Background: Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data. Methods: The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures. Results: A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures. Conclusion Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab.

Background: Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data. Methods: The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures. Results: A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures. Conclusion Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab.

Background: Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data. Methods: The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures. Results: A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures. Conclusion Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab.

Background: Inhibitory effects of denosumab on bone remodeling are reversible and disappear once treatment is discontinued. Herein, we examined whether and to what extent delayed denosumab administration is also associated with fracture risk using nation-wide data. Methods: The study cohort included women aged 45 to 89 years who were started on denosumab for osteoporosis between October 2017 and December 2019 using data from the Korean Health Insurance Review and Assessment service. Participants were stratified according to the time of their subsequent denosumab administration from the last denosumab administration, including those with within 30 days early dosing (ED30), within the planned time of 180–210 days (referent), within 30–90 days of delayed dosing (DD90), within 90–180 days of delayed dosing (DD180), and longer than 181 days of delayed dosing (DD181+). The primary outcome was the incidence of all clinical fractures. Results: A total of 149,199 participants included and 2,323 all clinical fractures (including 1,223 vertebral fractures) occurred. The incidence of all fractures was significantly higher in the DD90 compared to reference group (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.4). The risk of all fracture was even higher in the longer delayed DD180 group (HR, 1.9; 95% CI, 1.6 to 2.3) and DD181+ group (HR, 1.8; 95% CI, 1.5 to 2.2). Increased risks of fractures with delayed dosing were consistently observed for vertebral fractures. Conclusion Delayed denosumab dosing, even by 1 to 3 months, was significantly associated with increased fracture risk. Maintaining the correct dosing schedule should be emphasized when starting denosumab.

Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Background/Aims: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. Methods: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Results: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Conclusions Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients.Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features:T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.