1.Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset
Ki Hyeong LEE ; Byoung Chul CHO ; Myung-Ju AHN ; Yun-Gyoo LEE ; Youngjoo LEE ; Jong-Seok LEE ; Joo-Hang KIM ; Young Joo MIN ; Gyeong-Won LEE ; Sung Sook LEE ; Kyung-Hee LEE ; Yoon Ho KO ; Byoung Yong SHIM ; Sang-We KIM ; Sang Won SHIN ; Jin-Hyuk CHOI ; Dong-Wan KIM ; Eun Kyung CHO ; Keon Uk PARK ; Jin-Soo KIM ; Sang Hoon CHUN ; Jangyoung WANG ; SeokYoung CHOI ; Jin Hyoung KANG
Cancer Research and Treatment 2024;56(1):48-60
Purpose:
This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC).
Materials and Methods:
Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS).
Results:
In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib.
Conclusion
Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.
2.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.
3.Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404)
Hyungwoo CHO ; Dok Hyun YOON ; Dong-Yeop SHIN ; Youngil KOH ; Sung-Soo YOON ; Seok Jin KIM ; Young Rok DO ; Gyeong-Won LEE ; Jae-Yong KWAK ; Yong PARK ; Min Kyoung KIM ; Hye Jin KANG ; Jun Ho YI ; Kwai Han YOO ; Won Sik LEE ; Byeong Bae PARK ; Jae Cheol JO ; Hyeon-Seok EOM ; Hyo Jung KIM ; Seong Hyun JEONG ; Young-Woong WON ; Byeong Seok SOHN ; Ji-Hyun KWON ; Cheolwon SUH ; Won Seog KIM
Cancer Research and Treatment 2023;55(2):684-692
Purpose:
We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients.
Materials and Methods:
Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL.
Results:
A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS.
Conclusion
The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.
4.Development and Effectiveness of Non-Suicidal Self-Injury Prevention Program for Adolescents Using Brief Dialectical Behavioral Therapy Skills Training (DBT-ST)
Jonggook LEE ; Gyeong-min KIM ; Okran JANG ; Byeonguk PARK ; Hyunjeong KIM ; Gyeongmi HYEON ; Cheolgyu SHIN ; Je Jung LEE
Journal of Korean Neuropsychiatric Association 2023;62(3):102-110
Objectives:
The purpose of this study was to develop a non-suicidal self-injury (NSSI) prevention program for adolescents and confirm its effectiveness in primary prevention by applying dialectical behavior therapy skills training (DBT-ST).
Methods:
From September to December 2021, 217 first-year students in three middle schools in the Chungcheong Province were tested for changes from before and after the program using the Responses to Depressed Mood Questionnaire and Difficulties in Emotion Regulation Scale-16 using paired t-tests. McNemar’s test was conducted to confirm the changes in the perception and attitude scale of NSSI for each question.
Results:
A comparison of the changes from before and after the program revealed that the response to depressed mood (t=7.93, p<0.001), ruminant response (t=5.18, p<0.001), and distractive response (t=6.07, p<0.001) which are subfactors of the response to depressive moods, were significantly affected. There was a significant decrease in the difficulty in performing goaloriented behavior (t=3.34, p=0.01) and lack of emotional clarity (t=2.52, p=0.012), which are subfactors of emotional regulation difficulties. Also, in the comparison of the perception and attitude towards NSSI, statistically significant changes were confirmed in 7 out of a total of 9 questions (p<0.001).
Conclusion
It was confirmed that this program developed by applying DBT-ST was effective in the primary prevention of NSSI for adolescents.
5.SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model
Na Yun LEE ; Youn Woo LEE ; Seung‑Min HONG ; Dain ON ; Gyeong Min YOON ; See‑He AN ; Ki Taek NAM ; Jun‑Young SEO ; Jeon‑Soo SHIN ; Yang‑Kyu CHOI ; Seung Hyun OH ; Jun‑Won YUN ; Ho Young LEE ; Kang‑Seuk CHOI ; Je Kyung SEONG ; Jun Won PARK
Laboratory Animal Research 2023;39(2):165-171
Background:
The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection.
Results:
K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection.
Conclusion
Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
6.Validation of Cancer Diagnosis Based on the National Health Insurance Service Database versus the National Cancer Registry Database in Korea
Min Soo YANG ; Minae PARK ; Joung Hwan BACK ; Gyeong Hyeon LEE ; Ji Hye SHIN ; Kyuwoong KIM ; Hwa Jeong SEO ; Young Ae KIM
Cancer Research and Treatment 2022;54(2):352-361
Purpose:
This study aimed to assess the feasibility of operational definitions of cancer patients in conducting cancer-related studies using the claims data from the National Health Insurance Service (NHIS).
Materials and Methods:
Cancer incidence data were obtained from the Korean Central Cancer Registry, the NHIS primary diagnosis, and from the rare and intractable disease (RID) registration program.
Results:
The operational definition with higher sensitivity for cancer patient verification was different by cancer type. Using primary diagnosis, the lowest sensitivity was found in colorectal cancer (91.5%; 95% confidence interval [CI], 91.7 to 92.0) and the highest sensitivity was found in breast cancer (97.9%; 95% CI, 97.8 to 98.0). With RID, sensitivity was the lowest in liver cancer (91.9%; 95% CI, 91.7 to 92.0) and highest in breast cancer (98.1%; 95% CI, 98.0 to 98.2). In terms of the difference in the date of diagnosis in the cancer registration data, > 80% of the patients showed a < 31-day difference from the RID definition.
Conclusion
Based on the NHIS data, the operational definition of cancer incidence is more accurate when using the RID registration program claims compared to using the primary diagnosis despite the relatively lower concordance by cancer type requires additional definitions such as treatment.
7.Treatment results of carotid endarterectomy and carotid artery stenting for patients with radiation-induced carotid stenosis
Jihee KANG ; Shin-Young WOO ; Shin-Seok YANG ; Yang-Jin PARK ; Dong-Ik KIM ; Pyoung JEON ; Gyeong-Moon KIM ; Young-Wook KIM
Annals of Surgical Treatment and Research 2022;103(2):112-118
Purpose:
Exposure to ionizing radiation over the head and neck accelerates atherosclerotic changes in the carotid arteries. Owing to the characteristics of radiation-induced carotid stenosis (RICS), the results regarding the optimal revascularization method for RICS vary. This study compared treatment outcomes between carotid endarterectomy (CEA) and carotid artery stenting (CAS) in RICS.
Methods:
This was a single-center retrospective review of consecutive patients who underwent CEA or CAS for carotid stenosis. RICS was defined as carotid stenosis (>50%) with the prior neck irradiation for cancer treatment on either side.For the analyses, demographics, comorbid conditions, carotid lesion characteristics based on imaging studies, surgical complications, neurologic outcomes, and mortality during the follow-up period were reviewed. To compare CEA and CAS results in RICS, a 1:1 propensity score matching was applied.
Results:
Between November 1994 and June 2021, 43 patients with RICS and 2,407 patients with non-RICS underwent carotid revascularization with CEA or CAS. RICS had fewer atherosclerotic risk factors and more frequent severe carotid stenosis and contralateral carotid occlusions than non-RICS. CAS was more commonly performed than CEA (22.9% vs.77.1%) for RICS due to more frequent unfavorable carotid anatomy (0 vs. 16.2%). Procedure-related complications were more common in the CEA than in the CAS. However, there was no significant difference in neurologic outcomes and restenosis rates between CEA and CAS in RICS.
Conclusion
Considering its lesion characteristics and cumulative incidence, RICS requires more attention than non-RICS.Although CAS has broader indications for RICS, CEA has shown acceptable results if selectively performed.
8.Lower-Income Predicts Increased Smartphone Use and Problematic Behaviors Among Schoolchildren During COVID-19 Related School Modification: A Longitudinal Study
Eun Sil HER ; Sangha LEE ; Su-Jin YANG ; LiHae PARK ; Mi Gyeong PARK ; Seong-Ju KIM ; Yunmi SHIN
Journal of Korean Medical Science 2022;37(28):e225-
Background:
As the coronavirus disease 2019 (COVID-19) has continued for a couple of years, the long-term effects of the pandemic and the subsequent school curriculum modification on the mental health of children and parents need to be investigated. To clarify the changes that can occur during one school year and to predict the risk factors for vulnerable groups, this study identified parameters relative to children’s screen time, their problematic behavior, and parental depression.
Methods:
A total of 186 participants were analyzed who were parents of elementary schoolchildren in South Korea. These parents were required to complete a web-based questionnaire twice. The questionnaires were conducted in June 2020 and September 2021. Participants’ general demographics including family income, children’s screen time, sleep patterns, problematic behavior, and parental depression were assessed via the parental questionnaire that included various measurement tools.
Results:
Children’s body mass index (BMI) increased significantly in 2021 (18.94 ± 3.75 vs. 18.14 ± 3.30, P < 0.001). Smartphone frequency of use per week (5.35 vs. 4.54, P < 0.001) and screen time per day (3.52 vs. 3.16, P < 0.001) significantly increased during the period of the COVID-19 pandemic. The television screen time (2.88 vs. 3.26, P < 0.001), frequency of viewing (3.77 vs. 4.77, P < 0.001), and children’s problematic behaviors significantly decreased (9.15 vs. 11.85,P < 0.001). A lower income household was a key predictor of increased smartphone frequency (B = 1.840, 95% confidence interval [CI], 0.923–2.757, P < 0.001) and smartphone screen time (B = 1.992, 95% CI, 1.458–2.525, P < 0.001). The results showed that the lower income household (B = 5.624, 95% CI, 2.927–8.320, P < 0.001) and a child’s psychiatric treatment history (B = 7.579, 95% CI, 5.666–9.492, P < 0.001) was the most significant predictor of problematic behaviors of children and parental depression (B = 3.476, 95% CI, 1.628–5.325, P < 0.001; B = 3.138, 95% CI, 1.827–4.450, P < 0.001).
Conclusion
This study suggested that children’s smartphone screen time and BMI increased during COVID-19 because of the school curriculum modification following school closures in South Korea. The increased children’s problematic behaviors and parental depression were predicted by lower-income households and the previous psychiatric history of children. These results indicate that multiple social support systems to the vulnerable group are needed during the ongoing pandemic and that a modified school setting is required.
9.Choice of the correct size of endotracheal tube in pediatric patients
Seyeon PARK ; Sang-Wook SHIN ; Hye-Jin KIM ; Gyeong-Jo BYEON ; Ji-Uk YOON ; Eun-Jung KIM ; Hee Young KIM
Anesthesia and Pain Medicine 2022;17(4):352-360
Selection and insertion of an endotracheal tube (ETT) of appropriate size for airway management during general anesthesia in pediatric patients is very important. A very small ETT increases the risk of inadequate ventilation, air leakage, and aspiration, whereas a very large ETT may cause serious complications including airway damage, post-intubation croup, and, in severe cases, subglottic stenosis. Although the pediatric larynx is conical, the narrowest part, the rima glottidis, is cylindrical in the anteroposterior dimension, regardless of development, and the cricoid ring is slightly elliptical. A cuffed ETT reduces the number of endotracheal intubation attempts, and if cuff pressure can be maintained within a safe range, the risk of airway damage may not be greater than that of an ETT without cuff. The age-based formula suggested by Cole (age/4 + 4) has long been used to select the appropriate ETT size in children. Because age-based formulas in children are not always accurate, various alternative methods for estimating the ETT size have been examined and suggested. Chest radiography, ultrasound, and a three-dimensional airway model can be used to determine the appropriate ETT size; however, there are several limitations.
10.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.

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