Geant4 (GEometry ANd Tracking) provides various packages specialized in modeling electromagnetic interactions. The validation of Geant4 physics models is a significant issue for the applications of Geant4 based simulation in medical physics. The purpose of this study is to evaluate accuracy of Geant4 electromagnetic physics for proton therapy. The validation was performed both the Continuous slowing down approximation (CSDA) range and the stopping power. In each test, the reliability of the electromagnetic models in a selected group of materials was evaluated such as water, bone, adipose tissue and various atomic elements. Results of Geant4 simulation were compared with the National Institute of Standards and Technology (NIST) reference data. As results of comparison about water, bone and adipose tissue, average percent difference of CSDA range were presented 1.0%, 1.4% and 1.4%, respectively. Average percent difference of stopping power were presented 0.7%, 1.0% and 1.3%, respectively. The data were analyzed through the kolmogorov-smirnov Goodness-of-Fit statistical analysis test. All the results from electromagnetic models showed a good agreement with the reference data, where all the corresponding p-values are higher than the confidence level alpha=0.05 set.
Adipose Tissue ; Magnets ; Proton Therapy ; Protons ; Water

In proton therapy, the analysis of secondary particles is important due to delivered dose outside the target volume and thus increased potential risk for the development of secondary cancer. The purpose of this study is to analyze the influence of secondary particles from proton beams on fluence and energy deposition in the presence of inhomogeneous material by using Geant4 simulation toolkit. The inhomogeneity was modeled with the condition that the adipose tissue, bone and lung equivalent slab with thickness of 2 cm were inserted at 30% (Plateau region) and 80% (Bragg peak region) dose points of maximum dose in Bragg curve. The energy of proton was varied with 100, 130, 160 and 190 MeV for energy dependency. The results for secondary particles were presented for the fluence and deposited energy of secondary particles at inhomogeneous condition. Our study demonstrates that the fluence of secondary particles is neither influenced insertion of inhomogeneties nor the energy of initial proton, while there is a little effect by material density. The deposited energy of secondary particles has a difference in the position placed inhomogeneous materials. In the Plateau region, deposited energy of secondary particles mostly depends on the density of inserted materials. Deposited energy in the Bragg region, in otherwise, is influenced by both density of inserted material and initial energy of proton beams. Our results suggest a possibility of prediction about the distribution of secondary particles within complex heterogeneity.
Adipose Tissue ; Dependency (Psychology) ; Lung ; Population Characteristics ; Proton Therapy ; Protons

Abdominal aortic occlusion (AAO) caused by detachment of cardiac myxoma (CM) is a very rare complication in patients with CM. Although the nature of CMs has been well established, detachment of CM may cause unexpected serious complications such as vicious embolic events. Actually, in several cases of AAO caused by detachment of CM, it has been reported that CM fragments easily migrated to the brain, heart, and lungs, and caused lifelong neurological complications despite appropriate surgical therapy. Herein, we report a case of a patient with AAO caused by detachment of CM who underwent CM excision and abdominal aortic thromboembolectomy. Additionally, we have presented the preoperative and postoperative images using 64-multidetector computed tomography.
Aorta, Abdominal ; Brain ; Heart ; Humans ; Lung ; Myxoma

We studied a Monte Carlo simulation of the proton beam delivery system at the National Cancer Center (NCC) using the Geant4 Monte Carlo toolkit and tested its feasibility as a dose verification framework. The Monte Carlo technique for dose calculation methodology has been recognized as the most accurate way for understanding the dose distribution in given materials. In order to take advantage of this methodology for application to externalbeam radiotherapy, a precise modeling of the nozzle elements along with the beam delivery path and correct initial beam characteristics are mandatory. Among three different treatment modes, double/single.scattering, uniform scanning and pencil beam scanning, we have modeled and simulated the double.scattering mode for the nozzle elements, including all components and varying the time and space with the Geant4.8.2 Monte Carlo code. We have obtained simulation data that showed an excellent correlation to the measured dose distributions at a specific treatment depth. We successfully set up the Monte Carlo simulation platform for the NCC proton therapy facility. It can be adapted to the precise dosimetry for therapeutic proton beam use at the NCC. Additional Monte Carlo work for the full proton beam energy range can be performed.
Proton Therapy ; Protons* ; Radiotherapy

Purpose: To analyze the incidence and treatment costs associated with vision-threatening diabetic retinopathy (VTDR) in type 2 diabetes and to predict future VTDR populations and treatment expenditures. Methods: Using the data from the National Health Insurance Service from 2006 to 2017, we analyzed VTDR treatment costs by year, sex, and age. Based on the results and changes in future population distributions, we estimated the future number and cost of treatments for VTDR. Results: The number of treatments increased by 2.5-fold from 37,634 in 2006 to 96,214 in 2017, and treatment costs increased 3.4-fold from $13,528,587 in 2006 to $45,643,561 in 2017. When analyzed by year, age, and sex, all showed an increasing trend. Future number of treatments was estimated to increase from approximately 96,000 in 2017 to 220,000 by 2030 and treatment costs were projected to increase by 129% from about $45,643,561 in 2017 to about $1,043,055,262 by 2030. Conclusions As the incidence of VTDR rises due to an aging population and the frequency of intravitreal injections increases due to insurance reimbursement, future treatment expenditures for VTDR are expected to increase as well. Therefore, appropriate policies must be put in place now to secure medical and financial resources to manage VTDR and reduce medical expenditures in the future.

PURPOSE: Neoadjuvant chemotherapy (NC) is yet to be established as the definitive treatment regimen for locally advanced breast cancer (LABC). The aim of this study was to determine the efficacy and toxicity of NC with epirubicin and paclitaxel. METHODS: Between March 2007 and January 2009, 50 patients with LABC were enrolled in an open-label, phase II, multicenter study carried out at five distinct institutions. All patients were scheduled to receive four cycles of 60 mg/m2 epirubicin and 175 mg/m2 paclitaxel every 3 weeks, preoperatively, unless they developed profound side effects or disease progression. After curative surgery, two additional cycles of chemotherapy were administered to patients who had shown a positive response to NC. RESULTS: In all, 196 cycles of chemotherapy were administered preoperatively; 47 of the 50 patients (94%) underwent all four cycles of designated treatment. Complete disappearance of invasive foci of the primary tumor, and negative axillary lymph nodes were confirmed in eight patients (16.0%), post operation. The cumulative 5-year disease-free survival rate was 70.0% for patients with complete remission (CR) and partial remission (PR), and 33.3% for patients with stable disease (SD) and progressive disease (PD) (p=0.018). The cumulative 5-year overall survival was 90.0% for patients who achieved CR and PR and 55.6% for patients who had SD and PD (p=0.001). Neutropenia (42.0%) was the most common grade 3/4 toxicity. However, none of the toxicities resulted in cessation of the treatment. CONCLUSION: The encouraging pathologic response observed in the patients treated with epirubicin plus paclitaxel NC in this study suggests that epirubicin could be a substitute for doxorubicin, which is the most cardiotoxic agent.
Breast Neoplasms* ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; Drug Therapy* ; Epirubicin* ; Humans ; Lymph Nodes ; Neoadjuvant Therapy ; Neutropenia ; Paclitaxel

Fibroblast-like synoviocytes (FLSs) constitute a major cell subset of rheumatoid arthritis (RA) synovia. Dysregulation of microRNAs (miRNAs) has been implicated in activation and proliferation of RA-FLSs. However, the functional association of various miRNAs with their targets that are characteristic of the RA-FLS phenotype has not been globally elucidated. In this study, we performed microarray analyses of miRNAs and mRNAs in RA-FLSs and osteoarthritis FLSs (OA-FLSs), simultaneously, to validate how dysregulated miRNAs may be associated with the RA-FLS phenotype. Global miRNA profiling revealed that miR-143 and miR-145 were differentially upregulated in RA-FLSs compared to OA-FLSs. miR-143 and miR-145 were highly expressed in independent RA-FLSs. The miRNA-target prediction and network model of the predicted targets identified insulin-like growth factor binding protein 5 (IGFBP5) and semaphorin 3A (SEMA3A) as potential target genes downregulated by miR-143 and miR-145, respectively. IGFBP5 level was inversely correlated with miR-143 expression, and its deficiency rendered RA-FLSs more sensitive to TNFα stimulation, promoting IL-6 production and NF-κB activity. Moreover, SEMA3A was a direct target of miR-145, as determined by a luciferase reporter assay, antagonizing VEGF165-induced increases in the survival, migration and invasion of RA-FLSs. Taken together, our data suggest that enhanced expression of miR-143 and miR-145 renders RA-FLSs susceptible to TNFα and VEGF165 stimuli by downregulating IGFBP5 and SEMA3A, respectively, and that these miRNAs could be therapeutic targets.
Arthritis, Rheumatoid* ; Fibroblasts* ; Insulin-Like Growth Factor Binding Protein 5 ; Interleukin-6 ; Luciferases ; MicroRNAs ; Osteoarthritis ; Phenotype* ; RNA, Messenger ; Semaphorin-3A ; Synovial Fluid

BACKGROUND: Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new anti??neoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. METHODS: Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine 1000mg/m2 and intravenous vinorelbine 25mg/m2 on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. RESULTS: A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria.?The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. CONCLUSION: The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.
Carcinoma, Non-Small-Cell Lung ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Korea ; Lung Neoplasms ; Lung* ; Neutropenia ; Paclitaxel ; Survival Rate