• Radiation Oncology Journal
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• 제13권2호
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• pp.129-142
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• 1995

Purpose: Traditionally the patients with early stage non-Hodgkin's lymphoma of the head and neck was treated with radiotherapy. But the results were not satisfactory due to distant relapse. Although combined treatment with radiotherapy and chemotherapy was tried with some improved results and chemotherapy alone was also tried in recent years, the choice of treatment for the patients with early stage non-Hodgkin's lymphoma of the head and neck has not been defined Therefore, in order to determine the optimum treatment method, we analysed retrospectively the outcomes of the patients with Ann Arbor stage I and II non-Hodgkin's lymphoma localized to the head and neck who were treated at Severance Hospital. Materials and Methods: 159 patients with stage I and II non-Hodgkin's lymphoma localized to the head and neck were treated at our hospital from January, 1979 to December, 1992. Of these patients, 114 patients whose primary sites were Waldeyer's ring or nodal region, and received prescribed radiation dose and/or more than 2 cycles of chemotherapy. were selected to analyze the outcomes according to the treatment methods ( radiotherapy alone, chemotherapy alone. and combined treatment with radiotherapy and chemotherapy ). Results: Five year overall actuarial survival of the patients whose Primary site was Waldeyer's ring was $62.5\%.$ and that of the Patients whose primary site was nodal region was $53.8\%$ There was no statistically significant difference between survivals of both groups. Initial response rate to radiotherapy. chemotherapy, and combined treatment was $92\%,\;83\%,\;94\%$ respectively, and 5 year relapse free survival was $49.9\%,\;52.4\%,\;58.5\%$ respectively ( statistically not significant ). In the patients with stage I. 3 year relapse free survival of chemotherapy alone group was $75\%$ and superior to other treatment groups. In the Patients with stage II, combined treatment group revealed the best result with $60.1\%$ of 3 year relapse free survival. The effect of sequential schedule of each treatment method in the Patients who were treated by combined modality was analyzed and the sequence of primary chemotherapy + radiotherapy + maintenance chemotherapy showed the best result ( 3 year relapse free survival was $79.1\%).$ There was no significant survival difference between BACOP regimen and CHOP regimen. Response to treatment was only one significant (p(0.005) prognostic factor on univariate analysis and age and mass size was marginally significant ( p(0.1). On multivariate analysis, age (p=0.026) and mass size (p=0.013) were significant prognostic factor for the relapse free survival. Conclusion: In summary, the patients who have non-Hodgkin's lymphoma of the head and neck with stage I and mass size smaller than 10 cm, can be treated by chemotherapy alone, but remainder should be treated by combined treatment method and the best combination schedule was the sequence of initial chemotherapy followed by radiotherapy and maintenance chemotherapy.

• Radiation Oncology Journal
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• 제13권2호
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• pp.121-128
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• 1995

Purpose: The enhanced cytotoxic effect of combined treatment of hyper-thermia and chemotherapy by increasing intracellular acidity with HMA was investigated. Materials and Methods: FSall tumor cells were injected on the hindlegs of female $C_3H$ mice. When the tumor volume reached about 200mm3, experiments were performed on the groups classified as follows: Group I :Control, Group II : Melphalan alone (2.5mg/kg, 5mg/kg, 10mg/kg, 15mg/kg), Group III : Heat alone $(42.5^{\cdot}C$ for 1 hour) Group IV : Melphalan + Heat $(42.5^{\cdot}C$ for 1 hour), Group V : HMA(10mg/kg) + Melphalan(5.0mg/kg) + Heat$(42.5^{\cdot}C$ for 1hour). Each group included 8-12 mice on each experiment HMA (3-amino-6-chloro-5-(1-homopiperidyl )-N-(diaminomethylene) -c-pyrazinecarboxamide), an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoxide (DMS) and injected into the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of melphalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor volme reached at $1500mm^3$ Excision assay was performed on each group and repeated 2-4 times. Results : Tumor growth delay of each experimental groups at $1500mm^3$ were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using FSall tumor cells, the cytotoxicity of each experimental groups was $1.2{\times}10^7,\;1{\times}10^7,\;6{\times}10^6,\;1.7{\times}10^6\;and\;1{\times}10^5$ clonogenic cells/gm respectively When HMA was added to the combined treatment of heat and .chemotherapy, the tumor growth was delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at $1500mm^3$ of tumor volume. Conclusion: The combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.

• Radiation Oncology Journal
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• 제7권1호
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• pp.1-13
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• 1989

Effects of ionizing radiation alone and combined with chemotherapy on tumor growth and it's clonal specificity monitored by changes in distribution of chromosome number were studies in A549 ceil line originated from human adenocarcinoma of the lung. Radiation (300 rad, 600 rad and 900 rad) were delivered with or without 5-FU. Forty eight hours later, 57.5% of growth inhibition of cell w8s seen in cells treated with 5-FU concentration of $0.4{\mu}g/ml$ for 24hr exposure. Cell survival curves after radiation with and without 5-FU were made. Chromosomal analysis of cells in metaphase in control, and in cells treated with 300 rad of radiation, or $0.4{\mu}g/ml$ of 5-FU treatment, and combined treatment of both were done to examine the changes in ploidy and number of chromosome. Radiation combined with S-FU enhanced growth inhibition of A549 cells. However, no evidence of synergegic effects in growth. inhibition was observed in the cells treated with the combination therapy. Pattern of chromosomal distribution of survived cells were shifted from hyperploidy to hypoploidy by single dose of radiation (300 rad). As radiation dose increased a large number of hypoploidy cells were observed. Following treatment of cells with 5-FU, chomosomal distribution of survived cells were also shifted to hypodiploidy which were seen in cells treated with radiation, The ceil treated with 5-FU and fellowed by radiation within 24 hrs had cell with increased number of hypodiploidy cells. Almost same type of chromosomal changes were reproduced in cells treated with combined treatment with radiation and 5-FU. Minor differences were that cells with fewer number of chromosome were more frequent in cells treated with combined therapy. Further increase in cells of hypoploidy (93%) having 1-10 chromosome were induced by additional radiation. Therefore, the enhanced therapeutic effect of 5-FU combined with radiation of A549 cells appeared to be additive rather than synergistic.

• 대한두경부종양학회지
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• 제15권1호
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• pp.22-28
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• 1999

Purpose: We performed this study retrospectively to evaluate local control, survival, prognostic factors, and failure patterns in patients with non-Hodgkin's lymphoma of Waldeyer's ring. Materials and Methods: From April 1984 to November 1996,41 patients with non-Hodgkin's lymphoma of Waldeyer's ring were treated with combined chemotherapy and radiation therapy. Age was ranged from 19 to 73 years old with a median age of 55 years, and there were 26 male and 15 female patients. Primary site was tonsil in 26 and base of the tongue in 7 and nasopharynx in 8, and stage distribution showed stage I in 12 and stage II in 29 patients. Pathologic classification was done according to Working Formulation. There were 1 with follicular mixed small cleaved and large cell, 8 with diffuse small cleaved cell, 7 with diffuse mixed small and large cell, and 25 cases with diffuse large cell. All patients were treated with combination of chemotherapy and radiation therapy. Chemotherapy regimen consisted of either CHOP-Bleo(cyclophosphamide, adriamycin, vincristine, prednisolone, bleomycin) or COP-BLAM III(cyclophosphamide, vincristine, prednisolone, bleomycin, adriamycin, procarbazine). Radiation dose ranged from 3600cGy to 6620cGy with a median dose of 5040cGy. Follow-up time was ranged from 15 months to 159 months(median 55 months). Results: The complete response was achieved in 98%(40/41) and partial response in 2%(1/41). The complete response rate were the followings: 66.7% for stage I and 51.7% for stage II after chemotherapy, 100% for stage I and 96.6% for stage II after overall treatment respectively. The overall survival rate and disease-tree survival rates at 5 years were 82.6% and 79.5%, respectively. Prognostic factors for overall survival were age(p=0.007), stage(p=0.03), nodal status(p=0.006) and radiation dose(p=0.003). The factors associated with disease-tree survival were stage(p=0.04), nodal status(p=0.004) and radiation dose(p=0.009). The failure patterns were analized in evaluable 35 patients with complete response. Locoregional failure was noted in 2 patients and distant metastasis in 5 patients. Conclusion: Our results suggest that combined modality therapy is the appropriate treatment for stage I-II intermediate grade non-hodgkin's lymphoma of the Waldeyer's ring. However, our material is small and the analysis is retrospective. Randomized prospective studies for combined therapy, radiation therapy alone and chemotherapy alone are needed.

• Radiation Oncology Journal
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• 제11권2호
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• pp.303-309
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• 1993

Between November 1983 and December 1992, 121 patients with non-small cell lung cancer were treated with radiotherapy alone or combined with chemotherapy in Inje University, Seoul Paik Hospital. Of these,97 patients were evaluable and analyzed retrospectively. Group 1 (n=62)was treated with radiotherapy alone and group 2 (n=35) combined with chemotherapy. There were 7 patients, 1 patient with stage I and II ,20 patients, 11 patients with stage IIIA,28 patients, 20 patients with stage IIIB, and 6 patients, 3 patients with stage IV, respectively. Ninety percent of patients received more than 5000 cGy of radiaton. Median survival of patients in group 1 was 9 months, group 2 was 15 months. Overall 2 year survival rates of group 1 and 2 were $37\%\;and\;27\%$, respectively. Relapse free survival rates at 2 year were $27\%\;and\;15\%$, respectively. Overall survival rates at 5 year for group 1 and 2 were $15\%\;and\;11\%$, and relapse free survival rates were $16\%\;and\;6\%,$ respectively. Median survival of complete and partial responders was 47 months in group 1,18 months in group 2, and those of stable or progression was 6 months,11 months, respectively. The proportion of locoregional relapse and distant metastasis was not significantly different between group 1 and 2. The majority of relapse developed within 2 years. Although 2 cases of severe esophagitis and myelosuppression were noted in group 2, the treatment related toxicity was relatively acceptable. Our analysis showed no statistically significant differences between the two treatment groups in terms of response rate, survival, and sites of relapse.

• 대한두경부종양학회지
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• 제22권2호
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• pp.123-129
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• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.

• Radiation Oncology Journal
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• 제15권2호
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• pp.113-119
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• 1997

목적 : 국소적으로 진행된 위암치료는 수술이 주 치료로 5년 생존율은 그리높지 않아 좀더 완치율을 높이기 위하여 화학요법이나 화학요법과 병용하여 방사선치료 등이 시행되고 있다 저자들은 위암환자에서 수술후 방사선치료를 받은 환자의 치료성적을 후향적으로 분석하였다. 방법 : 1985년 3월부터 1993년 6월까지 한양대학병원 치료방사선과에서 위절제수술후 방사선 치료를 3500cGy 이상 받고 병기 3및 4기인 68명을 대상으로 후향적인 분석을 하였다. 연령분포는 28세부터 66세였고 중앙연령은 50세였다. 추적기간은 3개월에서 133개월(3명이 36개월 미만)로 중앙값은 50개월이었다. 조직병리상 37명이 non signet ring adenocarclnoma였고 29명이 signet ring cell이었다. 병기로 IIIA가 19명, IIIB가 25명, IV가 24명이었다. 항암화학요법은 65명의 환자에게 투여되었으며 FAM계통의 치료가 28예 cispiatln, 5FU계통이 26예이었다. 결과 : 5년생존율은 36.6% 5년무병생존율은 33.6%였다. 예후인자로 병소침입 임파선개수, 조직세포 종류 등이 생존율에 통계적으로 유의하게 영향을 주었고 잔존세포의 유무, 병기, 나이, 세포분화도 및, 방사선치료 총 기간 등도 생존율에 영향을 주었으나 통계적인 유의성은 없었고 항암화학제의 종류에따른 생존율의 차이는 없었다. 37명환자에서 재발이 있었고 위치로는 장망(omentum) 및 복막에 23.5%로 가장 재발율이 놀았으며 남은 위나 봉합부위에 13.2%의 재발율을 보였다. 전체 국소재발은 20.7% 전체 원격전이는 39.7%였다. 방사선치료로 인한 부작용은 22.1%에서 grade 3의 백혈구감소가 있었고 1.5%에서 grade 4 부작용이 있었다. 치료중 10% 이상의 체중감소는 8.8%였다. 결론 : 본 연구결과 수술후 화학요법과 방사선치료요법은 큰 부작용이 없었으며 실패양상은 주로 장망 및 복막이었고 치료부위내 국소재발율이 다음으로 많았다. 국소재발은 원격전이에 비해 많이 낮아지는 추세를 보였다 방사선역할에 평가를 조금 더 명확하게 규명하기위해 향후 재발 위험이 큰 환자에서 수술후 화학요법만 한 군과 화학요법 및 방사선치료를 병용한 군과의 재발 양상 및 생존율 등의 전향적 비교 연구가 필요할 것으로 생각되며 더 나아가 수술후 항암화학요법 및 방사선 병용요법에 복강내 약물치료도 고려되어야 하겠다.

• Radiation Oncology Journal
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• 제13권1호
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• pp.33-40
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• 1995

Purpose : To assess the efficacy and toxicity of the preoperative radiotherapy with or without chemotherapy in locally advanced rectal cancer Methods : Forty three patients (clinically diagnosed stages above or equal to Astler-Coiler stage B2 without distant metastasis) were assigned to preoperative radiotherapy alone arm (n=16) or combined preoperative radiotherapy and chemotherapy arm (n=27). Preoperative radiotherapy of 4500 cGy to whole pel-vis +/-540 cGy boost to primary site and concurrent chemotherapy of 2 cycles of 5-FU (500 mg/$m^2$) and leucovorin (20 mg/$m^2$) were used. Fifteen patients of preoperative radiotherapy alone arm and 19 of combined arm received surgical resection after preoperative treatment. Results : During the preoperative treatment, no significant complication was developed in both groups. Pathologic results were as follows; complete remission 1, Bl 1, B2 6, C1 2, C2, 5 in preoperative radiotherapy alone arm and complete remission 2, Bl 8, B2 4, C2 3, D 2 in combined arm. Postoperative complications were delayed perineal wound healing in three patients, intestinal obstruction in three patients (one managed by conservative medical treatment, two by surgical treatment). Conclusion : The combined preoperative radiotherapy and chemotherapy arm was more effective in pathological response and lymph node negativity rate than the preoperative radiotherapy alone arm. Both the preoperative radiotherapy alone arm and the combined arm were generally well tolerated and did not result in an increased postoperative morbidity.

• Journal of Korean Neurosurgical Society
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• 제57권5호
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• pp.315-322
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• 2015

Intracranial germ cell tumors (ICGCT) occur in 2-11% of children with brain tumors between 0-19 years of age. For treatment of germinoma, relatively low radiation doses with or without chemotherapy show excellent 10 year survival rate of 80-100%. Past studies showed that neoadjuvant chemotherapy combined with focal radiotherapy resulted in unacceptably high rates of periventricular tumor recurrence. The use of generous radiation volume which covers the whole ventricular space with later boost treatment to primary site is considered as standard treatment of intracranial germinomas. For non-germinomatous germ cell tumors (NGGCT), 10-year overall survival rate is still much inferior than that of intracranial germinoma despite intensive chemotherapy and high-dose radiotherapy. Craniospinal radiotherapy combined with cisplatin-based chemotherapy provides the best treatment outcome for NGGCT; 60-70% of overall survival rate. There is a debate on the surgical role whether surgery can contribute to improved treatment outcome of NGGCT when added to combined chemoradiotherapy. Because higher dose of radiotherapy is required for treatment of NGGCT than for germinoma, it is tested whether whole ventricular irradiation can replace craniospinal irradiation in intermediate risk group of NGGCT to minimize radiation-related late toxicity in the recent studies. To minimize the treatment-related neural deficit and late sequelae while maintaining long-term survival rate of ICGCT patients, optimized administration of chemotherapy and radiotherapy should be selected. Use of technically upgraded radiotherapy modalities such as intensity-modulated radiotherapy or proton beam therapy is expected to bring an improved neurocognitive outcome with longitudinal assessment of the patients.

• Radiation Oncology Journal
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• 제33권4호
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• pp.284-293
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• 2015

Purpose: To determine failure patterns and survival outcomes of T4N0-1 non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. Materials and Methods: Ninety-five patients with T4N0-1 NSCLC who received definitive radiotherapy with or without chemotherapy from May 2003 to October 2014 were retrospectively reviewed. The standard radiotherapy scheme was 66 Gy in 30 fractions. The main concurrent chemotherapy regimen was $50mg/m^2$ weekly paclitaxel combined with $20mg/m^2$ cisplatin or AUC 2 carboplatin. The primary outcome was overall survival (OS). Secondary outcomes were failure patterns and toxicities. Results: The median age was 64 years (range, 34 to 90 years). Eighty-eight percent of patients (n = 84) had an Eastern Cooperative Oncology Group performance status of 0-1, and 42% (n = 40) experienced pretreatment weight loss. Sixty percent of patients (n = 57) had no metastatic regional lymph nodes. The median radiation dose was EQD2 67.1 Gy (range, 56.9 to 83.3 Gy). Seventy-one patients (75%) were treated with concurrent chemotherapy; of these, 13 were also administered neoadjuvant chemotherapy. At a median follow-up of 21 months (range, 1 to 102 months), 3-year OS was 44%. The 3-year cumulative incidences of local recurrence and distant recurrence were 48.8% and 36.3%, respectively. Pretreatment weight loss and combined chemotherapy were significant factors for OS. Acute esophagitis over grade 3 occurred in three patients and grade 3 chronic esophagitis occurred in one patient. There was no grade 3-4 radiation pneumonitis. Conclusion: Definitive radiotherapy for T4N0-1 NSCLC results in favorable survival with acceptable toxicity rates. Local recurrence is the major recurrence pattern. Intensity modulated radiotherapy and radio-sensitizing agents would be needed to improve local tumor control.