• Radiation Oncology Journal
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• v.20 no.2
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• pp.108-115
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• 2002

Purpose : A retrospective study was undertaken to determine the role of conventional radiotherapy with or without surgery for treating a supraglottic carcinoma in terms of the local control and survival. Materials and Methods : From Jan. 1986 to Oct. 1996, a total of 134 patients were treated for a supraglottic carcinoma by radiotherapy with or without surgery. Of them, 117 patients who had completed the radiotherapy formed the base of this study. The patients were redistributed according to the revised AJCC staging system (1997). The number of patients of stage I, II, III, IVA, IVB were $6\;(5\%),\;16\;(14\%),\;53\;(45\%),\;32\;(27\%),\;10\;(9\%)$, respectively. Eighty patients were treated by radical radiotherapy in the range of $61.2\~79.2\;Gy$ (mean : 69.2 Gy) to the primary tumor and $45.0\~93.6\;Gy$ (mean : 54.0 Gy) to regional lymphatics. All patients with stage I and IVB were treated by radiotherapy alone. Thirty-seven patients underwent surgery plus postoperative radiotherapy in the range of $45.0\~68.4\;Gy$ (mean : 56.1 Gy) to the primary tumor bed and $45.0\~59.4\;Gy$ (mean : 47.2 Gy) to the regional lymphatics. Of them, 33 patients received a total laryngectomy (${\pm}lymph$ node dissection), three had a supraglottic horizontal laryngectomy (${\pm}lymph$ node dissection), and one had a primary excision alone. Results : The 5-year survival rate (5YSR) of all patients was $43\%$. The 5YSRs of the patients with stage I+II, III+IV were $49.9\%,\;41.2\%$, respectively (p=0.27). However, the disease-specific survival rate of the patients with stage I (n=6) was $100\%$. The 5YSRs of patients who underwent surgery plus radiotherapy (S+RT) vs radiotherapy alone (RT) in stage II, III, IVA were $100\%\;vs\;43\%$ (p=0.17), $62\%\;vs\;52\%$ (p=0.32), $58\%\;vs\;6\%$ (p<0.001), respectively. The 5-year actuarial locoregional control rate (5YLCR) of all the patients was $57\%$. The 5YLCR of the patients with stage I, II, III, IVA, IVB was $100\%,\;74\%,\;60\%,\;44\%,\;30\%$, respectively (p=0.008). The 5YLCR of the patients with S+RT vs RT in stage II, III, IVA was $100\%\;vs\;68\%$ (p=0.29), $67\%\;vs\;55\%$ (p=0.23), $81\%\;vs\;20\%$ (p<0.001), respectively. In the radiotherapy alone group, the 5YLCR of the patients with a complete, partial, and minimal response were $76\%,\;20\%,\;0\%$, respectively (p<0.001). In all patients, multivariate analysis showed that the N-stage, surgery or not, and age were significant factors affecting the survival rate and that the N-stage, surgery or not, and the ECOG performance index were significant factors affecting the locoregional control. In the radiotherapy alone group, multivariate analysis showed that the radiation response and N-stage were significant factors affecting the overall survival rate as well as locoregional control. Conclusion : In early stage supraglottic carcinoma, conventional radiotherapy alone is an equally effective modality compared to surgery plus radiotherapy and could preserve the laryngeal function. However, in the advanced stages, radiotherapy combined with concurrent chemotherapy for laryngeal preservation or surgery should be considered. In bulky neck disease, all the possible planned neck dissections after induction chemotherapy or before radiotherapy should be attempted.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.233-243
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• 2000

Purpose : First of all, this study was performed to assess the result of curative radiotherapy and to evaluate different possible prognostic factors for squamous cell carcinoma of the supraglottic larynx treated at the Pusan National University Hospital. The second goal of this study was by comparing our data with those of other study groups, to determine the better treatment policy of supraglottic cancer in future. Methods and Material : Thirty-two patients with squamous cell carcinoma of the supraglottic larynx were treated with radiotherapy at Pusan National University Hospital, from August 1985 to December 1996. Minimum follow-up period was 29 months, Twenty-seven patients (84.4$\%$) were followed up over 5 years. Radiotherapy was delivered with 6 MV photons to the primary laryngeal tumor and regional iymphatics with shrinking field technique. Ail patients received radiotherapy under conventional fractionated schedule (once a day). Median total tumor dose was 70.2 Gy (range, 55.8 to 75.6 Gy) on primary or gross tumor lesion. Thirteen patients had Induction chemotherapy with cisplatln and 5-fluorouracil (1-3 cycles). Patient distribution, according to the different stages, were as follows: stage I, 5/32 (15.6$\%$): stage II, 10/32 (31.3$\%$); stage III, 8/32 (25$\%$): stage IV, 9/32 (28.1$\%$). Results :The 5-year overall survival rate of the whole series (32 patients) was 51.7$\%$. The overall survival rate at 5-years was 80$\%$ in stage I, 66.7$\%$ in stage II, 42.9$\%$ in stage III, 25$\%$ in stage IV (p=0.0958). The S-year local control rates after radiotherapy were as fellows: stage I, 100$\%$; stage II, 60$\%$ stage III, 62.5$\%$; stage IV, 44.4$\%$ (p=0.233). Overall vocal preservation rates was 65.6$\%$, 100% In stage I, 70% in stage II, 62.5$\%$ In stage III, 44.4$\%$ in stage IV (p=0.210). There was no statistical significance in survival and local control rate between neoadjuvant chemotherapy followed by radiotherapy group and radiotherapy alone group. Severe laryngeal edema was found in 2 cases after radiotllerapy, emergent tracheostomy was done. Four patients were died from distant metastsis, . three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor ( p=0.0215), and radiation dose (more or less than 70.2 Gy) was an important factor on survival (p=0.002). Conclusion : The role of radiotherapy treatment of supraglottic carcinoma is to important factor on survival and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supragiottic carcinomas could be successfully treated with either consewative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone is Inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.9-18
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• 1995

Purpose : A retrospective analysis was performed to investigate the proper management of maxillary sinus carcinoma. Materials and Methods : Authors analysed 33 patients of squamous cell carcinoma of maxillary sinus treated at Chonnam University Hospital from January 1986 to December 1992. There were 24 men and 9 women with median age of 55 years. According to AJCC TNM system of 1988, a patient of T2, 10 patients of T3 and 22 patients of T4 were availalbe, respectively. Cervical lymph node metastases was observed in 5 patients(N 1;4/33, N2b; 1/33). Patients were classified as 3 groups according to management method. The first group, named as 'FAR' (16 patients), was consisted or preoperative intra-arterial chemotherapy with 5-fluorouracil(5-FU;mean of total dosage;3078mg) through the superficial temporal artery with concurrent radiation(mean dose delivered:3433cGy, daily 180-200cGy) and vitamin A(50,000 IU daily), and followed by total maxillectomy and postoperative radiation therapy(mean dose;2351cGy). The second group, named as 'SR'(7 patients), was consisted of total maxillectomy followed by postoperative radiation therapy(mean dose 5920 cGy). The third group, named as 'R'(6 patients), was treated with radiation alone(mean dose;7164cGy). Kaplan-Meier product limit method was used for survival analysis and Mantel-Cox test was performed for significance of survival difference between two groups. Results : Local recurrence free survival rate in the end of 2 year was $100\%$, $50\%$ and $0\%$ in FAR, SR and R group, respectively. Disease free survival rate in 2 years was $88.9\%$, $28.0\%$ and $0\%$ in FAR, SR and R group, respectively. Overall survival rate in 2 years was $88.9\%$, $40\%$ and $50\%$ in FAR, SR and R group, respectively. There were statistically significant difference between FAR and SR or FAR and R group in their local recurrence free, disease free and overall survial rates. But difference of each survival rate between SR and R group was not significant. Conclusion : In this study FAR group revealed better results than SR or R group. In the future prospective randomized study is in need.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3395-3402
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• 2015

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.193-200
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• 2007

Purpose: This study evaluated the pretreatment expression patterns of MDM2, p53, and pRb proteins to determine if the expression patterns could predict the outcome of concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma and aid in the decisions for the selection of treatment modalities. Materials and Methods: Fifty-one patients that were treated with definitive chemoradiotherapy for stage $I{\sim}IVa$ esophageal squamous cell carcinoma were selected for this study. Radiotherapy was administered with daily $1.8{\sim}2\;Gy$ fractions up to a median dose of 54 Gy for primary tumors, and with four cycles of cisplatin/5-fluorouracil chemotherapy that was administered every 4 weeks, the first two cycles of which were administered concurrently with radiotherapy. Expression of MDM2, p53, and pRb was investigated by immunohistochemical analysis using pretreatment biopsy specimens. Results: MDM2, p53, and pRb were detected with high immunoreactivity in 19.6%, 27.5%, and 66.7% of the patients, respectively. However, there was no significant correlation between expression of these factors and clinical outcome. By the use of multivariate analysis with nine covariates-age, tumor location, tumor length, stage, pathological response, clinical response, MDM2 expression, p53 expression, and pRb expression, only pathological response and stage were significant factors for cause-specific survival. Conclusion: Expression of MDM2, p53, and pRb was not found to be clinically significant for predicting outcomes after CCRT in this study. Further studies with a larger patient population and longer follow-up periods are needed to re-evaluate the expression pattern and to identify new predictors for CCRT response.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.124-129
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• 2004

Purpose : To evaluate the clinical findings, prognosis and treatment strategy of patients with neuroendocrine carcinoma of cervix. Materials and Methods: Thirteen patients with neuroendocrine carcinoma of cervix were included in this study, as confirmed histologically and immunohistochemically at the Dongsan Medical Center, Keimyung University, between May 1944 and October 2001. The mean age of patients was 56 years with a range of 32 to 78 years of age. According to the FIGO staging system, there were 5 patients with stage IB carcinoma, 5 patients with IIA, and 3 patients with stage IIB. Four patients underwent radical hysterectomy with pelvic lymphadenectomy, 3 of these patients also received postoperative radiotherapy, and one patient underwent extrafascial hysterectomy after radiotherapy. Primary radiotherapy was done in 9 patients, and 3 were irradiated postoperatively. Nine patients received chemotherapy, 7 received neoadjuvant and 2 received concurrent chemoradiotherapy. The radical purpose of radiotherapy consisted of external irradiation to the whole pelvis (4,500 $\~$5,400 cGy) and intracavitary irradiation (3,000 $\~$ 3,500 cGy). Results : The mean follow up duration was 36 months with a range of 3 to 104 months. The overall 5-year survival rate was 61.5$\%$ and the 5-year survival rates for stage IB, IIA, IIB were 60.0$\%$, 60.0$\%$, and 66.7$\%$ respectively (p=0.99). Eight patients are still alive without disease, and all of the 5 patients with recurrence are dead due to distant metastasis. Conclusion : Neuroendocrine carcinoma of cervix is highly aggressive, with early lymphatic dissemination and a high rate of distant recurrence. Therefore, an aggressive therapeutic strategy Is required to obtain pelvic and distant disease control. Multimodal therapy should be considered at the time of Initial diagnosis.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.167-173
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• 2007

Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

• Journal of radiological science and technology
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• v.29 no.2
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• pp.83-92
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• 2006

Based on the data of cervical cancer patients who were treated by the radiotherapy with concurrent chemotherapy at the radiation oncology department of National Cancer Center from January 2002 to February 2003, we have studied the method recommended by ICRU 38 to maximize the prescription dose to the planing target volume (PTV) with minimizing the dose to surrounding normal organs. Clinical stage of the patients are 1 patient for stage IB, 3 patients for IIA, 19 patients for IIB, 3 patients for IIIA, 3 patients for IIIB and 1 patient for IV. All patients took the MRI before treatment and the maximum size of the gross tumor volume were under 4cm for 17 patients and from 4 cm to 6 cm for 12 patients and above 6 cm for 1 patient. The results show that while the irradiated volume can be reduced with optimized dose distribution using PTV treatment planning (p<0.0001) when the remained tumor size is small, the surrounding normal organs will receive unnecessarily large dose when the irradiated tumor volume is relatively large. This is because there is some limitation in controling the intensity of radiation in Fletcher Williamson Applicator. To overcome the limit of applicator and to achieve the optimal dose distribution, we have virtually applied 4 needles with Fletcher Williamson Applicator for 10 patients who have relatively large tumor and studied the change in dose distribution before and after application. The results show that this new virtual treatment plan reduces the volume covered by 100 % isodose (p=0.0608, p=0.0607) and reduces the dose of normal organs (p=0.0162, p=0.008). This evidence suggest that this method is superior than the currently used method such as PTV treatment and ICRU treatment.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.79-84
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• 2010

Purpose: We retrospectively analyzed the long-term results of radical surgery and intraoperative radiation therapy (IORT) in patients with stomach cancer. Materials and Methods: From 1988 to 1994, 51 patients were treated with curative surgery and IORT. Postoperative external beam radiotherapy (EBRT) was administered to 30 patients, while adjuvant chemotherapy was administered to 35 patients. A dose of 15 Gy was irradiated with a 9 MeV electron beam as the IORT and a median dose of EBRT was 43.2 Gy (range, 7.2 to 45 Gy). The follow-up period ranged from 1~254 months, with a median follow-up period of 64 months. Results: The median age of all the patients was 58 years (range, 30 to 71 years). The distribution of pathologic stage (American Joint Committee on Cancer [AJCC] 2002 tumor-note-metastasis [TNM]) was as follows: 13 stage I (25.5%), 10 stage II (19.6%), 25 stage III (49.0%), and 3 stage IV (5.9%). Distant metastases occurred in 11 patients (10 in the peritoneum and 1 in bone), including one patient with concurrent local recurrence (anastomosis site). The 5-year locoregional control, disease free survival and overall survival rates were 94.7%, 66.5%, and 51.7%, respectively. For the multivariate analysis, age, TNM stage, and EBRT were significant prognostic factors for overall survival, and only TNM stage for disease free survival. Conclusion: We could have achieved a high loco-regional control rate in patients with locally advanced stomach cancer by adding IORT to radical surgery. However, the benefit of IORT on survival remains to be elucidated.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.181-188
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• 2009

Purpose: The aim of this study was to evaluate the results of postoperative radiotherapy in a case of perihilar cholagiocarcinoma by analyzing overall survival rate, patterns of failure, prognostic factors for overall survival, and toxicity. Materials and Methods: Between January 1998 and March 2008, 38 patients with perihilar cholangiocarcinoma underwent a surgical resection and adjuvant radiotherapy. The median patient age was 59 years (range, 28 to 72 years), which included 23 men and 15 women. The extent of surgery was complete resection in 9 patients, microscopically positive margins in 25 patients, and a subtotal resection in 4 patients. The tumor bed and regional lymphatics initially received 45 Gy or 50 Gy, but was subsequently boosted to a total dose of 59.4 Gy or 60 Gy in incompletely resected patients. The median radiotherapy dose was 59.4 Gy. Concurrent chemotherapy was administered in 30 patients. The median follow-up period was 14 months (range, 6 to 45 months). Results: The 3-year overall survival and 3-year progression free survival rates were 30% and 8%, respectively. The median survival time was 28 months. A multivariate analysis showed that differentiation was the only significant factor for overall survival. The 3-year overall survival was 34% in R0 patients and 20% in R1 patients. No statistically significant differences in survival were found between the 2 groups (p=0.3067). The first site of failure was local in 18 patients (47%). No patient experienced grade 3 or higher acute toxicity and duodenal bleeding developed in 2 patients. Conclusion: Our results suggest that adjuvant RT might be a significant factor in patients with a positive margin following a radical resection. However, there was still a high locoregional recurrence rate following surgery and postoperative radiotherapy. Further study is necessary to enhance the effect of the adjuvant radiotherapy.