• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.

• Journal of Nutrition and Health
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• v.7 no.3
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• pp.1-13
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• 1974

The relative state of human iron storage may be ascertained more reliably through determination of the serum iron, iron binding capacity, transferrin saturation and absorption of radioactive iron in conjunction with studies of red cell morphology than from the study of red cell morphology alone. Recent investigations have shown that there is an increase in red cell protoporphyrin concentration in iron deficiency anemia. The significance of the red cell protoporphyrin has been discussed greatly during the years since its discovery. Two of the main factors which appear to influence the amaunt of protoporphyrin are increased erythropoiesis and factors interfering with the utilization of iron in the synthesis of hemoglobin, and iron deficiency. Recently Heller et al. have described a simplified method for blood protoporphyrin assay and this technique could be used assess nutritional iron status, wherein even minor insufficiencies are detectable as increased protoporphyrin concentrations. Based on the evaluation of the relationship between nutritional iron status and red cell protoporphyrin as an index suitable for the detection of the iron deficiency is described in this paper. RESULTS 1. Hemoglobin Concentrations and Anthropometric Measurements. The mean and standard deviations of the various anthropometric measurements of different age and sex groups are shown in table 1. There measurements have been compared with the Korean Standard. In the absence of local standards for arm circumference and skin-fold thickness over triceps, they have been compared with the standard from Jelliffe. Table 2,3, and 4 give anthropometric measurements and frequency (%) of anemia in children surveyed. The mean height of the children studid was 10 to 20 percent; below the Korean Standard. The distribution of height below 80 percent of the Standard was 21.2 percent, however, among anemic group this percentage was 27.7 percent. In general, the mean weight of the children was 10 to 15 percent below the Korean Standard. The percentage of children with weight less than 80 percent of the Standard was about 35 percent. But in the anemic group of the children, this percentage was 44 percent. The mean arm circumference was about 15 percent lower than the Jelliffe's standard. 61.2 percent of the children had values of arm circumference below 80 percent of the standard. Children with low hemoglobin levels, this percentage was 80 percent. The mean skinfold thickness over the triceps of the children studied was about 25 Percent lower than the Jelliffe's standard and 61.2 percent of the children had the value less than 80 percent of the standard. Among anemic children, this percentage was 70.8%. As may be seen from table 5, the mean hemoglobin concentration of the total group was 11.3g/100ml. Hemoglobin concentration was less than 11.0g/100ml. in 65(36.5%) of the 178 children. The degree of anemia in most of these children was mild with a hemoglobin level of less than 8.0g/100ml. found in only one child. In general, the prevalence of anemia was high in female children than male and decreased its frequency with increasing age. Relatively close relationship was observed between hemoglobin level and anthrophometric measurements especially high between arm circumference and skinfold thickness and hemoglobin but very low in height and low in weight and hemoglobin level, estimated by chi-square value. II. Serum iron, Transferrin saturation (1) Serum iron, and transferrin saturation Serum iron, transferrin saturation and red cell protoporphyrin concentrations were estimated in sub-sample of 84 children from 1 to 6 years and 24 older children between 7 and 13 years of age. The findings are presented in table 6. The mean serum iron concentration of the total group was 59ug/100ml. However, the level incrased with age from 36.6ug/100ml. (1-3years) to 80.8ug/100ml. (7-13 years). 60 percent of these children had a serum iron level less than 50ug/10ml. in the 1-3 years age group and 31.4 percent for 4-6 years group. These contrast with the finding of 12.5 percent anemic children in the 7-13 years age group. The mean transferrin saturation for the total group was 18.1 percent and frequency of anemia by transferrin saturation was observed same pattern as serum iron concentration. (2) Red cell protoporphyrin concentrations. (a) Red cell protoporphrin levels of children: Red cell protoporphyrin and other biochemical data are shown in table 4. The mean concentration in red cell of all children was fround 46.3ug/100ml. RBC. and differences with age groups were observed; in the age group 1-3 years, the mean concentration was $59.5{\pm}32.14$ ug/100ml. RBC; 4-6 years $44.1{\pm}22.57$ ug/100ml. RBC. and 7-13 years, $39.0{\pm}13.56$ ug/100ml. RBC. (b) Normal protoporphyrin values in adults: It was observed that in 10 normal adult males studied here the level of protoporphyrin in red cell ranged from 18 to 54 ug/100ml. RBC. and the mean concentration was $47.5{\sim}14.47$ ug/100ml. RBC. Other biochemical determination made on the same subjects are presented in table 8. (c) Red tell protoporphyrin concentration of occupational blood donors: The results of analyses for red cell protoporphyrin as well as serum iron, transferrin saturation and hemoglobin in the 76 blood donors are presented in table 7 and 8. In this experiment, donors were selected at random, however, most of them bled repeatedly because of poor economic situation, I doubt. Table 9 shows the distribution of red cell protoporphyrin concentration and hemoglobin concentration of occupational donors. The mean hemoglobin value for the total was 11.9 g/100 ml. When iron deficiency anemia is defined as a transferrin saturation below 15%, prevalence of anemia was 47.4 percent and the mean serum iron was 27.1ug/100ml. and red cell protoporphyrin, 168.3ug/100ml. RBC. However, mean serum iron and protoporphyrin concentration of above 15% transferrin saturation were 11.6 ug/100 ml. and 58.8 ug/100 ml. RBC. respectively. The mean Protoporphyrin concentration of non-anemic (above 15% transferrin saturation) donors was slightly higher than the results of normal adult males.

• Journal of Society of Preventive Korean Medicine
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• v.4 no.2
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• pp.72-92
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• 2000

This research has conducted studies on an Oriental medicine-based method of diagnosing of occupational musculoskeletal system diseases. This researcher has searched through existing relevant medical literature. Also, this researcher has worked on a moire topography using moire topography. In this course, this researcher has reached the following conclusion in relation to the possibility of using a moire topography as a diagnosing device of musculoskeletal system diseases under Oriental medicine . 1 The Western medicine outlines its criteria of screening occupational musculoskeletal system diseases as follows A. The occupational musculoskeletal diseases must clearly include one or more of the subjective symptoms characterized by pain, hypoesthesia dysaesthesia, anaesthesia. etc . B, There should be clinically admitted objective observations and diagnosis outlining that the disease concerned shows symptoms such as tenderness, induration. and edema that can appear with occupational musculoskeletal system diseases. dyscinesia should be admitted with the disease concerned, or there should be observations and diagnosis outlining that abnormality exists in electric muscular or nervous diagnosis and examination . C. It should be admitted that prior to the occurrence of symptoms or observations and diagnosis on musculoskeletal system-related diseases, a patient has been engaged in works with conditions requiring improper work posture or work movement. That is, this is an approach whereby they see abnormality in the musculoskeletal system come from material and structural defect, and adjust and control abnormality in the musculoskeletal system and secreta . 2. The Oriental medicines sees that a patient develops the pain of occupational musculoskeletal diseases as he cannot properly activate the flow of his life force and blood thus not only causing formation of lumps in the body and blocking the flow of life force and blood in some parts of the body. Hence, The Oriental medicine focuses on resolving the cause of weakening the flow of life force and blood, instead of taking material approach of correcting structural abnormality Furthermore , Oriental medicine sees that when muscle tension builds up, this presses blood vessels and nerves passing by, triggering circulation dyscrasia and neurological reaction and thus leading to lesion. Thus, instead of taking skeletal or neurophysiological approach. it seeks to fundamentally resolve the cause of the flow of the life force and blood in muscles not being activated. As a result Oriental medicine attributes the main cause of musculoskeletal system diseases to muscle tension and its build-up that stem from an individual's long formed chronicle habit and work environment. This approach considers not only the social structure aspect including companies owners and work environment that the existing methods have looked at, but also individual workers' responsibility and their environmental factors. Hence, this is a step forward method. 3 The diagnosis of musculoskeletal diseases under Oriental medicine is characterized by the fact that an Oriental medicine doctor uses not only photos taken by himself, but also various detection devices to gather information and pass comprehensive judgment on it. Thus, it is the core of diagnosis under Oriental medicine to develop diagnosing devices matching the characteristics of information to be induced and to interpret information so induced from the views of Oriental medicine. Diagnosis using diagnosing devices values the whole state of a patient and formal abnormality alike, and the whole balance and muscular state of a patient serves as the basis of diagnosis. Hence, this method, instead of depending on the information gathered from devices under Western medicine, requires devices that provide information on the whole state of a patient in addition to the local abnormality information that X-ray. CT, etc., can offer. This method sees muscle as the central part of the abnormality in the musculoskeletal system and thus requires diagnosing devices enabling the muscular state. 4. The diagnosing device using moire topography under Oriental medicine has advantages below and can be used for diagnosing musculoskeletal system diseases with industrial workers . First, the device can Provide information on the body in an unbalanced state. and thus identify the imbalance and difference of height in the left and right stature that a patient can not notice at normal times. Second, the device shows the twisting of muscles or induration regions in a contour map. This is not possible with existing shooting machines such as X-ray, CT, etc., thus differentiating itself from existing machines. Third, this device makes it possible for Oriental medicine to take its unique approach to the abnormality in the musculoskeletal system. Oriental medicine sees the state and imbalance state in muscles as major factors in determining the lesion of musculoskeletal system, and the device makes it possible to shoot the state of muscles in detail. In this respect, the device is significant. Fourth, the device has an advantage as non-aggression diagnosing device.

• Journal of agricultural medicine and community health
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• v.30 no.3
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• pp.263-277
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• 2005

Objectives: This study aimed to reveal the oral health conditions based on the dental health behaviors of a community-dwelling elderly. Methods: The subjects included 206 rural dwellers(100 men & 106 women) aged over 65 years old, who received dental health check-ups in the local public health center and its branches attached to 6 respective Myons of Chunchongnamdo Province, during the 2-month period from Jan. 1st to Feb. 28th, 2005. They were examined by dentists and given self-administered questionnaires asking about their dental heaith behaviors and subjective symptoms of gingival bleeding. Results: The oral health conditions based on dental health behavior showed that those who have not taken dental health service a year were found to have significantly greater number of missing teeth(p=0.002), DMFT(p=0.002) and CPITN(p=0.018), and those who have not observed intra-oral conditions a week to have significantly less number of filled teeth(p=0.002) and significantly greater number of missing teeth(p=0.000) and CPITN (p=0.000) than their respective counterparts. In terms of brushing, those who brushed their teeth below "3 times/day" were found to have significantly greater number of decayed teeth(p=0.000), missing teeth(p=0.000), DMFT(p=0.000) and CPITN(p=0.000) than their counterparts. In terms of time spent in brushing, those who spends "below 3 minutes" had significantly greater number of missing teeth(p=0.002) and DMFT(p=0.041), and significantly less number of filled teeth(p=0.036). According to the use of aid tools for cleaning teeth, the group who don't use them had significantly greater number of DMFT(p=0.041) and CPITN(p=0.018) than its counterpart. Classified by smoking habits, smoking groups had significantly greater number of decayed teeth(p=0.035) and CPITN(p=0.001) than non-smoking groups. Multiple regression analysis of the study data revealed that the significant factors influencing number of decayed teeth were number of brushing, sex and intra-oral observation (explanatory power of 14.2%). The significant factors for number of filled teeth were sex, intra-oral observation, use of aid tools, frequency of brushing, subjective health conditions and drinking of sweet beverages(explanatory power of 18.2%), those for number of missing teeth, number of brushing and age(explanatory power of 13.9%) those for DMFT, number of brushing, sex, use of dental service, age(explanatory power: 13.5%), and those for CPITN included smoking habits, use of dental service, use of aid tools (explanatory power: 10.8%). Conclusions: The study results revealed that the dental health behavior of the elderly population is in poor conditions and their consequent intra-oral health conditions are not good. To improve their oral conditions, public campaign and education will be needed to modify unhealthy dental health behaviors.

• 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.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.195-202
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• 1999

Purpose : We peformed this study to evaluate the prognostic factors and the effect of induction chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and Methods : A retrospective analysis was done for 130 patients with locally advanced NSCLC treated with curative radiotherapy alone or induction chemo-radiotherapy from January 1986 to October 1996. Eighty-five patients were treated with radiotherapy alone, forty-five with induction chemotherapy and radiotherapy. Age, sex, performance status, histopathologic type, and stage were evenly distributed in both groups. The patients were treated with 6 MV or 10 MV X-ray. Conventional fractionation with daily fraction size 1$.8\~2.0$ Gy was done. Of the patients, 129 patients received total dose above 59.6 Gy ($56\~66$ Gy, median 60 Gy). Induction chemotherapy regimen were CAP (Cyclo-phosphamide, Adriamycin, Cisplatin) in 6 patients, MVP (Mitomycin, Vinblastine, Cisplatin) in 9 patients, MIC (Mitomycin, Ifosfamide Cisplatin) in 13 patients, and EP (Etoposide, Cisplatin) in 17 patients. Chemotherapy was done in $2\~5$ cycles (median 2). Results : Overall 1-, 2-, and 3-year survival rate (YSR) for all patients were $41.5\%,{\;}13.7\%,{\;}and{\;}7\%$, respectively (median survival time 11 months). According to treatment modality, median survival time, overall 1-, 2-, and 3-YSR were 9 months, $32.9\%,{\;}10.\5%,{\;}6\%$ for radiotherapy alone group, and 14 months, $57.8\%,{\;}20\%,{\;}7.6\%$ for induction chemotherapy group, respectively (f=0.0005). Complete response (CR) to overall treatments was $25\%$ (21/84) in radiotherapy alone and $40.5\%$ (17/42) in induction chemotherapy group (p=0.09). The Prognostic factors affecting overall survival were hemoglobin level (p=0.04), NSE (neuron-specific enolase) level (p=0.004), and respense to overall treatment(p=0.004). According to treatment modalities, NSE (neuron-specific enolase) (p=0.006) and response to overall treatment (p=0.003) were associated with overall survival in radiotherapy alone group, and response to overall treatment (p=0.007) in induction chemotherapy group. The failure Pattern analysis revealed no significant difference between treatment modalities. But, in patients with CR to overall treatment, distant metastasis were found in 11/19 patients with radiotherapy alone, and 3/13 patients with induction chemotherapy and radiotherapy (p=0.07). Locoregional failure patterns were not different between two groups (10/19 vs 6/13). Conclusion : Induction chemotherapy and radiotherapy achieved increased 2YSR compared to radiotherapy alone, At least in CR patients, there was decreased tendency in distant metastasis with induction chemotherapy. But, locoregional failures and long-term survival were not improved. Thus, there is need of more effort to increasing local control and further decreasing distant metastasis.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.204-212
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• 2008

Purpose: This study was performed to evaluate the disease-free survival and risk factors of recurrence in early breast cancer patients who have undergone breast conserving surgery and radiation therapy. Materials and Methods: From March 1997 to December 2002, 77 breast cancer patients who underwent breast conserving surgery and radiation therapy were reviewed retrospectively. The median follow-up time was 58.4 months (range $43.8{\sim}129.4$ months) and the mean subject age was 41 years. The frequency distribution of the different T stages, based on the tumor characteristics was 38 (49.3%) for T1, 28 (36.3%) for T2, 3 for T3, 7 for T is and 1 for an unidentified sized tumor. In addition, 52 patients (67.5%) did not have axillary lymph metastasis, whereas 14 patients (18.1%) had $1{\sim}3$ lymph node metastases and 3 (0.03%) had more than 4 lymph node metastases. The resection margin was negative in 59 patients, close (${\leq}2\;mm$) in 15, and positive in 4. All patients received radiation therapy at the intact breast using tangential fields with a subsequent electron beam boost to the tumor bed at a total dose ranging from 59.4 Gy to 66.4 Gy. Patients with more than four positive axillary lymph nodes received radiation therapy ($41.4{\sim}60.4\;Gy$) at the axillary and supraclavicular area. Chemotherapy was administered in 59 patients and tamoxifen or fareston was administered in 29 patients. Results: The 5 year overall survival and disease-free survival rates were 98.08% and 93.49%, respectively. Of the 77 patients, a total of 4 relapses (5.2%), including 1 isolated supraclavicular relapse, 1 supraclavicular relapse with synchronous multiple distant relapses, and 2 distant relapses were observed. No cases of local breast relapses were observed. Lymph node metastasis or number of metastatic lymph nodes was not found to be statistically related with a relapse (p=0.3289) nor disease-free survival (p=0.1430). Patients with positive margins had a significantly shorter disease-free survival period (p<0.0001) and higher relapse rates (p=0.0507). However, patients with close margins were at equal risk of relapse and disease-free survival as with negative margins (p=1.000). Patients younger than 40 years of age had higher relapse rates (9.3% vs. 0%) and lower disease-free survival periods, but the difference was not statistically significant (p=0.1255). The relapse rates for patients with tumors was 14% for tumor stage T2, compared to 0% for tumor stage T1 tumors (p=0.0284). A univariate analysis found that disease-free survival and relapse rates, T stage, positive resection margin and mutation of p53 were significant factors for clinical outcome. Conclusion: The results of this study have shown that breast conservation surgery and radiation therapy in early breast cancer patients has proven to be a safe treatment modality with a low relapse rate and high disease-free survival rate. The patients with a positive margin, T2 stage, and mutation of p53 are associated with statistically higher relapse rates and lower disease-free survival.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.17-25
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• 1998

Purpose : Although local recurrence rates of stomach cancer after radiocal surgery have been reported in the range of $30-70\%$, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. Materials and Methods : From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiornyosarcoma. The numbers of patients with stage I B, II, III A, III B, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion Minimum and median follow-up periods were 12 months and 18 months, respectively, Results : Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than $15\%$ of their pretreatment weight. But hematemesis. melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient Peritoneal seeding occurred in 6, liver metastases months and median disease free survival time was 26 months. Stages andradiation dose were not significant prognostic factors for locoregional in 2, and distant nodes in 2 patients. Four year disease specificsurvival rate was $40\%$ and disease free survival was $48\%$. Median survival was 35 failures. Conculsion : Although all patients in this study had positive surgical margins, locoregional failure rate was $28\%$, and 4 year disease specific survival rate was $40\%$. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences. but we could find a Possibility of the role of postoperative radiotherapy in Patients with high risk factors.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.27-36
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• 1997

Purpose : This study was tried to evaluate the Potential benefits of concurrent chemoradiation therapy (low dose daily cisplatin combined with split course radiation therapy) compared with conventional radiation therapy alone in stage III non-small cell lung cancer. The end points of analyses were response rate. overall survival, survival without locoregional failure, survival without distant metastasis, prognostic factors affecting survival and treatment related toxicities. Materials and Methods : Between April 1992 and March 1994, 32 patients who had stage III non-small cell lung cancer were treated with concurrent chemoradiation therapy. Radiation therapy for 2 weeks (300 cGy given 10 times up to 3000 cGy) followed by a 3 weeks rest period and then radiation therapy for 2 more weeks (250 cGy given 10 times up to 2500 cGy) was combined with $6mg/m^2$ of cisplatin. Follow-up period ranged from 13 months to 48 months with median of 24 months. Historical control group consisted of 32 patients who had stage III non-small cell lung cancer were received conventionally fractionated (daily 170-200 cGy) radiation therapy alone. Total radiation dose ranged from 5580 cGy to 7000 cGy with median of 5940 cGy. Follow-up Period ranged from 36 months to 105 months with median of 62 months. Result : Complete reponse rate was higher in chemoradiation therapy (CRT) group than radiation therapy (RT) group (18.8% vs. 6.3%, CRT group showed lower in-field failure rate compared with RT group(25% vs. 47%. The overall survival rate had no significant differences in between CRT group and RT group (17.5% vs. 9.4% at 2 years). The survival without locoregional failure (16.5% vs. 5.3% at 2 years) and survival without distant metastasis (17% vs. 4.6% at 2 years) also had no significant differences. In subgroup analyses for Patients with good performance status (Karnofsky performance scale 80), CRT group showed significantly higher overall survival rate compared with RT group (62.5% vs. 15.6% at 2 years). The prognostic factors affecting survival rate were performance status and pathologic subtype (squamous cell cancer vs. nonsquamous cell cancer) in CRT group. In RT alone group, performance status and stage (IIIa vs IIIb) were identified as a Prognostic factors. RTOG/EORTC grade 2-3 nausea and vomiting(22% vs 6% and bone marrow toxicities (25% vs. 15.6% were significantly higher in CRT group compared with RT alone group. The incidence of RTOG/EORTC grade 3-4 pulmonary toxicity had no significant differences in between CRT group and RT group (16% vs. 6%. The incidence of WHO grade 3-4 pulmonary fibrosis also had no significant differences in both group (38% vs. 25%. In analyses for relationship of field size and Pulmonary toxicity, the Patients who treated with field size beyond 200cm2 had significantly higher rates of pulmonary toxicities. Conclusion : The CRT group showed significantly higher local control rate than RT group. There were no significant differences of survival rate in between two groups. The subgroup of patients who had good performance status showed higher overall survival rate in CRT group than RT group. In spite of higher incidence of acute toxicities with concurrent chemoradiation therapy, the survival gain in subgroup of patients with good performance status were encouraging. CRT group showed higher rate of early death within 1 year, higher 2 year survival rate compared with RT group Therefore, to evaluate the accurate effect on survival of concurrent chemoradiation therapy, systematic follow-up for long term survivors are needed.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.143-156
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• 2005

Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of $23.4\~59.4$ Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-IBT) was also peformed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of $14.4\~43.2$ Gy (Median 36.0) of EBRT in 495 patients, while In the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ($\alpha/\beta$=10) and late-responding tissues ($\alpha/\beta$=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED $Gy_3$ and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED $Gy_3$ and rectal complications and between V-BED $Gy_3$ and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED $Gy_{10}$, and the treatment duration. Results: The overall complication rate for RTOG Grades $1\~4$ toxicities was $33.1\%$. The 5-year actuarial pelvic control rate for ail 743 patients was $83\%$. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 $Gy_{10}$ (median 93.0) for tumors and from 93.6 to 187.3 $Gy_3$ (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED $Gy_3$) and bladder Point BED (V-BED $Gy_3$) were 118.7 $Gy_3$ (range $48.8\~265.2$) and 126.1 $Gy_3$ (range: $54.9\~267.5$), respectively. MD-BED $Gy_3$ showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED $Gy_3$ had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED $Gy_3$. B-BED $Gy_3$ also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences In tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very Important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.