• Radiation Oncology Journal
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• v.9 no.2
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• pp.221-225
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• 1991

Twenty five patients with unresectable non-small cell carcinoma of the lung have been treated with hyperfractionated radiotherapy with concomitant boost technique since September, 1989. Those patients with history of previous surgery or chemotherapy, pleural effusion or significant weight loss (greater than $10\%$ of body weight) were excluded from the study. Initially, 27 Gy were delivered in 15 fractions in 3 weeks to the large field. Thereafter, large field received 1.8 Gy and cone down boost field received 1.4 Gy with twice a day fractinations up to 49.4 Gy. After 49.4Gy, only boost field was treated twice a day with 1.8 and 1.4 Gy. Total tumor doses were 62.2 Gy for 12 patients and 65.4 Gy for remaining 13 patients. Follow up period was ranged from 6 to 24 month. Actuarial survival rates at 6, 12, and 18 month were $88\%,\;62\%,\;and\;38\%$, respectively. Corresponding disease free suwival rates were $88\%,\;41\%,\;and\;21\%$, respectively. Actuarial cumulative local failure rates at 9, 12 and 15 month were $36\%,\;43\%,\;and\;59\%$, respectively. No significant increase of acute or late complications including radiation pneumonitis was noted with maximum follow up of 24 month. Although the longer follow up is needed, it is worthwhile to try the prospective randomized study to evaluate the efficacy of hyperfractionated radiotherapy with concomitant boost technique for unresectable non-small cell lung cancers in view of excellent tolerance of this treatment. In the future, further increase of total radiation dose might be necessary to improve local control for non-small cell lung cancer.

• Molecules and Cells
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• v.42 no.9
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• pp.672-685
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• 2019

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

• Korean Journal of Radiology
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• v.22 no.8
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• pp.1369-1378
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• 2021

Objective: Few attempts have been made to investigate the prognostic value of dynamic contrast-enhanced (DCE) MRI or dynamic susceptibility contrast (DSC) MRI of non-enhancing, T2-high-signal-intensity (T2-HSI) lesions of glioblastoma multiforme (GBM) in newly diagnosed patients. This study aimed to investigate the prognostic values of DCE MRI and DSC MRI parameters from non-enhancing, T2-HSI lesions of GBM. Materials and Methods: A total of 76 patients with GBM who underwent preoperative DCE MRI and DSC MRI and standard treatment were retrospectively included. Six months after surgery, the patients were categorized into early progression (n = 15) and non-early progression (n = 61) groups. We extracted and analyzed the permeability and perfusion parameters of both modalities for the non-enhancing, T2-HSI lesions of the tumors. The optimal percentiles of the respective parameters obtained from cumulative histograms were determined using receiver operating characteristic (ROC) curve and univariable Cox regression analyses. The results were compared using multivariable Cox proportional hazards regression analysis of progression-free survival. Results: The 95th percentile value (PV) of Ktrans, mean Ktrans, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, p = 0.005; AUC = 0.684, p = 0.021; and AUC = 0.670, p = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of Ktrans and the mean Ktrans were significant predictors of early progression (hazard ratio [HR] = 1.06, p = 0.009; HR = 1.25, p = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of Ktrans was the sole significant independent predictor of early progression (HR = 1.062, p < 0.009). Conclusion: The 95th PV of Ktrans from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.

• The Journal of the Korean bone and joint tumor society
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• v.1 no.2
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• pp.154-163
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• 1995

With the development of anticancer chemotherapy and improved radiographic imaging studies, limb salvage operation became possible in the treatment of malignant and aggressive benign tumors. High grade sarcomas of the shoulder or the upper extremity can be surgically treated with a forequarter amputation, shoulder disarticulation or limb salvage surgery such as Tikhoff-Linberg procedure, segmental resection and replacement with endoprosthesis, segmental resection and replantation, or segmental resection and free vascularized bone graft. Among them the limb salvage surgery showed not only preservation of the remained upper extremity but also the excellent functional results. When comparing amputation and limb salvage operation while performing anticancer chemotherapy in both cases, 5 year survival rate, local recurrence, and distant metastasis did not show much difference. We studied 13 cases of limb salvage for the malignant and aggressive benign bone tumor of the upper extremity from March 1986 to December 1993 at Severance hospital. The summarized results were as follows. 1. There were 21 cases of malignant bone tumors and 5 cases of benign aggressive ones. 2. Of the 26 cases of malignant and benign aggressive bone tumors, limb salvage procedures such as Tikhoff-Linberg operation(8 cases), endoprosthetic replacement(2 cases), segmental resection and replantation(2 cases), and segmental resection and free vascularized fibular graft(l case) were done in 13 cases. 3. In 13 patient on whom the limb salvage procedure was performed, there were 3 osteosarcomas, 4 chondrosarcomas, 3 giant cell tumors, 1 Ewing's sarcoma, 1 leiomyosarcoma and 1 chondroblastoma. 4. In 13 patients, there was no local recurrence nor distant metastasis except one who had a segmental resection of the entire humerus part including glenoid and then postoperative anticancer chemotherapy for the treatment of the Ewing's sarcoma of the entire shaft of the humerus with pathological fracture. Local recurrence occurred 2 years and 6 months postoperatively in this Ewing's sarcoma patient, so forequarter amputation was performed and the irradiation and the anticancer chemontherapy were performed, but multiple bony metastasis developed and died of the disease 22 months after local recurrence. 5. The patients were followed-up for I year to 7 years and 5 months(average 4 years 5 months). 6. In 8 cases in which Tikhoff-Linberg procedure was performed, the function of the hand was almost normal. 7. Segmental resection and endoprosthetic replacement was performed in 2 cases, and the function of the remained upper extremity was good with no evidence of aseptic loosening or nerve palsy. 8. In 1 case of segmental resection and free vascularized fibular graft for the patient of the chon drosarcoma in the humerus, the function of the shoulder, elbow and hand was nearly normal. 9. In I case of leiomyosarcoma which involved both forearm muscles and bone near wrist joint, segmental resection and replantation was performed, and the patient has useful hand function.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.53-61
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• 2002

Purpose : To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, Patterns of failure, toxicities in early and late radiotherapy groups using a Phase III randomized prospective clinical trial. Materials and Methods : From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm 1)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU $375\;mg/m^2/day$, leucovorin $20\;mg/m^2$, IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months. Results : Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were $78.3\%\;and\;68.7\%$ in arm I, and $78.4\%\;and\;67.5\%$ in arm II. The local recurrence rate was $6.6\%\;and\;6.4\%$ (p=0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms ($23.8\%\;and\;29.5\%$, p=0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in $63.0\%\;and\;58.2\%$ of the respective arms (p=N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only $1.3\%\;and\;2.6\%$ of patients in each respective arm. Conclusion : There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.1-9
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• 2008

Purpose: To evaluate the impact of postoperative radiotherapy on loco-regional failure in patients with vulvar carcinoma and to determine the treatment strategy for inguinal lymph nodes. Materials and Methods: Sixty-six patients who received treatment for primary vulvar carcinoma at Seoul National University Hospital, from October 1979 through June 2004, were retrospectively analyzed. Sixteen patients were excluded from the analysis due to the following reasons: distant metastases in two patients; palliative intent for six patients; previous radiotherapy given to the pelvis in three patients; follow-up loss after surgery for four patient; insufficient medical records for one patient. Of 50 eligible patients, 35 were treated with surgery alone(S), ten were treated with surgery followed by radiotherapy(S+RT), and five were treated with radiotherapy alone. Results: The 5-year overall survival(OS) and disease-free survival(DFS) rates of all patients were 91% and 78%, respectively. Twelve patients(26%) experienced treatment failures and the sites of initial failure were as follows: a primary site in eight patients; regional lymph nodes in three patients; the lung in one patient. Although risk factors for failure were more common in the S+RT group than the S group of patients(p<0.05), the DFS rates were similar for the two groups(5-year DFS rates, 78% vs. 83%, p=0.66). The incidences of occult lymph node metastases was 10%. Ten of 31 patients with clinically negative lymph nodes did not received inguinal lymph node dissection, but no patient experienced regional failure. Conclusion: Postoperative radiotherapy may have a potential benefit for patients with risk factors for failure. The omission of inguinal dissection or elective radiotherapy to the inguinal lymph nodes may be considered in low-risk patients with clinically negative lymph nodes.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.160-169
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• 2007

Purpose: This study reports the results of the use of preoperative concurrent radiochemotherapy (CRCT) for the treatment of locoregionally advanced esophageal cancer. Materials and Methods: From 1998 through 2005, 61 patients with intrathoracic esophageal cancer at stages II-IVB (without distant organ metastasis and presumed to be respectable) received preoperative CRCT. CRCT consisted of radiotherapy (45 Gy /25 fractions /5 weeks) and FP chemotherapy (5-FU 1 g/$m^{2}$/day, days 1-4 and 29-32, Cisplatin 60 mg/$m^{2}$/day, days 1 and 29). An esophagectomy was planned in $4{\sim}6$ weeks after the completion of CRCT. Results: There were two treatment-related deaths. Among the 61 patients, 53 patients underwent surgery and 17 patients achieved a pathological complete response (pCR). The overall survival (OS) rates of all 61 patients at 2 and 5 years were 59.0% and 38.0%, respectively. The rates of OS and disease-free survival (DFS) of the surgically resected patients at 2 and 5 years were 61.6%, 40.1 % and 53.3%, 41.8%, respectively. By univariate analysis, achieviement of pCR and a clinically uninvolved distant lymph node (cMO) were favorable prognostic factors for OS and DFS. There were 27 patients that experienced a relapse-a locoregional relapse occurred in 5 patients, a distant metastasis occurred in 12 patients and combined failure occurred in 10 patients. Conclusion: The results of the current study are favorable. pCR and an uninvolved distant lymph node were found to be favorable prognostic factors.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.163-171
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• 1995

Purpose: Primary radiation therapy following breast-conserving surgery has been an accepted alternative to mastectomy during the past 2 decades. In this country, however, the practice of conservative therapy for early invasive breast cancer has not been generalized yet. The purpose of this report was to evaluate the results and complications of breast conservation therapy in Korean Cancer Center Hospital(KCCH). Materials and Methods: From January 1987 to December 1989. 45 Patients with early breast cancer treated with conservative treatment in KCCH were studied retrospectively Median follow up was 54 months(range, 4 to 82 months) . All patients received partial mastectomy (biopsy, tumorectomy. or quadrantectomy) and radiation therapy. Twenty eight patients received axillary dissection The breast was treated with two opposing tangential fields (total 50 Gy or 50.4 Gy in 5 weeks with daily target dose of 2 Gy or 1.8 Gy) Thirty patients received chemotherapy before and after radio-therapy Eleven patients received hormonal therapy. Results: Five-year survival rate, 5-rear disease free survival rate and 5-year local control rate were 87.2%, 86.5% and 97.6%,$ respectively. Administration of systemic Therapy (chemotherapy or hormonal therapy) correlated with good prognosis but statistically not significant (0.05 < p < 0.1). The severe late complication rate was 8.9% Conclusion: Primary radiation therapy following breast-conserving surgery for early breast cancer is an alternative treatment comparing to radical treatment. Long term follow-up and more patients collection is needed to evaluate the Prognostic factor and cosmetic outcome.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.307-315
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• 2004

Purpose: The purpose of this work was to study the differences of cyclooxygenase (COX-2) expression between Korean and Caucasian patients with early-onset breast carcinoma by immunohistochemistry. The test were analyzed to find a correlation between COX-2 and other biomarkers including HER-2/neu amplification, because we previously reported that a significant difference had been found in the expression of HER-2/neu between the two races. Furthermore, we investigated prognostic significance of COX-2 in korean patients. Materials and Methods: Sixty Korean women who were diagnosed breast carcinoma at 45 years old or younger and 60 Caucasian women with breast carcinoma were selected for this study. The median age of both groups was 37 years and tumor sizes were distributed evenly between the two group. Paraffin embedded blocks of primary tumor were processed for immunohistochemical staining of COX-2. The COX-2 expression was evaluated according to the percentage of positive cells and the intensity of staining. And the results were compared with the data of the previous studies to find correlation between COX-2 and other parameters and survival data. Results: Proportion of the COX-2 expression in total patients was $27.6\%$. The percentage of tumors that stained positive for COX-2 in korean and Caucasian women with early-onset breast carcinoma were $37.9\%$ and $20.8\%$, respectively. The difference was statistically not significant(p=0.090). Expression of COX-2 was not associated with several clinicopathologic parameters including HER-2/neu overexpression, but negative estrogen receptor status was correlated with significance (p=0.046). The 5 year disease free survival rate for patients with COX-2 expression was $67.9\%$, compared to $81.9\%$ of the COX-2 negative patients and the result was statistically not significant. Conclusions : A significant difference was not found in the expression of COX-2 between the two groups of patients with early-onset breast carcinoma. And correlation between COX-2 and other parameters was not observed except estrogen receptor negativity. Large scaled further research including radiotherapy factors will be needed to identify COX-2 as a prognostic role in patients with early-onset breast carcinoma.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.100-106
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• 2001

Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.