• Radiation Oncology Journal
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• v.11 no.2
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• pp.355-361
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• 1993

Since May 1991, authors have conducted a pilot study to determine the feasibility and evaluate the effect of concurrent radiation therapy and chemotherapy with 5-FU and Cis-platinum for locally advanced cervical cancer (stage IIB-IVA). Radiation therapy consisted of external irradiation to whole pelvis (4140 cGy/23 fx) in 4.5 weeks followed by high dose rate intracavitary radiation therapy (HDR ICRT) to deliver a dose of 30 to 35 Gy to A point in 6 to 7 fractions. After the intracavitary radiation therapy, parametrial boost was delivered for B point dose of 60 Gy in Stage IIB and 65 Gy in stage IIIB. 5-FU (1000 $mg/m^2/24hr$ for 96 hour iv infusion) and Cis-platinum (20 $mg/m^2/day$ IV bolus for 3 days) were given during the second week of external RT and the second course chemotherapy administered at the first HDR ICRT with the same method as the first chemotherapy. Sixteen patients (10 stage IIB,4 stage IIIB,2 stage IVA) were registered to this protocol. Among these 16 patients, two refused treatment after 2 fractions of external irradiation, and one could not continue intracavitary irradiation because of treatment related genitourinary toxicity. So 14 patients were evaluated for toxicity and 13 patients were evaluated for response analysis. Five of 14 patients developed grade 3 gastrointestinal toxicity but 4 of them recovered at the completion of treatment. One stage IIIB patient with inguinal lymph node metastasis who received higher dose of radiation in spite of initial poor performance status did not recover from gastrointestinal toxicity at the completion of treatment. And she died of distant metastasis at one month after the completion of treatment. Two of 14 evaluable patients showed weight loss, more than $10\%$ of initial weight. One patient developed grade 3 leukopenia. In this study, the average total treatment period of completely treated patients was 75 days and three of them took more than 80 days (84, 84, 89 days). Toxicities were generally acceptable and there were no treatment related death. At the last follow-up, complete response was achieved in $62\%(8/13)$ and especially of nine patients with stage IIB, eight patients showed complete response. This study suggests that concurrent radiation therapy and chemotherapy (5-FU and Cis-platinum) is tolerable and effective. Further follow-up is needed to determine whether this protocol will have a favorable impact on survival and to evaluate the late effect on normal tissues. In future, prospective randomized trials are needed to compare the standard radiation therapy alone with concurrent chemotherapy and radiation therapy for locally advanced cervical carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.57-64
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• 2006

Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.293-299
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• 2000

Purpose :We conducted a prospective non-randomized clinical study to evaluate the efficacy and toxic of the preoperative concurrent chemoradiotherapy for locally advanced unresectable rectal cancer. Materials and Methods: Between January 1995 and June 1998, 37 conecutive patients with locally unresectable advanced rectal cancer were entered into the study. With 3- or 4- fields technique, a total of 45 Gy radiation was delivered on whole pelvis, followed by 5.4 Gy boost to the primary tumor in some cases. Chemotherapy was done at the first and fifth week of radiation with bolus i.v. 5-Fluorouracil (FU) 370$\~$450 mg/m$^{2}$, days 1$\~$5, plus Leucovorin 20 mg/m$^{2}$, days 1$\~$5. OF 37 patients, 6 patients did not receive all planned treatment course (refusal in 4, disease progression in 1, metastasis to lung in 1). Surgical resection was undergone 4$\~$6 weeks after preoperative concurrent chemoradiotherapy. Results :Complete resection rate with negative margins was 94$\%$ (29/31). Complete response was seen in 7 patients (23$\%$) clinically and 2 patients (6$\%$) pathologically. Down staging of tumor occured in 21 patients (68$\%$). Treatment related toxicity was minimal except grade III & IV leukopenia in 2 patients, respectively. Conclusion : Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer was effective in inducing down staging and complete resection rate. Treatment related toxicity was minimal. Further follow up is on-going to determine long term survival following this treatment.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.367-377
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• 1993

Background: The benefits of combination chemotherapy in unresectable non-small cell lung cancer remain uncertain. But, according to the recent reports, the response rates of cisplatin-based polychemotherapy regimens are higher than those of single agent. Also, the response rates of high-dose cisplatin group are higher than those of low-dose cisplatin group. In attemp to answer the question whether treatments, combination chemotherapy (high VPP) and combination chemotherapy with radiation therapy, improve survival in advanced non-small cell lung cancer, we begin to study. Method: Thirty-five patients above stage III, diagnosed histologically as non-small cell lung cancer, were enrolled. Among them, nineteen received a combination chemotherapy consisting of VP-16 & high-dose cisplatin (100 $mg/m^2$) and/or radiation therapy. The other group (16 subjects) received no therapy. To investigate the differences of survival and response rates between two groups and the side effects related to therapy, we reviewed patients' records. Results: 1) The overall objective response rate was 47%(9/19) with one complete remission. 2) In patients who received polychemotherapy and radiation therapy, the response rate was 60%(6/10) with one complete remission and survival rates of 3 months, 6 months and 12 months were 100%, 70% and 40%. 3) In patients who received polychemotherapy, the response rate was 33% (3/9) with no complete remission and survival rates of 3 months, 6 months and 12 months were 78%, 67% and 33%. 4) Overall, treated patients survived significantly longer (p<0.05) than non-treated patients (median survival 307 days versus 95 days). 5) Analysis of the various prognostic factors disclosed that good performance status, stage III and squamous cell type showed the good response rates. 6) The toxicities were nausea and/or vomiting (100%), alopecia (90%), anemia (79%), leukopenia (69%), thrombocytopenia (2%), increased creatinine (16%) and neurotoxicity (5%). Conclusion: According to above results, there are relatively good results that high VPP combination chemotherapy in advanced non-small cell lung cancer improves survival in the treated group than in the non-treated group. Thus, it is considerd that we select the patients with proper indications and treat them with effective chemotherpy and radiation therapy. But, because improvement related to high VPP ploychemotherapy is not marked in this study, it is necessary that we should investigate follow-up studies in many cases.

• Tuberculosis and Respiratory Diseases
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• v.61 no.5
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• pp.440-446
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• 2006

Background: Post-transplant tuberculosis (TB) is a serious complication in solid organ transplant recipients worldwide, However there is little or no data on TB in liver or heart transplant recipients in Korea. Methods: The incidence and clinical characteristics of TB of 730 patients who had undergone a liver transplant in a university hospital in Korea between 1992 and 2004, and 110 heart transplant recipients in the same period, were reviewed retrospectively. Results: The incidence of TB was 1.5%(11/730) and 2.7%(3/110) in the liver and heart transplantation, respectively. The median time from the transplant to the development of TB was 8.4 months(1.0-30.8). and the mean time from the symptoms to the diagnosis of TB was $2.1{\pm}3.6$ months(0.3-13.2). Nine patients (65%) had pulmonary TB and five (35%) had extrapulmonary TB. The leukopenia and positive HbeAg at the baseline, post-transplant diabetes mellitus, and chronic rejection were associated with the development of TB in the liver transplant recipients. Ten patients were treated with a 4-drug standard regimen for a mean duration of $7.8{\pm}3.5$ months. One patients died of TB. Conclusion: The incidence of TB in liver or heart transplant recipients was similar to that reported in other countries with a similar TB-burden.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.100-106
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• 2001

Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

• Pediatric Infection and Vaccine
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• v.8 no.2
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• pp.213-221
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• 2001

Propose : Tsutsugamushi fever is a acute febrile disease, which is caused by O. tsutsugamushi. Recently, this disease is increasingly reported in children. This study was undertaken to investigate clinical features of tsutsugamushi fever in children. Methods : This study involved 17 children with tsutsugamushi fever who were admitted to Masan Samsung hospital between September 1997 and December 2000. We investigated the age, sex ratio, clinical manifestations, laboratory findings, response of therapy and prognosis. Results : The age of patients was $6.9{\pm}3.6$ years, ranging from 6 months to 12 years and male predilection(58.8%) was noted and all cases of patients occured in October or November. The most common symptoms were fever in all cases and headache in 8(47.1%). The most common signs were skin rash in all cases, eschar in 14(82.4%) and lymphadenopathy 8(47.1%). Locations of the eschars were back and inguinal area in each 3 cases, neck and chest in each 2, popliteal area in 2, scalp and thigh in each 1. Laboratory findings included anemia in 1 case, leukopenia and thrombocytopenia in each 5, hematuria and proteinuria in each 1, ESR elevation in 2 and positive CRP in 12, AST elevation in 9 and ALT elevation in 7. Serologic diagnosis was made by passive hemagglutination assay(PHA) in 8 cases(47%) on admission, 4 cases in initial negative group were performed follow-up test at 2nd or 3rd weeks of illness and then all cases of 4 were converted to positive reaction. Clinical improvement was noticed in all cases after treatment to chloramhenicol or doxycycline. Mean duration for defervescence after treatment was $1.4{\pm}0.8$ days. Complications were interstitial pneumonia in 1 case and aseptic meningitis in 3, but all cases of patients were recovered without sequelae or recurrence. Conclusions : Tsutsugamushi fever in children was similiar to adult in the clinical features except male predilection. Early diagnosis and empirical treatment based on clinical manifestations such as fever, skin rash, eschar, lymphadenopathy is important and serologic diagnosis need to perform follow-up test at 2nd or 3rd weeks of illness.

• Radiation Oncology Journal
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• v.20 no.1
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• pp.53-61
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• 2002

Purpose : To determine the optimal scheme of postoperative chemoradiotherapy in rectal cancer by comparing survival, Patterns of failure, toxicities in early and late radiotherapy groups using a Phase III randomized prospective clinical trial. Materials and Methods : From January 1996 to March 1999, 307 patients with curatively resected AJCC stage II and III rectal cancer were assigned randomly to an 'early (151 patients, arm 1)' or a 'late (156 patients, arm II)' and were administered combined chemotherapy (5-FU $375\;mg/m^2/day$, leucovorin $20\;mg/m^2$, IV bolus daily, for 3 days with RT, 5 days without RT, 8 cycles with 4 weeks interval) and radiation therapy (whole pelvis with 45 Gy/25 fractions/5 weeks). Patients of arm I received radiation therapy from day 1 of the first cycle of chemotherapy and those of arm II from day 57 with a third cycle of chemotherapy. The median follow-up period of living patients was 40 months. Results : Of the 307 patients enrolled, fifty patients did not receive scheduled radiation therapy or chemotherapy. The overall survival rate and disease free survival rate at 5 years were $78.3\%\;and\;68.7\%$ in arm I, and $78.4\%\;and\;67.5\%$ in arm II. The local recurrence rate was $6.6\%\;and\;6.4\%$ (p=0.46) in arms I and II, respectively, no significant difference was observed between the distant metastasis rates of the two arms ($23.8\%\;and\;29.5\%$, p=0.16). During radiation therapy, grade 3 diarrhea or more, by the NCI common toxicity criteria, was observed in $63.0\%\;and\;58.2\%$ of the respective arms (p=N.S.), but most were controlled with supportive care. Hematologic toxicity (leukopenia) greater than RTOG grade 2 was found in only $1.3\%\;and\;2.6\%$ of patients in each respective arm. Conclusion : There was no significant difference in survival, patterns of failure or toxicities between the early and late radiation therapy arms. Postoperative adjuvant chemoradiation was found to be a relatively safe treatment but higher compliance is needed.

• 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.15 no.2
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• pp.121-128
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• 1997

Purpose : To evaluate the effect of postoperative adjuvant radiation therapy and chemotherapy on the survival, pattern of failure and complication for locally advanced rectal carcinoma Materials and Methods : From October 1992 to September 1995, twenty eight patients with rectal carcinoma were treated by postoperative adjuvant radiation therapy and chemotherapy Radiation therapy was delivered with 6MV and 15MV linear accelerator, 180c0y fractions 5 day per week. Total radiation doses were 5040cGy in $B_{2+3}$ and 5580cGy in $C_{2+3}$. Within 4 weeks after radical surgery. 5-FU$(400mg/m^2/day)\;and\;Leucovorin(20mg/m^2/day)$ were administered by intravenous injection for 4 days during the first and fifth week of radiation therapy. The median follow up was 19 months with a range 2 to 47 months. Results : The 2 year overall survival and disease free survival rates were $78.6\%\;and\;70.8\%$, respectively. The 2 year overall survival was $93.0\%\;in\;B_{2+3}$ and $76.2\%\;in\;C_{2+3}$(p=0.11) The 2 year disease free survival was $79.4\%\;in\;B_{2+3}\;and\;69.2\%\;in\;C_{2+3}(p=0.13)$. The overall failure rate was $21.42\%$(6/28) including $10.72\%$(3/28) locoregional recurrence, $3.62\%$(1/28) distant metastasis and $7.12\%$(2/28) locoregional recurrence with distant metastasis. The overall locoregional recurrence rate was $17.92\%$(5/28). The 2 year locoregional recurrence rates were $13.32\%(2/15)\;and\;23.12\%$(3/13) for respectively for $B_{2+3}\;and\;C_{2+3}$ The difference between the locoregional recurrence of $B_{2+3}\;and\;C_{2+3}$ patients was not significant(p=0.07). Complications developed in 13 patients$(46.42\%)$, including 8 dermatitis, 7 loose stool, 6 leukopenia, 4 tenesmus, 2 diarrhea. In Univariate analysis, there was no statistically significant factor except for tumor grade in locoregional recurrence, disease free survival and overall survival rate(p=0.04, 0.05, 0.04). Conclusion : This study sugges1s that postoperative adjuvant radiation therapy and chemotherapy is effective in patients with locally advanced rectal cancer. Therefore these results need to be confirmed with a long term follow-up and larger number of patients with the further clinical trials including prospective controlled studies.