• Biomolecules & Therapeutics
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• 제20권4호
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• pp.357-370
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• 2012

Radiation therapy, the most commonly used for the treatment of brain tumors, has been shown to be of major significance in tumor control and survival rate of brain tumor patients. About 200,000 patients with brain tumor are treated with either partial large field or whole brain radiation every year in the United States. The use of radiation therapy for treatment of brain tumors, however, may lead to devastating functional deficits in brain several months to years after treatment. In particular, whole brain radiation therapy results in a significant reduction in learning and memory in brain tumor patients as long-term consequences of treatment. Although a number of in vitro and in vivo studies have demonstrated the pathogenesis of radiation-mediated brain injury, the cellular and molecular mechanisms by which radiation induces damage to normal tissue in brain remain largely unknown. Therefore, this review focuses on the pathophysiological mechanisms of whole brain radiation-induced cognitive impairment and the identification of novel therapeutic targets. Specifically, we review the current knowledge about the effects of whole brain radiation on pro-oxidative and pro-inflammatory pathways, matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) system and extracellular matrix (ECM), and physiological angiogenesis in brain. These studies may provide a foundation for defining a new cellular and molecular basis related to the etiology of cognitive impairment that occurs among patients in response to whole brain radiation therapy. It may also lead to new opportunities for therapeutic interventions for brain tumor patients who are undergoing whole brain radiation therapy.

• Radiation Oncology Journal
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• 제30권2호
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• pp.53-61
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• 2012

Purpose: To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Materials and Methods: Nine patients with multiple (${\geq}4$) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. Results: The median biologically effective dose to metastatic tumors was 68.1 $Gy_{10}$ and 67.2 $Gy_{10}$ and the median brain volume irradiated more than 100 $Gy_3$ were 1.9% (24 $cm^3$) and 0.8% (13 $cm^3$) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. Conclusion: RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5699-5703
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• 2013

Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.

• 한국산학기술학회논문지
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• 제15권10호
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• pp.6187-6192
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• 2014

전이성 뇌종양의 증가에 따라 전뇌 방사선치료가 증가하게 되었다. 그리고 치료기법의 발전은 삶의 질 향상의 중요성을 증가시키게 되었다. 체적변조회전 전뇌조사는 용적별 선량을 차등시킬 수 있는 우수한 치료기법이다. 이에 두피선량 증가에 따른 탈모에 대하여 기존 전뇌조사와 체적변조회전 전뇌조사를 비교하고자 하였다. 두정부 인체모형을 이용하여 치료계획을 비교하였다. 뇌 실질의 경우 정합지수, 동질성지수, 범위의 질지수를 적용하였으며, 두피, 안구, 수정체, 경추의 경우 20%선량의 용적, 50%선량의 용적을 적용하여 비교하였다. 비교결과 뇌 실질은 기존 전뇌조사가 10%정도 우수하였지만, 두피, 안구, 수정체, 경추의 경우는 체적변조회전 전뇌조사가 1000%정도 우수하였다. 향후 체적변조회전 전뇌조사의 처방선량을 조정한다면 탈모를 방지하는 전이성 뇌종양 방사선치료로 선정될 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권9호
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• pp.4233-4235
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• 2016

Background: Whole brain radiotherapy (WBRT) and stereotactic radiosurgery were frequently used to palliate patients with brain metastases. It remains controversial which modality or combination of therapy is superior especially in the setting of limited number of brain metastases. The availability of newer medical therapy that improves survival highlighted the importance of reducing long term radiation toxicity associated with WBRT. In this study, we aim to demonstrate the hippocampal sparing technique with whole brain and integrated simultaneous boost Materials and Methods: Planning data from 10 patients with 1-5 brain metastases treated with SRS were identified. Based on the contouring guideline from RTOG atlas, we identified and contoured the hippocampus with 5mm isocentric expansion to form the hippocampal avoidance structure. The plan was to deliver hippocampal sparing whole brain radiotherapy (HSWBRT) of 30 Gy in 10 fractions and simultaneous boost to metastatic lesions of 30 Gy in 10 fractions each. Results: The PTV, hippocampus and hippocampal avoidance volumes ranges between 1.00 - 39.00 cc., 2.50 - 5.30 cc and 26.47 - 36.30 cc respectively. The mean hippocampus dose for the HSWBRT and HSWBRT and SIB plans was 8.06 Gy and 12.47 respectively. The max dose of optic nerve, optic chiasm and brainstem were kept below acceptable range of 37.5 Gy. Conclusions: The findings from this dosimetric study demonstrated the feasibility and safety of treating limited brain metastases with HSWBRT and SIB. It is possible to achieve the best of both worlds by combining HSWBRT and SIB to achieve maximal local intracranial control while maintaining as low a dose as possible to the hippocampus thereby preserving memory and quality of life.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3571-3574
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• 2014

Background: Brain metastasis occurs when cancerous cells come from a known (or sometimes an unknown) primary tumor to the brain and implant and grow there. This event is potentially lethal and causes neurologic symptoms and signs. These patients are treated in order to decrease their neurologic problems, increase quality of life and overall survival. Materials and Methods: In this study we evaluated clinical characteristics of 206 patients with brain metastases referred to our center from 2004 to 2011. Results: The mean age was 53.6 years. The primary tumors were breast cancer (32%), lung cancer (24.8%), lymphoma (4.4%), sarcoma (3.9%), melanoma (2.9%), colorectal cancer (2.4%) and renal cell carcinoma (1.5%). In 16.5% of the patients, brain metastasis was the first presenting symptom and the primary site was unknown. Forty two (20.4%) patients had a single brain metastasis, 18 patients (8.7%) had two or three lesions, 87 (42.2%) patients had more than three lesions. Leptomeningeal involvement was seen in 49 (23.8%) patients. Thirty five (17%) had undergone surgical resection. Whole brain radiation therapy was performed for all of the patients. Overall survival was 10.1 months (95%CI; 8.65-11.63). One and two year survival was 27% and 12% respectively. Conclusions: Overall survival of patients who were treated by combination of surgery and whole brain radiation therapy was significantly better than those who were treated with whole brain radiation therapy only [13.8 vs 9.3 months (p=0.03)]. Age, sex, primary site and the number of brain lesions did not show significant relationships with overall survival.

• Radiation Oncology Journal
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• 제6권2호
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• pp.169-176
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• 1988

1979년부터 1985년까지 서울대학교병원 치료방사선과에서 외부 방사선조사를 시행한 15명의 뇌하수체상부 배아세포종(전이송과선종) 환자에 대한 후향적 분석을 시행하였다. 생존자의 추적기간은 $30\~91$개월이었다. 10명의 환자는 방사선치료 전 조직학적으로 진단되었으며 나머지 5명은 조직학적 진단이 없이 방사선치료를 시행하였단 조직학적으로 진단된 9명중 배아세포종 환자 6명은 전뇌와 척추에 3명은 전뇌 조사를 시행하였다. 혼합 배아세포종 및 종양 marker양성인 5명의 환자 중 2명은 전뇌, 그리고 1명은 원발병소 부위에만 방사선치료를 시행하였다. 총 방사선량은 원발병소에 $5,000\~5,500 cGy$, 전뇌에 $3,000\~4,400 cGy$ 그리고 척추에 >$1,300\~3,000 cGy$였다. 상기 그룹 14명의 환자에서 원발병소는 완전 관해 되었으며 척추실패는 관찰되지 많았다. 조직학적 진만이 없고 marker의 상승이 없었던 한 환자에서 전뇌 방사선조사를 시행하였으나 원발병소의 완전관해 없이 척추 재발이 발생하였다. 방사선치료는 뇌하수체상부 배아세포종에 유효한 치료방법이며 신경 내분비학적 양상과 함께 조직학적 진단이 불가능한 경우에 있어서 소량의 방사선치료 후 관해정도 관찰은 이후의 치료방향설정에 유용한 수단으로 이용될 수 있다.

• Journal of Korean Neurosurgical Society
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• 제58권2호
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• pp.163-166
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• 2015

The prophylactic use of phenytoin during and after brain surgery and cranial irradiation is a common measure in brain tumor therapy. Phenytoin has been associated with variety of adverse skin reactions including urticaria, erythroderma, erythema multiforme (EM), Stevens-Johnson syndrome, and toxic epidermal necrolysis. EM associated with phenytoin and cranial radiation therapy (EMPACT) is a rare specific entity among patients with brain tumors receiving radiation therapy while on prophylactic anti-convulsive therapy. Herein we report a 41-year-old female patient with left temporal glial tumor who underwent surgery and then received whole brain radiation therapy and chemotherapy. After 24 days of continous prophylactic phenytoin therapy the patient developed minor skin reactions and 2 days later the patient returned with generalized erythamatous and itchy maculopapuler rash involving neck, chest, face, trunk, extremities. There was significant periorbital and perioral edema. Painful mucosal lesions consisting of oral and platal erosions also occurred and prevented oral intake significantly. Phenytoin was discontinued gradually. Systemic admistration of corticosteroids combined with topical usage of steroids for oral lesions resulted in complete resolution of eruptions in 3 weeks. All cutaneous lesions in patients with phenytoin usage with the radiotherapy must be evoluated with suspicion for EM.

• 대한방사선치료학회:학술대회논문집
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• 대한방사선치료학회 2004년도 춘계학술대회
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• pp.13-13
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• 2004

• 대한방사선치료학회지
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• 제26권1호
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• pp.77-81
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• 2014

목 적 : 현재 전뇌 방사선 치료 시 두부의 고정을 위하여 Optimold가 사용되고 있다. 하지만 Optimold로 인한 산란선에 의해 피부선량이 약 22% 증가하게 된다. 백내장을 일으키는 최소선량이 2 Gy 이므로 특히 수정체에서는 영향이 크다고 볼 수 있다. 이에 전뇌 방사선 치료 시 Optimold 안구 부분의 유무에 따른 수정체에 흡수되는 선량을 비교평가 하고자 한다. 대상 및 방법 : 안구 부분의 Optimold의 유무에 따른 수정체에 흡수되는 선량을 비교평가 하고자 인체모형팬텀(Anderson Rando Phantom, USA)의 수정체 부분에 5mm bolus를 올려 Optimold mask를 만들었다. 모의치료 시 수정체의 선량측정을 위해 bolus 밑에 GAFCHROMIC EBT3 film을 위치시켜 모의치료를 진행하고 전산화치료계획시스템(Pinnacle, PHILIPS, USA)을 통해 치료계획을 수립한 후 치료도 동일하게 진행하여 3회 반복측정 하였다. 안구 부분의 Optimold mask를 제거하고 위와 동일한 방법으로 측정하였다. 디지털 평판 스캐너(Expression 10000XL, EPSON, USA)를 이용하여 film을 스캔한 후 선량을 측정하여 안구 부분의 Optimold mask의 유무에 따른 선량을 비교평가 하였다. 결 과 : 안구 부분의 Optimold mask가 있을 때 모의치료 시 $10.2cGy{\pm}1.5$, 치료 시 $24.8cGy{\pm}2.7$, 안구 부분의 Optimold mask를 제거하였을 때 모의치료 시 $12.9cGy{\pm}2.2$, 치료 시 $17.6cGy{\pm}1.5$로 측정 되었다. 결 론 : 안구 부분의 Optimold mask를 제거하였을 경우 제거하지 않았을 경우에 비하여 모의치료 시 약 3 cGy의 선량이 증가하였고 치료 시 약 7 cGy의 선량이 감소하였다. 전 치료과정 중 수정체의 흡수선량이 약 27%감소되어 방사선감수성이 높은 수정체에 흡수되는 선량이 줄어 백내장을 일으킬 확률과 부작용을 감소시킬 수 있을 것으로 사료된다.