• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.223-235
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• 2000

Background: Liquid ventilation is associated with decreased inflammatory response in an injured lung. This study was performed to investigate if whether perfluorocarbon(PFC) can decrease chemokine expression in airway epithelial cells. Methods: A549 cells were used for airway epithelial cells and perfluorodecalin for PFC. To expose cells to PFC, lower chamber of Transwell$^{(R)}$plate was used. This study was performed in two parts. In the first part, we examined whether PFC could decrease chemokine expression in airway epithelial cells through inhibition of other inflammatory cells. Peripheral blood mononuclear cells(PBMC's) were isolated and stimulated with lipopolysaccharide(LPS, 10 ${\mu}g/mL$) for 24 hours with or without exposure to PFC. Then A549 cells were stimulated with conditioned media(CM) containing the culture supernatants of PBMC. After 24 hours, the expressions of interleukin-8(IL-8) and RANTES were measured. In the second part of the study, we studied whether PFC could directly suppress chemokine expression in airway epithelial cells. A549 cells were stimulated for 24 hours with interleukin-l$\beta$ and/or tumor necrosis factor-$\alpha$ with or without exposure to PFC, and then the chemokine expression was measured. Northern analysis was used to measure the mRNA expression, and ELISA was used for immunoreactive protein measurements in culture supernatant. Results: 1. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by CM from LPS-stimulated PBMC in A459 cells compared to with CM from unstimulated PBCM (p<0.05), but exposure of PFC had no significant effect on either mRNA expression or immunoreactive protein expression. 2. IL-8 and RANTES mRNA expression and immunoreactive protein production were increased significantly by IL-1$\beta$ and TNF-$\alpha$ in A549 cells(p<0.05), but exposure of PFC had no significant effect on neither either mRNA expression nor immunoreactive protein production. Conclusion : Decreased chemokine expression of airway epithelial cells may not be involved in decreased inflammatory response observed in liquid ventilation. Further studies on possible mechanisms of decreased inflammatory response are warranted.

• Radiation Oncology Journal
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• v.25 no.1
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• pp.43-53
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• 2007

[ $\underline{Purpose}$ ]: To evaluate the relationship between the expression of EGFR, p53, Cox-2, Bcl-2 and the clinical parameters of NPC (nasopharyngeal carcinoma) patients treated with radiotherapy with/without chemotherapy, and to determine if these could be used as a biologic marker. $\underline{Materials\;and\;Methods}$: This study retrospectively examined 75 NPC patients who were pathologically diagnosed at St. Mary's Hospital and Kangnam St Mary's Hospital from March 1988 to August 2002 and treated with radiotherapy with/without chemotherapy. The levels of EGFR, p53, Cox-2, and Bcl-2 expression were determined immunohistochemically. The relationship between the levels of EGFR, p53, Cox-2 and Bcl-2 expression and the H- E staining findings including the WHO classification, TNM stage, tumor response to chemotherapy and radiotherapy, disease free survival (DFS), and overall survival (OS) was analyzed. $\underline{Results}$: At a median follow up of 50.8 months (range: $5.5{\sim}201$ months), the 3 years OS rate and PFS rate were 68.7% and 68.2%, respectively. The five year OS rate and PFS rate were 53.5% and 51.1%, respectively. The median OS duration and PFS duration were 85.5 months and 61.1 months, respectively. The WHO classification correlated with the complete response rate, lymph node metastasis and distant metastasis. The expression of p53 was associated with increased mitosis and poor overall survival. The expression of Bcl-2 correlated with the DFS and WHO classification. The expression of Cox-2 correlated with a poor overall survival and response rate in the lymph node. However, EGFR was not correlated with any factors. $\underline{Conclusion}$: These results suggest that the expression of p53, Cox-2, Bcl-2 plays role in predicting prognostic factors for NPC treated with radiotherapy with/without chemotherapy. However, further study on a larger number of patients will be needed to identify more useful biomarkers of NPC.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.230-240
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• 2002

Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.93-99
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• 2002

Purpose : We intended to decrease late CNS reaction after radical radiotherapy for an intracranial germinoma by using combined neoadjuvant chemotherapy and involved-field radiotherapy. The efficacy in terms of its acute toxicity and short-term relapse patterns was analyzed. Materials and Methods : Eighteen patients were treated with combined neoadjuvant chemotherapy and radiotherapy between 1995 and 2001. The chemotherapy regimen used was the Children's Cancer Group (CCG) 9921A (cisplatin, cyclophosphamide, VP-16, vincristine) for 5 patients younger than 16 years, BEP (bleomycin, VP-16, cisplatin) for 12 patients, and EP (VP-16, cisplatin) for 1 patient. The radiotherapy covered the whole craniospinal axis for 5 patients, the whole brain for 1, and the partial brain (involved field) for 12. the primary lesion received tumour doses between 3,960 and 5,400 cGy. Results : The male to female ratio was 16:2 and the median age was 16 years old. The tumors were located in the pineal gland in 12 patients, in the suprasellar region in 1, in the basal ganglia In 1, in the thalamus in 1. Three patients had multiple lesions and ventricular seedings were shown at MRI. In 3 patients, tumor cells were detected in the cerebrospinal fluid and MRI detected a spinal seeding in 2 patients. The response to neoadjuvant chemotherapy was complete remission in 5 patients, partial remission in 12, and no response in 1. However, after radiotherapy, all except 1 patient experienced complete remission. The toxicity during or after chemotherapy greater than or equal to grade III was remarkable; hematologic toxicity was observed in 11 patients, liver toxicity in none, kidney toxicity in none, and gastrointestinal toxicity in one. One patient suffered from bleomycin-induced pneumonitis. Radiotherapy was therefore stopped and the patient eventually died of respiratory failure. The other 17 are alive without any evidence of disease or relapse during an average of 20 months follow-up. Conclusion : A high response rate and disease control was experienced, which was the same as observed other studies and the morbidity from chemotherapy-induced toxicity was similar. With these results, the results from adjuvant chemotherapy and involved-field radiotherapy cannot be concluded to be equal to those from extended-field radiotherapy. The long term follow-up study on later complications are required in order to draw definite conclusions on the optimal management with minimum side effects.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.233-241
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• 1997

Purpose : This study was done to evaluate the survival rate and Prognostic factors of patients with inoperable non-small cell lung cancer(NSCLC) treated with radiation therapy. Materials and Methods A retrospective analysis was undertaken of 62 Patients who had inoperable NSCLC treated with radiation therapy from January 1991 through December 1993. According to AJCC slaging, stage IIIA was 14 patients and stage IIIB was 48 patients. Forty Gy to 70.2Gy to the primary tumor site was delivered with daily fractions of 1.8Gy or 2Gy, 5days per week. Thirty-seven patients received neoadjuvant chemotherapy. Results : Complete, partial and no response to radiation therapy were 3 patients, 34 Patients and 25 patients, respectively The median survival period of all patients was 11 month. One rear survival rate, 2 year survival rateand 5 rear survival rate for all patients were 45.0%, 14.3%, and 6.0% respectively The median survival period was 6.5 months in stage IIIA and 13 months in stage IIIB. One year survival rates were 28.6% in stage IIIA and 50.3% in stage IIIB In univariaite analysis, prognostic factors affecting survival were T-s1aging, AJCC staging, and response after radiation therapy (P<0.05) . Pretreatment peformance status affected survival but was not statistically significant (0.050.1). In multivariate analysis, Pathology and response to radiation therapy are independently significant prognostic factor. T stage was marginally significant (P=0.0809). During follow-up duration, distant metastasis developed in 20 patients-bone metastasis in 10 patients, brain metastasis in 3 patients, liver mentastasis in 3 patients, contralateral lung metastasis in 1 patients and multiple metastases in 3 patients. Conclusion :　Conventional radiotherapy alone or combined chemoradiotherapy are unlikely to achieve long term survival in patients with NSCLC.　Surgery after concurrent chemoradiotherapy is Ivied to improve the local　control in our hospital

• Radiation Oncology Journal
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• v.12 no.1
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• pp.73-80
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• 1994

From December 1989 to February 1993, 108 patients with Non-Small Cell Lung Cancers(NSCLC) were studied retrospectively to evaluate radiotherapeutic significance of serum levels of NSE. We considered elevated serum neuron specific enolase(S-NSE) level as one of the neuroendocrine features in NSCLC. Histopathologic evaluation revealed 86 squamous cell carcinomas, 11 adenocarcinomas.3 large cell carcinomas, 3 mucoepidermoid carcinomas, and 5 unknown pathology. Eight Patients had stage 1,40 stage IlIA, and 60 stage lIIB.S-NSE level greater than 15 ng/ml was considered as elevated, and below this considered as normal. All patients recieved radiotherapy as primary treatment modality. The responders to radiotherapy had significantly higher mean S-NSE level than non-responders (28.5 ng/ml vs 20 ng/ml, p=0.01). Overall 2-year survival rate(YSR) was 23.6$ \% $. According to radiotherapy response, 2 YSR for Patients with CR, PR, and NR were 39.2$ \% $, 28.6$ \% $, and 6.2$ \% $ respectively(p=0.001). 2 YSR for patients with elevated and normal S-NSE were 14.6$ \% $ and 31.7$ \% $(p=0.02). The patients with NR showed no difference in survival according to S-NSE level. When we considered all patients, S-NSE level showed no significant impact on response. But for squamous cell carcinomas alone, patients with elevated S-NSE had more responders(80$ \% $ vs 61$ \% $, p=0.05). There was no correlation between tumor characteristics and S-NSE level. But the patients with elevated S-NSE had more patients with higher nodal stage, Based on our and other datas, NSCLC with neuroendocrine features have different response to treatment and clinical behavior compared to other NSCLC. Thus, this subgroup may need different treatment modality, and S-NSE level may have prognostic significance.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.81-90
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• 1994

Purpose : The aim of this study is to analyze the clinical results of thermo-irradiation treatment for surgically unresectable advanced hepatoma with or without hepatic arterial chemo-embolization (HACE), chemotherapy (CT) and interferon (IFN) therapy. Materials and Methods : Between February 1990 and December 1992, 45 Patients with surgically unresectable advanced hepatomas were treated by thermo-irradiation with or without hepatic arterial chemo-embolization and other treatment modalities. Among them, We analyzed retrospectively 25 patients who received more than three times of hyperthermias. Mean age was 50 years (range : 18-71 years) and male to female ratio was 20 : 5. In the study, treatment was administered as follows : 3 patients received radiation therapy(RT) and hyperthermia (HT). 3 received RT+HT+CT. 3 received RT+HT+HACE. 1 received RT+HT+CT+HACE. 2 received RT+HT+CT+IFN. 10 received RT+HT+HACE+IFN. 3 received RT+HT+CT+HACE+IFN. Radiation therapy was done by a 6 MV linear accelerator Patients were treated with daily fractions of 180 cGy to doses of 11Gy-50Gy (median 30Gy). Local hyperthermia was done by HEH-500C(Omron Co. Japan), 30-45 min/session, 2 sessions/wk and the number of HT sessions ranged from 3 to 17 (median 7 times). 15 patients of 25 were followed by abdominal CT scan or abdominal ultra-sonogram. The following factors were analyzed :Age, histologic grade, sex. number of hyperthermia, total RT dose, hepatic arterial chemo-embolization. Results : Of 25 patients. there were observed tumor regression (partial response and minimal response) in 6 (24$ \% $), no response in 8 (32$ \% $), progression in 1 (4$ \% $) and not evaluable ones in 10 (40$ \% $) radiographically. The over all 1-year survival was 25$ \% $, with a mean survival of 33 weeks. The treatment modes of partial and minimal responsive patients (PR+MR)were as follows : Two were treated with RT+HT+HACE, 2 were done with RT+HT+HACE+IFN Remaining 2 were treated with RT+HT+CT+HACE+IFN. The significant factor affecting the survival rate were RT dose (more than 25 Gy), HACE, number of HT (above 6 times), responsiveness after treatment (PR + MR). Age, sex, histologic differentiation, chemotherapy, interferon therapy were not statistically significant factors affecting the survival rate. Conclusion : Although follow-up duration was short, the thermo-irr3diBtion with/without hepatic arterial chemo-embolization was well tolerated and there were no serious complicatons. In future, it is considered the longer follow up and prospective, well controlled trials should be followed to evaluate the efficacies of survival advantage.

• The Korean Journal of Nuclear Medicine
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• v.28 no.1
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• pp.133-140
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• 1994

Recently, there are many considerations and studies on biological effects of radiations in radiation workers, as well as in accidentally or therapeutically irradiated persons. The most practical and reliable method of dosimetry for radiation accidents is the scoring of gross chromosomal aberrations in human lymphocytes (Ydr) as a biological dosimetry. By the way, although usual doses of $^{131}I$ administered therapeutically for thyroid cancer are ranging from 100 mCi to 200 mCi, there are differences of absorbed doses and Ydr, ranging from 0.004 to 0.04, on equally administered $^{131}I$ due to variations in metabolic characteristics, stage of tumors and physical status of subjects. In this study, We exert to obtain the dose-response relationships of $^{131}I$, as a good guide to evaluating acute effects of accidental irradiations and radiation induced leukemia or solid tumor, by in vitro induction of chromosomal aberrations. we studied the relationship between radiation dose (D) and the frequency of chromosomal aberrations (Ydr) obserbed in peripheral lymphocytes that were irradiated in vitro with $^{131}I$ at doses ranging from 0.05 to 6.00 Gy. By scoring cells with unstable chromosomal aberrations (dicentric chromosomes and ring chromosomes) we obtained this linear-quadratic dose response equation Ydr=0.064351 $D^2$-0.13143 D+0.045684 This dose-response relationship may be useful for evaluating acute and chronic $^{131}I$ induced biological effects.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.92-97
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• 2005

Purpose : Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. in this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. Materials and Methods : A retrospective analysis was peformed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was $2\~6.5$ cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was S or 10 Gy: each dose was prescribed based on the planning target volume and normalized to $85\~99\%$ isocenter dose. Patients were treated $3\~5$ times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was $\~55$ months (the median follow up period: 23 months). Results : The response rate was $50\%$ (12 patients), with 4 patients showing complete response ($20%$), 8 patients showing partial response ($40\%$), and 8 patients showing stable disease ($40\%$). The 1-year and 2-year survival rates were $70.0\%$ and $43.1\%$, respectively, and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were $65\%$ and $32.5\%$, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients ($60\%$), nausea/emesis in 8 patients ($40\%$), and transient liver function impairment in 6 patients ($30\%$). However, there was no treatment related death. Conclusion : The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.108-115
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• 2002

Purpose : A retrospective study was undertaken to determine the role of conventional radiotherapy with or without surgery for treating a supraglottic carcinoma in terms of the local control and survival. Materials and Methods : From Jan. 1986 to Oct. 1996, a total of 134 patients were treated for a supraglottic carcinoma by radiotherapy with or without surgery. Of them, 117 patients who had completed the radiotherapy formed the base of this study. The patients were redistributed according to the revised AJCC staging system (1997). The number of patients of stage I, II, III, IVA, IVB were $6\;(5\%),\;16\;(14\%),\;53\;(45\%),\;32\;(27\%),\;10\;(9\%)$, respectively. Eighty patients were treated by radical radiotherapy in the range of $61.2\~79.2\;Gy$ (mean : 69.2 Gy) to the primary tumor and $45.0\~93.6\;Gy$ (mean : 54.0 Gy) to regional lymphatics. All patients with stage I and IVB were treated by radiotherapy alone. Thirty-seven patients underwent surgery plus postoperative radiotherapy in the range of $45.0\~68.4\;Gy$ (mean : 56.1 Gy) to the primary tumor bed and $45.0\~59.4\;Gy$ (mean : 47.2 Gy) to the regional lymphatics. Of them, 33 patients received a total laryngectomy (${\pm}lymph$ node dissection), three had a supraglottic horizontal laryngectomy (${\pm}lymph$ node dissection), and one had a primary excision alone. Results : The 5-year survival rate (5YSR) of all patients was $43\%$. The 5YSRs of the patients with stage I+II, III+IV were $49.9\%,\;41.2\%$, respectively (p=0.27). However, the disease-specific survival rate of the patients with stage I (n=6) was $100\%$. The 5YSRs of patients who underwent surgery plus radiotherapy (S+RT) vs radiotherapy alone (RT) in stage II, III, IVA were $100\%\;vs\;43\%$ (p=0.17), $62\%\;vs\;52\%$ (p=0.32), $58\%\;vs\;6\%$ (p<0.001), respectively. The 5-year actuarial locoregional control rate (5YLCR) of all the patients was $57\%$. The 5YLCR of the patients with stage I, II, III, IVA, IVB was $100\%,\;74\%,\;60\%,\;44\%,\;30\%$, respectively (p=0.008). The 5YLCR of the patients with S+RT vs RT in stage II, III, IVA was $100\%\;vs\;68\%$ (p=0.29), $67\%\;vs\;55\%$ (p=0.23), $81\%\;vs\;20\%$ (p<0.001), respectively. In the radiotherapy alone group, the 5YLCR of the patients with a complete, partial, and minimal response were $76\%,\;20\%,\;0\%$, respectively (p<0.001). In all patients, multivariate analysis showed that the N-stage, surgery or not, and age were significant factors affecting the survival rate and that the N-stage, surgery or not, and the ECOG performance index were significant factors affecting the locoregional control. In the radiotherapy alone group, multivariate analysis showed that the radiation response and N-stage were significant factors affecting the overall survival rate as well as locoregional control. Conclusion : In early stage supraglottic carcinoma, conventional radiotherapy alone is an equally effective modality compared to surgery plus radiotherapy and could preserve the laryngeal function. However, in the advanced stages, radiotherapy combined with concurrent chemotherapy for laryngeal preservation or surgery should be considered. In bulky neck disease, all the possible planned neck dissections after induction chemotherapy or before radiotherapy should be attempted.