• Radiation Oncology Journal
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• v.26 no.1
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• pp.65-73
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• 2008

Purpose: Women with breast cancer diagnosed at an age of 40 years or younger have a greater prevalence of germline BRCA1 and BRCA2 mutations than the prevalence of women with breast cancer diagnosed at older ages. Several immunohistochemical characteristics have been identified in breast cancers from studies of Caucasian women with BRCA1/2 mutations having familial or early-onset breast cancers. The aim of this study is to determine whether early-onset breast cancer in BRCA1 or BRCA2 mutation carriers, who were not selected from a family history, could be distinguished by the use of immunohistochemical methods and could be distinguished from breast cancer in women of a similar age without a germline BRCA1 or BRCA2 mutation. We also analyzed the prognostic difference between BRCA1/2 related and BRCA1/2 non-related patients by the use of univariate and multivariate analysis. Materials and Methods: Breast cancer tissue specimens from Korean women with early-onset breast cancers were studied using a tumor tissue microarray. Immunohistochemical staining of estrogen receptor(ER), progesterone receptor(PR) and HER-2, as well as the histology and grade of these specimens, were compared. The prognostic impact of immunohistochemical and histological factors as well as the BRCA1/2 mutation status was investigated separately. Results: There were 14 cases and 16 deleterious BRCA1/2 mutations among 101 patients tested. A family history(4/14) and bilateral breast cancers(3/9) were high risk factors for BRCA1/2 mutations. BRCA1/2-associated cancers demonstrated more expression of ER-negative(19.4% versus 5.1%, p=0.038) and HER-2 negative than BRCA1/2 negative tumors, especially for tumors with BRCA1 tumors The BRCA1/2 mutation rate for patients with triple negative tumors(negative expression of ER, PR and HER-2) was 24.2%. Tumor size, nodal status, and HER-2 expression status were significantly associated with disease free survival, as determined by univariate and multivariate analysis, but the BRCA1/2 status was not a prognostic factor. Conclusion: Breast cancer that occurs in women with a germline BRCA1 or BRCA2 mutations have recognizable immunohistochemical features, which may be useful in identifying individuals that are more likely to carry germline mutations. Although the BRCA1/2 mutation status was not a prognostic factor in Korean women with early-onset breast cancer, more cases with a longer follow-up period are needed for further study.

• Journal of Chest Surgery
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• v.38 no.7 s.252
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• pp.483-488
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• 2005

Aortic valve-sparing procedures could reduce valve-related morbidity, but may increase operative risks; therefore, these procedures could not be performed routinely. We attempted to find out the early results while focusing on the operative risks associated with these procedures in our hospital. Material and Method: From May 1996 to July 2003, 26 patients underwent these procedures including 15 patients with Marfan syndrome and 1 patient with Behcet disease. There were 17 men and 9 women with mean age of $37.9\pm19.2$ years (range: 6 months-74 years). Ten patients had ascending aortic dissection, 18 patients had more than moderate degree of aortic valve insufficiency (AI). Two types of valve-sparing procedures were performed: valve reimplantation in 14 and root remodeling in 12 patients. Associated procedures were performed as follows: aortic valve plasty in 6, mitral valve plasty in 5, hemi-arch replacement in 4, total arch replacement in 2, coronary artery bypass surgery in 1 and Maze procedure in 1 patient(s). Result: In four patients, valve-sparing procedures were converted to Bentall procedures during operation. Including these patients, there was no operative deaths, 3 patients underwent re-operation due to bleeding, 1 patient had permanent pacemaker. The median duration of ICU stay was 45.5 hours, the median duration of hospital stay was 10.5 days. In 22 patients excluding 4 converted patients, intraoperative transesophageal echocardiogram (TEE) showed less than mild degree of AI in all except one who had not received intra-operative TEE in the beginning and showed moderate degree of AI at discharge. The mean duration of follow-up was $21.2\pm27.4$ months. All patients were alive except one who died during other departmental surgery. In 3 patients, more than moderate degree of AI was recurred, but there were no reoperation. Conclusion: Aortic valve-sparing procedures could be performed relatively safely in selected patients who had annuloaortic ectasia.

• Journal of Chest Surgery
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• v.39 no.2 s.259
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• pp.106-110
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• 2006

Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.

• Journal of Chest Surgery
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• v.37 no.1
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• pp.19-26
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• 2004

Background: The aims of this study are to verify the result of the surgical treatment of ALCAPA and to identify the postoperative changes of left ventricular dimensions and mitral regurgitation (MR), Material and Method: Fifteen patients operated on since 1985 were included in the study. The patients operated on before 1998 (n=9) showed heterogeneous properties with various surgical strategies and cardiopulmonary bypass techniques. However, six patients were operated on with the established surgical strategy since 1998; 1) Dual perfusion and dual cardioplegic solution delivery through ascending aorta and main pulmonary artery, 2) Coronary transfer by rolled-conduit made of pulmonary artery wall flap, and 3) Additional mitral valvular procedure was not peformed. Result: Median age of the study group was 6 months (1 month to 34 years). The operative methods were left subclavian artery to left coronary artery anastomosis in 1, simple ligation in 2, Takeuchi operation in 2, and coronary reimplantation in 10 patients. The mean follow up period was 5.5<5.8 years (2 months 14 years), There were one early death (6.7%) and one late death. Overall 5-year survival rate was 85.6$\pm$9.6%. The Z-value of left ventricular end-diastolic and end-systolic dimensions were 6.4$\pm$3.0 and 5.1 $\pm$3.6 preoperatively, and decreased to 1.7$\pm$ 1.9 and 0.8$\pm$ 1.6 in 3 months (p<0.05). Significant preoperative MR was identified in 6 patients (40%) and all the patients showed immediate improvement of MR within f month postoperatively. There were 3 cases of reoperation due to coronary anastomosis site stenosis and recurrence of MR. However, there was no mortality nor late reoperation in the patients operated on after 1998. Conclusion: The surgical treatment of ALCAPA showed favorable survival and early recovery of ventricular dimensions and mitral valvular function. Although long-term reintervention was required in some cases of earlier period, all the cases after 1998 showed excellent surgical outcome without long-term problem.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.316-322
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• 2002

Objective : A retrospective study was peformed to evaluate whether postoperative adjuvant radiotherapy can improve survival and decrease recurrence as compared with surgery alone in resected esophageal cancer. Materials and Methods : From Jan. 1985 to Dec. 1993, among 94 esophageal cancer Patients treated with surgery, fifty-one patients were included in this study. Transthoracic esophagectomy was peformed in 35 patients and transhiatal esophagectomy in 16. Postoperative adjuvant radiotherapy was peformed 4 weeks after surgery in 26 among 38 patients in stage II and III. A total dose of $30\~60\;Gy$ in 1.8 Gy daily fraction, median 54 Gy over 6 weeks, was delivered in the mediastinum+both supraclavicular lymph nodes or celiac lymph nodes according to the tumor location. Forty-seven patients$(92\%)$ had squamous histology. The median follow-up period was 38 months. Results : The overall 2-year and 5-year survival and median survival were $56.4\%,\;36.8\%$ and 45 months. Two-year and 5-year survival and median survival by stage were $92\%,\;60.3\%$ for stage I, $63\%,\;42\%$ and 51 months for stage II and $34\%,\;23\%$ and 19 months for stage III (p=0.04). For stage II and III patients, 5-year survival and median survival were $22.8\%$, 45 months for the surgery alone group and $37.8\%$, 22 months for the postoperative RT group (p=0.89). For stage III patients, 2-year survival and median survival were $0\%$, 11 months for the surgery alone group and $36.5\%$, 20 months for the postoperative RT group (p=0.14). Local and distant failure rates for stage II and III were $50\%,\;16\%$ for the surgery alone and $39\%,\;31\%$ for the postoperative RT group. For N1 patients, local failure rate was $71\%$ for the surgery alone group and $37\%$ for the postoperative RT group (p=0.19). Among 10 local failures in the postoperative RT group, in-field failures were 2, marginal failures 1, out-field 5 and anastomotic site failures 2. Conclusion : There were no statistically significant differences in either the overall survival or the patterns of failure between the surgery alone group and the postoperative RT group for resected stage II and III esophageal cancer. But this study showed a tendency of survival improvement and decrease in local failure when postoperative RT was peformed for stage III or N1 though statistically not significant. To decrease local failure, a more generous radiation field encompassing the supraclavicular, mediastinal, and celiac lymph nodes and anastomotic site in postoperative adjuvant treatment should be considered.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.323-327
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• 2002

Purpose : To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy alone and define the optimal radiotherapeutic regimen for these patients. Materials and Methods : A retrospective review was peformed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 59 Gy. No patients were lost to follow-up. Results : The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and $21\%$, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and $25\%$, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was $43\%$. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented $78\%$ of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm $(0\%\;vs\;36\%)$. Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70 $(25\%\;vs\;26\%,\;p>0.05)$. Conclusion : Radiation therapy 리one is an effective and safe treatment for early stage non-small ceil lung cancer patients who are medically inoperable or refuse surgery. Also we believe that a higher radiation dose to the primary site could improve the local control rate, and ultimately the overall survival rate.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.334-342
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• 2002

Purpose : The aim of this study was to determine if postoperative adjuvant chemotherapy (CT) alone and concurrent chemoradiation (CCRT), following radical surgery, improved the disease free survival (DFS) and overall survival (OS) in rectal cancer AJCC stage II and III patients. Materials and Methods : A total of 144 patients with AJCC stage II and III rectal cancer who had had radical surgery between 1989 and 1999 were included in the study. Of these patients, 72 had been treated with postoperative CT, and the other 72 with postoperative CCRT. The chemotherapy regimen consisted of oral UFT on a daily basis for $1\~12$ months (median 12 months) or 5-FU ($500\;mg/m^2$ for 5 days) intravenous (IV) chemotherapy with 4 week intervals for $1\~18$ cycles (median 6 cycles). Radiation of 4,500 cGy was delivered to the surgical bed and regional pelvic lymph nodes area, followed by $540\~1,440\;cGy$ (median 540 cGy) boost to the surgical bed. The follow-up period ranged from 20 to 150 months, with a median of 44 months. Results : The 5-year OS was $60.9\%\;and\;68.9\%$ (p=0.0915), and the 5-year DFS was $56.1\%\;and\;63.8\%$ (p=0.3510) for postoperative CT and postoperative CCRT, respectively. In the stage nm patients, the 5-year OS was $71.1\%\;and\;92.2\%$, and the 5-year DFS was $57.3\%\;and\;85.4\%$ for postoperative CT and CCRT, respectively. The OS was significantly improved (p=0.0379) but the DFS was not with postoperative CCRT compared to the postoperative CT (p=0.1482). In the stage III patients, the 5-year OS was $52.0\%\;and\;55.0\%$, and the 5-year DFS was $47.8\%\;and\;49.8\%$ for postoperative CT and postoperative CCRT. There were no statistically significant differences between postoperative CT and CCRT (p=0.4280 and p=0.7891) in OS and DFS. The locoregional relapses were $16.7\%\;and\;12.5\%$ for postoperative CT and CCRT, respectively. The distant relapses were $25.0\%\;and\;26.4\%$ for postoperative CT and CCRT, respectively. Conclusion : These results showed that postoperative CCRT compared with CT alone improved OS in stage II patients. Although there was no statistical significance, the addition of postoperative RT to CT reduced locoregional relapses compared to CT alone.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.125-134
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• 2003

Purpose: To report the early results of preopeartive concurrent radio-chemotherapy (CRCT) for treating rectal cancer. Materials and Methods: From June 1999 to April 2002, 40 rectal cancer patients who either had lesions with a questionable resectability or were candidates for sphincter-sacrificing surgery received preoperative CRCT. Thirty-seven patients completed the planned CRCT course. 45 Gy by 1.8 Gy daily fraction over 5 weeks was delivered to the whole pelvis in the prone position. The chemotherapy regimens were oral UFT plus oral leucovorin (LV) in 12 patients, intravenous bolus 5-FU plus LV in 10 patients, and intravenous 5-FU alone in 15 patients (bolus infusion in 10, continuous infusion in 5). Surgery was planned in 4$\~$6 weeks of the completion of the preoperative CRCT course, and surgery was attempted in 35 patients. Results: The compliance to the current preoperative CRCT protocol was excellent, where 92.5$\%$ (37/40) completed the planned treatment. Among 35 patients, in whom surgery was attempted after excluding two patients with new metastatic lesions in the liver and the lung, sphincter-preservation was achieved in 22 patients (62.9$\%$), while resection was abandoned during laparotomy in two patients (5.7$\%$). Gross complete resection was peformed in 30 patients, gross incomplete resection was peformed in one patient, and no detailed information on the extent of surgery was available in two patients. Based on the surgical and pathological findings, the down-staging rate was 45.5$\%$ (15/33), and the complete resection rate with the negative resection margin 78.8$\%$ (26/33). During the CRCT course, grade 3 $\~$4 neutropenia developed in four patients (10.8$\%$). Local recurrence after surgical resection developed in 12.1$\%$ (4/33), and distant metastases after the preoperative CRCT start developed in 21.6$\%$ (8/37). The overall 3-years survival rate was 87$\%$. Conclusion: Preoperative CRCT in locally advanced rectal cancer is well tolerated and can lead to high resection rate, down-staging rate, sphincter preservation rate, however, longer term follow-up will be necessary to confirm these results.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.200-207
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• 2004

Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.