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.

Background/Aims: Biliary tract cancer (BTC) is a rare malignancy with poor prognosis. We investigated genomic determinants of clinical benefit from gemcitabine, cisplatin, and nab-paclitaxel (GAP) versus gemcitabine and cisplatin (GC) in advanced BTC. Methods: Clinical and genomic data using TruSight Oncology 500 were analyzed from patients treated with GAP (N=198) or GC (N=89) as first-line therapy. Results: With a median follow-up of 33.0 months, GAP modestly improved progression-free survival (PFS) (hazard ratio [HR] 0.764; 95% confidence interval [CI] 0.591–0.989) without significant overall survival (OS) difference compared to GC. Genomic profiling revealed frequent alterations in TP53 (35.2%), KRAS (16.4%), SMAD4 (10.5%), and TNFRSF14 (10.5%), involving RTK/RAS (44.3%), TP53 (41.8%), and PI3K (20.2%) pathways. Single-gene mutations did not predict treatment benefit. However, pathway-level analysis identified PI3K pathway activation as significantly associated with inferior PFS (HR 2.148; 95% CI 1.478–3.124) and OS (HR 2.096; 95% CI 1.413–3.109) in patients receiving GAP, an effect not observed with GC. Importantly, GAP conferred clinical benefit only in patients without PI3K pathway activation, while no survival advantage was seen in those with such alterations (Pinteraction=0.023 for PFS, Pinteraction=0.003 for OS). Similar results were obtained in the independent validation cohort treated with GAP (N=103) or GC (N=64) for BTC. Conclusions Genomic profiling using next-generation sequencing identified PI3K pathway activation as key molecular determinant that differentiates patient outcomes between GAP and GC treatments in advanced BTC.

OBJECTIVES: The prevalence of aged individuals in the Korean workforce continues to increase. This research determined the health and working conditions of Korean older wage workers and confirmed the effects of factors on the health-related quality of life of Korean older workers. METHODS: Of the 25,534 persons surveyed in the fifth Korea National Health and Nutrition Examination Survey, 1368 older (>55 years of age) wage workers without missing variables were selected. Their general characteristics, health status (cardiovascular disease, musculoskeletal disease, and mental health), working conditions (type of occupation, employment status, full- or part-time work, weekly average working hours, and shift work), and health-related quality of life assessed by the EQ-5D questionnaire were examined. RESULTS: The mean values of the EQ-5D index of the male and female older workers were 0.956 +/- 0.087 and 0.917 +/- 0.124, respectively (p < 0.001). The factors that caused statistically significant differences in the EQ-5D index for all subjects were age, education, household income, cerebro-cardiovascular event, osteoarthritis, musculoskeletal pain, stress, occupation type, employment status, and working hours. In logistic regression analysis, the factors that associated with perceived problems in each EQ-5D dimensions were age, musculoskeletal pain, stress, diabetes, smoking, occupation type, employment status, and working hours. CONCLUSIONS: To eventually raise the quality of life of older workers through health maintenance and management, it is necessary to manage related factors that include of musculoskeletal pain and diseases, stress, diabetes, smoking, occupation, employment status, and working hours.
Education ; Employment ; Family Characteristics ; Female ; Humans ; Korea ; Logistic Models ; Male ; Musculoskeletal Diseases ; Musculoskeletal Pain ; Nutrition Surveys ; Occupations ; Osteoarthritis ; Prevalence ; Quality of Life* ; Salaries and Fringe Benefits ; Smoke ; Smoking

OBJECTIVES: Vitamin D deficiency is increasing worldwide. However, few studies have attempted to examine the vitamin D status of wage workers and the correlation between vitamin D deficiency and working conditions. Hence, we aimed to evaluate the prevalence of vitamin D deficiency and the association between occupational conditions and vitamin D deficiency among Korean wage workers. METHODS: Wage workers aged 20-65 years from the 5th Korea National Health and Nutrition Examination Survey (KNHANES 2010-2012; n = 5409) were included in our analysis. We measured the prevalence of vitamin D deficiency and identified the correlations with the working conditions of these subjects. RESULTS: The prevalence of vitamin D deficiency in male and female subjects was 69.5% and 83.1%, respectively. Among the male subjects, a significant correlation between vitamin D deficiency and working conditions was observed among shift workers, office workers, and permanent workers. No significant correlation with any type of working conditions was observed among female subjects. CONCLUSION: The prevalence of vitamin D deficiency among Korean wage workers was very high and was found to correlate significantly with working conditions, likely because of insufficient exposure to sunlight associated with certain types of work. Wage workers require more frequent outdoor activity and nutrition management to maintain sufficient vitamin D level.
Female ; Humans ; Korea* ; Male ; Nutrition Surveys* ; Prevalence ; Salaries and Fringe Benefits* ; Sunlight ; Vitamin D Deficiency ; Vitamin D* ; Vitamins*

To investigate the effects of short-term exposure of beryllium on the human immune system, the proportion of T-lymphocytes such as CD3+, CD4+, CD8+, CD95, and NK cells, andthe proportion of B cells and TNFalpha level in peripheral blood and immunoglobulins in the serum of 43 exposed workers and 34 healthy control subjects were studied. External exposure to beryllium was measured by atomic absorption spectrometer as recommended by the NIOSH analytical method 7300. T lymphocyte subpopulation analysis was carried out with flow cytometer. The working duration of exposed workers was less than 3 months and the mean ambient beryllium level was 3.4 microg/m3, 112.3 microg/m3, and 2.3 microg/m3 in molding (furnace), deforming (grinding), and sorting processes, respectively (cited from Kim et al., 2008). However, ambient beryllium level after process change was non-detectable (< 0.1 microg/m3). The number of T lymphocytes and the amount of immunoglobulins in the beryllium-exposed workers and control subjects were not significantly different, except for the total number of lymphocytes and CD95 (APO1/FAS). The total number of lymphocytes was higher in the beryllium-exposed individuals than in the healthy control subjects. Multiple logistic regression analysis showed lymphocytes to be affected by beryllium exposure (odd ratio = 7.293; p < 0.001). These results show that short-term exposure to beryllium does not induce immune dysfunction but is probably associated with lymphocytes proliferation.
Absorption ; B-Lymphocytes ; Beryllium ; Fungi ; Humans ; Immune System ; Immunoglobulins ; Killer Cells, Natural ; Logistic Models ; Lymphocyte Subsets ; Lymphocytes ; National Institute for Occupational Safety and Health (U.S.) ; T-Lymphocytes ; Tumor Necrosis Factor-alpha