1.Serum beta-2 microglobulin in malignant lymphomas: an old but powerful prognostic factor.
Changhoon YOO ; Dok Hyun YOON ; Cheolwon SUH
Blood Research 2014;49(3):148-153
Beta-2 microglobulin is synthesized in all nucleated cells and forms the light chain subunit of the major histocompatibility complex class I antigen. Despite its potential role as a convenient and non-invasive prognostic indicator in malignant lymphomas, the influence of serum beta2 microglobulin is currently underestimated, and therapeutic decision making is rarely affected by this marker. Recent studies that included relatively large numbers of patients with specific histologic subtypes showed that serum beta2 microglobulin is a potent prognostic marker in malignant lymphomas. In follicular lymphoma, this effort led to the incorporation of serum beta2 microglobulin as an indicator in a new prognostic model. In this review, we summarize the current evidence supporting the role of serum beta2 microglobulin as a prognostic factor in patients with malignant lymphoma and discuss perspectives for future investigations.
Decision Making
;
Humans
;
Lymphoma*
;
Lymphoma, Follicular
;
Major Histocompatibility Complex
2.Efficacy of Imatinib in Patients with Platelet-Derived Growth Factor Receptor Alpha-Mutated Gastrointestinal Stromal Tumors.
Changhoon YOO ; Min Hee RYU ; Jungmin JO ; Inkeun PARK ; Baek Yeol RYOO ; Yoon Koo KANG
Cancer Research and Treatment 2016;48(2):546-552
PURPOSE: The incidence of gastrointestinal stromal tumors (GISTs) harboring platelet-derived growth factor receptor alpha (PDGFRA) mutations is low, therefore further investigation of the efficacy of imatinib in this subgroup was needed. MATERIALS AND METHODS: Patients with PDGFRA-mutant GISTs who received imatinib as primary therapy for advanced disease between January 2000 and June 2012 were identified from the GIST registry of Asan Medical Center, Seoul, Korea. RESULTS: KIT and PDGFRA genotyping in 823 patients identified 18 patients (2%) with PDGFRA mutations who were treated with first-line imatinib. Exon 18 D842V substitution, non-D842V exon 18 mutations, and exon 12 mutations were detected in nine (50%), four (22%), and five (28%) patients, respectively. Objective response rate differed significantly between patients with the D842V mutation and those with non-D842V mutations (0% [0/5] vs. 71% [5/7], p=0.03). In all patients, median progression-free survival (PFS) and overall survival (OS) was 24.8 months (95% confidence interval [CI], 0.0 to 57.2) and 51.2 months (95% CI, 37.1 to 65.3), respectively. Significantly, poorer PFS was observed for patients with D842V-mutant GISTs than those with non-D842V PDGFRA-mutant GISTs: median 3.8 months (95% CI, 1.4 to 6.3) versus 29.5 months (95% CI, 18.3 to 40.7) (p < 0.001). Patients with the D842V mutation had poorer OS than those with non-D842V PDGFRA mutations: median 25.2 months (95% CI, 12.7 to 37.8) versus 59.8 months (95% CI, 43.0 to 76.5) (p=0.02). CONCLUSION: Imatinib is active against non-D842V PDGFRA-mutant GISTs, whereas GISTs harboring the D842V mutation are primarily resistant to imatinib.
Chungcheongnam-do
;
Disease-Free Survival
;
Exons
;
Gastrointestinal Stromal Tumors
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Humans
;
Incidence
;
Korea
;
Platelet-Derived Growth Factor*
;
Receptors, Platelet-Derived Growth Factor*
;
Seoul
3.Radiation-induced abscopal effect and its enhancement by programmed cell death 1 blockade in the hepatocellular carcinoma: A murine model study
Gyu Sang YOO ; Won-Gyun AHN ; Shin-Yeong KIM ; Wonseok KANG ; Changhoon CHOI ; Hee Chul PARK
Clinical and Molecular Hepatology 2021;27(1):144-156
Background/Aims:
The abscopal effect, a rare phenomenon induced by radiation, can be reinforced by immunotherapy. Although radiation therapy and immunotherapy are increasingly being utilized for the treatment of hepatocellular carcinoma (HCC), whether immunotherapy could boost the abscopal effect remains unclear. In this study, we aimed to elucidate the immunological mechanisms underlying the abscopal effect induced by the combination of irradiation and immunotherapy in a murine HCC model.
Methods:
A syngeneic HCC mouse model was established by transplanting murine Hepa 1–6 HCC cells into both hind legs of immunocompetent C57BL/6 mice. The tumors on the right hind legs were irradiated, and abscopal effects were observed in the non-irradiated tumors on the left hind leg with or without the coadministration of anti-programmed cell death 1 (PD-1) antibodies. Flow cytometric analyses were performed to analyze the distributions of immune cells infiltrating both irradiated and non-irradiated tumors and the tumor-draining lymph nodes (TDLNs).
Results:
Administration of 16 Gy in two fractions more effectively inhibited the growth of both irradiated and nonirradiated tumors with higher tumor infiltration of cytotoxic T cells than 8 Gy did in a single fraction. The higher dose also increased activated dendritic cells in TDLNs, which had higher expression of the programmed cell death ligand 1. Coadministration of anti-PD-1 antibodies significantly enhanced the abscopal effect and increased infiltration of activated cytotoxic T cells in both irradiated and non-irradiated tumors.
Conclusions
Our findings show that adding anti-PD-1 therapy to radiation enhanced the abscopal effect in a syngeneic murine model of HCC.
4.K-wire Fixation Supplemented with External Fixator Versus Volar Locked Plating for Unstable Fractures of the Distal Radius.
Sang Uk LEE ; Il Jung PARK ; Hyoung Min KIM ; Joo Yup LEE ; Hyun Ho YOO ; Changhoon JEONG
Journal of the Korean Society for Surgery of the Hand 2010;15(4):157-163
PURPOSE: To campare the outcomes between K-wire fixation with supplementary external fixator and volar locking plate in the treatment of the unstable distal radius fracture. MATERIALS AND METHODS: We reviewed 26 unstable AO type C3 distal radius fracture retrospectively, treated from January 2004 to February 2009. They were divided into two groups; group I (14 cases of open reduction and K-wire fixation supplemented with a external fixator) and group II (12 cases of volar locked plating). Each group was statistically compared in terms of surgery time, the difference of radiologic reduction, and loss of reduction, range of motion (ROM) and Mayo wrist score. RESULTS: No statistical difference was found in terms of surgery time, radiologic reduction, and loss of reduction between two treatment groups. After 1 year of surgery, the Mayo wrist score of group I was 80.5 points, and group II was 80, which shows that both groups achieved fairly good score. Although group II gained a statistically significant improvement in the ROM of the wrist except pronation at postoperative three months, no statistical difference of ROM was found between two groups at postoperative 1 year. CONCLUSION: When it comes to the treatment for an unstable intra-articular distal radius fracture, clinical and radiological outcomes are comparable between the patients treated with K-wire fixation supplemented with a external fixator and those with a volar locking plate.
External Fixators
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Humans
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Pronation
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Radius
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Radius Fractures
;
Range of Motion, Articular
;
Retrospective Studies
;
Wrist
5.Efficacy of Fulvestrant in Heavily Pretreated Postmenopausal Women with Advanced Breast Cancer: A Preliminary Report.
Changhoon YOO ; Sung Bae KIM ; Jin Hee AHN ; Kyung Hae JUNG ; Yongchel AHN ; Gyungyub GONG ; Hak Hee KIM ; Hee Jung KIM ; Byung Ho SON ; Sei Hyun AHN
Journal of Breast Cancer 2011;14(2):135-139
PURPOSE: Fulvestrant, a potent estrogen receptor (ER) antagonist with a novel mechanism of action, has shown efficacy in pretreated patients with advanced breast cancer. We assessed the efficacy and tolerability of fulvestrant in Korean postmenopausal women. METHODS: Of the 25 candidates identified at Asan Medical Center, Seoul, Korea, six were deemed ineligible due to inadequate baseline and follow-up imaging. The 19 patients included in this retrospective analysis received the approved dose of fulvestrant (250 mg intramuscular injection, once per month) as second- (n=8), third- (n=7), or fourth-line (n=4) endocrine therapy. RESULTS: At a median follow-up of 7.4 months (range, 1.2-34.8 months), the 19 patients received a median of four cycles (range, 1-34 cycles) of fulvestrant. Median time to progression was 5.5 months (95% confidence interval [CI], 0.4-10.7 months), and median overall survival was 17.9 months (95% CI, 2.7-33.1 months). Among 17 evaluable patients, one (5.3%) achieved a partial response, 10 (52.6%) showed stable disease, and six (31.6%) showed progressive disease. The clinical benefit rate was 26.3%. Four patients (21.1%) reported adverse events, but all were grade 1 or 2. CONCLUSION: Fulvestrant was effective and well tolerated in patients with advanced breast cancer who had been previously treated with several lines of endocrine and chemotherapeutic agents.
Breast
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Breast Neoplasms
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Estradiol
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Estrogens
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Female
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Follow-Up Studies
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Humans
;
Injections, Intramuscular
;
Korea
;
Retrospective Studies
6.Imatinib Plasma Monitoring-Guided Dose Modification for Managing Imatinib-Related Toxicities in Gastrointestinal Stromal Tumor Patients.
Shinkyo YOON ; Min Hee RYU ; Changhoon YOO ; Mo Youl BECK ; Baek Yeol RYOO ; Yoon Koo KANG
Journal of Korean Medical Science 2013;28(8):1248-1252
Imatinib, the first-line treatment in patients with advanced gastrointestinal stromal tumors (GIST), is generally well tolerated, although some patients have difficulty tolerating the standard dose of 400 mg/day. Adjusting imatinib dosage by plasma level monitoring may facilitate management of patients who experience intolerable toxicities due to overexposure to the drug. We present two cases of advanced GIST patients in whom we managed imatinib-related toxicities through dose modifications guided by imatinib plasma level monitoring. Imatinib blood level testing may be a promising approach for fine-tuning imatinib dosage for better tolerability and optimal clinical outcomes in patients with advanced GIST.
Aged
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Antineoplastic Agents/blood/*therapeutic use
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Benzamides/blood/*therapeutic use
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Drug Monitoring
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Exons
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Gastrointestinal Neoplasms/*drug therapy/pathology/radiography
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Gastrointestinal Stromal Tumors/*drug therapy/pathology/radiography
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Humans
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Liver Neoplasms/secondary
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Male
;
Mutation
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Piperazines/blood/*therapeutic use
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Positron-Emission Tomography
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Proto-Oncogene Proteins c-kit/genetics
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Pyrimidines/blood/*therapeutic use
;
Tomography, X-Ray Computed
7.Clinical features and outcomes in patients with human immunodeficiency virus-negative, multicentric Castleman's disease: a single medical center experience.
Seyoung SEO ; Changhoon YOO ; Dok Hyun YOON ; Shin KIM ; Jung Sun PARK ; Chan Sik PARK ; Jooryung HUH ; Cheolwon SUH
Blood Research 2014;49(4):253-258
BACKGROUND: Multicentric Castleman's disease (CD) is commonly associated with poor prognosis, and well-known prognostic factors are scarce. We performed a retrospective analysis to define the clinical features and prognostic factors for patients with multicentric CD. METHODS: Between 1990 and 2013, 32 patients with multicentric CD were identified from the database of the Asan Medical Center, Seoul, Korea. Clinicopathologic data were collected by reviewing the medical records. With the exclusion of 4 patients because of unknown human immunodeficiency virus infection status, 28 human immunodeficiency virus-negative patients with multicentric CD were included in this analysis. RESULTS: Most of the patients were male (76%) and had a median age of 54 years. Hyaline vascular variant was the most common subtype (N=11, 39%). Hepatosplenomegaly (61%), fever (39%), edema (29%), and ascites (18%) were the most frequently reported symptoms and signs at diagnosis. With a median follow-up of 67 months, the 5-year overall survival (OS) was 77%. Patients with extravascular fluid accumulation (i.e., peripheral edema, ascites, and/or pleural effusions) were significantly associated with a poor survival rate (5-year OS, 94% vs. 56%; P=0.04). The extent of disease involvement was also a significant prognostic factor (5-year OS, 91% for involvement on a single side vs. 73% on both sides of the diaphragm; P=0.03). Other clinicopathologic factors were not significantly associated with patient survival. CONCLUSION: Our findings suggest that the hyaline vascular variant is not a rare subtype of multicentric CD. Extravascular fluid accumulation and disseminated disease involvement seem to be significant prognostic factors.
Ascites
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Chungcheongnam-do
;
Diagnosis
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Diaphragm
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Edema
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Fever
;
Follow-Up Studies
;
Giant Lymph Node Hyperplasia*
;
HIV
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Humans
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Hyalin
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Korea
;
Male
;
Medical Records
;
Prognosis
;
Retrospective Studies
;
Seoul
;
Survival Rate
8.Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen.
Changhoon YOO ; Bum Jun KIM ; Kyu pyo KIM ; Jae Lyun LEE ; Tae Won KIM ; Baek Yeol RYOO ; Heung Moon CHANG
Cancer Research and Treatment 2017;49(3):759-765
PURPOSE: Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy. MATERIALS AND METHODS: Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea. RESULTS: The median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second-line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029). CONCLUSION: Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.
Acinar Cells*
;
Antineoplastic Agents
;
Capecitabine
;
Carcinoma, Acinar Cell*
;
Chemoradiotherapy
;
Chungcheongnam-do
;
Disease-Free Survival
;
Drug Therapy*
;
Fluorouracil
;
Humans
;
Incidence
;
Korea
;
Pancreas, Exocrine
;
Pancreatic Neoplasms
;
Retrospective Studies
9.Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen.
Changhoon YOO ; Bum Jun KIM ; Kyu pyo KIM ; Jae Lyun LEE ; Tae Won KIM ; Baek Yeol RYOO ; Heung Moon CHANG
Cancer Research and Treatment 2017;49(3):759-765
PURPOSE: Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy. MATERIALS AND METHODS: Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea. RESULTS: The median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second-line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029). CONCLUSION: Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.
Acinar Cells*
;
Antineoplastic Agents
;
Capecitabine
;
Carcinoma, Acinar Cell*
;
Chemoradiotherapy
;
Chungcheongnam-do
;
Disease-Free Survival
;
Drug Therapy*
;
Fluorouracil
;
Humans
;
Incidence
;
Korea
;
Pancreas, Exocrine
;
Pancreatic Neoplasms
;
Retrospective Studies
10.Primary central nervous system lymphoma: a new prognostic model for patients with diffuse large B-cell histology.
Yongchel AHN ; Heui June AHN ; Dok Hyun YOON ; Jung Yong HONG ; Changhoon YOO ; Shin KIM ; Jooryung HUH ; Cheolwon SUH
Blood Research 2017;52(4):285-292
BACKGROUND: Age and performance status are important prognostic factors in primary central nervous system (CNS) lymphoma. Although several prognostic models have been proposed, there is no consensus on the optimal model for patients with diffuse large B-cell histology. METHODS: Seventy-seven patients with primary CNS diffuse large B-cell lymphoma were retrospectively analyzed to determine factors affecting survival. Three Western models were applied to our eligible patients; we devised a novel model based on our findings. RESULTS: The median patient age was 59 years (range, 29–77); the median event-free and overall survival (OS) durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and Memorial Sloan Kettering Cancer Center models were applicable to our cohorts. Multivariate analysis showed that advanced age, multifocal lesions, and high cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A novel model for predicting prognosis was then developed based on these variables. Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3 were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very high-risk groups (N=4), respectively. Sixty-one patients were eligible considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the low-, moderate-, high-, and very high-risk groups, respectively (P < 0.01). CONCLUSION: Advanced age, multifocal lesions, and high CSF protein concentration were adversely related with prognosis. Our model can be helpful in pre-treatment risk stratification for patients with primary CNS lymphoma with diffuse large B-cell histology.
B-Lymphocytes*
;
Central Nervous System*
;
Cerebrospinal Fluid
;
Cohort Studies
;
Consensus
;
Humans
;
Lymphoma*
;
Lymphoma, B-Cell
;
Multivariate Analysis
;
Prognosis
;
Retrospective Studies