-versus-host disease (cGVHD) only temporarily impaired growth after HSCT. In Group 2, with younger age at HSCT, steroid treatment and hypogonadism did not significantly reduce FAH. History of RT significantly reduced FAH. Growth impairment after HSCT may occur in AML patients, but in patients without a history of RT, growth impairment seemed to be temporary and was mitigated by catch-up growth.
Adolescent ; Body Height/*radiation effects ; Child ; Child, Preschool ; Female ; Graft vs Host Disease/pathology/prevention & control ; *Hematopoietic Stem Cell Transplantation ; Humans ; Hypogonadism/drug therapy/pathology ; Infant ; Leukemia, Myeloid, Acute/radiotherapy/*therapy ; Male ; Recurrence ; Retrospective Studies ; Risk Factors ; Steroids/therapeutic use

BACKGROUND: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. METHODS: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. RESULTS: The mean plasma G-CSF levels were 12.2+/-0.3 pg/mL and 46.0+/-3.8 pg/mL (mean+/-SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Adrenal Glands ; Biomarkers ; Carcinoma, Large Cell ; Carcinoma, Squamous Cell ; Enzyme-Linked Immunosorbent Assay ; Granulocyte Colony-Stimulating Factor ; Humans ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Plasma ; Recurrence ; Research Personnel ; Small Cell Lung Carcinoma

PURPOSE: This retrospective study was carried out to evaluate the efficacy and toxicity of radiation therapy (RT) with/without cisplatin-based chemotherapy in nasopharyngeal cancer (NPC). MATERIALS AND METHODS: One hundred forty six patients with NPC received curative RT and/or cisplatin-based chemotherapy. Thirty-nine patients were treated with induction chemotherapy (IC), including cisplatin and 5-fluorouracil followed by RT. Another 63 patients were treated with concurrent chemoradiotherapy (CCRT) using cisplatin, and 22 patients were treated with IC followed by CCRT. The remaining 22 patients were treated with RT alone. RESULTS: One hundred four (80.0%) patients achieved complete response (CR), and 23 (17.7%) patients achieved partial response (PR). The patterns of failure were: locoregional recurrences in 21.2% and distant metastases in 17.1%. Five-year overall survival (OS) and progression free survival (PFS) were 50.7% and 45.0%, respectively. Multivariate Cox stepwise regression analysis revealed CR to chemoradiotherapy to be a powerful prognostic factor for OS. CR to chemoradiotherapy and completion of radiation according to the time schedule were favorable prognostic factors for PFS. A comparison of each treatment group (IC --> RT vs. CCRT vs. IC --> CCRT vs. RT alone) revealed no significant differences in the OS or PFS. However, subgroup analysis showed significant differences in both OS and DFS in favor of the combined chemoradiotherapy group compared with RT alone, for stage IV and T3-4 tumors. Grade 3-4 toxicities were more common in the combined chemoradiotherapy arm, particularly in the CCRT group. CONCLUSIONS: This study was limited in that it was a retrospective study, much time was required to collect patients, and there were imbalances in the number of patients in each treatment group. Combined chemoradiotherapy remarkably prolonged the OS and PFS in subgroup patients with stage IV or T3-4 NPC.
Appointments and Schedules ; Arm ; Chemoradiotherapy ; Cisplatin ; Disease-Free Survival ; Fluorouracil ; Humans ; Induction Chemotherapy ; Korea ; Nasopharyngeal Neoplasms ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies

BACKGROUND: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. METHODS: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. RESULTS: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. CONCLUSION: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.
Carcinoma, Squamous Cell ; Cohort Studies ; Epithelium ; Humans ; Lung ; Lung Neoplasms ; Male ; Neoplasm Staging ; Phosphotransferases ; Smoke ; Smoking

PURPOSE: Standardization quality assurance (QA) program of CyberKnife for suitable circumstances in Korea has not been established. In this research, we investigated the development of QA program for CyberKnife and evaluation of the feasibility under applications. MATERIALS AND METHODS: Considering the feature of constitution for systems and the therapeutic methodology of CyberKnife, the list of quality control (QC) was established and divided dependent on the each period of operations. And then all these developed QC lists were categorized into three groups such as basic QC, delivery specific QC, and patient specific QC based on the each purpose of QA. In order to verify the validity of the established QA program, this QC lists was applied to two CyberKnife centers. The acceptable tolerance was based on the undertaking inspection list from the CyberKnife manufacturer and the QC results during last three years of two CyberKnife centers in Korea. The acquired measurement results were evaluated for the analysis of the current QA status and the verification of the propriety for the developed QA program. RESULTS: The current QA status of two CyberKnife centers was evaluated from the accuracy of all measurements in relation with application of the established QA program. Each measurement result was verified having a good agreement within the acceptable tolerance limit of the developed QA program. CONCLUSION: It is considered that the developed QA program in this research could be established the standardization of QC methods for CyberKnife and confirmed the accuracy and stability for the image-guided stereotactic radiotherapy.
Constitution and Bylaws ; Humans ; Korea ; Mortuary Practice ; Quality Control ; Radiotherapy