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Prediction Formulas of Pulmonary Function Parameters Derived from the Forced Expiratory Spirogram for Healthy Nonsmoking and Smoking Adults and Effect of Smoking on Pulmonary Function Parameters (비흡연 및 흡연 성년 한국인에서의 노력성호기곡선을 이용한 폐활량측정법 검사지표들의 추정상치 및 이에 대한 흡연의 효과)

  • Cho, Won-Kyoung;Kim, Eun-Ok;Myung, Seung-Jae;Kwak, Seung-Min;Koh, Youn-Suck;Kim, Woo-Sung;Lee, Moo-Song;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.521-530
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    • 1994
  • Background : The past studies on prediction formulas of pulmonary function parameters in healthy nonsmoking Korean adults have been performed in relatively small number of subjects and the reported results were restricted on a few parameters. Also there was no systematic investigation into the effect of smoking on pulmonary function parameters in smokers who have no respiratory symptoms. Therefore we attempted to establish prediction formulas of pulmonary function parameters and examined the effect of smoking on pulmonary function parameters. Methods We analyzed the result of parameters derived from the forced expiratory spirogram in 1,067 nonsmoking subjects from June in 1990 to December in 1991. They consisted of 306 males and 761 females and had neither respitatory symptoms nor history of respiratory disease. We derived prediction formulas by multiple linear regression method from their age, heights, and weights in each sex. To examine the effect of smoking on pulmonary function parameters, we classified 383 smoking men into three groups according to the past amount of smoking as follows : i.e. group of smokers who have smoked below 10 pack-years, 10-20 pack-years and above 20 pack-years. Regarding each group of past smoking as an independent dummy variable, we analyzed pulmonary function parameters including nonsmoking men as a baseline by multiple linear regression. We evaluated the smoking effect on pulmonary function parameters according to estimated p-value. Result : 1) Prediction formulas for pulmonary function parameters in each sex were derived. 2) The past smoking less than 10 pack-years does not give any effect on pulmonary function parameters. The past smoking of 10~20 pack-years showed significant negative correlation with $FEV_1$/FVC and FEF 25~75%, and the smoking above 20 pack years showed negative correlation with $FEV_1$ and $FEV_1$/FVC. Conclusion : We have got prediction formulas of pulmonary function parameters which is driven from forced expiratory spirogram in nonsmoking Korean adults by multiple linear regression from age, heights and weights of subjects. The past smoking more than 10 pack-years showed negative correlation with some pulmonary function parameters of airflow obstruction.

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The Alignment Evaluation for Patient Positioning System(PPS) of Gamma Knife PerfexionTM (감마나이프 퍼펙션의 자동환자이송장치에 대한 정렬됨 평가)

  • Jin, Seong Jin;Kim, Gyeong Rip;Hur, Beong Ik
    • Journal of the Korean Society of Radiology
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    • v.14 no.3
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    • pp.203-209
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    • 2020
  • The purpose of this study is to assess the mechanical stability and alignment of the patient positioning system (PPS) of Leksell Gamma Knife Perfexion(LGK PFX). The alignment of the PPS of the LGK PFX was evaluated through measurements of the deviation of the coincidence of the Radiological Focus Point(RFP) and the PPS Calibration Center Point(CCP) applying different weights on the couch(0, 50, 60, 70, 80, and 90 kg). In measurements, a service diode test tool with three diode detectors being used biannually at the time of the routine preventive maintenance was used. The test conducted with varying weights on the PPS using the service diode test tool measured the radial deviations for all three collimators 4, 8, and 16 mm and also for three different positions of the PPS. In order to evaluate the alignment of the PPS, the radial deviations of the correspondence of the radiation focus and the LGK calibration center point of multiple beams were averaged using the calibrated service diode test tool at three university hospitals in Busan and Gyeongnam. Looking at the center diode for all collimators 4, 8, and 16 mm without weight on the PPS, and examining the short and long diodes for the 4 mm collimator, the means of the validation difference, i.e., the radial deviation for the setting of 4, 8, and 16 mm collimators for the center diode were respectively measured to 0.058 ± 0.023, 0.079 ± 0.023, and 0.097 ± 0.049 mm, and when the 4 mm collimator was applied to the center diode, the short diode, and the long diode, the average of the radial deviation was respectively 0.058 ± 0.023, 0.078 ± 0.01 and 0.070 ± 0.023 mm. The average of the radial deviations when irradiating 8 and 16 mm collimators on short and long diodes without weight are measured to 0.07 ± 0.003(8 mm sd), 0.153 ± 0.002 mm(16 mm sd) and 0.031 ± 0.014(8 mm ld), 0.175 ± 0.01 mm(16 mm ld) respectively. When various weights of 50 to 90 kg are placed on the PPS, the average of radial deviation when irradiated to the center diode for 4, 8, and 16 mm is 0.061 ± 0.041 to 0.075 ± 0.015, 0.023 ± 0.004 to 0.034 ± 0.003, and 0.158 ± 0.08 to 0.17 ± 0.043 mm, respectively. In addition, in the same situation, when the short diode for 4, 8, and 16 mm was irradiated, the averages of radial deviations were 0.063 ± 0.024 to 0.07 ± 0.017, 0.037 ± 0.006 to 0.059 ± 0.001, and 0.154 ± 0.03 to 0.165 ± 0.07 mm, respectively. In addition, when irradiated on long diode for 4, 8, and 16 mm, the averages of radial deviations were measured to be 0.102 ± 0.029 to 0.124 ± 0.036, 0.035 ± 0.004 to 0.054 ± 0.02, and 0.183 ± 0.092 to 0.202 ± 0.012 mm, respectively. It was confirmed that all the verification results performed were in accordance with the manufacturer's allowable deviation criteria. It was found that weight dependence was negligible as a result of measuring the alignment according to various weights placed on the PPS that mimics the actual treatment environment. In particular, no further adjustment or recalibration of the PPS was required during the verification. It has been confirmed that the verification test of the PPS according to various weights is suitable for normal Quality Assurance of LGK PFX.

Leukocyte count and hypertension in the health screening data of some rural and urban residents (일부 농촌과 도시의 건강선별조사 자료로 본 백혈구수와 고혈압과의 관계)

  • Lee, Choong-Won;Yoon, Nung-Ki;Lee, Sung-Kwan
    • Journal of Preventive Medicine and Public Health
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    • v.24 no.3 s.35
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    • pp.363-372
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    • 1991
  • We used the health screening data of some rural and urban residents to examine the cross-sectional association between leukocyte count and hypertension. The 206 male and 203 female rural residents were selected by multi-stage cluster sampling method in Kyungsan-Kun area of Kyungbuk province in 1985 and 600 urban residents were selected by the same sampling method as the rural residents in Daegu city of the same province in 1986 compatible with age-sex distribution of Daegu city of 1985 census, but of whom 384 actually responded. The rest of 600 were replaced by age and sex with those who were members of the medical insurance plan visiting the health management department of the university hospital to get the biannual preventive medical checkups. Excluded in the analysis were those having hypertensive history, diseases and extreme outlying values of the screening tests, leaving 373 rural and 571 urban residents. Leukocyte count was measured with ELT-8 Laser shadow method and the unit $cells/mm^3$, Blood pressures were determined with an aneroid sphygmomanometer with pre-standardized method and hypertensives were defined as those showing systolic blood pressure more than 140mmHg and/or diastolic blood pressure more than 90mmHg. Total residents pooled (N=944) showed a significant difference between hypertensives and normotensives ($6965.93{\pm}1997.01\;vs\;6490.61{\pm}1941.32,\;P=0.00$) and in rural residents was noted the similar significant difference (P=0.03). None of significant differences were noted in any stratum stratified by residency and sex. Compared to the lowest quintile of WBC, 2/5 quintile showed odds ratio 0.99 (95% Confidence interval, Ci 0.62-1.59), 3/5 quintile 1.41 (95% CI 0.90-2.21), 4/5 quintile 1.76 (95% CI. 1.14-2.72), and highest quintile 1.80 (1.15-2.82) in the total residents. Likelihood ratio test for linear trend for it indicated a significant trend ($X^2_{trend}=5.53,\;df=1,\;P<0.05$). There were no other significant odds ratios compared to the lowest quintile of WBC in strata stratified by residency and sex. The odds ratios in total residents which had showed significant odds ratios became nonsignificant and of reduced magnitude after controlling age, frequency of smoking and drinking with multiple logistic. regression. In each stratum, it changed magnitudes of odds ratios slightly and unstably. None of the trend tests showed any significant trend. These results suggest that the Friedman et al's finding of association between leukocyte count and hypertension may be due to an statistical type I error resulting from the data dredging in an exploratory study, in which more than 800 variables were screened as possible predictors of hypertension.

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Feed Intake and Digestibility in Korean Native Goats Fed Fermented Domestic Agricultural By-Products (국내산 농산부산물 발효사료를 급여한 재래산양의 사료섭취량 및 소화율)

  • 안종호;유황종;김현진;조익환;이주삼
    • Korean Journal of Organic Agriculture
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    • v.8 no.3
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    • pp.111-120
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    • 2000
  • In this study, by-products of rice bran, rice hull, bean curd dregs and food waste were fermented with different ratios of 26, 26, 34 and 14% respectively and the experimental diets were prepared mixing it with various ratios of commercial diets (fermented feed commercial feed : A 80 : 20, B 70 : 30, C 60 : 40, D 50:50). In Experiment I, feed intake, nutrients digestibilities and nitrogen retention were investigated and body weight gain in Experiment 1. For chemical composition of experimental diets, crude protein contents were 13.73, 13.78, 14.45 and 15.14% in A, B, C and D respectively and the contents of crude fat and crude fiber were highest in A as 8.66 and 27.82% respectively. 2. Dry hurler intakes were significantly higher (P<0.05) in A(362.06g/d) and C(358.49g/d) than B and D. Intakes of crude protein and crude fat were not significantly different (P>0.05) among treatments however those of crude fiber and crude ash were significantly higher (P>0.05) in A(101.47g/d). 3. Dry matter digestibilities in the range of 53.38∼68.81% in all treatments have shown the highest value in C of 60% fermented feed plus 40% commercial diet but the lowest in A of 80% of fermented feed plus 20% commercial diet (P<0.05). 59.85% of digestibility of crude protein in A was also lowest among all treatments (p<0.05), 4. 8.47g/d of nitrogen intake in C was recorded highest (P<0.05) however the highest nitrogen retention was marked in B of 50% fermented feed plus 50% of commercial diet due mainly to lower excretion of nitrogen through feces. 5. The data of live weight gain in Experiment II has not been shown as a result since the proper daily gain of body weight was achieved only in D as 88.89g/d and the goats in other treatments have shown frequent diarrhea. However, neglecting the animals with diarrhea, higher amounts of concentrates in the diets (C and D) showed the tendency of higher weight gain. 6. In this study, feeding 60% fermented feed manufactured with domestic agricultural by-products of rice bran, rice hull, bean curd dregs and food waste to Korean native goats have shown satisfactory results of intake and digestibility and it indicates that utilization of domestic agricultural by-products in goats could be improved by the process of fermentation. However it's effects on body weight gain and nitrogen retention were below than expected. Different sources of feedstuff for fermentation may result in different performances of animals. However, to draw overall conclusion from this study, 50∼60% of fermented feed can be recommended in the case of mixing with concentrates.

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CAS 500-1/2 Image Utilization Technology and System Development: Achievement and Contribution (국토위성정보 활용기술 및 운영시스템 개발: 성과 및 의의)

  • Yoon, Sung-Joo;Son, Jonghwan;Park, Hyeongjun;Seo, Junghoon;Lee, Yoojin;Ban, Seunghwan;Choi, Jae-Seung;Kim, Byung-Guk;Lee, Hyun jik;Lee, Kyu-sung;Kweon, Ki-Eok;Lee, Kye-Dong;Jung, Hyung-sup;Choung, Yun-Jae;Choi, Hyun;Koo, Daesung;Choi, Myungjin;Shin, Yunsoo;Choi, Jaewan;Eo, Yang-Dam;Jeong, Jong-chul;Han, Youkyung;Oh, Jaehong;Rhee, Sooahm;Chang, Eunmi;Kim, Taejung
    • Korean Journal of Remote Sensing
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    • v.36 no.5_2
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    • pp.867-879
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    • 2020
  • As the era of space technology utilization is approaching, the launch of CAS (Compact Advanced Satellite) 500-1/2 satellites is scheduled during 2021 for acquisition of high-resolution images. Accordingly, the increase of image usability and processing efficiency has been emphasized as key design concepts of the CAS 500-1/2 ground station. In this regard, "CAS 500-1/2 Image Acquisition and Utilization Technology Development" project has been carried out to develop core technologies and processing systems for CAS 500-1/2 data collecting, processing, managing and distributing. In this paper, we introduce the results of the above project. We developed an operation system to generate precision images automatically with GCP (Ground Control Point) chip DB (Database) and DEM (Digital Elevation Model) DB over the entire Korean peninsula. We also developed the system to produce ortho-rectified images indexed to 1:5,000 map grids, and hence set a foundation for ARD (Analysis Ready Data)system. In addition, we linked various application software to the operation system and systematically produce mosaic images, DSM (Digital Surface Model)/DTM (Digital Terrain Model), spatial feature thematic map, and change detection thematic map. The major contribution of the developed system and technologies includes that precision images are to be automatically generated using GCP chip DB for the first time in Korea and the various utilization product technologies incorporated into the operation system of a satellite ground station. The developed operation system has been installed on Korea Land Observation Satellite Information Center of the NGII (National Geographic Information Institute). We expect the system to contribute greatly to the center's work and provide a standard for future ground station systems of earth observation satellites.

Optimization of Multiclass Support Vector Machine using Genetic Algorithm: Application to the Prediction of Corporate Credit Rating (유전자 알고리즘을 이용한 다분류 SVM의 최적화: 기업신용등급 예측에의 응용)

  • Ahn, Hyunchul
    • Information Systems Review
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    • v.16 no.3
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    • pp.161-177
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    • 2014
  • Corporate credit rating assessment consists of complicated processes in which various factors describing a company are taken into consideration. Such assessment is known to be very expensive since domain experts should be employed to assess the ratings. As a result, the data-driven corporate credit rating prediction using statistical and artificial intelligence (AI) techniques has received considerable attention from researchers and practitioners. In particular, statistical methods such as multiple discriminant analysis (MDA) and multinomial logistic regression analysis (MLOGIT), and AI methods including case-based reasoning (CBR), artificial neural network (ANN), and multiclass support vector machine (MSVM) have been applied to corporate credit rating.2) Among them, MSVM has recently become popular because of its robustness and high prediction accuracy. In this study, we propose a novel optimized MSVM model, and appy it to corporate credit rating prediction in order to enhance the accuracy. Our model, named 'GAMSVM (Genetic Algorithm-optimized Multiclass Support Vector Machine),' is designed to simultaneously optimize the kernel parameters and the feature subset selection. Prior studies like Lorena and de Carvalho (2008), and Chatterjee (2013) show that proper kernel parameters may improve the performance of MSVMs. Also, the results from the studies such as Shieh and Yang (2008) and Chatterjee (2013) imply that appropriate feature selection may lead to higher prediction accuracy. Based on these prior studies, we propose to apply GAMSVM to corporate credit rating prediction. As a tool for optimizing the kernel parameters and the feature subset selection, we suggest genetic algorithm (GA). GA is known as an efficient and effective search method that attempts to simulate the biological evolution phenomenon. By applying genetic operations such as selection, crossover, and mutation, it is designed to gradually improve the search results. Especially, mutation operator prevents GA from falling into the local optima, thus we can find the globally optimal or near-optimal solution using it. GA has popularly been applied to search optimal parameters or feature subset selections of AI techniques including MSVM. With these reasons, we also adopt GA as an optimization tool. To empirically validate the usefulness of GAMSVM, we applied it to a real-world case of credit rating in Korea. Our application is in bond rating, which is the most frequently studied area of credit rating for specific debt issues or other financial obligations. The experimental dataset was collected from a large credit rating company in South Korea. It contained 39 financial ratios of 1,295 companies in the manufacturing industry, and their credit ratings. Using various statistical methods including the one-way ANOVA and the stepwise MDA, we selected 14 financial ratios as the candidate independent variables. The dependent variable, i.e. credit rating, was labeled as four classes: 1(A1); 2(A2); 3(A3); 4(B and C). 80 percent of total data for each class was used for training, and remaining 20 percent was used for validation. And, to overcome small sample size, we applied five-fold cross validation to our dataset. In order to examine the competitiveness of the proposed model, we also experimented several comparative models including MDA, MLOGIT, CBR, ANN and MSVM. In case of MSVM, we adopted One-Against-One (OAO) and DAGSVM (Directed Acyclic Graph SVM) approaches because they are known to be the most accurate approaches among various MSVM approaches. GAMSVM was implemented using LIBSVM-an open-source software, and Evolver 5.5-a commercial software enables GA. Other comparative models were experimented using various statistical and AI packages such as SPSS for Windows, Neuroshell, and Microsoft Excel VBA (Visual Basic for Applications). Experimental results showed that the proposed model-GAMSVM-outperformed all the competitive models. In addition, the model was found to use less independent variables, but to show higher accuracy. In our experiments, five variables such as X7 (total debt), X9 (sales per employee), X13 (years after founded), X15 (accumulated earning to total asset), and X39 (the index related to the cash flows from operating activity) were found to be the most important factors in predicting the corporate credit ratings. However, the values of the finally selected kernel parameters were found to be almost same among the data subsets. To examine whether the predictive performance of GAMSVM was significantly greater than those of other models, we used the McNemar test. As a result, we found that GAMSVM was better than MDA, MLOGIT, CBR, and ANN at the 1% significance level, and better than OAO and DAGSVM at the 5% significance level.

The Signal Transduction Mechanisms on the Intestinal Mucosa of Rat Following Irradiation (방사선조사후 백서소장점막에서 발생하는 신호전달체계에 관한 연구)

  • Yoo Jeong Hyun;Kim Sung Sook;Lee Kyung Ja;Rhee Chung Sik
    • Radiation Oncology Journal
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    • v.15 no.2
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    • pp.79-95
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    • 1997
  • Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

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Effects of Formaldehyde/Urea Molar Ratio on Bonding Strength of Plywood and Properties of Sliver-PB and Strand-PB (F/U 몰비의 변이가 합판의 접착성과 Sliver-PB, Strand-PB의 물성에 미치는 영향)

  • Park, Heon;You, Young-Sam
    • Journal of the Korean Wood Science and Technology
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    • v.27 no.2
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    • pp.38-45
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    • 1999
  • This study was to figure out proper Formaldehyde/Urea molar ratio of UF resin with satisfactory bonding strength of plywood and properties of particleboard. The six kinds of UF resins were manufactured with F/U molar ratio 1.0, 1.2, 1.4, 1.6, 1.8, and 2.0. The boards were made of three kinds of raw materials : Veneer, Sliver-Particle and Strand-Particle. Manufacturing condition of plywood : amount of mixing resin was 150g/$m^2$. The fourty secs/mm simple-pressing schedule in the pressure 10kgf/$m^2$ was applied for 480mm${\times}$700mm board at the temperature of $110^{\circ}C$ in a hot press. Manufacturing condition of particleboard : Target density was 0.65g/$cm^2$. The stepwise 9 minutes- multi-pressing schedule in the maximum pressure 40kgf/$cm^2$, the minimum pressure 15kgf/$cm^2$ was applied for $480mm{\times}634mm{\times}12mm$ board at the temperature of $150^{\circ}C$ in a hot press. The results are as follows : I. In bonding strength, plywood which was made by F/U molar ratio 1.2 showed the highest value. Other molar ratio resin also gave the satisfied value of KS standard, 7.5kgf/$cm^2$. 2. In internal bond strength of particleboard, Sliver-Particleboard(SLPB) and Strand-Particleboard(STPB) varied respectively from 5.9kgf/$cm^2$ to 4.8kgf/$cm^2$, from 6.7kgf/$cm^2$ to 5.4kgf/$cm^2$. SLPB with F/U=1.2 and STPB with F/U=1.6 had higher IB value. Also, both SLPB and STPB showed lower IB value in F/U molar ratio 2.0 and 1.0. 3. SLPB and STPB with six kinds of UF resin respectively satisfied bending strength of KS standard 150 Type(130kgf/$cm^2$) and 200 Type(180kgf/$cm^2$). Bending strength data for both of SLPB and STPB showed little or no loss from F/U=1.8 to F/U=1.2. Also, STPB was approximately two times higher than that of SLPB. Therefore, the raw material's shape had more effect on bending strength than the FlU molar ratio. 4. F/U=1.6 and 1.4 showed the lower thickness swelling in SLPB and STPB. All of STPBs satisfied thickness swelling of KS standard, under 12%.

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The Role of Intraluminal Brachytherapy in Management of Esophageal Cancer (식도암 치료에 있어 관내근접치료의 역할)

  • Lee Chang Geol;Suh Chang Ok;Kim Gwi Eon;Chu Sung Sil;Chung Eun Ji;Kim Woo Cheol
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.331-338
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    • 1995
  • Purpose : To evaluate our clinical experience with the combination of teletherapy and intraluminal brachytherapy in patients with unresectable or inoperable esophageal cancers. Materials and Methods : From Nov 1989 to Mar 1993, twenty patients with esophageal cancer were treated with radical radiotherapy and intraluminal brachytherapy at Yonsei Cancer Center. All patients had squamous histolgy and stage distribution was as follows: stage II, 4($20{\%}$)patients; III, 15 ($75{\%}$)patients; IV, 1($5{\%}$)patients. A dose of S-12Gy/1-3weeks with intraluminal brachytherapy (3-5Gy/fraction) to 5mm from the outside of the esophageal tube using high dose rate Iridium-192 remotely afterloading brachytherapy machine was given 2 weeks after a total dose of 59-64Gy with external radiotherapy. Induction chemotherapy using cisplatin and 5-FU was performed in 13 patients with median 3 cycles(1-6 cycles), Response rate, local control rate, survival and complications were analysed retrospectively. Results : Two-year overall survival rate and median survival were $15.8{\%}$ and 13.5 months. Response rates were as follows complete remission(CR) 5($25{\%}$): partial remission a(PRa) 7($35{\%}$): partial remission b(PRb) 7($35{\%}$), no response(NR) 1($5{\%}$). Patterns of failure were as follows; local failure 13($65{\%}$), local and distant failure 3($15{\%}$), distant failure 0($0{\%}$). Ultimate local control rate was $20{\%}$. Treatment related complications included esophageal ulcer in two patients and esophageal stricture in one. Conclusion : Though poor local conrol rate, median survival was improved as compared with previous results of radiation therapy alone(8months) and chemoradiation combined treatment(11 months) in Yonsei Cancer Center High-dose-rate intraluminal brachytherapy following external irradiation is an effective treatment modality with acceptable toxicity in esophageal cancer.

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A Phase I/II Trial of $DCVac/IR^{(R)}$ Dendritic Cell Immunotherapy Combined with Irradiation in Cases of Refractory Colorectal Cancer with Multiple Liver Metastases (기존의 치료에 반응하지 않는 다발성 간전이 대장암 환자에서 방사선조사와 병합한 수지상세포 면역치료의 1, 2상 임상시험)

  • Choi, Young-Min;Lee, Hyung-Sik;Kwon, Hyuk-Chan;Han, Sang-Young;Choi, Jong-Cheol;Chung, Ju-Seop;Kim, Chang-Won;Kim, Dong-Won;Kang, Chi-Duk
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.104-112
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    • 2008
  • Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.