Fexuprazan (DWP14012), a potassium-competitive acid blocker, is a medical formulation prescribed to inhibit the secretion of gastric acid. The present study encompasses a comparative evaluation of pharmacokinetic (PK) analysis between the previous (reference) and size-reduced (test) formulation of fexuprazan 20 mg in healthy subjects. The study employed a randomized, open-label, single-dose, 2-sequence, 2-period, crossover design with a 7-day wash-out between periods. A total of 24 subjects were enrolled in this randomized study. During each period, the 21 subjects received either the test or reference formulation. Blood samples were collected at multiple time point ranging from 0 (pre-dose) to 48 hours post-dosing for PK analysis. The calculated PK parameters were considered bioequivalent when the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) were within the bioequivalence limit of 0.8–1.25. Safety and tolerability were included in the evaluation. A total of 20 subjects completed the study. Point estimates (90% CIs) of the GMRs were 1.1014 (0.9892–1.2265) for the maximum plasma concentration and 1.0530 (0.9611–1.1536) for the area under the plasma concentration-time curve from zero to the time of the last quantifiable concentration, between the test and reference formulations.The reference and size-reduced test formulations of fexuprazan were well tolerated with no reports of serious adverse events. In conclusion, size-reduced and previous formulations of fexuprazan 20 mg were bioequivalent with regard to PKs, safety and tolerability.

PURPOSE: The aim of this study was to analyze the patterns of care and treatment outcomes in patients with primary thyroid lymphoma (PTL) in a single institution. MATERIALS AND METHODS: Medical records of 29 patients with PTL treated between April 1994 and February 2012 were retrospectively reviewed. Diagnosis was confirmed by biopsy (n = 17) or thyroidectomy (n = 12). Treatment modality and outcome were analyzed according to lymphoma grade. RESULTS: The median follow-up was 43.2 months (range, 3.8 to 220.8 months). The median age at diagnosis was 57 years (range, 21 to 83 years) and 24 (82.8%) patients were female. Twenty-five (86.2%) patients had PTL with stage IEA and IIEA. There were 8 (27.6%) patients with mucosa-associated lymphoid tissue (MALT) lymphoma and the remaining patients had high-grade lymphoma. Patients were treated with surgery (n = 2), chemotherapy (n = 7), radiotherapy (n = 3) alone, or a combination of these methods (n = 17). Treatment modalities evolved over time and a combination of modalities was preferred, especially for the treatment of high-grade lymphoma in recent years. There was no death or relapse among MALT lymphoma patients. Among high-grade lymphoma patients, 5-year overall survival (OS) and 5-year progression-free survival (PFS) were 75.6% and 73.9%, respectively. Complete remission after initial treatment was the only significant prognostic factor for OS (p = 0.037) and PFS (p = 0.003). CONCLUSION: Patients with PTL showed a favorable outcome, especially with MALT lymphoma. Radiotherapy alone for MALT lymphoma and chemotherapy followed by radiotherapy for high-grade lymphoma can be effective treatment options for PTL.
Biopsy ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphoid Tissue ; Lymphoma* ; Lymphoma, B-Cell, Marginal Zone ; Lymphoma, Non-Hodgkin ; Medical Records ; Methods ; Physician's Practice Patterns ; Radiotherapy ; Recurrence ; Retrospective Studies ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroidectomy ; Treatment Outcome

PURPOSE: In some patients who receive adjuvant radiotherapy (RT) for the left breast, the stomach is located inside the RT field. This study investigates the incidence of gastric complications following adjuvant RT for breast cancer using data of the Health Insurance Review and Assessment Service in South Korea. METHODS: We identified 37,966 women who underwent surgery and received adjuvant RT for breast cancer. The cumulative incidence rate of gastric hemorrhage and gastric cancer was calculated and compared for left and right breast cancers. RESULTS: Among 37,966 patients, 19,531 (51.4%) and 18,435 (48.6%) had right and left breast cancers, respectively. After a median follow-up duration of 6.3 years, the cumulative incidence of gastric cancer and gastric hemorrhage did not differ between right and left breast cancers (p = 0.414 and p = 0.166, respectively). The multivariable analysis revealed that old age was the only factor associated with the development of gastric cancer (p < 0.001) and gastric hemorrhage (p < 0.001). The incidence of gastric cancer and hemorrhage did not differ between patients who received adjuvant RT for right and left breast cancers. CONCLUSION: Irradiation-related chronic complications of the stomach in patients with breast cancer are minimal. A study with a longer follow-up duration might be needed to assess the risk of gastric cancer.
Breast Neoplasms ; Breast ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage ; Hemorrhage ; Humans ; Incidence ; Insurance, Health ; Korea ; Radiotherapy ; Radiotherapy, Adjuvant ; Stomach ; Stomach Neoplasms

PURPOSE: Early prediction of treatment outcomes represents an essential step towards increased treatment efficacy and survival in patients with hepatocellular carcinoma (HCC). In this study, we performed two-dimensional electrophoresis (2-DE) followed by protein profiling to identify biomarkers predictive of therapeutic outcomes in patients with HCC who received liver-directed therapy (LDTx) involving local radiotherapy (RT), and studied the underlying mechanisms of the identified proteins. MATERIALS AND METHODS: 2-DE analysis was conducted by pooling sera from patients with a good or poor prognosis; serum proteomic profiles of the two groups were compared and analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Identified proteins were confirmed via enzyme-linked immunosorbent assay. An invasion assay was performed after overexpression and knockdown of target protein in Huh7 cells. RESULTS: Levels of inter-alpha inhibitor H4 (ITIH4), fibrinogen gamma chain, keratin 9/1 complex, carbonic anhydrase I, and carbonmonoxyhemoglobin S were changed by more than 4-fold in response to LDTx. In particular, pre-LDTx ITIH4 expression was more than 5-fold higher in patients with a good prognosis, compared to patients with a poor prognosis. The migration ability of Huh7 cells was significantly suppressed and enhanced by ITIH4 overexpression and knockdown, respectively. The tumors of patients with HCC and a good prognosis expressed high levels of ITIH4, compared to those of patients with a poor prognosis. CONCLUSION: Taken together, ITIH4 may be a potential therapeutic target that could inhibit cancer metastasis, as well as a prognostic marker for patients with HCC who are receiving LDTx.
Biomarkers ; Carbonic Anhydrase I ; Carboxyhemoglobin ; Carcinoma, Hepatocellular* ; Electrophoresis ; Enzyme-Linked Immunosorbent Assay ; Fibrinogen ; Humans ; Mass Spectrometry ; Neoplasm Metastasis ; Prognosis ; Radiotherapy ; Treatment Outcome

Purpose: High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. Materials and Methods: We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. Results: Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. Conclusion We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

PURPOSE: The aim of this study was to examine patterns of radiotherapy (RT) in Korean patients with hepatocellular carcinoma (HCC) according to the evolving guideline for HCC established by the Korean Liver Cancer Study Group-National Cancer Center (KLCSG-NCC). MATERIALS AND METHODS: We reviewed 765 patients with HCC who were treated with RT between January 2011 and December 2012 in 12 institutions. RESULTS: The median follow-up period was 13.3 months (range, 0.2 to 51.7 months). Compared with previous data between 2004 and 2005, the use of RT as a first treatment has increased (9.0% vs. 40.8%). Increased application of intensity-modulated RT resulted in an increase in radiation dose (fractional dose, 1.8 Gy vs. 2.5 Gy; biologically effective dose, 53.1 Gy10 vs. 56.3 Gy10). Median overall survival was 16.2 months, which is longer than that reported in previous data (12 months). In subgroup analysis, treatments were significantly different according to stage (p < 0.001). Stereotactic body RT was used in patients with early HCC, and most patients with advanced stage were treated with three-dimensional conformal RT. CONCLUSION: Based on the evolving KLCSG-NCC practice guideline for HCC, clinical practice patterns of RT have changed. Although RT is still used mainly in advanced HCC, the number of patients with good performance status who were treated with RT as a first treatment has increased. This change in practice patterns could result in improvement in overall survival.
Carcinoma, Hepatocellular* ; Follow-Up Studies ; Humans ; Liver Neoplasms ; Practice Patterns, Physicians'* ; Radiation Oncology* ; Radiotherapy*

PURPOSE: We investigated the effect of location changes in the inferior border of the belly board (BB) aperture by adding a bladder compression device (BCD). MATERIALS AND METHODS: We respectively reviewed data from 10 rectal cancer patients with a median age 64 years (range, 45~75) and who underwent computed tomography (CT) simulation with the use of BB to receive pelvic radiotherapy between May and September 2010. A CT simulation was again performed with the addition of BCD since small bowel (SB) within the irradiated volume limited boost irradiation of 5.4 Gy using the cone down technique after 45 Gy. The addition of BCD made the inferior border of BB move from symphysis pubis to the lumbosacral junction (LSJ). RESULTS: Following the addition of BCD, the irradiated volumes of SB and the abdominopelvic cavity (APC) significantly decreased (174.3+/-89.5 mL vs. 373.3+/-145.0 mL, p=0.001, 1282.6+/-218.7 mL vs. 1571.9+/-158 mL, p<0.001, respectively). Bladder volume within the treated volume increased with BCD (222.9+/-117.9 mL vs. 153.7+/-95.5 mL, p<0.001). The ratio of irradiated bladder volume to APC volume with BCD (33.5+/-14.7%) increased considerably compared to patients without a BCD (27.5+/-13.1%) (p<0.001), and the ratio of irradiated SB to APC volume decreased significantly with BCD (13.9+/-7.6% vs. 24.2+/-10.2%, p<0.001). The ratios of the irradiated SB volumeand irradiated bladder volume to APC volume negatively correlated (p=0.001). CONCLUSION: This study demonstrated that the addition of BCD, which made the inferior border of BB move up to the LSJ, increased the ratio of the bladder to APC volume and as a result, decreased the irradiated volume of SB.
Humans ; Rectal Neoplasms ; Urinary Bladder

PURPOSE: This study aimed to identify risk factors that have significant interaction with radiation exposure to the heart, and thus to determine candidates for heart-sparing radiotherapy (RT) among women with left breast cancer. METHODS: We identified 4,333 patients who received adjuvant RT following breast-conserving surgery for ductal carcinoma in situ or invasive breast cancer from 1996 to 2010. Incidence rates of cardiovascular disease were compared between left-sided and right-sided RT, and stratified by age and risk factors such as body mass index (BMI), smoking, hyperlipidemia, hypertension, diabetes, administration of anthracycline, and trastuzumab. RESULTS: In all patients, the cumulative incidence of cardiovascular disease was greater in patients treated with left-sided RT than in those treated with right-sided RT, but the difference was not significant (p=0.428). Smoking (hazard ratio [HR], 5.991; 95% confidence interval [CI], 2.109–17.022; p=0.002) and hyperlipidemia (HR, 5.567; 95% CI, 3.235–9.580; p<0.001) were the most powerful risk factors for cardiovascular disease. There was no significant factor that further increased the risk of cardiovascular disease after left breast RT compared to right breast RT. CONCLUSION: Although hyperlipidemia and smoking are risk factors for cardiovascular disease, they have not been proven to increase the risk of RT-related cardiovascular disease in Korean women.
Body Mass Index ; Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Cardiotoxicity ; Cardiovascular Diseases ; Female ; Heart ; Humans ; Hyperlipidemias ; Hypertension ; Incidence ; Mastectomy, Segmental ; Radiation Exposure ; Radiotherapy* ; Risk Factors ; Smoke ; Smoking ; Trastuzumab