• 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.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.247-256
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• 2008

Purpose: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of $1.8{\sim}2.0\;Gy$ at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of $43.2{\sim}54\;Gy$ (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range $11{\sim}107$ months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p<0.001). The 5-year locoregional control rates were 88.9% for stage 0, 93.8% for stage I, 91.1% for stage II, 68.2% for stage III, and one patient with pathologic stage IV was alive without local recurrence (p=0.01). The results of a multivariate analysis with age (${\leq}55$ vs. >55), clinical stage (I+II vs. III), radiotherapy to surgery interval (${\leq}6$ weeks vs. >6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity ($\geq$grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. Conclusion: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.

• Radiation Oncology Journal
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• v.14 no.2
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• pp.95-103
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• 1996

Purpose : A retrospective analysis for patients with oropharyngeal carcinoma who were treated with radiation was performed to assess the results of treatment and patterns of failure, and to identify the factors that might influence survival. materials and methods : From March 1985 through June 1993, 53 patients with oropharyngeal carcinoma were treated with either radiation therapy alone or combination of neoadjuvant chemotherapy and radiation therapy at the Department of Radiation Oncology, Kyungpook National University Hospital. Patients' ages ranged from 31 to 73 years with a median age of 54 years. There were 47 men and 6 women, Forty-two Patients ($79.2\%$) had squamous cell carcinoma, 10 patients ($18.9\%$) had undifferentiated carcinoma and 1 patient ($19\%$) had adenoid cystic carcinoma. There were 2 patients with stage I, 12 patients with stage II, 12 Patients with stage III and 27 patients with stage IV. According to the TNM classification, patients were distributed as follows: T1 7, T2 28, T3 10, T4 7, TX 1, and N0 17, Nl 13, N2 21, N3 2. The primary tumor sites were tonsillar region in 36 patients ($67.9\%$), base of the tongue in 12 patients ($22.6\%$), and soft palate in 5 patients ($9.4\%$). Twenty-five patients were treated with radiation therapy alone and twenty-eight Patients were treated with one to three courses of chemotherapy followed by radiation therapy. Chemotherapeutic regimens used were either CF (cisplatin and 5-fluorouracil) or CVB (cisplatin, vincristine and bleomycin). Radiation therapy was delivered 180-200 cGy daily, five times a week using 6 MV X-ray with or without 8-10 MeV electron beams A tumor dose ranged from 4500 cGy to 7740 cGy with a median dose of 7100 cGy. The follow-up time ranged from 4 months to 99 months with a median of 21 months. Results : Thirty-seven patients ($69.8\%$) achieved a CR (complete response) and PR (partial response) in 16 patients ($30.2\%$) after radiation therapy. The overall survival rates were $47\%$ at 2 years and $42\%$ at 3 years, respectively. The median survival time was 23 months. Overall stage (p=0.02) and response to radiation therapy (p=0.004) were significant prognostic factors for overall survival. The 2-year disease-free survival rate was $45.5\%$. T-stage (p=0.03), N-stage (p=0.04) and overall stage (P=0.04) were significant prognostic factors for disease-free survival. Age, sex, histology, primary site of the tumor, radiation dose, combination of chemotherapy were not significantly associated with disease-free survival. Among evaluable 32 Patients with CR to radiation therapy, 12 patients were considered to have failed Among these, 8 patients failed locoregionally and 4 Patients failed distantly. Conclusion : T-stage, N-stage and overall stage were significant prognostic factors for disease-free survival in the treatment of oropharyngeal cancer Since locoregional failure was the predominant pattern of relapse, potential methods to improve locoregional control with radiation therapy should be attempted. More controlled clinical, trials should be completed before acceptance of chemotherapy as a part of treatment of oropharyngeal carcinoma.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.21-26
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• 2001

Purpose : This study was peformed to evaluate the cosmetic outcome of conservative treatment for early breast cancer and to analyze the factors influencing cosmetic outcome. Materials and Methods : From February 1992 through January 1997, 120 patients with early breast cancer were treated with conservative surgery and postoperative radiotherapy. The types of conservative surgery were quadrantectomy and axillary node dissection for 108 patients $(90\%)$ and lumpectomy or excisional biopsy for 10 patients $(8.3\%)$. Forty six patients $(38\%)$ received adjuvant chemotherapy (CMF or CAF). Cosmetic result evaluation was carried out between 16 and 74 months (median, 33 months) after surgery. The cosmetic results were classified into four categories, i.e., excellent, good, fair, and poor. The appearances of the patients' breasts were also analyzed for symmetry using the differences in distances from the sternal notch to right and left nipples. A logistic regression analysis was performed to identify independent variables influencing the cosmetic outcome. Results : Cosmetic score was excellent or good in $76\%$ (91/120), fair in $19\%$ (23/120) and poor in $5\%$ (6/120) of the patients. Univariate analysis showed that tumor size (T1 versus T2) (p=0.04), axillary node status (N0 versus N1) (p=0.0002), extent of surgery (quadrantectomy versus lumpectomy or excisional biopsy) (p=0.02), axillary node irradiation (p=0.0005) and chemotherapy (p=0.0001) affected cosmetic score. Multivariate analysis revealed that extent of surgery (p=0.04) and chemotherapy (p=0.0002) were significant factors. For breast symmetry, univariate analysis confirmed exactly the same factors as above. Multivariate analysis revealed that tumor size (p=0.003) and lymph node status (p=0.007) affected breast symmetry. Conclusion : Conservative surgery and postoperative radiotherapy resulted in excellent or good cosmetic outcome in a large portion of the patients. Better cosmetic results were achieved generally in the group of patients with smaller tumor size, without axillary node metastasis and treated with less extensive surgery without chemotherapy.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.