• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.322-332
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• 1998

Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.

• 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.

• Journal of Gastric Cancer
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• v.6 no.1
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• pp.36-42
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• 2006

Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.

• Tuberculosis and Respiratory Diseases
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• v.44 no.5
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• pp.1094-1104
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• 1997

Background : Spontaneous pneumothoraces(SP) are divided into primary spontaneous pneumothoraces (PSP) which develop in healthy individuals without underlying pulmonary disorders and secondary spontaneous pneumothoraces(SSP) which occur in those who have underlying disorders such as tuberculosis or chronic obstructive lung diseases. Yet there is no established standard therapeutic approach to this disorder, i.e., from the spectrum of noninvasive treatment such as clinical observation with or without oxygen therapy, to aggressively invasive thoracoscopic bullectomy or open thoracotomy. Although chest tube thoracostomy has been most widely used, the patients should overcome pain in the initiation of tube insertion or during indwelling it potential infection and subcutaneous emphysema. Thus smaller-caliber tube has been challenged for the treatment of pneumothorax. Previously, we studied the therapeutic efficacy of 8 French catheter for spontaneous pneumothorax. But there has been few data for effectiveness of small-caliber catheterization in comparison with that of chest tube. In this study, we intended to observe the long-term effectiveness of 8 French catheter for the treatment of spontaneous pneumothoraces in comparison with that of chest tube thoracostomy. Method : From January, 1990 to January, 1996, sixty two patients with spontaneous pneumothoraces treated at Chung-Ang University Hospital were reviewed retrospectively. The patients were sub-divided into a group treated with 8 French catheter(n=23) and the other one with chest tube insertion(n=39). The clinical data were reviewed(age, sex, underlying pulmonary disorders, past history of pneumothorax, size of pneumothorax, follow-up period). And therapeutic effect of two groups was compared by treatment duration(duration of indwelling catheter or tube), treatment-associated complications and recurrence rate. Results : The follow-up period(median) of 8 French catheter group and chest tube group was 28 and 22 months, which had no statistical significance. Ther was no statistically significant difference of clinical characteristics between two groups with SP, PSP, SSP. The indwelling time of 8 French catheter group was $6.2{\pm}3.8$ days, which was significantly shorter than that of chest tube group in SP, $9.1{\pm}7.5$ days(p=0.047). In comparison of treatment-related complication in PSP, 8 French catheter group as 6.25% of complication showed lower tendency than the other group as 23.8% (p=0.041 ; one-tailed, p=0.053; two-tailed). The recurrence rate in each group of SP was 17.4%, 10.3%, which did not show any statistically significant difference. Conclusion : Treatment with 8 French catheter resulted in shorter indwelling time in sponteous pneumothorax, and lower incidence of treatment-related complication in primary spontaneous pneumothorax. And the recurrence rate in each of treatment group showed no statistically significant difference. So, we can recommend the 8 French small-caliber catheter for the initial therapy for spontaneous pneumothorax for the replacement of conventional chest tube thoracostomy. But further prospective study with more subjects of spontaneous pneumothorax will be needed for the evaluation of effectiveness of 8 French cateter.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.299-305
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• 2003

Purpose: In order to develop the national guide-lines for the standardization of radiotherapy we are planning to establish a web-based, on-line data-base system for laryngeal cancer. As a first step this study was performed to accumulate the basic clinical information of laryngeal cancer and to determine the items needed for the data-base system. Materials and Methods: We analyzed the clinical data on patients who were treated under the diagnosis of laryngeal cancer from January 1998 through December 1999 In the South-west area of Korea. Eligiblity criteria of the patients are as follows: 18 years or older, currently diagnosed with primary epithelial carcinoma of larynx, and no history of previous treatments for another cancers and the other laryngeal diseases. The items were developed and filled out by radiation oncologlst who are members of forean Southwest Radiation Oncology Group. SPSS vl0.0 software was used for statistical analysis. Results: Data of forty-five patients were collected. Age distribution of patients ranged from 28 to 88 years(median, 61). Laryngeal cancer occurred predominantly In males (10 : 1 sex ratio). Twenty-eight patients (62$\%$) had primary cancers in the glottis and 17 (38$\%$) in the supraglottis. Most of them were diagnosed pathologically as squamous cell carcinoma (44/45, 98$\%$). Twenty-four of 28 glottic cancer patients (86$\%$) had AJCC (American Joint Committee on Cancer) stage I/II, but 50$\%$ (8/16) had In supraglottic cancer patients (p=0.02). Most patients(89$\%$) had the symptom of hoarseness. indirect laryngoscopy was done in all patients and direct laryngoscopy was peformed in 43 (98$\%$) patients. Twenty-one of 28 (75$\%$) glottic cancer cases and 6 of 17 (35$\%$) supraglottic cancer cases were treated with radiation alone, respectively. The combined treatment of surgery and radiation was used in 5 (18$\%$) glottic and 8 (47$\%$) supraglottic patients. Chemotherapy and radiation was used in 2 (7$\%$) glottic and 3 (18$\%$) supraglottic patients. There was no statistically significant difference in the use of combined modality treatments between glottic and supraglottic cancers (p=0.20). In all patients, 6 MV X-ray was used with conventional fractionation. The iraction size was 2 Gy In 80$\%$ of glottic cancer patients compared with 1.8 Gy in 59$\%$ of the patients with supraglottic cancers. The mean total dose delivered to primary lesions were 65.98 ey and 70.15 Gy in glottic and supraglottic patients treated, respectively, with radiation alone. Based on the collected data, 12 modules with 90 items were developed or the study of the patterns of care In laryngeal cancer. Conclusion: The study Items for laryngeal cancer were developed. In the near future, a web system will be established based on the Items Investigated, and then a nation-wide analysis on laryngeal cancer will be processed for the standardization and optimization of radlotherapy.

• Journal of Chest Surgery
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• v.29 no.11
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• pp.1173-1181
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• 1996

The causes of degenerative changes in allograft cardiac valves are not well known to this day. Today's preserved allografts possess highly viable endothelial cells and degeneration of allografts can be facilitated by immune reaction which may be mediated by these viable cells. To test the antigenicity of endothelial cells, pieces from aortic wall were obtained from fresh and cryo-preserved rat allograft. Timings of sampling were prior to sterilization, after sterilization, after 1, 2, 7, 14 days of fresh preservation and cryopreservation. Endothelial cells were tested by immunohistochemical methods using monoclonal antibodies to MHC class I(MRC OX-18), class II(MRC OX-6) and ICAM-1 antigens. After transplantation of each group of aortic allograft at the subcutaneous layers of rats, population of CD4$^{+}$ T cell and CD8$^{+}$ T cell were analyzed with monoclonal antibodies after 1, 2, 3, 4, 6 and 8 weeks. MHC class I expression was 23.95% before preservation and increased to 35.53~48.08% after preservation(p=0.0183). MHC Class II expression was 9.72% before preservation and 10.13~13.39% after preservation(P=0.1599). ICAM-1 expression was 15.02% before preservation and increased to 19.85~35.33% after preservation(P=0.001). The proportion of CD4$^{+}$ T-cell was 42.13% before transplantation. And this was 49.23~36.8% after transplantation in No treat group (p=0.955), decreased to 29.56~32.80% in other group(p=0.0001~0.008). In all the groups, the proportion of CD8$^{+}$ T-cell increased from 25.57% before transplantation to 42.32~58.92% after transplantation(p=0.000l~0.0002). The CD4$^{+}$/CD8$^{+}$ ratio decreased from 1.22~2.28 at first week to 0.47~0.95 at eighth week(p=0.0001). The results revealed that the expression of MHC class I and ICAM-1 in aortic allograft endothelium were increased but that of MHC class II were not changed, despite the different method of preservation. During 8 weeks after transplantation of aortic allograft, the subpopulations of CD4$^{+}$ T cell were not changed or only slightly decreased but those of CD8$^{+}$ T cell were progressively increased.ely increased.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.5
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• pp.263-270
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• 2006

Purpose: Several radioisotope-labeled thymidine derivatives such as $[^{11}C]$thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with $[^{11}C]$thymidine due to rapid in vivo degradation and its short physical half-life. 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-$[^{18}F]$fluoro-3'-deoxythymidine ($[^{18}F]$FLT) and compared with $([^{18}F]FET)\;and\;([^{18}F]FDG)$ in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor hearing rats. Material and Methods: For the synthesis of $[^{18}F]$FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimet hoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-${\beta}$-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with $^{18}F$ was performed in acetonitrile at $120^{\circ}C$ and deproteced with 0.5 N HCI. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. Results: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of $[^{18}F]$FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were $1.61{\pm}0.34,\;1.70{\pm}0.30\;and\;9.33{\pm}2.22$, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. Conclusion: The uptake of $[^{18}F]$FLT in tumor was higher than in normal brain and PET image of $[^{18}F]$FLT was acceptable. These results suggest the possibility of $[^{18}F]$FLT at an imaging agent for brain tumor.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.210-217
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• 2009

Purpose: To assess the influence of cyclooxygenase-2 (COX-2) expression on the survival of patients with a combination of rectal cancer and lymph node metastasis. Materials and Methods: The study included rectal cancer patients treated by radical surgery and postoperative radiotherapy at the Dong-A university hospital from 1998 to 2004. A retrospective analysis was performed on a subset of patients that also had lymph node metastasis. After excluding eight of 86 patients, due to missing tissue samples in three, malignant melanoma in one, treatment of gastric cancer around one year before diagnosis in one, detection of lung cancer after one year of diagnosis in one, liver metastasis in one, and refusal of radiotherapy after 720 cGy in one, 78 patients were analyzed. The immunohistochemistry for COX-2 was conducted with an autostainer (BenchMark; Ventana, Tucson, AZ, USA). An image analyzer (TissueMine; Bioimagene, Cupertino, CA, USA) was used for analysis after scanning (ScanScope; Aperio, Vista, CA, USA). A survival analysis was performed using the Kaplan Meier method and significance was evaluated using the log rank test. Results: COX-2 was stained positively in 62 patients (79.5%) and negatively in 16 (20.5%). A total of 6 (7.7%), 15 (19.2%), and 41 (52.6%) patients were of grades 1, 2, and 3, respectively for COX-2 expression. No correlation was found between being positive of COX-2 patient characteristics, which include age (<60-year old vs. $\geq$60), sex, operation methods (abdominoperineal resection vs. lower anterior resection), degrees of differentiation, tumor size (<5 cm vs. $\geq$5 cm), T stages, N stages, and stages (IIIa, IIIb, IIIc). The 5-year overall and 5-year disease free survival rates for the entire patient population were 57.0% and 51.6%, respectively. The 5-year overall survival rates for the COX-2 positive and negative patients were 53.0% and 72.9%, respectively (p=0.146). Further, the 5-year disease free survival rates for the COX-2 positive and negative patients were 46.3% and 72.7%, respectively (p=0.118). The 5-year overall survival rates were significantly different (p<0.05) for the degree of differentiation, N stage, and stage, whereas the 5-year disease free survival rates were significant for N stage and stage. Conclusion: Being positive for and the degree of COX-2 expression did not have a significant influence on the survival of rectal cancer patients with lymph node metastasis. However, N stage and stage did significantly influence the rateof survival. Further analysis of a greater sample size is necessary for the verification of the effect of COX-2 expression on the survival of rectal cancer patients with lymph node involvement.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.218-227
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• 2006

Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage that direct monitoring is possible without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. In this study, we investigate the usefulness of the reporter probe (substrate), $9-(4-[^{18}F]Fluoro-3-hydroxymethylbutyl)$guanine ($[^{18}F]FHBG$) for non-invasive reporter gene imaging using PET in HSV1-tk expressing hepatoma model. Materials and Methods: Radiolabeled FHBG was prepared in 8 steps from a commercially available triester. The labeling reaction was carried out by NCA nucleophilic substitution with $K[^{18}F]/K2.2.2.$ in acetonitrile using N2-monomethoxytrityl-9-14-(tosyl)-3-monomethoxytritylmethylbutyl]guanine as a precursor, followed by deprotection with 1 N HCl. Preliminary biological properties of the probe were evaluated with MCA cells and MCA-tk cells transduced with HSV1-tk reporter gene. In vitro uptake and release-out studies of $[^{18}F]FHBG$ were performed, and was analyzed correlation between $[^{18}F]FHBG$ uptake ratio according to increasing numeric count of MCA-tk cells and degree of gene expression. MicroPET scan image was obtained with MCA and MCA-tk tumor bearing Balb/c-nude mouse model. Results: $[^{18}F]FHBG$ was purified by reverse phase semi-HPLC system and collected at around 16-18 min. Radiothemical yield was about 20-25%) (corrected for decay), radiochemical purity was >95% and specific activity was around >55.5 $GBq/{\mu}\;mol$. Specific accumulation of $[^{18}F]FHBG$ was observed in HSV1-tk gene transduced MCA-tk cells but not in MCA cells, and consecutive 1 hour release-out results showed more than 86% of uptaked $[^{18}F]FHBG$ was retained inside of cells. The uptake of $[^{18}F]FHBG$ was showed a highly significant linear correlation ($R^2=0.995$) with increasing percentage of MCA-tk numeric cell count. In microPET scan images, remarkable difference of accumulation was observed for the two type of tumors. Conclusion: $[^{18}F]FHBG$ appears to be a useful as non-invasive PET imaging substrate in HSV1-tk expressing hepatoma model.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.22-31
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• 2005

Purpose : To conduct a nationwide survey on the principals in radiotherapy for rectal cancer, and produce a database of Korean Patterns of Care Study. Materials and Methods : We developed web-based Patterns of Care Study system and a national survey was conducted using random sampling based on power allocation methods. Eligible patients were who had postoperative radiotherapy for rectal cancer without gross residual tumor after surgical resection and without previous history of other cancer and radiotherapy to pelvis. Data of patients were Inputted to the web based PCS system by each investigators in 19 institutions. Results : Informations on 309 patients with rectal cancer who received radiotherapy between 1998 and 1999 were collected. Male to female ratio was 59 : 41, and the most common location of tumor was lower rectum ($46\%$). Preoperative CEA was checked in $79\%$ of cases and its value was higher than 6 ng/ml in $32\%$. Pathologic stage were I in $1.5\%$, II in $32\%$, III in $53\%$, and IV in $1.6\%$. Low anterior resection was the most common type of surgery and complete resection was peformed in $95\%$ of cases. Distal resection margin was less than 2 cm in $30\%$, and number of lymph node dissected was less than 12 in $31\%$. Chemotherapy was peformed in $91\%$ and most common regimen was 5-FU and leucovorine ($59\%$). The most common type of field arrangement used for the initial pelvic field was the four field box (Posterior-Right-Left) technique ($65.0\%$), and there was no AP-PA parallel opposing field used. Patient position was prone in $81.2\%$, and the boost field was used in $61.8\%$. To displace bowel outward, pressure modulating devices or bladder filling was used in $40.1\%$. Radiation dose was prescribed to isocenter in $45.3\%$ and to isodose line in 123 cases ($39.8\%$). Percent delivered dose over $90\%$ was achieved in $92.9\%$. Conclusion : We could find the Patterns of Care for the radiotherapy in Korean rectal cancer patients was similar to that of US national survey. The type of surgery and the regimen of chemotherapy were variable according to institutions and the variations of radiation dose and field arrangement were within acceptable range.