Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19 + B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.

Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19 + B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.

Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19 + B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.

Purpose: To evaluate set-up error for head and neck cancer (HNC) patients according to each neck lymph node (LN) level. And clinical factors affecting set-up error were analyzed. Materials and Methods: Reference points (RP1, RP2, RP3, and RP4) representing neck LN levels I to IV were designated. These RP were contoured on simulation computed tomography (CT) and cone-beam CT of 89 HNC patients with the same standard. After image registration was performed, movement of each RP was measured. Univariable logistic regression analyses were performed to analyze clinical factors related to measured movements. Results: The mean value of deviation of all axes was 1.6 mm, 1.3 mm, 1.8 mm, and 1.5 mm for RP1, RP2, RP3, and RP4, respectively. Deviation was over 3 mm in 24 patients. Movement of more than 3 mm was observed only in RP1 and RP3. In RP1, it was related to bite block use. Movement exceeding 3 mm was most frequently observed in RP3. Primary tumor and metastatic LN volume change were clinical factors related to the RP3 movement. Conclusion Planning target volume margin of 4 mm for neck LN level I, 3 mm for neck LN level II, 5 mm for neck LN level III, and 3 mm for neck LN level IV was required to include all movements of each LN level. In patients using bite block, changes in primary tumor volume, and metastatic LN volume were related to significant movement.

Purpose: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. Materials and Methods: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). Results: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Growing evidence suggests that environmental air pollution adversely affects kidney health. To date, the association between carbon monoxide (CO) and mortality in patients with end-stage renal disease (ESRD) has not been examined. Methods: Among 134,478 dialysis patients in the Korean ESRD cohort between 2001 and 2014, 8,130 deceased hemodialysis patients were enrolled, and data were analyzed using bidirectional, unidirectional, and time-stratified case-crossover design. We examined the association between short-term CO concentration and mortality in patients with ESRD. We used a two-pollutant model, adjusted for temperature as a climate factor and for nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter less than 10 μm in diameter as air pollution variables other than CO. Results: Characteristics of the study population included age (66.2 ± 12.1 years), sex (male, 59.1%; female, 40.9%), and comorbidities (diabetes, 55.6%; hypertension, 14.4%). Concentration of CO was significantly associated with all-cause mortality in the three case-crossover designs using the two-pollutant model adjusted for SO2. Patients with diabetes or age older than 75 years had a higher risk of mortality than patients without diabetes or those younger than 75 years. Conclusion: Findings presented here suggest that higher CO concentration is correlated with increased all-cause mortality in hemodialysis patients, especially in older high-risk patients.

Purpose: Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. Materials and Methods: The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. Results: Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest. Conclusion The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

Purpose: Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. Materials and Methods: The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. Results: Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest. Conclusion The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

Purpose: In pulmonary oligometastases from colorectal cancer (POM-CRC), the primarily recommended local therapy is metastasectomy. Stereotactic body radiotherapy (SBRT) is another local therapy modality that is considered as an alternative option in patients who cannot undergo surgery. The purpose of this meta-analysis is to demonstrate the effects of SBRT on POM-CRC by integrating the relevant studies. Materials and Methods: The authors explored MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS, and selected studies including patients treated with SBRT for POM-CRC and availability of local control (LC) or overall survival (OS) rate. In this meta-analysis, the effect of SBRT was presented in the form of the LC and OS rates for 1, 2, 3, and 5 years after SBRT as pooled estimates, and the frequency of pulmonary toxicity of grade 3 or higher after SBRT (PTG3-SBRT). Results: Fourteen full texts among the searched 4,984 studies were the objects of this meta-analysis. The overall number of POM-CRC patients was 495 as per the integration of 14 studies. The pooled estimate LC rate at 1, 2, 3, and 5 years after SBRT was 81.0%, 71.5%, 56.0%, and 61.8%, and the OS rate was 86.9%, 70.1%, 57.9%, and 43.0%, respectively. The LC and OS rates gradually declined until 3 years after SBRT in a similar pattern. Among the 14 studies, only two studies reported PTG3-SBRT as 2.2% and 10.8%, respectively. Conclusion For POM-CRC, SBRT is an ablative therapy with a benefit on LC and OS rates and less adverse effects on the lung.

BACKGROUND: Although intracavitary radiotherapy (ICR) is essential for the radiation therapy of cervical cancer, few institutions in Korea perform 3-dimensional (3D)-based ICR. To identify patients who would benefit from 3D-based ICR, dosimetric parameters for tumor targets and organs at risk (OARs) were compared between 2-dimensional (2D)- and 3D-based ICR. METHODS: Twenty patients with locally advanced cervical cancer who underwent external beam radiation therapy (EBRT) following 3D-based ICR were retrospectively evaluated. New 2D-based plans based on the Manchester system were developed. Tumor size was measured by magnetic resonance imaging. RESULTS: The mean high risk clinical target volume (HR-CTV) D90 value was about 10% lower for 2D- than for 3D-based plans (88.4% vs. 97.7%; P = 0.068). Tumor coverage did not differ between 2D- and 3D-based plans in patients with tumors ≤ 4 cm at the time of brachytherapy, but the mean HR-CTV D90 values in patients with tumors > 4 cm were significantly higher for 3D-based plans than for 2D-based plans (96.0% vs. 78.1%; P = 0.017). Similar results were found for patients with tumors > 5 cm initially. Other dosimetric parameters for OARs were similar between 2D- and 3D-based plans, except that mean sigmoid D2cc was higher for 2D- than for 3D-based plans (67.5% vs. 58.8%; P = 0.043). CONCLUSION: These findings indicate that 3D-based ICR plans improve tumor coverage while satisfying the dose constraints for OARs. 3D-based ICR should be considered in patients with tumors > 4 cm size at the time of brachytherapy or > 5 cm initially.
Brachytherapy* ; Colon, Sigmoid ; Humans ; Imaging, Three-Dimensional ; Korea ; Magnetic Resonance Imaging ; Organs at Risk ; Radiotherapy ; Retrospective Studies ; Uterine Cervical Neoplasms*