1.Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer
Jang Ho LEE ; Eun Young KIM ; Cheol-Kyu PARK ; Shin Yup LEE ; Min ki LEE ; Seong-Hoon YOON ; Jeong Eun LEE ; Sang Hoon LEE ; Seung Joon KIM ; Sung Yong LEE ; Jun Hyeok LIM ; Tae-Won JANG ; Seung Hun JANG ; Kye Young LEE ; Seung Hyeun LEE ; Sei Hoon YANG ; Dong Won PARK ; Chan Kwon PARK ; Hye Seon KANG ; Chang Dong YEO ; Chang-Min CHOI ; Jae Cheol LEE
Cancer Research and Treatment 2023;55(1):112-122
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.
2.Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort
Jin Young LEE ; Jean Kyung BAK ; Mina KIM ; Ho-Gyun SHIN ; Kyun-Ik PARK ; Seung-Pyo LEE ; Hee-Sun LEE ; Ju-Yeun LEE ; Kwang-il KIM ; Si-Hyuck KANG ; Jang Hoon LEE ; Se Yong JANG ; Ju-Hee LEE ; Kye Hun KIM ; Jae Yeong CHO ; Jae-Hyeong PARK ; Sue K. PARK ; Hae-Young LEE
The Korean Journal of Internal Medicine 2023;38(1):56-67
Background/Aims:
This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension.
Methods:
The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension.
Results:
The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events.
Conclusions
This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.
3.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
Taeyun KIM ; Tae Won JANG ; Chang Min CHOI ; Mi-Hyun KIM ; Sung Yong LEE ; Yoon Soo CHANG ; Kye Young LEE ; Seung Joon KIM ; Sei Hoon YANG ; Jeong Seon RYU ; Jeong Eun LEE ; Shin Yup LEE ; Chan Kwon PARK ; Sang Hoon LEE ; Seung Hun JANG ; Seong Hoon YOON ; Hyung-Joo OH
Cancer Research and Treatment 2023;55(4):1152-1170
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+.
4.The Korean Hypertension Cohort study: design and baseline characteristics
Hae-Young LEE ; Ju-Yeon LEE ; Ho-Gyun SHIN ; Song-Hee CHO ; Kyun-Ik PARK ; Gyu-Chul OH ; Seung-Pyo LEE ; Hogon KIM ; Hee-Sun LEE ; Kwang-Il KIM ; Si-Hyuck KANG ; Jang Hoon LEE ; Se Yong JANG ; Ju-Hee LEE ; Kye Hun KIM ; Jae Yeong CHO ; Jae-Hyeong PARK ; Jieun JANG ; Sue K. PARK ; Jean Kyung BAK
The Korean Journal of Internal Medicine 2021;36(5):1115-1125
Background/Aims:
Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients.
Methods:
The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data.
Results:
This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively.
Conclusions
The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.
5.The Korean Hypertension Cohort study: design and baseline characteristics
Hae-Young LEE ; Ju-Yeon LEE ; Ho-Gyun SHIN ; Song-Hee CHO ; Kyun-Ik PARK ; Gyu-Chul OH ; Seung-Pyo LEE ; Hogon KIM ; Hee-Sun LEE ; Kwang-Il KIM ; Si-Hyuck KANG ; Jang Hoon LEE ; Se Yong JANG ; Ju-Hee LEE ; Kye Hun KIM ; Jae Yeong CHO ; Jae-Hyeong PARK ; Jieun JANG ; Sue K. PARK ; Jean Kyung BAK
The Korean Journal of Internal Medicine 2021;36(5):1115-1125
Background/Aims:
Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients.
Methods:
The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data.
Results:
This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively.
Conclusions
The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.
6.Nutritional Therapy Related Complications in Hospitalized Adult Patients: A Korean Multicenter Trial
Eun Mi SEOL ; Kye Sook KWON ; Jeong Goo KIM ; Jung Tae KIM ; Jihoon KIM ; Sun Mi MOON ; Do Joong PARK ; Jung Hyun PARK ; Je Hoon PARK ; Ji Young PARK ; Jung Min BAE ; Seung Wan RYU ; Ji Young SUL ; Dong Woo SHIN ; Cheung Soo SHIN ; Byung Kyu AHN ; Soo Min AHN ; Hee Chul YU ; Gil Jae LEE ; Sanghoon LEE ; A Ran LEE ; Jae Young JANG ; Hyun Jeong JEON ; Sung Min JUNG ; Sung Sik HAN ; Suk Kyung HONG ; Sun Hwi HWANG ; Yunhee CHOI ; Hyuk Joon LEE
Journal of Clinical Nutrition 2019;11(1):12-22
PURPOSE: Nutritional therapy (NT), such as enteral nutrition (EN) or parenteral nutrition (PN), is essential for the malnourished patients. Although the complications related to NT has been well described, multicenter data on symptoms in the patients with receiving NT during hospitalization are still lacking. METHODS: Nutrition support team (NST) consultations, on which NT-related complications were described, were collected retrospectively for one year. The inclusion criteria were patients who were (1) older than 18 years, (2) hospitalized, and (3) receiving EN or PN at the time of NST consultation. The patients' demographics (age, sex, body mass index [BMI]), type of NT and type of complication were collected. To compare the severity of each complication, the intensive care unit (ICU) admission, hospital stay, and type of discharge were also collected. RESULTS: A total of 14,600 NT-related complications were collected from 13,418 cases from 27 hospitals in Korea. The mean age and BMI were 65.4 years and 21.8 kg/m2. The complications according to the type of NT, calorie deficiency (32.4%, n=1,229) and diarrhea (21.6%, n=820) were most common in EN. Similarly, calorie deficiency (56.8%, n=4,030) and GI problem except for diarrhea (8.6%, n=611) were most common in PN. Regarding the clinical outcomes, 18.7% (n=2,158) finally expired, 58.1% (n=7,027) were admitted to ICU, and the mean hospital days after NT-related complication were 31.3 days. Volume overload (odds ratio [OR]=3.48) and renal abnormality (OR=2.50) were closely associated with hospital death; hyperammonemia (OR=3.09) and renal abnormality (OR=2.77) were associated with ICU admission; “micronutrient and vitamin deficiency” (geometric mean [GM]=2.23) and volume overload (GM=1.61) were associated with a longer hospital stay. CONCLUSION: NT may induce or be associated with several complications, and some of them may seriously affect the patient's outcome. NST personnel in each hospital should be aware of each problem during nutritional support.
Adult
;
Body Mass Index
;
Demography
;
Diarrhea
;
Enteral Nutrition
;
Hospitalization
;
Humans
;
Hyperammonemia
;
Intensive Care Units
;
Korea
;
Length of Stay
;
Multicenter Studies as Topic
;
Nutrition Therapy
;
Nutritional Support
;
Parenteral Nutrition
;
Referral and Consultation
;
Retrospective Studies
;
Vitamins
7.Multidisciplinary Approach to Decrease In-Hospital Delay for Stroke Thrombolysis.
Sang Beom JEON ; Seung Mok RYOO ; Deok Hee LEE ; Sun U KWON ; Seongsoo JANG ; Eun Jae LEE ; Sang Hun LEE ; Jung Hee HAN ; Mi Jeong YOON ; Soo JEONG ; Young Uk CHO ; Sungyang JO ; Seung Bok LIM ; Joong Goo KIM ; Han Bin LEE ; Seung Chai JUNG ; Kye Won PARK ; Min Hwan LEE ; Dong Wha KANG ; Dae Chul SUH ; Jong S KIM
Journal of Stroke 2017;19(2):196-204
BACKGROUND AND PURPOSE: Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day. METHODS: We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016. RESULTS: A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation (P<0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36–57 min) to 20.5 min (IQR 15.8–32.5 min; P<0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5–212.5 min) to 86.5 min (IQR 67.5–102.3 min; P<0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; P=0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; P=0.035). CONCLUSIONS: SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.
Ambulances
;
Cerebral Infarction
;
Humans
;
Intracranial Hemorrhages
;
Mortality
;
Stroke*
;
Thrombectomy
;
Thrombolytic Therapy
;
Tissue Plasminogen Activator
8.Current Awareness and Use of the Strain Echocardiography in Routine Clinical Practices: Result of a Nationwide Survey in Korea.
Ju Hee LEE ; Jae Hyeong PARK ; Seung Woo PARK ; Woo Shik KIM ; Il Suk SOHN ; Jung Yeon CHIN ; Jung Sun CHO ; Ho Joong YOUN ; Hae Ok JUNG ; Sun Hwa LEE ; Seong Hwan KIM ; Wook Jin CHUNG ; Chi Young SHIM ; Jin Won JEONG ; Eui Young CHOI ; Se Joong RIM ; Jang Young KIM ; Kye Hun KIM ; Joon Han SHIN ; Dae Hee KIM ; Ung JEON ; Jung Hyun CHOI ; Yong Jin KIM ; Seung Jae JOO ; Ki Hong KIM ; Kyoung Im CHO ; Goo Yeong CHO
Journal of Cardiovascular Ultrasound 2017;25(3):91-97
BACKGROUND: Because conventional echocardiographic parameters have several limitations, strain echocardiography has often been introduced in clinical practice. However, there are also obstacles in using it in clinical practice. Therefore, we wanted to find the current status of awareness on using strain echocardiography in Korea. METHODS: We conducted a nationwide survey to evaluate current use and awareness of strain echocardiography from the members of the Korean Society of Echocardiography. RESULTS: We gathered total 321 questionnaires from 25 cardiology centers in Korea. All participants were able to perform or interpret echocardiographic examinations. All participating institutions performed strain echocardiography. Most of our study participants (97%) were aware of speckle tracking echocardiography and 185 (58%) performed it for clinical and research purposes. Two-dimensional strain echocardiography was the most commonly used modality and left ventricle (LV) was the most commonly used cardiac chamber (99%) for clinical purposes. Most of the participants (89%) did not think LV strain can replace LV ejection fraction (LVEF) in their clinical practice. The common reasons for not performing routine use of strain echocardiography was diversity of strain measurements and lack of normal reference value. Many participants had a favorable view of the future of strain echocardiography. CONCLUSION: Most of our study participants were aware of strain echocardiography, and all institutions performed strain echocardiography for clinical and research purposes. However, they did not think the LV strain values could replace LVEF. The diversity of strain measurements and lack of normal reference values were common reasons for not using strain echocardiography in clinical practice.
Cardiology
;
Echocardiography*
;
Heart Ventricles
;
Korea*
;
Reference Values
9.Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation.
Mi Young YEOM ; Yoo Jin KIM ; Nack Gyun CHUNG ; Jae Wook LEE ; Pil Sang JANG ; Bin CHO ; Chul Seung KYE ; Dae Chul JEONG
Blood Research 2015;50(3):140-146
BACKGROUND: The outcome of hematopoietic stem cell transplantation (HSCT) is poor in patients with secondary iron overload (SIO). We evaluated the relationship between SIO and veno-occlusive disease (VOD) in an animal model with radiation for HSCT. METHODS: We used a 6-week-old female BDF1 (H-2b/d) and a male C57/BL6 (H-2b) as recipient and donor, respectively. Recipient mice were injected intraperitoneally with 10 mg of iron dextran (cumulative doses of 50 mg, 100 mg, and 200 mg). All mice received total body irradiation for HSCT. We obtained peripheral blood for alanine transaminase (ALT) and liver for pathologic findings, lipid hyperoxide (LH) as reactive oxygen species (ROS), and liver iron content (LIC) on post-HSCT day 1 and day 7. The VOD score was assessed by pathologic findings. RESULTS: ALT levels increased depending on cumulative iron dose, with significant differences between days 1 and 7 for mice loaded with 200 mg of iron (P<0.01). LH levels significantly increased in mice loaded with 200 mg of iron compared to those in other groups (P<0.01). For mice loaded with 100 mg of iron, the LH level depended on the radiation dose (P<0.01). There was a statistically significant relationship among ALT, LH, and LIC parameters (P<0.05). Pathologic scores for VOD correlated with LIC (P<0.01). CONCLUSION: Livers with SIO showed high ROS levels depending on cumulative iron dose, and correlations with elevated liver enzyme and LIC. The pathologic score for VOD was associated with the LIC. Our results suggest that SIO may induce VOD after HSCT with irradiation.
Alanine Transaminase
;
Animals
;
Dextrans
;
Female
;
Hematopoietic Stem Cell Transplantation*
;
Hematopoietic Stem Cells*
;
Hepatic Veno-Occlusive Disease*
;
Humans
;
Iron Overload*
;
Iron*
;
Liver
;
Male
;
Mice*
;
Models, Animal
;
Reactive Oxygen Species
;
Tissue Donors
;
Whole-Body Irradiation
10.The Korean guideline for lung cancer screening.
Seung Hun JANG ; Seungsoo SHEEN ; Hyae Young KIM ; Hyeon Woo YIM ; Bo Young PARK ; Jae Woo KIM ; In Kyu PARK ; Young Whan KIM ; Kye Young LEE ; Kyung Soo LEE ; Jong Mog LEE ; Bin HWANGBO ; Sang Hyun PAIK ; Jin Hwan KIM ; Nak Jin SUNG ; Sang Hyun LEE ; Seung Sik HWANG ; Soo Young KIM ; Yeol KIM ; Won Chul LEE ; Sook Whan SUNG
Journal of the Korean Medical Association 2015;58(4):291-301
Lung cancer is the leading cause of cancer death in many countries, including Korea. The majority of patients are inoperable at the time of diagnosis because symptoms are typically manifested at an advanced stage. A recent large clinical trial demonstrated significant reduction in lung cancer mortality by using low dose computed tomography (LDCT) screening. A Korean multisociety collaborative committee systematically reviewed the evidences regarding the benefits and harms of lung cancer screening, and developed an evidence-based clinical guideline. There is high-level evidence that annual screening with LDCT can reduce lung cancer mortality and all-cause mortality of high-risk individuals. The benefits of LDCT screening are modestly higher than the harms. Annual LDCT screening should be recommended to current smokers and ex-smokers (if less than 15 years have elapsed after smoking cessation) who are aged 55 to 74 years with 30 pack-years or more of smoking-history. LDCT can discover non-calcified lung nodules in 20 to 53% of the screened population, depending on the nodule positivity criteria. Individuals may undergo regular LDCT follow-up or invasive diagnostic procedures that lead to complications. Radiation-associated malignancies associated with repetitive LDCT, as well as overdiagnosis, should be considered the harms of screening. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Education and actions to stop smoking must be offered to current smokers. Chest radiograph, sputum cytology at regular intervals, and serum tumor markers should not be used as screening methods. These guidelines may be amended based on several large ongoing clinical trial results.
Biomarkers, Tumor
;
Diagnosis
;
Early Detection of Cancer
;
Education
;
Follow-Up Studies
;
Humans
;
Korea
;
Lung
;
Lung Neoplasms*
;
Mass Screening*
;
Mortality
;
Radiography, Thoracic
;
Smoke
;
Smoking
;
Sputum

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