Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS(N = 1,244) or AML (N = 2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/ R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF > 50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Objective: To investigate the prevalence of pathological findings and clinical outcomes of riskreducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). Methods: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/ LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea.Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. Results: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/ LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9–71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. Conclusion Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

Hyperthyroidism is a clinical condition characterized by excessive production of thyroid hormones, leading to thyrotoxicosis, with Graves’ disease being the most common underlying etiology. The treatment options for hyperthyroidism include antithyroid drug (ATD) therapy, radioactive iodine (RAI) therapy, and thyroidectomy. To establish standardized clinical recommendations specific to RAI therapy focusing on the safety, efficacy, pre- and post-treatment protocols, and follow-up monitoring, the Korean Thyroid Association convened a Task Force dedicated to developing evidence-based guidelines. Six key clinical questions were identified through expert panel discussion. A systematic review of literature published between 2013 and 2022 was conducted using PubMed and Embase with “hyperthyroidism” and “Graves’ disease” as search terms. Additional studies published during manuscript development were also included. The guideline classifies the clinical indications for RAI therapy into three categories: cases in which RAI is strongly recommended, may be considered, or not recommended. A fixed dose of 10–15 mCi is recommended for RAI therapy. While a routine low-iodine diet is not required, patients should avoid iodine-rich foods for at least one week before treatment. ATD should be discontinued 3–7 days prior to RAI and may be resumed afterward in selected cases. Prophylactic glucocorticoids are advised for patients with mild active thyroid eye disease and may be considered in those with additional risk factors. Thyroid function should be monitored at 4–6 weeks post-treatment, then every 2–3 months until stabilization, and subsequently at 6–12 month intervals or as clinically indicated. This guideline reflects recent advances in RAI therapy for hyperthyroidism and emphasizes the importance of individualized treatment decisions based on clinical characteristics, comorbidities, and patient preferences in Korea.

The increasing detection of papillary thyroid microcarcinoma (PTMC) has raised concerns about overtreatment.For low-risk PTMC, either immediate surgery or active surveillance (AS) can be considered. To support AS implementation, the Korean Thyroid Association convened a multidisciplinary panel and developed the first Korean guideline. AS is recommended to adults with pathologically proven Bethesda V-VI PTMC without clinical evidence of lymph node or distant metastasis, gross extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, or aggressive histology. Baseline assessment requires high‑resolution cervical ultrasound by experienced operators to rule out extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, and lymph node metastasis;contrast‑enhanced neck computed tomography is optional. Patient characteristics such as age, comorbidities, and capacity for long-term follow-up should be assessed. Shared decision-making should weigh the benefits and risks of surgery and AS, expected oncologic outcomes, complications, quality of life, anxiety, medical cost, and patient preference. Follow-up includes cervical ultrasound and thyroid function test every six months for two years, then annually. Disease progression, defined as significant tumor growth or newly detected nodal or distant metastasis, warrants surgery. Despite remaining uncertainties, this guideline offers a framework to ensure oncologic safety and support patient-centered active surveillance.

Glycemic control is particularly important in hemodialysis (HD) patients with diabetes mellitus (DM). Although fasting blood glucose (FBG) level is an important indicator of glycemic control, a clear target for reducing mortality in HD patients with DM is lacking. Methods: A total of 26,162 maintenance HD patients with DM were recruited from the National Health Insurance Database of Korea between 2002 and 2018. We analyzed the association of FBG levels at the baseline health examination with the risk of all-cause and cause-specific mortality. Results: Patients with FBG 80–100 mg/dL showed a higher survival rate compared with that of other FBG categories (p < 0.001). The risk of all-cause mortality increased with the increase in FBG levels, and adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [CI], 1.04–1.17), 1.21 (95% CI, 1.13–1.29), 1.36 (95% CI, 1.26–1.46), and 1.61 (95% CI, 1.51–1.72) for patients with FBG 100–125, 125–150, 150–180, and ≥180 mg/dL, respectively. The HR for mortality was also significantly increased in patients with FBG <80 mg/dL (adjusted HR, 1.14; 95% CI, 1.05–1.23). The analysis of cause-specific mortality also revealed a J-shaped curve between FBG levels and the risk of cardiovascular deaths. However, the risk of infection or malignancy-related deaths was not linearly increased as FBG levels increased. Conclusion: A J-shaped association was observed between FBG levels and the risk of all-cause mortality, with the lowest risk at FBG 80–100 mg/dL in HD patients with DM.

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.