• Biomolecules & Therapeutics
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• v.20 no.4
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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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• v.1 no.1
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• pp.37-40
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• 1983

Whole brain irradiation is one mode in the treatment of brain cancer and brain metastasis, but it might cause brain injury such as brain necrosis. It has been studied whether the dose distribution could be a cause of brain injury. The dose distribution in whole brain irradiated by Co-60 beam has been measured by means of calibrated TLD chips inserted in the brain of Humanoid phantom. The following results were obtained. 1. Dose distribution on each transverse section of the brain was uniform. 2. On the midsagital plane of the brain, the dose was highest in upper portion and lowest in lower portion, varying 8 from 104% to 90%. 3. When the radiation field includes free space of 2cm or more width out of the head, the dose distribution in the whole brain is almost independent of the field width. 4. It is important to determine adequate shielding area and to set shielding block exactly in repetition of treatment.

• The Journal of Korean Society for Radiation Therapy
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• v.17 no.1
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• pp.9-17
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• 2005

Purpose : Uniform dose distribution of the target volume is very important in the radiation treatment. We will evaluate the usefulness of Field-in-Field Technique use to get uniform dose distribution of the target volume and try to find Apply possibility out to a whole brain treatment patient of various thickness. Material and method : We compare the dose distribution when we applied Field-in-Field Technique and parallel opposed fields technique. establish the treatment plan to a phantom(acryl 16cm spheral phantom) and do the measurement, assessment use the TLD and Low sensitivity film. Also the assessment did Apply possibility of Field-in-Field Technique to 20 patient object of various thickness. Result : In the case to use the parallel opposed fields at the whole brain treatment $10-12\%$ high dose region appeared but reduce to $3-4\%$ lesses when we used the Field-in-Field technique. We could get similar numerical value the film and TLD measurement result also. The change of the dose distribution appeared to its ${\pm}1{\sim}2\%$ although it applied such Field-in-Field technique to various patient so that we were identical. Conclusion : We can get uniform dose distribution of in the treatment region if we apply the Field-in-Field technique at the whole brain treatment. Also alternate can play the role of the wedge filter and 3D compensator and We are thought by minimizing the obstacle to be happened due to the high dose region when radiation treatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.4
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• pp.379-383
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• 2014

The purpose of this study is to investigate the effects of silkworm extracts (SWE) on reactive oxygen species formation in mice (C57BL/6). Mice were administrated intraperitoneally with SWE (20 mg/kg/day) for 14 days. All animals were sacrificed 24 hours after the last SWE treatment and then extracted the blood and brain tissue in mouse. The researcher measured several parameters related to reactive oxygen species formation, malondialdehyde (MDA) and hydrogen peroxide ($H_2O_2$) contents in serum, whole brain, cerebral cortex and cerebellum. The results showed that MDA content of pre-SWE treatment was decreased significantly in serum, mitochondrial and cytosolic fraction of whole brain and cerebellum (P<0.01). The $H_2O_2$ content of pre-SWE treatment was decreased significantly in mitochondrial fraction of whole brain, cerebral cortex and cerebellum (P<0.01). These results suggest that SWE plays an important role for inhibition of oxidative damage of cells as well as antioxidant effect, aging delay and cells protected from irradiation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7595-7597
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• 2015

Background: The aim of this study was to evaluate the effect of whole brain radiotherapy (WBRT) combined with streotactic radiosurgery versus stereotactic radiosurgery (SRS) alone for patients with brain metastases. Materials and Methods: This was a retrospective study that evaluated the results of 46 patients treated for brain metastases at Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Radiation Oncology Department, between January 2012 and January 2015. Twenty-four patients were treated with WBRT+SRS while 22 patients were treated with only SRS. Results: Time to local recurrence was 9.7 months in the WBRT+SRS arm and 8.3 months in SRS arm, the difference not being statistically significant (p=0.7). Local recurrence rate was higher in the SRS alone arm but again without significance (p=0,06). Conclusions: In selected patient group with limited number (one to four) of brain metastases SRS alone can be considered as a treatment option and WBRT may be omitted in the initial treatment.

• Radiation Oncology Journal
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• v.2 no.1
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• pp.33-39
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• 1984

One hundred and twenty patients with brain metastases were seen and evaluated in the Dept. of Therapeutic Radiology, Seoul National University Hospital between 1979 and 1983. Of these, 90 Patients received whole brain irradiation with 2,000 ra4 in 1 week or 3,000 rad in 2 weeks for Palliative Purpose and 30 patients failed to complete the planned treatment. Carcinoma of the lung(44 cases), choriocarcinoma(11 cases), breast(8 cases) were common Primary tumors of 90 patients receiving planned treatment. Symptomatic subjective response was obtained in $92\%$ of Patients and meurologic functional improvement was obtained in $42\%$ of patients. Median survival was 6.4 months in patients with complete treatment an·d less than 2 months in Patients with incomplete treatment, overall survival rate at 1 year and 2 year were $26\%,\;16\%$ in Patients with complete treatment and $8\%,\;0\%$ in patients with incomplete treatment. Primary site, extent of metastases and interval from diagnosis of primary tumor to brain metastases were identified as prognostic factors.

• Radiation Oncology Journal
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• v.34 no.1
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• pp.1-9
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• 2016

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5401-5406
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• 2015

Background: Brain metastases are the most common intra-cranial neoplasms. The incidence is on a rise due to advanced imaging techniques. Aims: The objective of the study was to analyse the clinical and demographic profile of patients with brain metastases from primary solid tumors. Materials and Methods: This is a retrospective single institutional study covering 130 consecutive patients with brain metastases from January 2007 to August 2014. Results: Some 64.6% of the patients were females. The majority were in the sixth decade of life. The site of the primary tumor was the lungs in 50.8% of the cases. The overall median time from the diagnosis of the primary malignancy to detection of brain metastases was 21.4 months. Survival was found to be significantly improved in patients with solitary brain lesions when compared to patients with multiple brain metastases, and in patients undergoing surgical excision with or without cranial irradiation when compared to whole brain irradiation alone. The majority of the cases belonged to the recursive partitioning analysis class II group. Whole brain radiation therapy was delivered to 79% of the patients. Conclusions: Most of the patients with brain metastases in the study belonged to recursive partitioning analysis classes II or III, and hence had poor prognosis. Most of the patients in the Indian context either do not satisfy the indications for surgical excision or are incapable of bearing the high cost associated with stereotactic radiosurgery. Treatment should be tailored on an individual basis to all these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1435-1442
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• 2015

Purpose: To study the patient load, treatment pattern, survival outcome and its predictors in patients with brain metastases treated by radiotherapy. Materials and Methods: Data for patients with brain metastases treated by radiotherapy between 2003 and 2007 were collected from medical records, the hospital information system database, and a population-based tumor registry database until death or at least 5 years after treatment and retrospectively reviewed. Results: The number of treatments for brain metastases gradually increased from 48 in 2003 to 107 in 2007, with more than 70% from lung and breast cancers. The majority were treated with whole brain radiation of 30 Gy (3 Gy X 10 fractions) by cobalt-60 machine, using radiation alone. The overall median survival of the 418 patients was 3.9 months. Cohort analysis of relative survival after radiotherapy was as follows: 52% at 3 months, 18% at 1 year and 3% at 5 years in males; and 66% at 3 months, 26% at 1 year and 7% at 5 years in females. Multivariate analysis demonstrated that the patients treated with combined modalities had a better prognosis. Poor prognostic factors included primary cancer from the lung or gastrointestinal tract, emergency or urgent consultation, poor performance status (ECOG 3-4), and a hemoglobin level before treatment of less than 10 g/dl. Conclusions: This study identified an increasing trend of patient load with brain metastases. Possible over-treatment and under-treatment were demonstrated with a wide range of survival results. Practical prognostic scoring systems to assist in decision-making for optimal treatment of different patient groups is absolutely necessary; it is a key strategy for balancing good quality of care and patient load.

• Radiation Oncology Journal
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• v.33 no.1
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• pp.36-41
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• 2015

Purpose: To evaluate the incidence and risk factors of post-treatment intracranial hemorrhage of brain metastases from hepatocellular carcinoma (HCC). Materials and Methods: Medical records of 81 patients who have been diagnosed of brain metastases from HCC and underwent surgery, radiosurgery and/or whole brain radiotherapy (WBRT) between January 2000 and December 2013 were retrospectively reviewed. Results: Intracranial hemorrhage was present in 64 patients (79%) at the time of diagnosis. Median value of alpha-fetoprotein (AFP) level was 1,700 ng/mL. The Eastern Cooperative Oncology Group (ECOG) performance status for 20 patients was greater than 2. Fifty-seven patients underwent WBRT and the others were treated with surgery and/or radiosurgery without WBRT. During follow-up, 12 events of intracranial hemorrhage after treatment were identified. Three-month post-treatment hemorrhage rate was 16.1%. Multivariate analyses revealed that ECOG performance status, AFP, and WBRT were associated with post-treatment hemorrhage (p = 0.013, 0.013, and 0.003, respectively). Kaplan-Meier analysis showed that 3-month post-treatment hemorrhage rate of new lesion was higher in patients treated without WBRT, although statistical significance was not reached. (18.6% vs. 4.6%; p = 0.104). Ten of 12 patients with post-treatment hemorrhage died with neurologic cause. Conclusion: WBRT should be considered to prevent post-treatment hemorrhage in the treatment of brain metastases from HCC.