• Radiation Oncology Journal
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• v.14 no.1
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• pp.17-23
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• 1996

Purpose : To evaluate the role of combination therapy of external radio-therapy and chemotherapy in the management of advanced esophageal cancer as a primary treatment compared with radiation therapy alone. Materials and Methods : A retrospective review of evaluable 55 esophageal cancer patients referred to the Department of Therapeutic Radiology, Paik Hospital for the external radiotherapy between Jul, 1983 and Dec. 1994 was undertaken. Combined therapy patients (A group) were 30 and radiation alone patients (B group) were 25. Median age was 60 years old in A group (ranges : 42-81) and 65 years old in B group (ranges : 50-81). The male patients were 53. The fifty patients had squamous cell carcinomas. Radiation doses of 2520-6480c0y were delivered over a period of 4-7weeks, using 4MV LINAC. Chemotherapy was administered in bolus injection before, after, or during the course of external radiotherapy. The local control rate and patterns of failure according to both treatment modalities and 1, 2 year survival rates according to prognostic factors (stage, tumor length, radiation dose etc.) were analysed. Resuts : Median follow up Period was 7 months (range : 2-73 months). Median survival was 7.5 months (20 days-29 months) in A group and 5 months (20 days-73 months) in B group. The 1, 2 YSRs were $26.7\%$, $8.9\%$ in A group, $12.7\%$, $4.3\%$ in B group (p>0.05), respectively. The 1, 2 YSRs according to stage(II/III), tumor length (5cm more or less). radiation dose (5000cGymore or less) of A and B group were analyzed and the differences of survival rates of both treatments were not statistically significant. But among group B, patients who received 5000cGy or more showed significant survival benefits (p<0.05). The treatment response rates of A and B group were $43.8\%$. $25.0\%$, respectively. Complete response rate of $25.0\%$ in A and $8.3\%$ in B were achieved. The local failure and distant metastsis were $52.4\%$. $23.8\%$ in A group, $64.3\%$, $14.3\%$ in 8 group, respectively. The combination therapy revealed more frequent leukopenia and nausea/vomiting than radiation alone group, but degree of side effects was only mild to moderate. Conclusion : The combined external radiotherapy and chemotherapy for advanced esophageal cancer appears to improve the response rate, local control rate and survival rate, but the improvement was not statistically significant. The side effects of combined modalities were mild to moderate without significant morbidity. Therefore it may be worthwhile to continue the present combined external radiotherapy and chemotherapy in the management of advanced esophageal cancer to confirm our result.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.149-158
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• 1993

This is a retrospective analysis of 135 patients with invasive carcinoma of the uterine cervix treated with curative radiotherapy from March 1983 through October 1989 at the Department of Therapeutic Radiology, Kang-Nam 51. Mary's Hospital. Among them, 78 patients received radiotherapy alone and 42 patients treated with neoadjuvant chemotherapy followed by radiotherapy and 15 patients were lost to follow up. All patients had follow up from 2 to 106 months (median; 62 months). Age of the patients ranged from 32 to 79 years at presentation (median; 59 years). According to FIGO classification, there were 20 ($16.7{\%}$) in stage IB, 19 ($15.8{\%}$) in stage IIA,49 ($40.8{\%}$) in stage IIB, 5 ($4.2{\%}$) in stage IIIA, 13 ($10.8{\%}$,) in stage IIIB,14 ($11.7{\%}$) in stage IVA. The pathological classification showed 96 ($80.0{\%}$) squamous cell carcinomas, 5 ($4.2{\%}$) adenocarcinomas and 19 ($15.8{\%}$) proven by cytology. The overall 5-year survival rates was $50.8{\%}$, and the 5-year survival rates by stage IB, IIA, IIB, IIIA, IIIB, IVA was $47.7{\%},\;70.2{\%},\;64.1{\%},\;40.0{\%},\;23.1{\%},\;14.3{\%}$, respectively. The 5-year survival rates was noted $51.2{\%}$ of radiotherapy alone and $50.4{\%}$of neoadjuvant chemotherapy followed by radiotherapy. The overall failure rate was $18.3{\%}$(22/120) including $11.7{\%}$ (14/120) locoregional failure, $5.8{\%}$ (7/120) distant metastasis and $0.8{\%}$(1/120) locoregional failure with distant metastasis. Treatment failure rates by the stages were $15{\%}$ (3/20) in stage IB. $10.5{\%}$ (2/19) in stage IIA, $10.2{\%}$, (5/49) in stage IIB, $20{\%}$ (1/5) in stage IIIA, $61.5{\%}$(8/13) in stage IIB, and $28.6{\%}$ (4/14) in stage IVA. The overall complication rate was $34.2{\%}$(41/120) including wet desquamation $7.5{\%}$, (9/120), diarrhea $6.7{\%}(8/120), radiation proctitis $5.8{\%}$(7/120) in decreasing order. A multivariate analysis of factors influencing the survival showed patient age (p < 0.0291), FIGO stage (p<0.0001), Karnofsky performance status (p<0.0043), initial hemoglobin level (p<0.0001), and intracavitary radiation (p<0.0004), but, no significancy in histology (p<0.29) and treatment method (p < 0.87).

• Radiation Oncology Journal
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• v.14 no.1
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• pp.41-52
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• 1996

Purpose : This paper reports a dosimetric study of 88 patients treated with a combination of external radiotherapy and high dose rate ICR for FIGO stage IIB carcinoma of the cervix. The purpose is to investigate the correlation between the radiation doses to the rectum, external radiation dose to the whole pelvis, ICR reference volume, TDF BED and the incidence of late rectal complications, retrospectively. Materials and Methods : From November 1989 through December 1992, 88 patients with stage IIB cervical carcinoma received radical radiotherapy at Department of Radiation Oncology in Yonsei University Hospital. Radiotherapy consisted of 44-54 Gy(median 49 Gy) external beam irradiation plus high dose rate intracavitary brachytherapy with 5 Gy per fraction twice a week to a total dose of 30 Gy on point A. The maximum dose to the rectum by contrast(r, R) and reference rectal dose by ICRU 38(dr, DR) were calculated. The ICR reference volume was calculated by Gamma Dot 3.11 HDR planning system, retrospectively The time-dose factor(TDF) and the biologically effective dose (BED) were calculated. Results : Twenty seven($30.7\%$) of the 88 patients developed late rectal complications:12 patients($13.6\%$) for grade 1, 12 patients($13.6\%$) for grade 2 and 3 patients($3.4\%$) for grade 3. We found a significant correlation between the external whole pelvis irradiation dose and grade 2, 3 rectal complication. The mean dose to the whole pelvis for the group of patients with grade 2, 3 complication was Higher, $4093.3\pm453.1$ cGy, than that for the patients without complication, $3873.8\pm415.6$ (0.05$7163.0\pm838.5$ cGy, than that for the Patients without rectal complication, $0772.7\pm884.0$ (p<0.05). There was no correlation of the rate of grade 2, 3 rectal complication with the iCR rectal doses(r, dr), ICR reference volume, TDF and BED. Conclusion : This investigation has revealed a significant correlation between the dose calculated at the rectal dose by ICRU 38(DR) or the most anterior rectal dose by contrast(R) dose to the whole pelvis and the incidence of grade 2, 3 late rectal complications in patients with stage IIB cervical cancer undergoing external beam radiotherapy and HOR ICR. Thus these rectal reference points doses and whole pelvis dose appear to be useful Prognostic indicators of late rectal complication in high dose rate ICR treatment in cervical carcinoma.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.1-8
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• 1996

Purpose: We tried to evaluate the role of conventional radiotherapy alone or with neoadjuvant chemotherapy in oropharyngeal cancer in terms of survival rates and to identify prognostic factors affecting survival by retrospective analysis. Materials and Methods: Forty seven patients of oropharyngeal cancer were treated by conventional radiotherapy in our hospital from Nov. 1985 to APr. 1993. Of these, twenty six patients were treated by conventional radio-therapy alone, and 21 patients with neoadjuvant chemotherapy of mostly two or more cycles of cisplatin and pepleomycin. The Patient characteristics of radiotherapy alone group and neoadjuvant chemotherapy group were not different generally. Radiotherapy was performed by 6MV-LINAC and the total radiation doses of Primary tumors were 54.0-79.2 Gy and cervical lymph nodes were 55.8-90.0 Gy with a fraction size of 1.8 or 2.0 Gy per day. The range of follow-up periods was 3-102 months and median was 20 months. The range of a9e was 33-79 years old and median was 58 years old. Results : Overall 3-year actuarial survival rate (3YSR) of all patients was $39\%$. The 3YSRS of stage I (n=5), II (n=11), III (n=12) and IV (n=19) were 60, 55, 33 and $32\%$, respectively The 3YSRS of Tl+2, T3+4 and No, N+ were 55, $18\%$ (p=0.005) and 43, $36\%$ (p>0.1), respectively. There was no difference in 3YSRS between radiotherapy alone group and neoadjuvant chemotherapy group (38 vs $43\%$, p>0.1). According to the original site of primary tumor, the 3YSRS of tonsil (n=32), base of tongue (n=8), soft palate or uvula (n=6) and pharyngeal wall (n=1) were 36 38, 67 and $0\%$, respectively The Patients of soft palate or uvular cancer had longer survival than other primaries but the difference was not significant statistically (p>0.1). Of 32 patients of tonsillar cancer, 22 Patients who had primary extension to adjacent tissue showed inferior survival rate to the ones who had not Primary extension, but the difference was marginally significant statistically (24 vs $60\%$, p=0.08). On Cox multivariate analysis in entire patients with variables of age, T stage, N stage, total duration of radiotherapy, the site of primary tumor and the use of neoadjuvant chemotherapy, only T stage was a significant Prognostic factor affecting 3YSR. Conclusion : The difference of 3YASRS of conventional radiotherapy alone group and neoadjuvant chemotherapy group was not significant statistically. These treatments could be effective in oropharyngeal cancer of early stage, especially such as soft palate, uvular or tonsillar cancer which did not extend to adjacent tissue. But in order to improve the survival of patients of most advanced oropharyngeal cancer, other altered fractionated radiotherapy such as hyperfractionation rather than conventional fractionation or multi-modal approach combining radiotherapy and accessible surgery or concurrent chemotherapy might be beneficial.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.27-31
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• 2000

Purpose : The aim of this study was to investigate treatment results, toxicity and efficacy of hypefractionated radiation therapy combined with paclitaxel for paraaortic node recurrence in cervix cancer. Materials and Methods: Between September 1997 to March 1999, 12 patients with paraaortic node recurrence in cervix cancer who previously received radical or postoperative radiotherapy were treated with hypefractionated radiation therapy combined with paclitaxel. Of these, 2 patients who irradiated less than 30 Gy were excluded, 10 patients were eligible for this study. Median age was 51 years. Initial FIGO stage was 1 stage IBI, 2 stage IIA, 7 stage IIB. For initial treatment, 7 patients received radical radiotherapy and 3 received postoperative radiotherapy. The paraaortic field encompassed the gross recurrent disease with superior margin at T12, and inferior margin was between L5 and S1 with gap for previously pelvic radiation field. The radiation field was initially anterior and posterior opposed field followed by both lateral field. The daily dose was 1.2 Gy, twice daily fractions, and total radiotherapy dose was between 50.4 and 60 Gy(median, 58.8 Gy). Concurrent chemotherapy was done with paclitaxel as a radiosensitizer. Dose range was from 20 mg/m$^{3}$ to 30 mg/m$^{3}$ (median, 25 mg/m$^{3}$), and cycle of chemotherapy was from 3 to 6 (median, 4.5 cycle). Follow-up period ranged from 3 to 21 months. Results : Interval between initial diagnosis and paraaortic node recurrence was range from 2 to 63 months (median, 8 months). The 1 year overall survival rate and median survival were 75$\%$ and 9.5 months, respectively. The 1 year disease free survival rate and median disease free survival were 30$\%$ and 7 months, respectively. At 1 month after treatment, 4 (40$\%$) achieved a complete response and 6 (60$\%$) experienced a partial response and all patients showed response above the partial response. There was distant metastasis in 6 patients and pelvic node recurrence In 2 patients after paraaortic node irradiation. There was 2 patients with grade 3 to 4 leukopenla and 8 patients with grade 1 to 2 nausea/ vomiting which was usually tolerable with antlemetic drug. There was no chronic complication in abdomen and pelvis during follow up period. Conclusion : hypefractionated radiation therapy combined with paclitaxel chemotherapy diosensitizer showed high response rate and few complication rate in paraaortic node recurrence in cervix cancer Therefore, present results suggest that hypefractionated radiation therapy combined with paclitaxel chemotherapy can be used as optimal treatment modality in this patients.

• Radiation Oncology Journal
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• v.18 no.2
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• pp.133-137
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• 2000

Purpose :To investigate whether combined beta-carotene with X-Irradiation has more enhanced radition response than X-irradiation or not, we peformed a experiment about in vitro cytotoxlcity of beta-carotene and/or X-irradiation in the fibrosarcoma cells, tumor growth delay of combined beta-caroten with/or X-irradiation in the mouse fibrosarcoma. Materials and Methods : 2$\%$ emulsion of beta-carotene was serially diluted and used. X-Irradiation was given by 6 MeV linear accelerator. The cytotoxicity of beta-carotene in vitro was evaluated from clonogenic assay. To compare the cytotoxiclty between combined beta-carotene with X-irradiation and X-irradiation group, 2 mg/ml of beta-carotene was contacted to fibrosarcoma (FSall) cells for 1 hour before X-irradiation. For the tumor growth delay, single 20 Gy was given to FSall tumor hearing C3H/N mice whic was classified as beta-crotene with X-irradiation group (n=5) and X-irradiation alone group (n=5). 0.2 ml of 20 mg/kg of beta-carotene were i.p. injected to mice 30 minute before X-irradiation in the beta-crotene with X-irradiation group. The tumor growth delay defined as the time which reach to 1,000 mm$^{3}$ of tumor volume. Results : (1) Cytotoxicity in vitro: 1) survival fraction at beta-carotene concentration of 0.002,0.02,0.2 and 2 mg/ml were 0.69$\pm$0.07, 0.59$\pm$0.08, 0.08$\pm$0.008 and 0.02$\pm$0.006, respectively. 2) each survival fraction at 2, 4, 6 and 8 Gy in the 2 mg/ml of beta-carotene + X-irradiation group were 0.13$\pm$0.05, 0.03$\pm$0.005, 0.01 $\pm$0.002 and 0.009$\pm$0.0008, respectively. But each survival fraction at same irradiation dose in the X-irradiation group were 0.66$\pm$0.05, 0.40$\pm$0.04, 0.11$\pm$0.01 and 0.03$\pm$0.006, respectively(p<0.05). (2) The time which reach to 1,000 mm$^{3}$ of tumor volume of beta-carotene + X-irradiation group and X-irradiation alone group were 18, 19 days, respectively(p>0.05) Conclusion : The contact of beta-caroten to Fsall cells showed mild cytotoxicity which 띤as increased according to concentration. The cytotoxicity of combined beta-carotene with X-irradiation more increased than that of X-irradiation, additionally, And there was significant difference of cytotoxicity between two groups. But there were no significant difference of the growth delay of fibrosarcoma between two groups.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.210-217
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• 2009

Purpose: To assess the influence of cyclooxygenase-2 (COX-2) expression on the survival of patients with a combination of rectal cancer and lymph node metastasis. Materials and Methods: The study included rectal cancer patients treated by radical surgery and postoperative radiotherapy at the Dong-A university hospital from 1998 to 2004. A retrospective analysis was performed on a subset of patients that also had lymph node metastasis. After excluding eight of 86 patients, due to missing tissue samples in three, malignant melanoma in one, treatment of gastric cancer around one year before diagnosis in one, detection of lung cancer after one year of diagnosis in one, liver metastasis in one, and refusal of radiotherapy after 720 cGy in one, 78 patients were analyzed. The immunohistochemistry for COX-2 was conducted with an autostainer (BenchMark; Ventana, Tucson, AZ, USA). An image analyzer (TissueMine; Bioimagene, Cupertino, CA, USA) was used for analysis after scanning (ScanScope; Aperio, Vista, CA, USA). A survival analysis was performed using the Kaplan Meier method and significance was evaluated using the log rank test. Results: COX-2 was stained positively in 62 patients (79.5%) and negatively in 16 (20.5%). A total of 6 (7.7%), 15 (19.2%), and 41 (52.6%) patients were of grades 1, 2, and 3, respectively for COX-2 expression. No correlation was found between being positive of COX-2 patient characteristics, which include age (<60-year old vs. $\geq$60), sex, operation methods (abdominoperineal resection vs. lower anterior resection), degrees of differentiation, tumor size (<5 cm vs. $\geq$5 cm), T stages, N stages, and stages (IIIa, IIIb, IIIc). The 5-year overall and 5-year disease free survival rates for the entire patient population were 57.0% and 51.6%, respectively. The 5-year overall survival rates for the COX-2 positive and negative patients were 53.0% and 72.9%, respectively (p=0.146). Further, the 5-year disease free survival rates for the COX-2 positive and negative patients were 46.3% and 72.7%, respectively (p=0.118). The 5-year overall survival rates were significantly different (p<0.05) for the degree of differentiation, N stage, and stage, whereas the 5-year disease free survival rates were significant for N stage and stage. Conclusion: Being positive for and the degree of COX-2 expression did not have a significant influence on the survival of rectal cancer patients with lymph node metastasis. However, N stage and stage did significantly influence the rateof survival. Further analysis of a greater sample size is necessary for the verification of the effect of COX-2 expression on the survival of rectal cancer patients with lymph node involvement.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.201-209
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• 2009

Purpose: To investigate the care patterns for radiation therapy and to determine inter-hospital differences for patients with laryngeal carcinoma in Korea. Materials and Methods: A total of 237 cases of laryngeal carcinoma (glottis, 144; supraglottis, 93) assembled from 23 hospitals, who underwent irradiation in the year of 1998 and 1999, were retrospectively analyzed to investigate inter-hospital differences with respect to radiotherapy treatment. We grouped the 23 hospitals based on the number of new patients annually irradiated in 1998; and designated them as group A (${\geq}$900 patients), group B (${\geq}$400 patients and <900 patients), and group C (<400 patients). Results: The median age of the 237 patients was 62 years (range, 25 to 88 years), of which 216 were male and 21 were female. The clinical stages were distributed as follows: for glottis cancer, I; 61.8%, II; 21.5%, III; 4.2%, IVa; 11.1%, IVb; 1.4%, and in supraglottic cancer, I; 4.3%, II; 19.4%, III; 28.0%, IVa; 43.0%, IVb; 5.4%, respectively. Some differences were observed among the 3 groups with respect to the dose calculation method, radiation energy, field arrangement, and use of an immobilization device. No significant difference among 3 hospital groups was observed with respect to treatment modality, irradiation volume, and median total dose delivered to the primary site. Conclusion: This study revealed that radiotherapy process and patterns of care are relatively uniform in laryngeal cancer patients in Korean hospitals, and we hope this nationwide data can be used as a basis for the standardization of radiotherapy for the treatment of laryngeal cancer.

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

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

• Radiation Oncology Journal
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• v.25 no.4
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• pp.242-248
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• 2007

Purpose: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. Materials and Methods: Twenty-four ICR mice were divided into three groups-the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days $1{\sim}5$. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. Results: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of. the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. Conclusion: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.