1.Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts
Jun Ho YI ; Seong Hyun JEONG ; Seok Jin KIM ; Dok Hyun YOON ; Hye Jin KANG ; Youngil KOH ; Jin Seok KIM ; Won-Sik LEE ; Deok-Hwan YANG ; Young Rok DO ; Min Kyoung KIM ; Kwai Han YOO ; Yoon Seok CHOI ; Whan Jung YUN ; Yong PARK ; Jae-Cheol JO ; Hyeon-Seok EOM ; Jae-Yong KWAK ; Ho-Jin SHIN ; Byeong Bae PARK ; Seong Yoon YI ; Ji-Hyun KWON ; Sung Yong OH ; Hyo Jung KIM ; Byeong Seok SOHN ; Jong Ho WON ; Dae-Sik HONG ; Ho-Sup LEE ; Gyeong-Won LEE ; Cheolwon SUH ; Won Seog KIM
Cancer Research and Treatment 2023;55(1):325-333
Purpose:
Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal.
Materials and Methods:
We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation.
Results:
Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529).
Conclusion
In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.
2.Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study
Seong Hyun JEONG ; Seok Jin KIM ; Dok Hyun YOON ; Yong PARK ; Hye Jin KANG ; Youngil KOH ; Gyeong-Won LEE ; Won-Sik LEE ; Deok-Hwan YANG ; Young Rok DO ; Min Kyoung KIM ; Kwai Han YOO ; Yoon Seok CHOI ; Hwan Jung YUN ; Jun Ho YI ; Jae-Cheol JO ; Hyeon-Seok EOM ; Jae-Yong KWAK ; Ho-Jin SHIN ; Byeong Bae PARK ; Shin Young HYUN ; Seong Yoon YI ; Ji-Hyun KWON ; Sung Yong OH ; Hyo Jung KIM ; Byeong Seok SOHN ; Jong Ho WON ; Se-Hyung KIM ; Ho-Sup LEE ; Cheolwon SUH ; Won Seog KIM
Cancer Research and Treatment 2022;54(4):1268-1277
Purpose:
Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP).
Materials and methods:
We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485).
Results:
Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047).
Conclusion
Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.
3.Guidelines for Safe Drug Use
Su Hyun KIM ; Hye-Kyung JUNG ; Ein-Soon SHIN ; Jin Seo LEE ; Yon Ju RYU ; Kyoung Sup HONG ; Soo Mee BANG ; Yoon-Seok CHANG ; Chan Kyu KIM ; Byung Wan LEE ; Seung-Jae HONG ; Chang Oh KIM ;
Korean Journal of Medicine 2021;96(3):225-235
Background/Aims:
In Korea, medications are available by prescription from a physician, or can be purchased over-the-counter (OTC) without a prescription. Education regarding both prescribed and OTC drugs is important to minimize side effects and avoid drug abuse. The risk of side effects due to polypharmacy is increasing due to the growing number of elderly patients with comorbidities.
Methods:
There are various clinical guidelines for physicians, but it is difficult for patients and their caregivers to find published guidelines regarding drug use. In this regard, experts from nine subspecialties of internal medicine, geriatric medicine, and guideline development methodology formed a working group to develop guidelines for safe drug use under the Clinical Practice Guidelines Committee of the Korean Association of Internal Medicine.
Results:
The main contents of this guideline are 1) safe and effective drug administration, 2) the proper use of analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs), 3) the proper use of tranquilizers and sleeping pills to prevent drug abuse, 4) points to be aware of when taking multiple medications.
Conclusions
The guidelines were developed for patients and their caregivers to understand the general principles and precautions for drug use, including commonly used painkillers, mood stabilizers, sleeping pills, and polypharmacy. These guidelines could also be used as educational materials for physicians, nurses, and healthcare workers to educate patients and their caregivers.
4.Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells
Youn Kyung CHOI ; Jung-Il KANG ; Jin Won HYUN ; Young Sang KOH ; Ji-Hoon KANG ; Chang-Gu HYUN ; Kyung-Sup YOON ; Kwang Sik LEE ; Chun Mong LEE ; Tae Yang KIM ; Eun-Sook YOO ; Hee-Kyoung KANG
Biomolecules & Therapeutics 2021;29(2):211-219
Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β ( Ser9 ) and β-catenin (Ser 552 and Ser675 ). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202 /Tyr204 )-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.
5.Guidelines for Safe Drug Use
Su Hyun KIM ; Hye-Kyung JUNG ; Ein-Soon SHIN ; Jin Seo LEE ; Yon Ju RYU ; Kyoung Sup HONG ; Soo Mee BANG ; Yoon-Seok CHANG ; Chan Kyu KIM ; Byung Wan LEE ; Seung-Jae HONG ; Chang Oh KIM ;
Korean Journal of Medicine 2021;96(3):225-235
Background/Aims:
In Korea, medications are available by prescription from a physician, or can be purchased over-the-counter (OTC) without a prescription. Education regarding both prescribed and OTC drugs is important to minimize side effects and avoid drug abuse. The risk of side effects due to polypharmacy is increasing due to the growing number of elderly patients with comorbidities.
Methods:
There are various clinical guidelines for physicians, but it is difficult for patients and their caregivers to find published guidelines regarding drug use. In this regard, experts from nine subspecialties of internal medicine, geriatric medicine, and guideline development methodology formed a working group to develop guidelines for safe drug use under the Clinical Practice Guidelines Committee of the Korean Association of Internal Medicine.
Results:
The main contents of this guideline are 1) safe and effective drug administration, 2) the proper use of analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs), 3) the proper use of tranquilizers and sleeping pills to prevent drug abuse, 4) points to be aware of when taking multiple medications.
Conclusions
The guidelines were developed for patients and their caregivers to understand the general principles and precautions for drug use, including commonly used painkillers, mood stabilizers, sleeping pills, and polypharmacy. These guidelines could also be used as educational materials for physicians, nurses, and healthcare workers to educate patients and their caregivers.
6.Choosing Wisely: The Korean Perspective and Launch of the ‘Right Decision in Cancer Care’ Initiative
Joo-Young KIM ; Kyoung Eun LEE ; Kyubo KIM ; Myung Ah LEE ; Won Sup YOON ; Dong Seok HAN ; Sung Gwe AHN ; Jung-Hun KANG
Cancer Research and Treatment 2020;52(3):655-660
Government healthcare expenditure is rising in Korea, and the costs incurred by patients in Korea exceed those incurred by patients in other Organization for Economic Co-operation and Development countries. Despite the increasing health expenditure, patient demand for services is increasing as well, so it is now becoming recognized that cancer care needs to be balanced. The most important measure in cancer care optimization is to provide high-quality care while keeping costs sustainable. The Korean Cancer Association considers the current situation of cancer therapy in Korea the foremost issue, which has led to the implementation of the nationwide ‘Right Decisions in Cancer Care’ initiative. This initiative is based on the concepts of medical professionalism in that it should be led by physicians working in the field of oncology, that education should be offered to patients and clinicians, and that it should influence healthcare policy. In this article, we introduce the nationwide ‘Right Decision in Cancer Care’ initiative and highlight the five initial items on its agenda. The agenda is open to expansion and update as the medical environment evolves and additional clinical evidence becomes available.
7.The Korean Society for Neuro-Oncology (KSNO) Guideline for Glioblastomas: Version 2018.01
Young Zoon KIM ; Chae Yong KIM ; Jaejoon LIM ; Kyoung Su SUNG ; Jihae LEE ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Tae Hoon ROH ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Chan Woo WEE ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Je Beom HONG ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(1):1-9
BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
Brain
;
Central Nervous System
;
Chemoradiotherapy
;
Diagnosis
;
Drug Therapy
;
Glioblastoma
;
Humans
;
Korea
;
Radiotherapy
8.The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade II Cerebral Gliomas in Adults: Version 2019.01
Young Zoon KIM ; Chae Yong KIM ; Chan Woo WEE ; Tae Hoon ROH ; Je Beom HONG ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Kyoung Su SUNG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Jihae LEE ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Jaejoon LIM ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(2):74-84
BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
Adult
;
Astrocytoma
;
Brain
;
Central Nervous System
;
Drug Therapy
;
Drug Therapy, Combination
;
Follow-Up Studies
;
Glioblastoma
;
Glioma
;
Humans
;
Isocitrate Dehydrogenase
;
Korea
;
Oligodendroglioma
;
Radiotherapy
;
World Health Organization
9.The Korean Society for Neuro-Oncology (KSNO) Guideline for WHO Grade III Cerebral Gliomas in Adults: Version 2019.01
Young Zoon KIM ; Chae Yong KIM ; Jaejoon LIM ; Kyoung Su SUNG ; Jihae LEE ; Hyuk Jin OH ; Seok Gu KANG ; Shin Hyuk KANG ; Doo Sik KONG ; Sung Hwan KIM ; Se Hyuk KIM ; Se Hoon KIM ; Yu Jung KIM ; Eui Hyun KIM ; In Ah KIM ; Ho Sung KIM ; Tae Hoon ROH ; Jae Sung PARK ; Hyun Jin PARK ; Sang Woo SONG ; Seung Ho YANG ; Wan Soo YOON ; Hong In YOON ; Soon Tae LEE ; Sea Won LEE ; Youn Soo LEE ; Chan Woo WEE ; Jong Hee CHANG ; Tae Young JUNG ; Hye Lim JUNG ; Jae Ho CHO ; Seung Hong CHOI ; Hyoung Soo CHOI ; Je Beom HONG ; Do Hoon LIM ; Dong Sup CHUNG ;
Brain Tumor Research and Treatment 2019;7(2):63-73
BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
Adult
;
Astrocytoma
;
Brain
;
Brain Neoplasms
;
Central Nervous System
;
Drug Therapy
;
Drug Therapy, Combination
;
Glioblastoma
;
Glioma
;
Humans
;
Isocitrate Dehydrogenase
;
Korea
;
Lomustine
;
Oligodendroglioma
;
Radiotherapy
;
World Health Organization
10.Primary epiploic appendagitis: compared with diverticulitis and focused on obesity and recurrence
Youn I CHOI ; Hyun Sun WOO ; Jun Won CHUNG ; Young Sup SHIM ; Kwang An KWON ; Kyoung Oh KIM ; Yoon Jae KIM ; Dong Kyun PARK
Intestinal Research 2019;17(4):554-560
BACKGROUND/AIMS: There is limited data to compare the clinical characteristics and recurrence rates between left-sided primary epiploic appendagitis (PEA) versus left-sided acute colonic diverticulitis (ACD), and right-sided PEA versus right-sided ACD, respectively.METHODS: We retrospectively reviewed the medical records and radiologic images of the patients who presented with left-sided or right-sided acute abdominal pain and had computer tomography performed at the time of presentation showing radiological signs of PEA or ACD between January 2004 and December 2014. We compared the clinical characteristics of left PEA versus left ACD and right PEA versus right ACD, respectively.RESULTS: Fifty-six patients (left:right = 27:29) and 308 patients (left:right = 24:284) were diagnosed with symptomatic PEA and ACD, respectively. Left-sided PEA were statistically significantly younger (50.2 ± 15.4 years vs. 62.1 ± 15.8 years, P= 0.009), more obese (body mass index [BMI]: 26.3 ± 2.9 kg/m² vs. 22.3 ± 3.1 kg/m² , P< 0.001), and had more tendencies with normal or mildly elevated high-sensitivity C-reactive protein (hsCRP) (1.2 ± 1.3 mg/dL vs. 8.4 ± 7.9 mg/dL, P< 0.001) than patients with left-sided ACD. The discriminative function of age, BMI and CRP between left-sided PEA versus left-sided ACD was 0.71 (cutoff: age ≤ 59 years, sensitivity of 66.7%, specificity of 77.8%), 0.84 (cutoff: BMI > 24.5 kg/m² , sensitivity of 80.0%, specificity of 80.0%) and 0.80 (cutoff: CRP < 1.8 mg/dL, sensitivity of 72.2%, specificity of 85.7%).CONCLUSIONS: If patients with left lower quadrant abdominal pain are less than 60 years, obese (BMI > 24.5 kg/m² ) with or without normal to mild elevated CRP levels (CRP < 1.8 mg/dL), it might be necessary for clinicians to suspect the diagnosis of PEA rather than ACD.
Abdominal Pain
;
C-Reactive Protein
;
Diagnosis
;
Diverticulitis
;
Diverticulitis, Colonic
;
Humans
;
Medical Records
;
Obesity
;
Peas
;
Recurrence
;
Retrospective Studies
;
Sensitivity and Specificity

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