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The Lancet | 2012

Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

Yung Jue Bang; Young-Woo Kim; Han-Kwang Yang; Hyun Cheol Chung; Young Kyu Park; Kyung Hee Lee; Keun Wook Lee; Yong Ho Kim; Sang Ik Noh; Jae Yong Cho; Young Jae Mok; Yeul Hong Kim; Jiafu Ji; Ta Sen Yeh; Peter Button; Florin Sirzén; Sung Hoon Noh

BACKGROUNDnD2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer.nnnMETHODSnThe capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229).nnnFINDINGSn1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294).nnnINTERPRETATIONnAdjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer.nnnFUNDINGnF Hoffmann-La Roche and Sanofi-Aventis.


Lancet Oncology | 2012

S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial

Yong Sang Hong; Young Suk Park; Ho Yeong Lim; Jeeyun Lee; Tae Won Kim; Kyu Pyo Kim; Sunyoung Kim; Ji Yeon Baek; Jee Hyun Kim; Keun Wook Lee; Ik Joo Chung; Sang Hee Cho; Kyung Hee Lee; Sang Joon Shin; Hye Jin Kang; Dong Bok Shin; Sook Jung Jo; Jae Won Lee

BACKGROUNDnCapecitabine plus oxaliplatin (CapeOX) is one of the reference doublet cytotoxic chemotherapy treatments for patients with metastatic colorectal cancer. We aimed to compare the efficacy and safety of CapeOX with that of S-1 plus oxaliplatin (SOX), a promising alternative treatment for patients with metastatic colorectal cancer.nnnMETHODSnIn this open-label, multicentre, randomised phase 3 trial, we randomly assigned patients (1:1) from 11 institutions in South Korea to receive either CapeOX (capecitabine 1000 mg/m(2) twice daily on days 1-14 and oxaliplatin 130 mg/m(2) on day 1) or SOX (S-1 40 mg/m(2) twice daily on days 1-14 and oxaliplatin 130 mg/m(2) on day 1). Treatment was repeated every 3 weeks and continued for as many as nine cycles of oxaliplatin-containing chemotherapy, except in instances of disease progression, unacceptable toxicity, or a patients refusal. Maintenance chemotherapy with S-1 or capecitabine was allowed after discontinuation of oxaliplatin. Randomisation was done with a computer-generated sequence (stratified by primary sites, previous adjuvant or neoadjuvant treatment, and the presence of measurable lesions). The primary endpoint was to show non-inferiority of SOX relative to CapeOX in terms of progression-free survival (PFS). The primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00677443.nnnFINDINGSnBetween May 14, 2008, and Sept 23, 2009, we randomly assigned 168 patients to receive SOX and 172 to receive CapeOX. Median PFS was 8·5 months (95% CI 7·6-9·3) in the SOX group and 6·7 months (6·2-7·1) in the CapeOX group (hazard ratio, 0·79 [95% CI 0·60-1·04]; p(non-inferiority)<0·0001, p(log-rank)=0·09). The upper limit of the CI was below the predefined margin of 1·43, showing the non-inferiority of SOX to CapeOX. We recorded a higher incidence of grade 3-4 neutropenia (49 [29%] vs 24 [15%]), thrombocytopenia (37 [22%] vs 11 [7%]), and diarrhoea (16 [10%] vs seven [4%]) in the SOX group than in the CapeOX group. The frequency of any grade of hand-foot syndrome was greater in the CapeOX group than it was in the SOX group (51 [31%] vs 23 [14%]).nnnINTERPRETATIONnThe SOX regimen could be an alternative first-line doublet chemotherapy strategy for patients with metastatic colorectal cancer. Further investigation is needed to explore its potential when used together with other targeted agents or as adjuvant chemotherapy.nnnFUNDINGnKorea Healthcare Technology Research and Development Project, Ministry of Health and Welfare, South Korea.


Lancet Oncology | 2018

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial

Manish R. Patel; John Ellerton; Jeffrey R. Infante; Manish Agrawal; Michael S. Gordon; Raid Aljumaily; Carolyn D. Britten; Luc Dirix; Keun Wook Lee; Mathew Taylor; Patrick Schöffski; Ding Wang; Alain Ravaud; Arnold Gelb; Junyuan Xiong; Galit Rosen; James L. Gulley; Andrea B. Apolo

BACKGROUNDnThe approval of anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 agents has expanded treatment options for patients with locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal anti-PD-L1 antibody, has shown promising antitumour activity and safety in this disease. We aimed to assess the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab and to assess antitumour activity of this drug in post-platinum patients.nnnMETHODSnIn this pooled analysis of two cohorts from the phase 1 dose-expansion JAVELIN Solid Tumor study, patients aged 18 years and older with histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma that had progressed after at least one previous platinum-based chemotherapy were enrolled from 80 cancer treatment centres or hospitals in the USA, Europe, and Asia. Eligible patients had adequate end-organ function, an Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of at least 3 months, and at least one measurable lesion. Cisplatin-ineligible patients who might have been previously treated in the perioperative setting, including platinum-naive patients, were also eligible. Patients unselected for PD-L1 expression received avelumab (10 mg/kg, 1 h intravenous infusion) every 2 weeks until confirmed disease progression, unacceptable toxicity, or other criterion for withdrawal. The primary endpoint for this efficacy expansion cohort was confirmed best overall response (according to RECIST version 1.1), adjudicated by independent review. Safety analysis was done in all patients who received at least one dose of avelumab. Antitumour activity was assessed in post-platinum patients who received at least one dose of avelumab. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort of patients with metastatic urothelial carcinoma is closed and the trial is ongoing.nnnFINDINGSnBetween Sept 3, 2014, and March 15, 2016, 329 patients with advanced metastatic urothelial carcinoma were screened for enrolment into this study; 249 patients were eligible and received treatment with avelumab for a median of 12 weeks (IQR 6·0-19·7) and followed up for a median of 9·9 months (4·3-12·1). Safety and antitumour activity were evaluated at data cutoff on June 9, 2016. In 161 post-platinum patients with at least 6 months of follow-up, a best overall response of complete or partial response was recorded in 27 patients (17%; 95% CI 11-24), including nine (6%) complete responses and 18 (11%) partial responses. The most frequent treatment-related adverse events (any grade in ≥10% patients) were infusion-related reaction (73 [29%]; all grade 1-2) and fatigue (40 [16%]). Grade 3 or worse treatment-related adverse events occurred in 21 (8%) of 249 patients, the most common of which were fatigue (four [2%]), and asthenia, elevated lipase, hypophosphataemia, and pneumonitis in two (1%) patients each. 19 (8%) of 249 patients had a serious adverse event related to treatment with avelumab, and one treatment-related death occurred (pneumonitis).nnnINTERPRETATIONnAvelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients. These data provide the rationale for therapeutic use of avelumab in metastatic urothelial carcinoma and it has received accelerated US FDA approval in this setting on this basis.nnnFUNDINGnMerck KGaA, and Pfizer Inc.


Cancer Chemotherapy and Pharmacology | 2013

Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer

Kyung Hun Lee; Hye Jung Chang; Sae Won Han; Do Youn Oh; Seock-Ah Im; Yung Jue Bang; Sunyoung Kim; Keun Wook Lee; Jee Hyun Kim; Yong Sang Hong; Tae Won Kim; Young Suk Park; Won Ki Kang; Sang Joon Shin; Joong Bae Ahn; Gyeong Hoon Kang; Seung Yong Jeong; Kyu Joo Park; Jae-Gahb Park; Tae-You Kim

PurposeEthnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy.MethodsWe analyzed 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) from prospectively enrolled 292 Korean patients treated with adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) for colon cancer.ResultsIn contrast to previous studies in Caucasians, neutropenia (grade 3–4, 60.5xa0%) was frequently observed, whereas only 16.4xa0% experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95xa0% confidence interval (CI) 1.19–4.55] and ERCC1 19007TT (adjusted OR 4.58, 95xa0% CI 1.20–17.40) genotypes. Patients harboring XRCC1 23885GG experienced less grade 2–4 neuropathy [adjusted OR 0.52, 95xa0% CI 0.27–0.99]. MTHFR 677TT (pxa0=xa00.002) and XRCC1 23885GG (pxa0=xa00.146) genotypes were also more prevalent in Koreans compared to Caucasians. TS ‘low’ genotype (adjusted HR 1.83, 95xa0% CI 1.003–3.34) was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms.ConclusionsPolymorphisms in MTHFR,XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. The ethnic differences in frequencies of genotypes may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.


Journal of Korean Medical Science | 2014

Prevalence and Risk Factors for Iron Deficiency Anemia in the Korean Population: Results of the Fifth Korea National Health and Nutrition Examination Survey

Jeong Ok Lee; Ju Hyun Lee; Soyeon Ahn; Jin Won Kim; Hyun Chang; Yu Jung Kim; Keun Wook Lee; Jee Hyun Kim; Soo Mee Bang; Jongseok Lee

This study assessed the prevalence of, and risk factors for, iron deficiency (ID) and iron deficiency anemia (IDA) among participants of the fifth Korean Health and Nutrition Examination Survey, 2010. Of 8,958 participants, 6,758 individuals ≥10 yr had sufficient data for the analysis of anemia and iron status. ID was defined as a transferrin saturation <10% or serum ferritin <15 µg/L. The prevalence of ID and IDA was 2.0% (95% confidence interval [CI], 1.3%-2.6%) and 0.7% (95% CI, 0.3%-1.0%), respectively, in males, and 22.4% (95% CI, 20.7%-24.2%) and 8.0% (95% CI, 6.8%-9.2%), respectively, in females. In reproductive age females, the prevalence of ID and IDA was 31.4% (95% CI, 28.9%-33.8%) and 11.5% (95% CI, 9.6%-13.4%), respectively. Compared to the prevalence of IDA in adult males 18-49 yr, the relative risks of IDA in adults ≥65 yr, lactating females, premenopausal females, and pregnant females were 8.1, 35.7, 42.8, and 95.5, respectively. Low income, underweight, iron- or vitamin C-poor diets were also associated with IDA. For populations with defined risk factors in terms of age, gender, physiological state and socioeconomic and nutritional status, national health policy to reduce IDA is needed. Graphical Abstract


Cancer Research and Treatment | 2015

Cisplatin-Based Chemotherapy Is a Strong Risk Factor for Thromboembolic Events in Small-Cell Lung Cancer.

Yun Gyoo Lee; Eun Young Lee; Inho Kim; Keun Wook Lee; Tae Min Kim; Se-Hoon Lee; Dong-Wan Kim; Dae Seog Heo

Purpose Cisplatin-associated arterial and venous thromboembolic events (TEEs) are becoming an increasing concern. In patients with small-cell lung cancer (SCLC) who are treated using cisplatin-based chemotherapy, we assume that the overall risk of TEEs is high. However, cisplatin-associated vascular toxicity in patients with SCLC has been overlooked to date. The aim of this study was to determine the incidence of TEEs in patients with SCLC and to analyze the predictors for TEE occurrence. Materials and Methods We retrospectively analyzed 277 patients who received chemotherapy for SCLC between 2006 and 2012. As the influence of chemotherapy on TEE occurrence developed after its initiation, a time-dependent Cox regression analysis was used to estimate the significant predictors for TEE. Results Among the 277 patients, 30 patients (11%) developed a TEE. The 3-month, 6-month, and 1-year cumulative incidences of TEEs were 5.0%, 9.1%, and 10.2%, respectively. Of 30 total TEEs, 22 (73%) occurred between the time of initiation and 4 weeks after the last dose of platinum-based chemotherapy. Approximately 218 patients (79%) received cisplatin-based chemotherapy. In multivariate analysis, cisplatin-based chemotherapy was an independent risk factor for TEE occurrence (hazard ratio [HR], 4.36; p=0.05). Variables including smoking status (common HR, 2.14; p=0.01) and comorbidity index (common HR, 1.60; p=0.05) also showed significant association with TEE occurrence. Conclusion The 1-year cumulative incidence of TEE is 10.2% in Asian patients with SCLC. Cisplatin-based chemotherapy in SCLC might be a strong predictor for the risk of TEE.


Investigational New Drugs | 2013

Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer

Keun Wook Lee; S. R. Park; Do-Youn Oh; Y.-I. Park; R. Khosravan; X. Lin; S.-Y. Lee; E.-J. Roh; Olga Valota; Mariajose Lechuga; Yung-Jue Bang

SummaryBackground We evaluated the maximum tolerated dose (MTD) and safety of sunitinib plus capecitabine/cisplatin (XP) or capecitabine/oxaliplatin (XELOX) in Korean patients with advanced gastric cancer (GC). Methods Sunitinib (37.5 or 25xa0mg/day) was administered on a 2-week-on/1-week-off schedule with chemotherapy. Assessments included dose-limiting toxicity (DLT), safety, pharmacokinetics, and antitumor activity. Results Twenty-eight patients received sunitinib/XP; 48 received sunitinib/XELOX. The MTDs were: sunitinib 25xa0mg/day, cisplatin 80xa0mg/m2, and capecitabine 1,000xa0mg/m2; sunitinib 37.5xa0mg/day, oxaliplatin 110xa0mg/m2, and capecitabine 800xa0mg/m2; and sunitinib 25xa0mg/day, oxaliplatin 110xa0mg/m2, and capecitabine 1,000xa0mg/m2. DLTs at the MTDs comprised grade (G) 4 febrile neutropenia plus G3 diarrhea (nu2009=u20091; sunitinib/XP), dose delays due to hematologic toxicity (nu2009=u20092; both sunitinib/XP), G3 bleeding (menorrhagia; nu2009=u20091; sunitinib/XELOX), and G3 increased alanine aminotransferase levels (nu2009=u20091; sunitinib/XELOX). There was a high frequency of G3/4 hematologic adverse events observed with both treatment regimens, particularly with sunitinib/XP. Frequent non-hematologic, G3/4 adverse events were nausea, stomatitis, and hypophosphatemia with sunitinib/XP and hypophosphatemia and pulmonary embolism with sunitinib/XELOX. No drug–drug interactions were apparent. At the MTDs, median progression-free survival was 6.4xa0months and 5.5–8.0xa0months for sunitinib/XP and sunitinib/XELOX, respectively; and the objective response rate was 46.7xa0% and 43.5–45.5xa0% for sunitinib/XP and sunitinib/XELOX, respectively. Conclusions At the MTD, sunitinib/XELOX had an acceptable safety profile in patients with advanced GC.


Investigational New Drugs | 2012

A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer: combined analysis with translational research

Do-Youn Oh; Keun Wook Lee; Kyung-Hee Lee; Chang-Hak Sohn; Young Suk Park; Dae Young Zang; Hun-Mo Ryoo; Hong-Suk Song; Jin-Soo Kim; Hye-Jin Kang; Bongseog Kim; Yung-Jue Bang

SummaryBackground To confirm the efficacy and toxicity of Erlotinib in combination with Gemcitabine and Capecitabine when used as a first-line therapy in metastatic/recurrent pancreatic cancer (PC). Methods Locally advanced PC was excluded. Erlotinib was given at a dose of 100xa0mg daily from D1 to D28. 1000xa0mg/m2 of gemcitabine was given on D1,8,15 and 1660xa0mg/m2/day of capecitabine was given from D1 to 21, repeated every 4xa0weeks. Response was assessed every 8xa0weeks. Results A total of 47 patients were enrolled. Response rate and disease control rate was 32.6% (95% CI, 18.6–46.6%) and 83.7% (95% CI, 72.7–94.7%) respectively. The PFS was 6.5xa0months (95% CI, 3.4–9.7) and OS was 12.0xa0months (95% CI, 8.6–15.9). The Gr 3/4 toxicities were: neutropenia (6.8%), thrombocytopenia (3.2%), anemia (1.6%). nausea (1.6%), vomiting (1.6%), anorexia (5.3%), rash (2.4%). The EGFR expression was associated with shorter OS and ERCC2 expression was associated with longer PFS and OS. PFS and OS were not different according to K-RAS mutation or polymorphism of RRM1 and CDA. Conclusions Erlotinib, gemcitabine and capecitabine combination showed promising efficacy and good tolerability in metastatic PC. This efficacy was observed irrespective of K-RAS mutation, and EGFR expression was poor prognostic factor for OS.


Cancer Research and Treatment | 2006

An Evaluation of Nutrition Support for Terminal Cancer Patients at Teaching Hospitals in Korea

Do Yeun Kim; Sang Min Lee; Kyoung Eun Lee; Hye Ran Lee; Jee Hyun Kim; Keun Wook Lee; Jongseok Lee; Soon Nam Lee

PURPOSEnWe wanted to analyze the use of nutrition support for terminal cancer patients, the effect of discussing withdrawal of nutrition support and do-not-resuscitate (DNR) consent on the use of intravenous nutrition during the patients last week of life and at the time of death.nnnMATERIALS AND METHODSnThe study involved 362 patients with terminal cancer from four teaching hospitals, and they all died between January 1 2003 and December 31 2005. The basic demographic data, the use of intravenous nutrition during the patients last week of life and at death, discussion of terminal nutrition withdrawal and DNR consent were evaluated.nnnRESULTSnIn the week before death, the patients received artificial nutrition such as total parenteral nutrition (31%), intravenous albumin infusion (25%), and feeding tube placements (9%). A discussion concerning withdrawal of nutrition support was limited to 25 (7%) patients. DNR consent was obtained from 294 (81%) patients. None of the patients were directly involved in any of these decisions. The discussion about withdrawal of terminal nutrition and DNR consent with the patients surrogates did not have any effect on reducing the use of parenteral nutrition.nnnCONCLUSIONnThe majority of patients dying of terminal cancer were still given potentially futile nutritional support. Modern clinical guidelines and ethical education about nutritional support at the end of life care is urgently needed in Korean medical practice to provide proper administration of terminal nutrition for end of life care.


Breast Cancer | 2014

Lamivudine prophylaxis for hepatitis B virus carrier patients with breast cancer during adjuvant chemotherapy

Hyun Jung Lee; Dae Young Kim; Bhumsuk Keam; Jeong-Hoon Lee; Sae-Won Han; Do-Youn Oh; Jung Hwan Yoon; Tae-You Kim; Yu Jung Kim; Keun Wook Lee; Jin-Wook Kim; Sook-Hyang Jeong; Jongseok Lee; Jee Hyun Kim; Seock-Ah Im

BackgroundThis study aimed to assess the efficacy of lamivudine prophylaxis on hepatic complications in HBsAg-positive patients with breast cancer undergoing adjuvant chemotherapy and to describe the temporal trend in HBV surveillance and prophylaxis during the last decade.MethodsPatients with stage I–III curatively resected invasive breast cancer who received adjuvant and/or neoadjuvant chemotherapy between 2000 and 2009 were eligible for this study. Patients with positive HBsAg and normal liver function were enrolled. Hepatotoxicity, defined as alanine aminotransferase (ALT) ≥100xa0IU/ml, and HBV reactivation were compared according to lamivudine prophylaxis. Annual trends in HBV surveillance and use of lamivudine prophylaxis were also reviewed.ResultsOne hundred sixty-five HBsAg-positive patients with breast cancer were enrolled. After the year 2004, surveillance of HBV infection status and use of lamivudine prophylaxis increased significantly (2.5 vs. 57.6xa0%, Pxa0<xa00.001). Seventy-three (44.2xa0%) patients received lamivudine prophylaxis and 92 (55.8xa0%) patients did not. The incidence of hepatotoxicity was significantly lower in the group receiving prophylaxis (2.7 vs. 14.1xa0%, Pxa0=xa00.011) with fewer premature terminations of planned adjuvant chemotherapy (0 vs. 10.9xa0%, Pxa0=xa00.004) in the prophylaxis group. Among the patients for whom the baseline HBV DNA titer was available, the HBV reactivation rate was lower, albeit not significantly, in the prophylaxis group (0xa0%) compared with the no prophylaxis group (20xa0%) (Pxa0=xa00.104). Lamivudine-withdrawal hepatitis was not detected; however, one case of breakthrough HBV reactivation during lamivudine treatment was observed in this study.ConclusionsOver the past decade, there has been an increase in the awareness of HBV reactivation and in the use of lamivudine during cytotoxic chemotherapy. Lamivudine prophylaxis reduced hepatic complications during adjuvant chemotherapy in patients with breast cancer. Lamivudine prophylaxis should be considered in HBsAg-positive patients with breast cancer who are candidates for adjuvant chemotherapy.

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Jee Hyun Kim

Seoul National University Bundang Hospital

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Yung-Jue Bang

Seoul National University Hospital

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Jin Won Kim

Seoul National University Bundang Hospital

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Yu Jung Kim

Seoul National University Bundang Hospital

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Bhumsuk Keam

Seoul National University Hospital

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Dae Seog Heo

Seoul National University Hospital

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Do-Youn Oh

Seoul National University

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Jeong Ok Lee

Seoul National University Bundang Hospital

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Seock-Ah Im

Seoul National University

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