• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.281-287
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• 2005

Purpose: This study was conducted to evaluate the effectiveness and the role of post-operative adjuvant chemoradiation therapy in a stage-II (UICC, 1997) primary gastric cancer. Materials and Methods: From September 1994 to December 2004, 954 stage-II gastric-cancer patients were seen, and all of them underwent a curative resection with extensive (D2) lymph-node dissection. The chemotherapy consisted of fluorouracil $(400mg/m^2)$ plus leucovorin $(20mg/m^2)$ for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks with fluorourcil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two five-day cycles of chemotherapy were given four weeks after the completion of radiotherapy. The Kaplan-Meier method was used to estimate the survival rates. To assess the importance of potential prognostic factors, we performed univariate and multivariate analyses using a log-rank test and Cox's proportional hazards regression model. A P value <0.05 was considered significant. Results: Univariate analysis revealed that age, tumor size, gross type, surgical method, and postoperative adjuvant therapy had statistical significance. Among these factors, age, surgical method, tumor size, surgical method, and postoperative adjuvant therapy were found to be independent prognostic factors by using a multivariate analysis. The postoperative adjuvant chemotherapy group and the chemoradiation therapy group had survival benefit compared to the surgery-only group. However the chemoradiation therapy group had no significant survival benefit compared to the chemotherapy group. Conclusion: The postoperative adjuvant therapy in stage-II gastric-cancer patients had significant benefit. Therefore, postoperative adjuvant chemoradiation therapy has an acceptable effect. A large-scale, randomized study is needed to evaluate the effectiveness and the role of postoperative radiation therapy.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.56-64
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• 2008

Purpose: Cathepsin D(CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. Materials and Methods: Eighty-nine patients with locally advanced rectal cancer(cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. Results: Positive CD expression was found in 57(64%) of the tumors and 32(35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression(p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival(OS) and disease-free survival(DFS) rates were not different between tumor CD-negative and positive patient biopsy samples(69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients(p=0.013). Conclusion: Overexpression of p53 in rectal biopy tissue was not associated with prognostic significance. In the pretreatment biopsy specimens, an exclusive increase in CD expression in stromal cells without tumor expression was related to poor overall survival in patients with locally advanced rectal cancer treated with preoperative chemoradiation.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.339-348
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• 1997

Purpose : To evaluate the role of postoperative radiation therapy after curative resection of sigmoid colon cancer Materials and Methods : From 1988 to 1993, a total of 93 Patients with curative resectable sigmoid colon cancer of modified Astler-Coiler (MAC) stage B2, B3, C2, C3 was divided into two groups on the basis of those who received radiation treatment and those who did not. Forty-three patients who treated by surgery alone were classified as postop RT (-) group The remaining 50 patients who underwent postoperative radiotherapy were classified as postop RT (+) group. In all patients in Postop RT (+) group. radiation therapy was delivered using 4 or 10 MV linear accelerators to treat the tumor bed with approximately 5cm margin to a total dose 50.4-61Gy(median 54Gy) in 1.8Gy per fraction. Thirty-two patients were treated. with 5-Fluorouracil based adjuvant chemotherapy at least 3 cycles. but these was no significant difference between two groups. Treatment failure Pattern, 5-year local failure-free survival rates (LFFS), and 5-year disease-free survival rates (DFS) were compared between two groups. Result : Five year LFFS and DFS were $85.1\%,\;68.5\%$, respectively, In Postop RT (-) group, LFFS was $76.2\%$ compared with $91.7\%$ in Postop RT (+) group. Improved LFFS and DFS were seen for patients with stage C3 sigmoid colon carcinoma with postoperative radiation therapy compared with postop RT (-) group (P=0.01, p=0.06 respectively), in stage B3, LFFS washigher in postop RT (+) group than that in Postop RT (-) group. although itwas not significant. Especially, local control was higher in stage 74 inpostop RT (+) group than that in postop RT (-) group, Conclusion : This studv showed significantly improved LFFS and DFS in MAC Stage C3 and improved tendency of LFFS and DFS in MAC Stage B3 disease. Large scale prospective study is required to verify the role of adjuvant radiation therapy in resectable sigmoid colon cancer.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.157-163
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• 2006

[ $\underline{Purpose}$ ]: To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. $\underline{Materials\;and\;Methods}$: A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil ($500\;mg/m^2/day$) with leucovorin ($20\;mg/m^2/day$), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for $6{\sim}12$ months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by $5.4{\sim}9\;Gy$ boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. $\underline{Results}$: Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients (p=0.012, p=0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively (p=0.006). Multivariate analysis showed that N stage (p=0.012) was significant prognostic factor for OS and that N stage (p=0.001) and location of tumor (p=0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. $\underline{Conclusion}$: Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.213-221
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• 2008

Purpose: The objective of this retrospective study was to identify predictive factors for the complete pathologic response and tumor downstaging after preoperative concurrent chemoradiotherapy for locally advanced rectal cancer. Materials and Methods: Between the years 2000 and 2008, 39 patients with newly diagnosed rectal cancer without prior evidence of distant metastasis received preoperative concurrent chemoradiotherapy followed by surgery. The median radiation dose was 50.4 Gy (range, $45{\sim}59.4\;Gy$)). Thirty-eight patients received concurrent infusional 5-fluorouracil and leucovorin, while one patient received oral capecitabine twice daily during radiotherapy. Results: A complete pathologic response (CR) was demonstrated in 12 of 39 patients (31%), while T-downstaging was observed in 24 of 39 patients (63%). N-downstaging was observed in 18 of 28 patients (64%), with a positive node in the CT scan or ultrasound. Two patients with clinical negative nodes were observed in surgical specimens. The results from a univariate analysis indicated that the tumor circumferential extent was less than 50% (p=0.031). Moreover, the length of the tumor was less than 5 cm (p=0.004), while the post-treatment carcinoembryonic antigen (CEA) levels were less than or equal to 3.0 ng/mL (p=0.015) and were significantly associated with high pathologic CR rates. The univariate analysis also indicated that the adenocarcinoma (p=0.045) and radiation dose greater than or equal to 50 Gy (p=0.021) were significantly associated with high T-downstaging, while a radiotherapy duration of less than or equal to 42 days (p=0.018) was significantly associated with N-downstaging. The results from the multivariate analysis indicated that the lesser circumferential extent of the tumor (hazard ratio [HR] 0.150; p=0.028) and shorter tumor length (HR, 0.084; p=0.005) independently predicted a higher pathologic CR. The multivariate analysis also indicated that a higher radiation dose was significantly associated with higher T-downstaging (HR, 0.115; p=0.025), while the shorter duration of radiotherapy was significantly associated with higher N-downstaging (HR, 0.028; p=0.010). Conclusion: The circumferential extent of the tumor and its length was a predictor for the pathologic CR, while radiation dose and duration of radiotherapy were predictors for tumor downstaging. Hence, these factors may be used to predict outcomes for patients and to develop further treatment guidelines for high-risk patients.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.259-264
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• 1998

Purpose : This study was to evaluate the effectiveness of preoperative radiotherapy in maxillary sinus cancer. Materials and Methods : A retrospective analysis was done for 42 patients with maxillary sinus cancer who were treated with radiation with or without surgery from April 1986 to September 1996. There were 27 male and 15 female patients. Patients' age ranged from 24 to 75 years (median 56 years). Stage distribution showed 2 in T2, 19 in T3, and 21 in T4 lesions The histologic type was squamous cell carcinoma in 38, undifferentiated carcinoma in 1, transitional cell carcinoma in 1, and adenoid cystic carcinoma in 2 patients. All patients were treated with radiation initially with a dosage range of 50.4-70.2 Gy (median 70.2 Gy) before further evaluation of remnant disease. Eleven patients were given induction chemotherapy (2cycles of 5-fluorouracil and cisplatin) concurrently with radiotherapy. Six to eight weeks after radiotherapy with or without chemotherapy computerized tomography (CT) of paranasal sinus was taken to evaluate remnant disease. If the CT finding showed remnant disease, a Caldwell-Luc procedure was done to get the specimen of suspicious lesions. A radical maxillectomy was done if the specimen was proven to contain malignancy. In contrast periodic follow-up examination was done without any radical surgery if the tissue showed only granulation tissue. Follow-up period ranged from 3 to 92 months with a median 16 months. Results : Nine (21.4$\%$) patients showed complete response (CR) and 33 patients (78.6$\%$) showed persistent disease (PER) to initial radiotherapy. Among the 9 CR patients, 7 patients had no evidence of disease (NED), 1 patient had local failure, and 1 patient had regional failure. Among 33 PER patients, salvage total maxillectomy was done in 10 patients, and the surgery was not feasible or refused in 23 patients. Following the salvage radical surgery, 2 patients were NED and 8 patients were PER status. Overall and disease- free survival rate at 5 years was 23.1$\%$ and 16.7$\%$, respectively. The only factors associated with the overall survival rate was the response to radiotherapy (P<0.01). Conclusion : The only factors associated with the overall survival rate was the response to radiotherapy. We could omit a radical mutilating surgery by preoperative irradiation in 7 of 42 patients (21.4$\%$) so as to preserve their facial integrity.

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.169-175
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• 2008

Purpose: The main target of 5-fluorouracil (5-FU) is thymidylate synthase (TS). A high TS expression has been identified as promoting resistance to 5-FU. For colorectal cancers, the response to 5-FU based adjuvant chemotherapy is different according to the microsatellite instability (MSI) status. The reports on the relationship between MSI and the TS expression in colorectal cancer have been inconsistent. No data is available for gastric cancer regarding the relationship between MSI and the TS expression. Therefore, we studied the relationship between MSI and the TS expression in gastric cancer. Materials and Methods: Ninety-nine consecutive patients who underwent radical gastrectomy for gastric cancer from January 2004 to May 2006 at Bundang CHA hospital were studied. MSI was assessed for five markers (BAT25, BAT26, D2S123, D5S346, and D17S250) by PCR and with using an ABI prism 3100 Genetic analyzer. The TS expression was analyzed by immunohistochemistry with using mouse anti-thymidylate synthase monoclonal antibody to the TS 106 clone. Results: Out of the ninety-nine patients, MSS/MSI-L was detected in 92 (92.1%) cases and 7 cases (7.1%) were MSI-H. A negative TS expression was found in 46 (46.5%) cases, a low TS expression was found in 33 (33.3%) and a high TS expression was found in 20 (20.2%). Out of 92 MSS/MSI-L patients, the number of patients with negative, low and high TS expressions were 46 (50%), 30 (32.6%) and 16 (17.4%), respectively. Out of the 7 MSI-H patients, the number of patients with negative, low and high TS expressions were 0 (0%), 3 (42.9%) and 4 (57.1%), respectively. The relationship between MSI-H and a high TS expression was statistically significant. Conclusion: Gastric cancer with MSI-H showed higher levels of a TS expression compared to the gastric cancer with MSS/MSI-L.

• 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.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.11-19
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• 2011

Purpose: To evaluate the pathological and clinical effects of preoperative chemoradiation (CCRT) in cases of locally advanced rectal cancer and to determine the predictive factors for tumor downstaging. Materials and Methods: From March 2004 to August 2008, 33 patients with locally advanced rectal cancer were treated with preoperative CCRT. Twenty-eight patients (84.8%) were treated using a concomitant boost technique while five (15.2%) patients were treated using a cone down boost technique. All patients received 50.4 Gy of irradiation and concurrent chemotherapy with 5-fluorouracil. The median follow-up duration was 24.2 months (range, 9.8 to 64.7 months). Results: Thirty-one (93.9%) patients underwent surgery. Twenty-four patients (72.7%) underwent anal sphincter-preserving surgery. The 3-year disease free survival (DFS) and overall survival rates were 63.4% and 78.8%, respectively. Post-operative factors were more important for DFS. Pathologic N stage, margin status, and pathologic differentiation were significant prognostic factors (p=0.001, 0.029, 0.030). Tumor size and lymphovascular invasion were also associated with marginal significance (p=0.081, 0.073). However, only pre-treatment T stage was a significant pre-operative factor (p=0.018). The complete pathological response rate was 9.1 %. T-downstaging was observed in ten (30.3%) patients, whereas N-downstaging was found in 24 (72.7%) patients. Pre-treatment T stage and the interval between CCRT and operation were the predictive factors for downstaging in a univariate analysis (p=0.029, 0.027). Pre-treatment carcinoembryogenic antigen was also associated with marginal significance (p=0.068). Conclusion: The survival of rectal cancer patients can be better determined based on post-operative findings. Therefore, pre-operative CCRT for downstaging of the tumor seems to be important. Pre-treatment T stage and the interval between CCRT and operation can be used to predict downstaging.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.20-27
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• 2011

Purpose: This study was designed to evaluate the results of local control, survival rate, prognostic factors, and failure pattern in locally advanced esophageal cancer. Materials and Methods: We retrospectively studied 50 patients with locally advanced esophageal cancer treated with concurrent chemoradiotherapy at Keimyung University Dongsan Medical Center from June of 1999 to August of 2008. Seven patients with inappropriate data were excluded, and 43 patients were analyzed. There were 39 males and four female patients ranging in age from 43 to 78 years (median, 63 years). There were seven patients with stage IIA and 36 with stage III. Irradiation from 46 Gy to 63 Gy (median, 54 Gy) was carried out 5 days per week, 1.8 Gy once a day. There were eight patients with neo-adjuvant chemotherapy, and we mostly used 5-fluorouracil, cisplatin with 3 cycles for concurrent chemotherapy. The range of follow up periods was from 2 to 82 months (median, 15.5). Results: There were nine patients that exhibited a cornplete response, 23 that exhibited a partial response, 9 that exhibited no response, and 2 that exhibited disease progression. The median survival time was 15 months. Two-year and 5-year survival rates were 36.5% and 17.3%, respectively. Two-year and 5-year disease-free survival rates were 32.4% and 16%, respectively. Treatment failure occurred in 22 patients (51.2%). Patterns of failure were categorized as local failure in 18 patients and distant metastasis in four patients. In a univariate analysis for prognostic factors related to overall survival and disease-free survival, the hemoglobin levels during chemoradiotherapy (${\geq}$ 12 vs. <12, p=0.02(p=0.1) and the response to the treatments (CR/PR vs. NR/PD, p=0.002/p< 0.0001) were statistically significant. In a multivariate analysis, only response to the treatments was revealed to be statistically significant. There was no statistical significance associated with patient age, gender, disease stage, T-stage, smoking history, tumor location, or neo-adjuvant chemotherapy. Conclusion: Our survival rate was similar to those of other institutions. Local recurrence was the main reason for failure. It is suggested that further prospective studies should be performed to improve local control.