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Inhibition of Vascular Endothelial Growth Factor-induced Endothelial Cell Differentiation by Intravenous Immunoglobulin and Methylprednisolone (혈관내막 성장인자에 의해 유도된 내막세포 분화에 대한 정맥용 면역글로불린과 메틸프레드니솔론의 효과)

  • Choi, Hyoun Ah;Ha, Kyung Hwa;Yoon, Jong Seo;Lee, Yoon;Lee, Joon Sung;Han, Ji Wwan
    • Clinical and Experimental Pediatrics
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    • v.48 no.8
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    • pp.886-893
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    • 2005
  • Purpose : Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin(IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor(VEGF)-induced tube formation of endothelial cells in vitro on Matrigel assay. Methods : Human umbilical vein endothelial cells(HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents : VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. Results : IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. Conclusion : We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.

Clinical Study on Fluvoxamine Combined with Oxycodone Prolonged-Release Tablets in Treating Patients with Moderate to Severe Cancer Pain

  • Xiao, Yang;Liu, Jun;Huang, Xin-En;Ca, Li-Hua;Ma, Yi-Min;Wei, Wei;Zhang, Rong-Xia;Huang, Xiao-Hong;Chang, Juan;Wu, Yi-Jia
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10445-10449
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    • 2015
  • Objective: To observe treatment effects and safety of fluvoxamine combined with oxycodone prolonged-release tablets in treating patients with moderate to severe cancer pain. Methods: Patients confirmed pathologically with cancer and complicated with moderate to severe pain, were divided into control and experimental groups. Oxycodone prolonged-release tablets, with or without fluvoxamine, were administrated to all study patients until pain relief. Degree of pain relief, dose of oxycodone prolonged-release tablets, side effects and quality of life were compared before and after treatment. Results: In total, 120 patients were recruited. No statistically significant difference was detected regarding age, gender, types of cancer, KPS between two groups of patients (P>0.05). Baseline pain score of patients with moderate pain in treatment and control group was $4.9{\pm}0.8$ and $5.1{\pm}0.8$, respectively; and decreased to $1.8{\pm}1.1$ and $1.2{\pm}1.1$ after treatment, respectively. Pain intensity was significantly reduced in the treatment group (P=0.028). Average daily consumption of oxycodone prolonged-release tablets was ($54.0{\pm}19.6$) mg and ($44.7{\pm}18.7$) mg respectively, which is lower in treatment grpup than in control group, but the difference was not statistically significant (P=0.065). Baseline pain score of patients with severe pain in treatment and control groups were $8.3{\pm}1.1$ and $8.3{\pm}1.1$, respectively; and pain intensity after treatment decreased to $2.9{\pm}1.0$ and $2.3{\pm}1.0$. Pain intensity was significantly reduced in the treatment group, with statistical significance (P=0.026). Average daily consumption of oxycodone prolonged-release tablets was ($132.0{\pm}42.2$) mg and ($110.7{\pm}33.9$) mg, respectively, which is lower in treatment group than in control group, and the difference was statistically significant (P=0.035). In terms of quality of life, patients in treatment group had better performance status, daily activity, mood, and sleep than that in control group (P < 0.05). Patients in two groups had similar side effects, eg., constipation, nausea/vomiting, lethargy, dizziness, itchy skin, dysuria, and ataxia. Lower incidence of nausea/vomiting, lethargy, was obtained from patients in treatment than in control group, while significant low constipation was observed in treatment than in control group (35.0% vs 49.2%, P=0.026). Conclusion: Fluvoxamine combined with oxycodone prolonged-release tablets could be more effective in treating patients with cancer pain, and could reduce the dosage of oxycodone prolonged-release tablets and thus be associated with lower side effects, and improved quality of life.

Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

  • Berk, Veli;Kaplan, Mehmet Ali;Tonyali, Onder;Buyukberber, Suleyman;Balakan, Ozan;Ozkan, Metin;Demirci, Umut;Ozturk, Turkan;Bilici, Ahmet;Tastekin, Didem;Ozdemir, Nuriye;Unal, Olcun Umit;Oflazoglu, Utku;Turkmen, Esma;Erdogan, Bulent;Uyeturk, Ummugul;Oksuzoglu, Berna;Cinkir, Havva Yesil;Yasar, Nurgul;Gumus, Mahmut
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7367-7369
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    • 2013
  • Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

Effect of Soybean Curd Residue Fermented by Monascus pilosus on the High fat Diet-Induced Obese Mice (Monascus pilosus로 발효시킨 비지의 항비만 효과)

  • Lee, Sang-Il;Lee, Ye-Kyung;Kim, Soon-Dong;Lee, In-Ae;Choi, Jongkeun;Suh, Joo-Won
    • Journal of Applied Biological Chemistry
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    • v.57 no.1
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    • pp.7-15
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    • 2014
  • This study investigated anti-obesity and antioxidant effects of dietary non-fermented soybean crud residue (SCR) and fermented SCR by Monascus pilosus (FSCR) in high-fat induced-obese mice. SCR and FSCR were supplemented with high-fat diet at 2% (wt/wt) dose for 8 weeks. Both SCR and FSCR significantly lowered body weight, epididymal fat weight and weight gain rate compared to high-fat diet control (HC) group and FSCR group showed lowest weight gain rate. In addition, it was observed that serum and hepatic lipid profiles including triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol were significantly improved by supplementing SCR or FSCR. Furthermore, SCR and FSCR administration showed increase of glutathione content and decrease of hepatic lipid peroxide content, serum aminotransferase activity, and hepatic xanthine oxidase activity. On the other hand, activities of reactive oxygen species scavenging enzyme such as superoxide dismutase, glutathione S-transferase and glutathione peroxidase in two test groups were higher than those of HC. Lastly, in comparison with SCR, FSCR was more effective in restoring obesity-related biomarkers to normal level in high-diet induced obese mice. In conclusion, the present study indicates that FSCR could have not only anti-obese effects such as inhibition of abdominal fat accumulation, but also protective effects of cardiovascular disease such as atherosclerosis by decreasing serum and hepatic lipid contents. Furthermore, these results suggest that experimental diets in this study could alleviate hepatic damage caused by overproduction of reactive oxygen spices (ROS) due to obesity via inhibition of ROS generating activities and induction of ROS scavenging activities.

A study of the development of macrovascular complications and factors related to these complications in young adults with childhood/adolescence-onset type 1 diabetes mellitus (소아청소년기에 1형 당뇨병으로 진단된 젊은 성인에서 대혈관 합병증의 발생과 이에 연관된 인자에 대한 연구)

  • Kang, Min Jae;Kim, Joo Hwa;Chung, Hye Rim;Lee, Young Ah;Shin, Choong Ho;Yang, Sei Won;Kim, You Yeh;Jin, Seon Mi;Noh, Chung Il
    • Clinical and Experimental Pediatrics
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    • v.52 no.2
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    • pp.220-226
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    • 2009
  • Purpose : Macrovascular complications are the main cause of mortality in type 1 diabetes mellitus (T1DM). The purpose of this study was to clarify the presence of early vascular changes and to assess the risk factors of macrovascular complications in young adults with T1DM diagnosed in childhood and adolescence. Methods : Seventy-two patients ($23.9{\pm}2.4$ years) with T1DM diagnosed before 18 years of age and twenty normal controls were included. The incidence of hypertension, dyslipidemia, and other risk factors of macrovascular complication were reviewed. Flow-mediated vasodilation (FMD) and mean intima-media thickness (IMT) measured by ultrasound were compared between patients and control subjects, and their correlations with macrovascular risk factors were analyzed. Results : Of the 72 patients, 32 (44.4%) had hypertension. The proportions of maleness (P=0.03) and mean body mass index (P=0.04) were higher in the hypertensive patients than in normotensive patients. Thirty-one (N=69, 44.9%) patients had dyslipidemia and LDL-cholesterol was positively correlated with mean HbA1c (r=0.32, P=0.008) and total daily insulin dose (r=0.27, P=0.02). The mean IMT was significantly higher in patients than in control subjects ($0.43{\pm}0.06$ mm vs $0.39{\pm}0.06$ mm, P=0.03). There was no difference in the value of FMD between patients and controls, but the duration of the disease after pubertal onset was negatively correlated with FMD (r=-0.34, P=0.01). Conclusion : Hypertension, dyslipidemia and atherosclerotic vascular change were observed in young adults with T1DM diagnosed during childhood and adolescence; this strongly suggests that meticulous screening of macrovascular complications and control of their risk factors should be conducted.

Evaluate the implementation of Volumetric Modulated Arc Therapy QA in the radiation therapy treatment according to Various factors by using the Portal Dosimetry (용적변조회전 방사선치료에서 Portal Dosimetry를 이용한 선량평가의 재현성 분석)

  • Kim, Se Hyeon;Bae, Sun Myung;Seo, Dong Rin;Kang, Tae Young;Baek, Geum Mun
    • The Journal of Korean Society for Radiation Therapy
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    • v.27 no.2
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    • pp.167-174
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    • 2015
  • Purpose : The pre-treatment QA using Portal dosimetry for Volumetric Arc Therapy To analyze whether maintaining the reproducibility depending on various factors. Materials and Methods : Test was used for TrueBeam STx$^{TM}$ (Ver.1.5, Varian, USA). Varian Eclipse Treatment planning system(TPS) was used for planning with total of seven patients include head and neck cancer, lung cancer, prostate cancer, and cervical cancer was established for a Portal dosimetry QA plan. In order to measure these plans, Portal Dosimetry application (Ver.10) (Varian) and Portal Vision aS1000 Imager was used. Each Points of QA was determined by dividing, before and after morning treatment, and the after afternoon treatment ended (after 4 hours). Calibration of EPID(Dark field correction, Flood field correction, Dose normalization) was implemented before Every QA measure points. MLC initialize was implemented after each QA points and QA was retried. Also before QA measurements, Beam Ouput at the each of QA points was measured using the Water Phantom and Ionization chamber(IBA dosimetry, Germany). Results : The mean values of the Gamma pass rate(GPR, 3%, 3mm) for every patients between morning, afternoon and evening was 97.3%, 96.1%, 95.4% and the patient's showing maximum difference was 95.7%, 94.2% 93.7%. The mean value of GPR before and after EPID calibration were 95.94%, 96.01%. The mean value of Beam Output were 100.45%, 100.46%, 100.59% at each QA points. The mean value of GPR before and after MLC initialization were 95.83%, 96.40%. Conclusion : Maintain the reproducibility of the Portal Dosimetry as a VMAT QA tool required management of the various factors that can affect the dosimetry.

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Analyses of the Setup Errors using on Board Imager (OBI) (On Board Imager (OBI)를 이용한 Setup Error 분석에 대한 연구)

  • Kim, Jong-Deok;Lee, Haeng-O;You, Jae-Man;Ji, Dong-Hwa;Song, Ju-Young
    • The Journal of Korean Society for Radiation Therapy
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    • v.19 no.1
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    • pp.1-5
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    • 2007
  • Purpose: The accuracy and advantages of OBI(On Board Imager) against the conventional method like film and EPID for the setup error correction were evaluated with the analysis of the accumulated data which were produced in the process of setup error correction using OBI. Materials and Methods: The results of setup error correction using OBI system were analyzed for the 130 patients who had been planned for 3 dimensional conformal radiation therapy during March 2006 and May 2006. Two kilo voltage images acquired in the orthogonal direction were fused and compared with reference setup images. The setup errors in the direction of vertical, lateral, longitudinal axis were recorded and calculated the distance from the isocenter. The corrected setup error were analyzed according to the lesion and the degree of shift variations. Results: There was no setup error in the 41.5% of total analyzed patients and setup errors between 1mm and 5mm were found in the 52.3%. 6.1% patients showed the more than 5mm shift and this error were verified as a difference of setup position and the movement of patient in a treatment room. Conclusion: The setup error analysis using OBI in this study verified that the conventional setup process in accordance with the laser and field light was not enough to get rid of the setup error. The KV images acquired using OBI provided good image quality for comparing with simulation images and much lower patients' exposure dose compared with conventional method of using EPID. These advantages of OBI system which were confirmed in this study proved the accuracy and priority of OBI system in the process of IGRT(Image Guided Radiation Therapy).

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P53 Overexpression and Outcome of Radiation Therapy in Head & Neck Cancers (두경부종양 환자에서 p53의 과발현과 방사선치료결과)

  • Kim In Ah;Choi Ihl Bhong;Kang Ki Mun;Jang Ji Young;Kim Kyung Mi;Park Kyung Shin;Young Shin Kim;Kang Chang Suk;Cho Seung Ho;Kim Hyung Tae
    • Radiation Oncology Journal
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    • v.17 no.1
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    • pp.1-8
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    • 1999
  • Purpose : Experimental studies have implicated the wild type p53 In cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancels. Methods : Immunohistochemical analysis with a mouse monoclonal antibody (DO-7) specific for human p53 was used to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at 51. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using Kaplan-Meier method. A Cox regression multi-variate analysis was peformed that included all clinical variables and status of p53 expression. Results : Thirty-seven (67.2$\%$) patients showed overexpression of p53 by immunohistochemical staining in their tumor. One hundred percent of oral cavity, 70$\%$ of laryngeal, 66.7$\%$ of oropharyngeal, 66.7$\%$ of hypopharyngeal cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease (P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival. Conclusions : The p53 overexpression as detected by immunohistochemical staining had significant correlation with stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.

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Postoperative External Beam Radiotherapy for Retroperitoneal Soft Tissue Sarcoma (후복막 연조직 육종의 수술 후 외부 방사선 치료)

  • Jang, Na-Young;Kim, Il-Han;Choi, Jin-Hwa;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.26 no.3
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    • pp.135-141
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    • 2008
  • Purpose: To evaluate the clinical outcomes and prognostic factors in retroperitoneal soft tissue sarcomas treated by postoperative radiotherapy. Materials and Methods: The records of 23 patients with retroperitoneal soft tissue sarcomas, who underwent postoperative radiotherapy between 1985 and 2003, were analyzed. The median follow-up period was 77 months (range, $8{\sim}240$ months). A total of 21 patients presented with primary disease, and two patients presented with recurrent disease. Liposarcomas and leiomyosarcomas represented 78% of the diagnosed tumor cases. Moreover, 17 cases were of high grade (grade 2 or 3). The median tumor size was 13 cm (range, $3{\sim}50\;cm$). Complete excision was achieved in 65% of patients. The median radiation dose was 50.4 Gy (range, 45.0 to 59.4 Gy), with conventional fractionation. Results: The 5-year overall, local recurrence-free, and distant metastasis-free survival rates were 68%, 58%, and 71%, respectively. Eleven patients experienced local recurrence, while 9 patients experienced distant metastasis. The most common site for distant metastasis was the liver. A univariate analysis revealed that adjacent organ invasion and age (>60 years) as the significant risk factors contributing to the prediction of poor overall survival. Moreover, multivariate analyses indicated that adjacent organ invasion remained significantly associated with a higher risk of death. In addition, patient age (>60 years) was the other identified risk factor for local recurrence by univariate and multivariate analyses. Except for one case of grade 3 diarrhea, no patient suffered grade 3 or higher complications. Conclusion: Our results were comparable to previous reports in that adjacent organ invasion and patient age (>60 years) were significant predictors of poor survival and tumor recurrence, respectively.

Concurrent Chemoradiotherapy with Biweekly Gemcitabine and Cisplatin in Patients with Locally Advanced Non-small Cell Lung Cancer (진행성 비소세포폐암 환자에서 Gemcitabine/Cisplatin을 이용한 동시 화학 방사선 요법)

  • Oak, Chul-Ho;Kim, Ja-Kyung;Jang, Lee-La;Moon, Dae-Sung;Jang, Tae-Won;Jung, Maan-Hong;Cho, Sung-Whan;Jeung, Tae-Sig
    • Radiation Oncology Journal
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    • v.26 no.3
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    • pp.160-165
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    • 2008
  • Purpose: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy(CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine ($1,200\;mg/m^2$, $1^{st}$ and 8th day) and cisplatin ($60\;mg/m^2$) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range $3{\sim}39$ months) and the median survival time was 16 months (95% CI; $2.4{\sim}39.2$ months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.