• Radiation Oncology Journal
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• v.20 no.4
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• pp.334-342
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• 2002

Purpose : The aim of this study was to determine if postoperative adjuvant chemotherapy (CT) alone and concurrent chemoradiation (CCRT), following radical surgery, improved the disease free survival (DFS) and overall survival (OS) in rectal cancer AJCC stage II and III patients. Materials and Methods : A total of 144 patients with AJCC stage II and III rectal cancer who had had radical surgery between 1989 and 1999 were included in the study. Of these patients, 72 had been treated with postoperative CT, and the other 72 with postoperative CCRT. The chemotherapy regimen consisted of oral UFT on a daily basis for $1\~12$ months (median 12 months) or 5-FU ($500\;mg/m^2$ for 5 days) intravenous (IV) chemotherapy with 4 week intervals for $1\~18$ cycles (median 6 cycles). Radiation of 4,500 cGy was delivered to the surgical bed and regional pelvic lymph nodes area, followed by $540\~1,440\;cGy$ (median 540 cGy) boost to the surgical bed. The follow-up period ranged from 20 to 150 months, with a median of 44 months. Results : The 5-year OS was $60.9\%\;and\;68.9\%$ (p=0.0915), and the 5-year DFS was $56.1\%\;and\;63.8\%$ (p=0.3510) for postoperative CT and postoperative CCRT, respectively. In the stage nm patients, the 5-year OS was $71.1\%\;and\;92.2\%$, and the 5-year DFS was $57.3\%\;and\;85.4\%$ for postoperative CT and CCRT, respectively. The OS was significantly improved (p=0.0379) but the DFS was not with postoperative CCRT compared to the postoperative CT (p=0.1482). In the stage III patients, the 5-year OS was $52.0\%\;and\;55.0\%$, and the 5-year DFS was $47.8\%\;and\;49.8\%$ for postoperative CT and postoperative CCRT. There were no statistically significant differences between postoperative CT and CCRT (p=0.4280 and p=0.7891) in OS and DFS. The locoregional relapses were $16.7\%\;and\;12.5\%$ for postoperative CT and CCRT, respectively. The distant relapses were $25.0\%\;and\;26.4\%$ for postoperative CT and CCRT, respectively. Conclusion : These results showed that postoperative CCRT compared with CT alone improved OS in stage II patients. Although there was no statistical significance, the addition of postoperative RT to CT reduced locoregional relapses compared to CT alone.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.209-216
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• 1999

Purpose : To evaluate the effectiveness of external radiation therapy and the prognostic factors, we retrospectively analyzed therapeutic results of malignant extrahepatic biliary obstruction (EHBO). Methods and Materials : We analyzed the results of the external radiation therapy in 59 patients of inoperable malignant EHBO who had been treated with more than 10 Gy of external radiation therapy from April 1984 to December 1990. There were 21 stomach cancer ($35.6\%$), 12 pancreas cancer ($20.3\%$), 15 extrahepatic biliary cancer ($18.0\%$) and 11 another cancer ($18.0\%$). Their pathologies were confirmed in 31 patients ($52.5\%$). They divided into 27 adenocarcinoma and 4 nonadenocarcinoma. Their chief complaints were jaundice in 47 patients ($79.7\%$) and abdominal pain in 15 patients ($49.2\%$). Twelve patients had slightly increased bilirubin level in liver function test without jaundice. We treated twenty four patients ($40.6\%$) with percutaneous transhepatic biliary drainage (PTBD) and 32 patients ($54\%$) with systemic chemotherapy (CT). We performed external radiation therapy (ERT) upto $10.8\~55.8$ Gy (median 37.8 Gy) with palliative aim. Results : Overall median survival duration was $7.80\pm1.15$ months. The response rates of jaundice were $81.8\%$ in PTBO group and $66.7\%$ in non-PTBD group without statistical significance. The improving rate of jaundice was not significantly different in decreased ratio of total bilirubin level. But abdominal pain was more decreased in CT group than non-CT group (p<0.05). The significant prognostic factors were high performance status (Karnofski Performance Status >70), total radiation dose more than 35 Gy and good response of pain after therapy. There were increased in bacterial cholagitis in PTBD group and gastrointestinal complications in CT group. Conclusion : External radiotheapy could improve jaundice and abdominal pain in malignant EHBO patients, Overall survival duration was prolonged in patients with higher performance status and patients who had been treated with more than 35 Gy of total radiation dose. In the future, we expect not only better palliative role but also the prolongation of survival of using the ERT combined with other treatment method. But to achieve certain conclusion, we need luther study consisted with many kinds of treatment methods including new technologies in RT.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.17-24
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• 2004

Purpose: To evaluate the treatment outcomes after postmastectomy radiotherapy (PMRT) and chemotherapy in patients with breast cancer. Materials and Methods: The PMRT were retrospectively analyzed in 83 patients with stage II-III female breast cancer treated between 1989 and 1995. The median age was 46 years (range, 23-77): Seventy-seven patients had modified radical mastectomies, 5 radical mastectomies and 1 simple mastectomy. Three patients ($4\%$) had pathologically negative axillae, and the remaining 80 ($96\%$) had positive axillae. Eleven, 23, 44 and 5 patients had pathological stages IIA, IIB, IIIA, and IIIB, retrospectively. Eighty ($96\%$) patients were treated with hockey-stick fields. The median dose of PMRT was 50.4 ey, in 1.8 Gy fractions. Adjuvant systemic chemotherapy was given to 74 patients ($89\%$). CMF-based or doxorubicin-containing regimens were given to 54 patients ($55\%$). The median follow-up time was 82 months (range, 8-171) after the mastectomy. Results: The 5 and 10-year overall survival rates for all patients were 65 and $49\%$, respectively. The univariate and multivariate analyses of the factors affecting the overall survival revealed the stage to be the most significant prognostic factor (p=0.002), followed by the combination of chemotherapy. Thirteen patients $16\%$ developed a LRF, at an interval of 4-84 months after radiotherapy, with a median of 20 months. The only significant prognostic factor affecting LRF was the combination of chemotherapy, in both the univariate and multivariate analyses. With respect to the sequence of chemoradiation, the sequence had no saatistical significance (p=0.90). According to the time interval from mastectomy to the onset of radiotherapy, the LRFR of the patients group treated by RT within or after 6 month postmastectomy 6 months were 14 vs. $27\%$ respectively (p=0.24). One third of the pa41en1s (26/83) developed distant metastasis, in 2-92 months, after radiotherapy, with a median of 21 months. The most commonly involved site was bone in 13 cases. The pathological staging was the only significant prognostic factor in both the univariate and multivariate analyses that affected distant failure. Radiological finding of radiation pneumonitis on a simple chest x-ray was shown in $20\%$ (17/83), with a time interval ranging from 2 to 7 months post-radiotherapy, with a median of 3 months. The stable lung fibrosis settled in 11 patients ($65\%$). Conclusion: It was concluded through this analysis that the combination of PMRT with in chemotherapy resulted in better overall survival and local control than PMRT alone in patients needing PMRT.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.265-274
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• 1998

Purpose : This prospective study has been conducted to assess the value of three dimensional conformal radiation therapy (3DCRT) for lung cancer and to determine its potential advantage over current treatment approaches. Specific aims of this study were to 1) find the most ideal 3DCRT technique 2) establish the maximum tolerance dose that can be delivered with 3DCRT and 3) identify patients at risk for development of radiation pneumonitis. Materials and Methods : Beginning in Nov. 1994, 95 patients with inoperable non-small cell lung cancer (stage I; 4, stage II; 1, stage IIIa; 14, stage IIIb; 76) were entered onto this 3D conformal trial Areas of known disease and elective nodal areas were initially treated to 45 Gy and then using 3DCRT technique 65 to 70 Gy of total dose were delivered to the gross disease. Sixty nine patients received 65 Gy of total dose and 26 received 70 Gy Seventy eight patients (82.1$\%$) also received concurrent MVP chemotherapy. 3DCRT plans were compared with 2D plans to assess the adequacy of dose delivery to target volume, dose volume histograms for normal tissue, and normal tissue complication Probabilities (NTCP). Results : Most of plans (78/95) were composed of non-coplanar multiple (4-8) fields. Coplanar segmented conformal therapy was used in 17 pateints, choosing the proper gantry angle which minimize normal lung exposure in each segment. 3DCRT gave the full dose to nearly 100$\%$ of the gross disease target volume in all patients. The mean NTCP for ipsilateral lung with 3DCRT (range; 0.17-0.43) was 68$\%$ of the mean NTCP with 2D treatment planning (range; 0.27-0.66). DVH analysis for heart showed that irradiated volume of heart could be significantly reduced by non-coplanar 3D approach especially in the case of left lower lobe lesion. Of 95 patients evaluable for response, 75 (79$\%$), showed major response including 25 (26$\%$) with complete responses and 50 (53$\%$) with partial responses. One and two rear overall survivals of stage III patients were 62.6$\%$ and 35.2$\%$ respectively. Twenty percent (19/95) of patients had pneumonitis; Eight patients had grade 1 pneumonitis and 11 other patients had grade 2. Comparison of the average of NTCP for lung showed a significant difference between patients with and without radiation pneumonitis. Average NTCP for Patients without complication was 62$\%$ of those with complications. Conclusions : This study showed that non-coplanar multiple fields (4-8) may be one of the ideal plans for 3DCRT for lung cancer. It also suggested that 3DCRT may provide superior delivery of high dose radiation with reduced risk to normal tissue and that NTCP can be used as a guideline for the dose escalation.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.4
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• pp.23-40
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• 2011

Objectives: This study was designed to examine the effects of extracts of Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) on the lipid lowering, anti-oxidation and concentration of proinflammatory cytokines and was investigated on hyperlipidemic rats. Methods: Male rats weighing $182.39{\pm}4.71g$ were fed high fat diet for 8 weeks and 36 rats(above 400 g) were divided into 4 groups. Each of 9 rats was divided a control group and experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1 time/1 day) for 4 weeks. And we fed each experimental group of rats basal diet and administered an extract of Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) extracts(100 mg/kg, 200mg/kg, 300 mg/kg, 300 mg/kg, 1 time/1 day) for 4 weeks. At the end of the experiment, the rats were sacrificed to determine their chemical composition. We measured lipid of plasma and liver, concentration of proinflmmatory cytokines, anti-oxidative activity and $TNF-{\alpha}$, Apo-B, Apo-E and leptin gene expression. Results: 1. Concentration of plasma free fatty(FFA) showed no significant difference in all the treatment groups. Concentration of plasma triglyceride(TG) showed a significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. 2. Concentration of plasma total cholesterol showed a significant decrement in the 200 and 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. Concentration of plasma low density lipoprotein(LDL)-cholesterol showed a Significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. Concentration of plasma high density lipoprotein(HDL)-cholesterol showed a significant increment in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group. 3. Concentration of liver total cholesterol showed a tendence to decrease in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups. Concentration of liver TG showed a significant decrement in all Ojeoksangamibang groups than that of control group. 4. Concentration of plasma and liver thiobarbituric acid reactive substance(TBARS) showed a tendence to decrease in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups. 5. The values of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and catalase(CAT) activity showed a significant increment in all Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups than that of control group. 6. The values of plasma aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activity showed no significant different in all treatment group. 7. Concentration of plasma $interleukin(IL)-1{beta}$ showed no significant difference in all the treatment groups. Concentration of plasma IL-6 showed a significant decrement in the 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group than that of control group. Concentration of plasma tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ a siginifant decrement in the 200 and 300 mg/kg in Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) group than that of control group. However the concentration of plasma IL-10 in the 300 mg/kg Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a significant increment than that of control group. 9. In the analysis of reverse transcription-polymerase chain reaction(RT-PCR), gene expression of $TNF-{\alpha}$, Apo-B and Apo-E in the Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a lower expression than that of control group. However the gene expression of leptin showed no difference in the treatment groups. 10. The ratio of $TNF-{\alpha}$, Apo-B, and Apo-E per ${\beta}-actin$ expression in the Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) groups showed a significant decrement than that of control group. However The ratio of leptin expression per ${\beta}-actin$ expression showed no significant difference among all the treatment groups. Conclusions: According to above results, in lowering lipid effect, anti-oxidation and control of pro-inflammatory cytokines production, Ojeoksangamibang($W{\check{u}}j\bar{i}s\check{a}nji\bar{a}w\grave{e}if\bar{a}ng$) gives effect.

• Progress in Medical Physics
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• v.23 no.2
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• pp.91-98
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• 2012

Verification of internal organ motion during treatment and its feedback is essential to accurate dose delivery to the moving target. We developed an offline based internal organ motion verification system (IMVS) using cine EPID images and evaluated its accuracy and availability through phantom study. For verification of organ motion using live cine EPID images, a pattern matching algorithm using an internal surrogate, which is very distinguishable and represents organ motion in the treatment field, like diaphragm, was employed in the self-developed analysis software. For the system performance test, we developed a linear motion phantom, which consists of a human body shaped phantom with a fake tumor in the lung, linear motion cart, and control software. The phantom was operated with a motion of 2 cm at 4 sec per cycle and cine EPID images were obtained at a rate of 3.3 and 6.6 frames per sec (2 MU/frame) with $1,024{\times}768$ pixel counts in a linear accelerator (10 MVX). Organ motion of the target was tracked using self-developed analysis software. Results were compared with planned data of the motion phantom and data from the video image based tracking system (RPM, Varian, USA) using an external surrogate in order to evaluate its accuracy. For quantitative analysis, we analyzed correlation between two data sets in terms of average cycle (peak to peak), amplitude, and pattern (RMS, root mean square) of motion. Averages for the cycle of motion from IMVS and RPM system were $3.98{\pm}0.11$ (IMVS 3.3 fps), $4.005{\pm}0.001$ (IMVS 6.6 fps), and $3.95{\pm}0.02$ (RPM), respectively, and showed good agreement on real value (4 sec/cycle). Average of the amplitude of motion tracked by our system showed $1.85{\pm}0.02$ cm (3.3 fps) and $1.94{\pm}0.02$ cm (6.6 fps) as showed a slightly different value, 0.15 (7.5% error) and 0.06 (3% error) cm, respectively, compared with the actual value (2 cm), due to time resolution for image acquisition. In analysis of pattern of motion, the value of the RMS from the cine EPID image in 3.3 fps (0.1044) grew slightly compared with data from 6.6 fps (0.0480). The organ motion verification system using sequential cine EPID images with an internal surrogate showed good representation of its motion within 3% error in a preliminary phantom study. The system can be implemented for clinical purposes, which include organ motion verification during treatment, compared with 4D treatment planning data, and its feedback for accurate dose delivery to the moving target.

• Tuberculosis and Respiratory Diseases
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• v.58 no.6
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• pp.590-599
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• 2005

Object : Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. Methods : A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). Results : 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). Conclusion : The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.35-41
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• 1998

Purpose : To investigate the role of adjuvant chemoradiotherapy in adenocarcinoma of the rectum, we retrospectively compared the treatment results between postoperative adjuvant radiotherapy alone and combined chemoradiotherapy. Material and Methods : From October 1989 to May 1994, 141 patients with rectal carcinoma were treated by postoperative adjuvant therapy in Yonsei Cancer Center. Sixty eight patients were treated by radiation therapy alone. Seventy three patients were treated by combined chemoradiotherapy. Radiation therapy was delivered with 10 MV linear accelerator, 180cGy fraction/5 days per week. Total radiation doses were 5400cGy in the postoperative radiotherapy alone group. Three to twelve cycles of Fluorouracil(mean dose $393.9mg/m^2$) with Leucovorin($20mg/m^2$) and 5040cGy of radiation were delivered in the combined chemoradiotherapy group. Third and 4th cycle of chemotherapy were administrated during the radiation treatment in the combined group. The median follow up was 38 months with a range of 3 to 81 months. Results : The 5 year overall survival rate of radiation alone group and combined group were $60.1\%$ and $66.3\%$, respectively. The 5 year disease free survival rate of radiation aione group and combined group were $54.2\%$ and $65.5\%$, respectively There was no significant difference of overall survival and disease free survival between RT alone group and combined group(p<0.05). But the 5 year Local failure free survival rate of combined group was significantly better than radiotherapy alone group($05.8\%\;vs.\;50.3\%.\;p=0.04$). Conclusion : There was no significant difference in overall survival, disease free survival, and distant metastasis free survival between postoperative adjuvant radiotheray alone group and combinded chemoradiotherapy group. Only the Local failure free survival rate was superior in the combined treatment group. These results confirm the radiosensitizing effect of the chemotherapeutic agent in the combined chemoradiotherapy treatment.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.237-246
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• 2004

Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.