Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: Stem cell transplantation (SCT) has historically played a major role in the long-term remission of mantle cell lymphoma (MCL), an incurable hematological malignancy. Using data from the Korean Society of Bone and Marrow Transplantation registry, we retrospectively analyzed the role of autologous (auto) and allogeneic (allo) SCT in longterm MCL survival. Methods: This study analyzed data from 188 patients (age ≥ 19 years at the time of transplantation) who underwent a transplant for MCL from 2011 to 2020. Progression-free survival (PFS) was defined as the time from transplantation to disease progression, relapse, or death from any cause. Overall survival (OS) was defined as the time from transplan‑ tation to death from any cause or the last follow-up. Results: In total, 109 patients underwent consolidative SCT after first-line chemotherapy. The 3-year PFS and OS rates were 65.4% and 78.5%, respectively, in the auto-SCT group, and 66.7% and 71.4%, respectively, in the allo-SCT group. The PFS and OS did not differ significantly between the auto- and allo-SCT groups. As part of salvage treatment, 52 patients with relapsed or refractory disease underwent auto- or allo-SCT. Patients who underwent auto-SCT with complete remis‑ sion/partial remission status reported better outcomes. In patients with refractory status, allogeneic transplantation using human leukocyte antigen (HLA) fully matched donors was a significantly favorable factor for PFS and OS. Conclusion The long-term survival of patients who underwent consolidative transplantation was similar to that reported in previous studies. Auto-SCT may be beneficial in patients who respond to salvage therapy, whereas allo-SCT with HLA-matched donors may be an alternative for patients with refractory disease. 

Purpose: To evaluate whether extended pelvic lymph node dissection (PLND) improves survival outcomes compared with standard PLND in patients with bladder cancer (BCa) undergoing radical cystectomy (RC), and to assess its potential benefits in patients with prior or concurrent radical nephroureterectomy (p/cRNU). Materials and Methods: A multicenter analysis included 2202 patients with BCa undergoing RC with standard or extended PLND at 11 tertiary centers from 2003 to 2023. Following propensity score matching, 659 pairs (n=1,318), including 128 patients with p/cRNU, were analyzed. Recurrence-free survival (RFS) was the primary outcome, while overall survival (OS), cancer-specific survival (CSS), and readmission rates were secondary outcomes. Survival analyses performed using Kaplan-Meier methods and clustered Cox models. Results: Extended PLND yielded significantly more lymph nodes than standard PLND (median: 27.0 vs. 17.0, p<0.001) but did not improve RFS, CSS, or OS in the overall cohort (all p>0.05). Extended PLND increased readmission rates (28.4% vs. 20.2%, p=0.001) and readmission risk (odds ratio, 1.57; 95% confidence interval [CI], 1.15–2.16, p=0.005). However, subgroup analysis revealed extended PLND significantly improved RFS in patients with p/cRNU (hazard ratio, 0.54; 95% CI, 0.38–0.77; p<0.001). Conclusion Extended PLND does not provide survival benefits for overall patient population and increases readmission risk but significantly improves RFS in patients with p/cRNU. Tailoring PLND extent based on upper tract disease status is recommended.

Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.