Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Purpose: Current guidelines recommend vaccination at least 2 weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response. Materials and Methods: Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated 2 weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, 3 years, and 5 years. Immune responses were measured using enzyme-linked immunosorbent assay and multiplex opsonophagocytosis assay. Results: Including 63 patients, both groups showed an initial increase in the geometric mean titers of opsonophagocytic activity and the geometric mean concentrations of serotype-specific IgG levels after one month, followed by a decline at 3 and 5 years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for 5 years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen. Conclusion Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for > 5 years, and global response remained in over half of patients.

Objective: Cognitive impairment is common in patients with Parkinson’s disease (PD), and few pharmacological options are available for treating this condition. We evaluated the effects of a digital cognitive training program (SUPERBRAIN), which was previously shown to be effective in populations at risk of Alzheimer’s disease, on cognitive function in individuals with PD. Methods: Twenty-three individuals with PD and mild cognitive impairment (PD-MCI) from four clinics were randomized to the intervention (n=16) or control (n=7) groups. The intervention group completed a 12-week, home-based, tablet-based cognitive training program (25–30 min/day, 7 days/week). Cognitive outcomes were assessed using the Seoul Neuropsychological Screening Battery pre- and post-intervention. Results: The adherence rate was 79.36%. The intervention group showed significant improvements in the Seoul Verbal Learning Test (SVLT) delayed recall and the Controlled Oral Word Association Test, while no changes were observed in the control group. Analysis of covariance confirmed greater SVLT improvement in the intervention group (F statistic=7.15, p=0.015, partial η2=0.28). Conclusion SUPERBRAIN is feasible and can improve cognitive function in individuals with PD-MCI.

Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Heart failure (HF) is a major cause of mortality and morbidity in South Korea, imposing substantial physical, emotional, and financial burdens on patients and society. Despite the high burden of symptom and complex care needs of HF patients, palliative care and hospice services remain underutilized in South Korea due to cultural, institutional, and knowledge-related barriers. This position statement from the Korean Society of Heart Failure emphasizes the need for integrating palliative and hospice care into HF management to improve quality of life and support holistic care for patients and their families. By clarifying the role of palliative care in HF and proposing practical referral criteria, this position statement aims to bridge the gap between HF and palliative care services in South Korea, ultimately improving patient-centered outcomes and aligning treatment with the goals and values of HF patients.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Society of Osteoporosis, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining Stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3-4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management.This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.

With a rapidly aging population and increasing use of antiresorptive agents, medication-related osteonecrosis of the jaw (MRONJ) represents a growing clinical challenge worldwide. To address the need for tailored clinical guidance, a multidisciplinary task force was convened. Five Korean academic societies—the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Society of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Osteoporosis Society, and the Korean Endocrine Society—collaborated to develop this position statement. The consensus was formulated through comprehensive reviews of literature, combined with three rounds of formal surveys to consolidate expert opinion on controversial topics. This position paper provides evidence-based clinical guidelines for the prevention, diagnosis, and management of MRONJ tailored to the Korean healthcare environment. The diagnostic criteria affirm the standard definition but add a provision for diagnosis based on clinical or radiographic evidence of necrotic bone, even if the traditional 8-week timeframe has not been met. The committee advocates for retaining stage 0 in the staging system to emphasize early detection and preventive intervention. Key recommendations include prescriptive, drug-specific guidelines for prophylactic drug holidays (e.g., a 2-month pause for oral bisphosphonates; timing surgery 3 to 4 months after the last denosumab injection) to minimize MRONJ risk from dental procedures. This statement also provides a clear framework for therapeutic drug holidays in established MRONJ, carefully balancing the need for jaw healing against systemic fracture risk. For treatment, this statement advocates for early and active surgical intervention across all MRONJ stages, supported by evidence of superior long-term outcomes compared to conservative management. This position statement offers a unique, evidence-based Korean clinical practice guideline for managing MRONJ. It is intended to standardize care, reduce clinical confusion, and ultimately improve patient outcomes by providing a clear framework for decision-making.

Purpose: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. Materials and Methods: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. Results: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). Conclusion Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Background/Aims: Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods: This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results: This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. Conclusions In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.