• 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.18 no.1
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• pp.17-25
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• 2000

Purpose : To evaluate the side effects, pattern of failure, and survival rate according to the sequence of postoperative adjuvant radiotherapy and chemotherapy, patients with stages II and III rectal cancer who had undergone curative resection were randomized to 'early radiotherapy group (arm I)' or' late radiotherapy group (arm II)', then we intend to determine the most effective sequence of the radiotherapy and chemotherapy. Materials and Methods . From January 1996 to March 1999, 313 patients with curatively resected stages II and III rectal cancer have been randomized to' early' or' late' radiation therapy group and received combined chemotherapy (5-FU 375 mg/m$^{2}$/day, ieucovorin 20 mg/m$^{2}$, IV bolus daily Dl-5, 8 cycles) and radiation therapy (whole pelvis with 45 Gy/25 fractions/s weeks). Arm I received radiation therapy from day 1 with first cycle of chemotherapy and arm II received radiation therapy from day 57 with third cycle of chemotherapy after completion of first two cycles. Preliminary analysis was peformed with 228 patients registered up to Jun 1998. Two out of the 228 patients were excluded because of double primary cancer. Median follow-up period was 23 months. Results :Local recurrence occurred in 11 patients (9.7$\%$) for arm I and 9 patients (8$\%$) for arm 11. There was no significant difference between both groups ( p=0.64). However, distant metastasis was found in 22 patients (19.5$\%$) for arm I and 35 patients (31.0$\%$) for arm II and which showed statistically significant difference between the two groups ( p=0.046). And neither 3-year disease-free survival (70.2$\%$ vs 59.2$\%$, p=0.2) nor overall survival (89.4$\%$ vs 88.0$\%$, p=0.47) showed significant differences. The incidence of leukopenia during radiation therapy and chemotherapy was 78.3$\%$ and 79.9$\%$ respectively but leukopenia more than RTOG grade 3 was only 2.1$\%$ and 6.0$\%$ respectively. The incidence of diarrhea more than 10 times per day was significantly higher in the patients for arm I than for arm II (71.2$\%$ vs 41.6$\%$, p=0.02) but this complication was controlled with supportive cares. Conclusion : Regardless of the sequence of postoperative adjuvant radiation therapy and chemotherapy after curative resection for rectal cancer, local recurrence rate was low with combined chemoradlotherapy. But distant metastasis rate was lower in early radiation therapy group than in late radiation therapy group and the reason is unclear. Most patients completed these treatments without severe complication, so these were thought to be safe treatments but the treatment compliance should be improved.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.545-558
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• 2003

Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.

• 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.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.221-227
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• 2002

Purpose : To evaluate the role of postoperative chemoradiotherapy in locally advanced rectal cancer, we retrospectively analyzed the treatment results of patients treated by curative surgical resection and postoperative chemoradiotherapy. Materials and Methods : From April 1989 through December 1998, 119 patients were treated with curative surgery and postoperative chemoradiotherapy for rectal carcinoma in Gyeongsang National University Hospital. Patient age ranged from 32 to 73 years, with a median age of 56 years. Low anterior resection was peformed in 59 patients, and abdominoperineal resection in 60. Forty-three patients were AJCC stage II and 76 were stage III. Radiation was delivered with 6 MV X rays using either AP-PA two fields, AP-PA both lateral four fields, or PA both lateral three fields. Total radiation dose ranged from 40 Gy to 56 Gy. In 73 patients, bolus infusions of 5-FU $(400\;mg/m^2)$ were given during the first and fourth weeks of radiotherapy. After completion of radiotherapy, an additional four to six cycles of 5-FU were given. Oral 5-FU (Furtulone) was given for nine months in 46 patients. Results : Forty $(33.7\%)$ of the 119 patients showed treatment failure. Local failure occurred in 16 $(13.5\%)$ patients, 1 $(2.3\%)$ of 43 stage II patients and 15 $(19.7\%)$ of 76 stage III patients. Distant failure occurred in 31 $(26.1\%)$ patients, among whom 5 $(11.6\%)$ were stage II and 26 $(34.2\%)$ were stage III. Five-year actuarial survival was $56.2\%$ overall, $71.1\%$ in stage II patients and $49.1\%$ in stage III patients (p=0.0008). Five-year disease free survival was $53.3\%$ overall, $68.1\%$ in stage II and $45.8\%$ in stage III (p=0.0006). Multivariate analysis showed that T stage and N stage were significant prognostic factors for five year survival, and that T stage, N stage, and preoperative CEA value were significant prognostic factors for five year disease free survival. Bowel complication occurred in 22 patients, and was treated surgically in 15 $(12.6\%)$, and conservatively in 7 $(5.9\%)$. Conclusion : Postoperative chemoradiotherapy was confirmed to be an effective modality for local control of rectal cancer, but the distant failure rate remained high. More effective modalities should be investigated to lower the distant failure rate.