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Radiation Induced Changes in the Expression of Fibronectin, Pai-1, MMP in Rat Glomerular Epithelial Cell (백서 사구체 상피세포에서 방사선에 의한 Fibronectin, Pai-1, MMP 발현의 변화)

  • Park Woo-Yoon;Kim Won-Dong;Zheng Ying;Ha Tae-Sun;Kim Jae-Sung;Cho Moon-June
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.58-66
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    • 2006
  • Purpose: Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. Materials and Methods: Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Results: Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-1 mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. Conclusion: Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy.

Intratumoral Administration of Dendritic Cells Combined with Hyperthermia Induces Both Local and Systemic Antitumor Effect in Murine Tumor Models (온열 요법 후 종양 내 주입한 수지상 세포의 국소 및 원격 항종양 효과)

  • Kwon Byung-Hyun;Kim Won-Taek;Kim Young-Kan;Kim Dong-Won
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.51-57
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    • 2006
  • Puroose: We examined whether intratumoral (i.t.) administration of dendritic cells (DCs) into a treated tumor could induce local and systemic antitumor effects in a mouse tumor model. Methods and Materials: C57BL/6 mice were inoculated s.c. in the right and left thighs with MCA-102 fibrosarcoma cells on day 0 and on day 7, respectively. On day 7, the tumors (usually 6 mm in diameter) on the right thigh were heated by immersing the tumor-bearing leg in a circulating water bath at $43^{\circ}C$ for 30 min; thereafter, the immature DCs were i.t administered to the right thigh tumors. This immunization procedure was repeated on days 7, 14 and 21. The tumors in both the right and left thighs were measured every 7 days and the average sizes were determined by applying the following formula, tumor $size=0.5{\times}(length+width)$. Cytotoxicity assay was done to determine tumor-specific cytotoxic T-lymphocyte activity. Results: Hyperthermia induced apoptosis and heat shock proteins (HSPs) in tumor occurred maximally after 6 hr. For the local treated tumor, hyperthermia (HT) alone inhibited tumor growth compared with the untreated tumors (p<0.05), and furthermore, the i.t. administered DCs combined with hyperthermia (HT + DCs) additively inhibited tumor growth compared with HT alone (p<0.05). On the distant untreated tumor, HT alone significantly inhibited tumor growth (p<0.05), and also HT + DCs potently inhibited tumor growth (p<0.001); however, compared with HT alone, the difference was not statistically significant. In addition, HT + DCs induced strong cytotoxicity of the splenocytes against tumor cells compared to DCs or HT alone. Conclusion: HT + DCs induced apoptosis and increased the expression of HSPs, and so this induced a potent local and systemic antitumor response in tumor-bearing mice. This regimen may be beneficial for the treatment of human cancers.

An Analysis of Prognostic Factors Affecting the Outcome of Radiation Therapy for Nasopharyngeal Carcinoma (비인강암의 방사선치료 곁과 및 생존율에 관한 예후인자 분석)

  • Jung, Young-Yeon;Kim, Ok-Bae;Kim, Jin-Hee
    • Radiation Oncology Journal
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    • v.23 no.2
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    • pp.71-77
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    • 2005
  • Purpose: This retrospective study was conduced to analyze the treatment results and to evaluate the prognostic factors affecting the survival of nasopharyngeal carcinoma patients. Materials and Methods: From 1987 to 2002, we analyzed 43 patients who had nasopharyngeal carcinomas that were histologically confirmed and who had also completed the planned radiation therapy course at Keimyung University Dongsan Medical Center According to the 6th edition of American Joint Committee on Cancer staging system, 12 patients ($27.9\%$) were at Stage 11, 13 ($30.2\%$) were at Stage III and 18 ($41.9\%$) were at Stage IV Histopathologically, there were 15 ($34.9\%$) squamous cell carcinomas, 8 ($18.5\%$) nonkeratinizing carcinomas, 17 ($39.5\%$) undifferentiated carcinomas, and 3 ($7.0\%$) lymphoepitheliomas. Among the total 43 patients, 31 patients ($72.1\%$) were treated with only radiation therapy. Neoadjuvant chemotherapy was peformed on 7 patients ($16.3\%$) and concurrent chemoradiotherapy was performed on S patients ($11.6\%$). Cisplatin and 5-Fluorouracil were administered to 11 patients for 4 cycles, and Cisplatin and Taxotere were administered to 1 patient for 6 cycles. The range of the total radiation dose delivered to the primary tumor was from 61.2 to 84 Gy (median 70.4 Gy), The follow-up period ranged from 2 to 197 months with median follow-up of 84 months. Results: The local control rate at 6 months after radiation therapy was $90.7\%$. The five year overall survival and disease free survival rates were $50.7\%$ and $48.9\%$, respectively. On the multivariate analysis, the age, T-stage ($T_{1-3}\;vs\;T_4$), N-stage and AJCC stage were the statistically significant prognostic factors affecting survival (p<0.05). The patterns of failure were as follows: local failure only in 3 patients ($7.0\%$), local and systemic failure in 1 patient ($2.3\%$), and distant metastasis only in 11 patients ($25.6\%$). Conclusion: The prognostic factors affecting the outcome of nasopharyngeal carcinoma were age, T-stage (7$T_{1-3}\;vs\;T_4$), N-stage and stage. Because systemic metastasis was the main failure pattern noted for nasopharyngeal carcinoma, systemic chemotherapy is needed to decrease the rate of distant metastasis for nasopharyngeal carcinoma. In audition, research for more effective chemotherapeutical regimens and schedules is also needed.

Treatment Outcome of Thymic Epithelial Tumor: Prognostic Factors and Optimal Postoperative Radiation Therapy (흉선상피종의 치료 성적: 예후 인자 및 방사선치료 방법에 대한 연구)

  • Oh Dong Ryul;Ahn Yong Chan;Kim Kwan Min;Kim Jhingook;Shim Young Mog;Han Jung Ho
    • Radiation Oncology Journal
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    • v.23 no.2
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    • pp.85-91
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    • 2005
  • Purpose : This study was conducted to analyze treatment outcome and prognostic significance of World Health Organization (WHO)-defined thymic epithelial tumor (TET) subtype and to assess optimal radiation target volume in patients receiving surgery and adjuvant radiation therapy with TET. Materials and Methods: The record of 160 patients with TET, who received surgical resection at the Samsung medical Center, from December 1994 to June 2004, were reviewed. 99 patients were treated with postoperative radiation therapy (PORT). PORT was recommended when patients had more than one findings among suspicious Incomplete resection or positive resection margin or Wasaoka stage $II\~IV$ or WHO type $B2\~C$. PORT peformed to primary tumor bed only with a mean dose of 54 Gy. The prognostic factor and pattern of failure were analyzed retrospectively. Results : The overall survival rate at 5 years was $87.3\%$. Age (more than 60 years $77.8\%$, less than 60 years $91.1\%$; p=0.03), Wasaoka stage (I $92.2\%$, II $95.4\%$, III $82.1\%$, IV $57.5\%$; p=0.001), WHO tumor type (A-Bl $96.0\%$, B2-C $82.3\%$; p=0.001), Extent of resection (R0 resection $92.3\%$, R1 or 2 resection $72.6\%$, p=0.001) were the prognostic factors according to univariate analysis. But WHO tumor type was the only significant prognostic factor according to multivariate analysis. Recurrence was observed in 5 patients of 71 Masoka stage I-III patients who received grossly complete tumor removal (R0, R1 resection) and PORT to primary tumor bed. Mediastinal recurrence was observed In only one patients. There were no recurrence within irradiation field. Conclusion : WHO tumor type was the important prognostic factor to predict survival of patients with TET. This study suggest that PORT to only primary tumor bed was optimal. To avoid pleura- or pericardium-based recurrence, further study of effective chemotherapy should be investigated.

Effects of Postoperative Radiotherapy on Distribution of Bone Metastases in Breast Cancer (유방암환자에서 수술 후 방사선치료가 골전이 분포에 미치는 영향)

  • Kim, Bo-Kyoung;Ha, Sung-Whan
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.211-215
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    • 2001
  • Purpose : This study was done to evaluate the efficacy of low-dose radiation in reduction of thoracic vertebral metastases in patients with breast cancer. Materials and Methods : 109 patients who were treated for bone metastasis from breast cancer from June, 1988 to June, 1998 in the Department of Therapeutic Radiology, Seoul National University were included. Of the 109 patients, 40 patients had been previously treated by postoperative radiotherapy and 69 had not. Postoperative radiotherapy had been given using Co-60 teletherapy device in 30 patients or 6 MV linear accelerator in 10. Thoracic spines from 1 to 10 were usually irradiated except in 1 patient and cervical vertebrae 6 and/or 7 were partially included in ,: patients. A total of 50.4 Gy was given with 1.8 Gy fraction. Metastatic bone diseases were scored in 11 regions, i. e., skull, conical spine, thoracic spine from 1 to 4, from 5 to 8, 9 and 10, 11 and 12, lumbar spine, pelvis, femur, ribs and others. Results : In no postoperative parasternal irradiation group, lumbar vertebrae were the most common metastatic sites $(55.1\%)$ followed by pelvis $(44.9\%)$, ribs $(40.6\%)$, thoracic vertebrae 11 and 12 $(37.7\%)$, thoracic vertebrae between 5 and 8 $(36.2\%)$, thoracic vertebrae 9 and 10 $(34.8\%)$, and thoracic vertebrae between 1 and 4 $(26.1\%)$. In postoperative parasternal irradiation group, lumbar vertebrae and pelvis were also the most common sites of metastases ($55.0\%$, respectively) followed by ribs $(37.5\%)$, and thoracic vertebrae 11 and 12 $(32.5\%)$. But significant less metastases were seen at thoracic vertebrae from 1 to 10. Conclusion : We can find that the were significantly less bony metastases at thoracic vertebrae which had been previously irradiated postoperatively.

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Reirradiation in Rcurrent Cervical Cancer Following Definite Radiation Therapy (근치적 방사선치료 후 재발한 자궁경부암의 재 방사선치료)

  • Kim, Jin-Hee;Choi, Tae-Jin;Kim, Ok-Bae
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.230-236
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    • 2001
  • Purpose : To evaluate treatment results in terms of local control, complications and survival after reirraidiation in recurrent cervical cancer following definite radiation therapy. Material and methods : From November 1987 through March 1998, eighteen patients with recurrent cervical cancer following definite radiation therapy were subsequently treated with reirradiation at Keimyung University Dongsan Medical Center. In regard to the initial FIGO stage, one patient was stage la, five were stage IIa, three were IIb, two were IIb and two were IVa. The age range was 37 to 79 years old with median age of 57. The time interval from initial definite radiation therapy to recurrence ranged from 6 to 122 months with a median of 58 months. The recurrent sites were the uterine cervix in seven patients, vagina in ten and pelvic lymph node in one. Reirradiation was peformed with external radiation and intracavitary radiation in twelve patients, external radiation and implantation in four and external radiation alone in two. The range of external radiation dose was $2,100\~5,400\;cGy$ and the range of the total radiation dose was $3,780\~8,550\;cGy$. The follow-up periods ranged from 8 to 20 months with median of 25 following reirradiation. Results : Fourteen of eighteen patients $(78\%)$ had local control just after reirradiation. The two year disease free survival (2YDFS) rate was $53.6\%$. There were statistically significant differences in the 2YDFS according to both recurrent site (2YDFS $28.5\%$ in uterine cervix, $71.4\%$ in vagina, (p=0.03)) and the total dose (2YDFS $71.8\%$ in >6,000 cGy , $25\%$ in $\leq6,000$ cGy, p=0.007). Seven of ten patients who were followed for more than 20 months remain alive and disease free (7/18, $39\%$). Patients treated with external radiation and intracavitary radiation had a higher rate of 2YDFS. Seven patients including 4 patients with no local control experienced local failure in the uterus or vagina and two patients died with distant metastasis. Complications included rectal bleeding in 3 patients, bowel obstruction treated with surgery in two, hematuria in one, radiation cystitis in two, soft tissue swelling in two and vaginal necrosis spontaneously healed in one. There was no statistical difference in complications according to the total dose or the time to recurrence from initial radiation. Conclusion : In patients with recurrence following definite radiation therapy in the uterine cervical cancer, reirradiation may be effective but requires an effort to reduce radiation induced severe complications.

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Results of Radiotherapy in Hypopharyngeal Cancer (하인두암의 방사선치료)

  • Shin Byung Chul;Yum Ha Yong;Moon Chang Woo;Jeong Tae Sik
    • Radiation Oncology Journal
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    • v.20 no.3
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    • pp.206-214
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    • 2002
  • Purpose : The aim of this study was to assess the effectiveness, survival rate and complications of radiation therapy and chemoradiation treatment in hypopharyngeal cancer. Methods and Materials : From January 1984 to December 1999, 56 patients who had hypopharyngeal carcinoma treated with curative radiation therapy were retrospectively studied. Twenty four patients $(42.9\%)$ were treated with radiation therapy alone (Group I) and $32\;(57.1\%)$ treated with a combination of chemotherapy and radiation (Group II). Total radiation dose ranged from 40.5 to 83. 5 Gy (median 67.9 Gy). Radiotherapy was given with conventional technique in 9 patients $(16.4\%)$, with hyperfractionation I ($1.15\~1.2$ Gy/fr., BID) in 26 $(47.2\%)$, hyperfractionation II (1.35 Gy/fr., BID) in 18 $(32.7\%)$, and accelerated fractionation (1.6 Gy/fr., BID) in 2 $(3.6\%)$. In chemotherapy, 5-FU ($1,000\;mg/m^2$ daily for 5 consecutive days) and cisplatin ($100\;mg/m^2$ on day 1) were administered in a cycle of 3 weeks interval, and a total of 1 to 3 cycles (average 2..3 cycles) were given prior to radiation therapy. Follow up duration was $1\~195$ months (median 28 months). Results : Overall 2 and 5 year survival rates were $40.6\%\;and\;27.6\%;\;50.0\%\;and\;30.0\%$ in Group I, and $36.4\%\;and\;26.3\%$ in Group II, respectively. Complete local control rates in Group I and II were $70.0\%\;and\;67.7\%$, respectively. The response to radiotherapy and nodal stage were statistically significant prognostic factors. The complication rate was increased in Group II and was decreased in hyperfractionation. Conclusion : The response to radiotherapy and nodal stage were valid factors to indicate the degree of control over the hypopharyngeal cancer. The induction cisplatin, 5-Fu chemotherapy was not valid in terms of local control rate and survival rate, but did contribute to an increased complication rate. The use of hyperfractionation was valid to reduce the late radiation complications.

Radiation Dose of Lens and Thyroid in Linac-based Radiosurgery in Humanoid Phantom (선형가속기형 방사선수술시 인형 팬텀에서 수정체 및 갑상선 선량)

  • Kim, Dae-Yong;Kim, Il-Han
    • Radiation Oncology Journal
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    • v.16 no.4
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    • pp.517-529
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    • 1998
  • Purpose : Although many studies have investigated the dosimetric aspects of stereotactic radiosurgery in terms of target volume, the absorbed doses at extracranial sites: especially the lens or thyroid - which are sensitive to radiation for deterministic or stochastic effect -have infrequently been reported. The aim of this study is to evaluate what effects the parameters of radiosurgery have on the absorbed doses of the lens and thyroid in patients treated by stereotactic radiosurgery, using a systematic plan in a humanoid phantom. Materials and Methods : Six isocenters were selected and radiosurgery was planned using the stereotactic radiosurgery system which the Department of Therapeutic Radiology at Seoul National University College of Medicine developed. The experimental radiosurgery plan consisted of 6 arc planes per one isocenter, 100 degrees for each arc range and an accessory collimator diameter size of 2 cm. After 250 cGy of irradiation from each arc, the doses absorbed at the lens and thyroid were measured by thermoluminescence dosimetry. Results : The lens dose was 0.23$\pm$0.08$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the lens and was 0.76$\pm$0.12$\%$ of the maximum dose for each isocenter when the exit beam passed through the lens. The thyroid dose was 0.18$\pm$0.05$\%$ of the maximum dose for each isocenter when the exit beam did not pass through the thyroid and was 0.41$\pm$0.04$\%$ of the maximum dose for each isocenter when the exit beam Passed through the thyroid. The passing of the exit beam is the most significant factor of organ dose and the absorbed dose by an arc crossing organ decides 80$\%$ of the total dose. The absorbed doses of the lens and thyroid were larger as the isocenter sites and arc planes were closer to each organ. There were no differences in the doses at the surface and 5 mm depth from the surface in the eyelid and thyroid areas. Conclusion : As the isocenter and arc plane were placed closer to the lens and thyroid, the doses increased. Whether the exit beams passed through the lens or thyroid greatly influenced the lens and thyroid dose. The surface dose of the lens and thyroid consistently represent the tissue dose. Even when the exit beam passes through the lens and thyroid, the doses are less than 1$\%$ of the maximum dose and therefore, are too low to evoke late complications, but nevertheless, we should try to minimize the thyroid dose in children, whenever possible.

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Radiotherapy Results of Uterine Cervix Cancer Stape IIB : Overall Survival, Prognostic factors, Patterns of Failure and Late Complications (자궁경부암 병기 IIB에서의 방사선 치료 성적: 생존율 및 예후인자, 치료 후 실패양상, 만성 합병증)

  • Kim Eun-Seog;Choi Doo-Ho;Huh Seung-Jae
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.51-61
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    • 1998
  • Purpose : Treatment of choice for uterine cervix cancer stage IIB is radiotherapy. We analyzed survivals, Prognostic factors, patterns of failure and complications. Materials and Methods : This is a retrospective analysis of 167 patients with stage IIB carcinoma of uterine cervix treated with curative external pelvic and high dose rate intracavitary radiotherapy at the Department of Therapeutic Radiology, Soonchunhyang University Hospital from August 1985 to August 1994. All the patients followed up from 3 to 141 months(mean 60 months) and age of patients ranged from 31 to 78 years at presentation(mean : 55 years). Results : Overall complete response rate was $84\%$. The response rate for squamous cell carcimoma and adenocarcinoma were $86\%$ and $60\%$, respectively. Overall 5-years survival rate and disease free survival rate was 62 and $59\%$, respectively Mass size and treatment response were significant Prognostic factors for survival Pathologic type and parametrial involvement were marginally significants Prognostic factors. Local failure was 43 cases, distant metastasis was 14 cases and local failure plus distant metastasis was 3 cases, and most of local failures occurred within 24 months, distant metastasis within 12 months after treatment Twenty eight($16.8\%$) patients developed late rectal and urinary complications There were tendency to increasing severity and frequency according to increased fractional dose and total(rectal and bladder) dose. Conclusions : Survival rate was significantly related to tumor size and radiotherapy response. Tumor size should be considered in the clinical s1aging. To increased survival and local control, clinical trials such as decreasing duration of radiotherapy or addition of chemotherapy is needed. To detect early recurrence, regular follow up after RT is important. Because total rectal and bladder dose affected late complications. meticulous vaginal packing is needed to optimize dose of normal tissues and to decrease late complications.

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Efficacy of Small Bowel Displacement System in Post-Operative Pelvic Radiation Therapy of Rectal Cancer (소장 용적 측정을 통한 직장암의 수술 후 방사선치료 시 사용하는 소장 전위 장치(Small Bowel Displacement System : SBDS) 의 효용성 검토)

  • Ahn Yong Chan;Lim Do Hoon;Kim Moon Kyung;Wu Hong Gyun;Kim Dae Yong;Huh Seung Jae
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.63-69
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    • 1998
  • Purpose : This study is to evaluate the efficacy of small bowel displacement system(SBDS) in post-operative pelvic radiation therapy(RT) of rectal cancer patients by measurement of small bowel volume included in the radiation fields receiving therapeutic dose. Materials and Method : Ten consecutive new rectal cancer patients referred to the department of Radiation Oncology of Samsung Medical Center in May of 1997 were included in this study. All patients were asked to drink $Castrographin^(R)$ before simulation and were laid prone for conventional simulation and CT scans with and without SBDS. The volume of opacified small bowel on CT scans, which was to be included in the radiation fields receiving therapeutic dose, was measured using Picture archiving and communication system (PACS). Results : The average small bowel volumes with and without SBDS were 176.0ml(5.2-415.6ml) and 185.1ml(54.5-434.2ml), respectively The changes of small bowel volume with SBDS compared to those without SBDS were more than $10\%$ decrease in three, less than 10% decrease in two, less than $10\%$ increase in three, and more than $10\%$ increase in two patients. Conclusion : No significant advantage of using SBDS in post-operative pelvic RT for rectal cancer patients has been shown by small bowel volume measurement using CT scan considering additional effort and time needed for simulation and treatment setup.

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