• Radiation Oncology Journal
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• v.25 no.1
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• pp.43-53
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• 2007

[ $\underline{Purpose}$ ]: To evaluate the relationship between the expression of EGFR, p53, Cox-2, Bcl-2 and the clinical parameters of NPC (nasopharyngeal carcinoma) patients treated with radiotherapy with/without chemotherapy, and to determine if these could be used as a biologic marker. $\underline{Materials\;and\;Methods}$: This study retrospectively examined 75 NPC patients who were pathologically diagnosed at St. Mary's Hospital and Kangnam St Mary's Hospital from March 1988 to August 2002 and treated with radiotherapy with/without chemotherapy. The levels of EGFR, p53, Cox-2, and Bcl-2 expression were determined immunohistochemically. The relationship between the levels of EGFR, p53, Cox-2 and Bcl-2 expression and the H- E staining findings including the WHO classification, TNM stage, tumor response to chemotherapy and radiotherapy, disease free survival (DFS), and overall survival (OS) was analyzed. $\underline{Results}$: At a median follow up of 50.8 months (range: $5.5{\sim}201$ months), the 3 years OS rate and PFS rate were 68.7% and 68.2%, respectively. The five year OS rate and PFS rate were 53.5% and 51.1%, respectively. The median OS duration and PFS duration were 85.5 months and 61.1 months, respectively. The WHO classification correlated with the complete response rate, lymph node metastasis and distant metastasis. The expression of p53 was associated with increased mitosis and poor overall survival. The expression of Bcl-2 correlated with the DFS and WHO classification. The expression of Cox-2 correlated with a poor overall survival and response rate in the lymph node. However, EGFR was not correlated with any factors. $\underline{Conclusion}$: These results suggest that the expression of p53, Cox-2, Bcl-2 plays role in predicting prognostic factors for NPC treated with radiotherapy with/without chemotherapy. However, further study on a larger number of patients will be needed to identify more useful biomarkers of NPC.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.65-72
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• 1991

One hundred and thirty five patients with carcinoma of the nasopharyx were treated by radiation therapy in the Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University between August 1977 and July 1987. Of the 30 patients omitted: 8 had distant metastases at initial diagnosis or during radiotherapy; 18 Patients refused or did not receive a full course of radiation therapy, and four had not been confirmed histologically. The remaining 105 patients were analysed to determine the incidence and pattern of distant metastases. Diagnosis of distant metastases was made based on clinical signs and radiography, even though histologic confirmation was not made. Twenty-six patients developed distant metastases after definite irradiation of nasopharyx and neck, an incidence rate of $24.8\%$ . The common sites of distant metastases were, in descending order, bone, lung, liver, and brain. There was a strong correlation between Ho's N stage and distant metastases rate. But sex, age, histologic subtype (squamous cell and undifferentiated cell), AJC T and N stage, treatment modalities (radiotherapy alone and radiotherapy combined with chemotherapy) were not significant. Of those patients who developed distant metastases, $80.8\%$ were discovered within 2 years of their radical radiotherapy. The prognosis for nasopharyngeal carcinoma patients developing distant metastases was poor: median survival was nine months and $80\%$ of those patients died within two years of the initial diagnosis of distant metastasis.

• Molecules and Cells
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• v.37 no.9
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• pp.699-704
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• 2014

Themetastasis-associated gene 1 (MTA1) oncogene hasbeen suggested to be involved in the regulation of cancer progression. However, there is still no direct evidence that MTA1 regulates cisplatin (CDDP) resistance, as well as cancer stem cell properties. In this study, we found that MTA1 was enriched in CNE1/CDDP cells. Knock down of MTA1 in CNE1/CDDP cells reversed CSCs properties and CDDP resistance. However, ectopic expression of MTA1 in CNE1 cells induced CSCs phenotypes and CDDP insensitivity. Interestingly, ectopic overexpression of MTA1-induced CSCs properties and CDDP resistance were reversed in CNE1 cells after inhibition of PI3K/Akt by LY294002. In addition, MTA1 expression and Akt activity in CNE1/CDDP cells was much higher than that in CNE1 cells. These results suggested that MTA1 may play a critical role in promoting CDDP resistance in NPC cells by regulatingcancer stem cell properties via thePI3K/Akt signaling pathway. Our findings suggested that MTA1 may be a potential target for overcoming CDDP resistance in NPC therapy.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.1-8
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• 2005

Purpose : The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-PKcs, influence the response to radiotherapy (RT) and outcome of treatment of non-disseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Materials and Methods : Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The over-expression of Ku70 or DNA-PKcs groups Included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were peformed to determine the prognostic factors that influenced locoregional control of NPC. Results : The five-year locoregional control rate was significantly higher in the low Ku70 group (Ku(-)) (85%) than in the high Ku70 group (Ku(+)) (42%) (p=0.0042). However, there were no differences in the metastases-free survival rates between the two groups (Ku70 (+), 82%; Ku70 (-), 78%; p=0.8672). Univariate analysis indicated that the over-expression of Ku70 surpassed other well-known predictive clinocopathologic parameters as an Independent prognostic factor for locoregionai control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an over-expression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Conclusion : Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with non-disseminated NPC.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.183-188
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• 1990

Between January 197l and December 1987, 113 patients with nasopharyngeal cancer (NPC) were treated by radiation therapy with or without chemotherapy in the department of Radiation Oncology, Yonsei University Hospital. There were 19 patients under thirty years of age. The histology was undifferentiated carcinoma in $68\%$ of the younger patients as compared to $47\%$ of the older patients. Sex, stage, initial symptoms and treatment modalities differed little from those of older patients. In younger patients, the initial complete response rate was $79\%$ as compared to older patients with $54\%$, distant metastases were more common and the overall five year survival rate was not significantly different between the two age groups ($33.7\%$ for the young vs. $37.4\%$ for the old). The five year survival rates for stage III and IV were $60.0\%$ and $24.5\%$, respectively. Histologic subtype was not correlated with survival. The best survival was found only in patients who obtained a complete clearance of disease after radiation therapy.

• Radiation Oncology Journal
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• v.33 no.3
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• pp.188-197
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• 2015

Purpose: To investigate the patterns of care for patients with nasopharyngeal carcinoma (NPC) in South Korea. Materials and Methods: A multi-institutional retrospective study was performed (Korean Radiation Oncology Group [KROG] 11-06) on a total of 1,445 patients from 15 institutions. Results: Of the 1,445 patients, more than half were stages III (39.9%) and IV (35.8%). In addition to patterns of care, we also investigated trends over time with the periods 1988-1993, 1994-2002, and 2003-2011. The frequencies of magnetic resonance imaging and positron emission tomography-computed tomography were markedly increased in the third period compared to previous 2 periods. Concurrent chemoradiation (CCRT) was performed on 894 patients (61.9%), neoadjuvant chemotherapy on 468 patients (32.4%), and adjuvant chemotherapy on 366 patients (25.3%). Of stage II-IV patients, CCRT performed on 78.8% in 2003-2011 compared to 15.0% in 1988-1993. For patients treated with CCRT, cisplatin was the most commonly used agent in 81.3% of patients. Over the periods of time, commonly used radiotherapy (RT) techniques were changed from 2-dimensional RT (1988-1993, 92.5%) to 3-dimensional RT (2003-2011, 35.5%) or intensity-modulated RT (IMRT; 2003-2011, 56.5%). Median RT doses given to primary tumors, high-risk lymphatics, and low-risk lymphatics were 70.0 Gy, 58.1 Gy, and 48.0 Gy, respectively. Adoption of IMRT increased the dose per fraction and escalated total radiation dose. Conclusion: Assessment of the patterns of care for NPC patients in South Korea demonstrated that management for NPC including diagnostic imaging, treatment regimen, RT techniques and dose schedule, advanced in accordance with the international guidelines.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.9-16
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• 2005

Purpose : To prospectively evaluate the use of positron emission tomography with the glucose analog fluoro-deoxyglucose (FDG-PET) to deoxyglucose (FDG-PET) to predict disease-free survival (DFS) after concurrent chemo-radiotherapy (CCRT) in patients with non-disseminated nasopharyngeal carcinoma (NPC). Materials and Methods : We studied 41 patients with non-disseminated NPC scheduled to undergo platinum-based CCRT were eligible for this study. Patients were studied by FDG-PET prior to the CCRT. FDG uptake of tumors were measured with the maximal standardized uptake value (SUV). Results : Complete response rate was $100\%$. In ten patients who presented with any component of treatment failure, the median $SUV_{max}$ was 8.55 (range: $2.49\~14.81$) in any component of failure and the median $SUV_{max}$ was 5.48 (range: $2.31\~26.07$) In the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year DFS ($51\%\;{\nu}91\%$, p=0.0070) compared with patients having low uptake tumors. Conclusion : FDG uptake, as measured by the SUV, has potential value in predicting DFS in NPC treated by CCRT, High FDG uptake may be a useful parameter for Identifying patients requiring more aggressive treatment approaches.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.1-10
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• 2006

Puroose: To present preliminary results of intensity-modulated radiotherapy (IMRT) using the simultaneous modulated accelerated radiation therapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Materials and Methods: Twenty patients who underwent IMRT for non-metastatic NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. IMRT was delivered using the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume (GTV), 60 Gy (2 Gy/day) to the clinical target volume (CTV) and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received concurrent chemotherapy using cisplatin once per week. Results: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had RTOG grade 3 mucositis, whereas nine (45%) had grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no grade 3 or 4 chronic xerostomia. All patients showed complete response. Two patients had distant metastases and loco-regional recurrence, respectively. Conclusion: IMRT using the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and may also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

• The Journal of Korean Society for Radiation Therapy
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• v.22 no.2
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• pp.105-111
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• 2010

Purpose: There are various beam parameter in intensity modulated radiation therapy (IMRT). The aim of this study is to investigate how various dose rate affect the parotid in treatment plan of IMRT. Materials and Methods: The study was performed on 10 nasopharyngeal carcinoma patients who have undergone IMRT. CT images were scanned 3 mm of thickness in the same condition and the treatment plan was performed by Eclipse (Ver.7.1, Varian, Palo Alto, USA). The parameters for planning used 6 MV energy and 8 beams under the same dose volume constraint. The variation of dose rates were used 300, 400, 500 MU/min. The mean dose of both parotid was accessed from the calculated planning among the 10 patients. The mean dose of parotid was verificated by 2D diode array (Mapcheck from Sun Nuclear Corporation, Melbourne, Florida). Also, Total monitor unit (MU) and beam-on time was analysed. Results: According to the dose rate, the mean dose of parotid was increased by 0.8%, 2.0% each, when dose rate was changed from 300 MU/min to 400, 500 MU/min, moreover Total MU was increased by 5.4% and 10.6% each. There was also a dose upward trend in the dose measurement of parotid by 2D diode array. However, beam - on time difference of 1~2 minutes was no signigicant in the dose rate increases. Conclusion: From this study, when the dose rates increase, there was a signigicant increase of Total MU and the parotid dose accordingly, however the shortened treatment time was not significant. Hence, it is considered that there is a significant decrease of late side effect in parotid radiation therapy, if the precise dose rate in IMRT is used.