• 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.

• Journal of Radiation Protection and Research
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• 제38권4호
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• pp.166-171
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• 2013

While high-dose ionizing radiation results in long term cellular cytotoxicity, chronic low-dose (<0.2 Gy) of X- or ${\gamma}$-ray irradiation can be beneficial to living organisms by inducing radiation hormesis, stimulating immune function, and adaptive responses. During chronic low-dose-rate radiation (LDR) exposure, whole body of mice is exposed to radiation, however, it remains unclear if LDR causes changes in gene expression of the whole brain. Therefore, we aim to investigate expressed genes (EGs) and signaling pathways specifically regulated by LDR-irradiation ($^{137}Cs$, a cumulative dose of 1.7 Gy for total 100 days) in the whole brain. Using microarray analysis of whole brain RNA extracts harvested from ICR and AKR/J mice after LDR-irradiation, we discovered that two mice strains displayed distinct gene regulation patterns upon LDR-irradiation. In ICR mice, genes involved in ion transport, transition metal ion transport, and developmental cell growth were turned on while, in AKR/J mice, genes involved in sensory perception, cognition, olfactory transduction, G-protein coupled receptor pathways, inflammatory response, proteolysis, and base excision repair were found to be affected by LDR. We validated LDR-sensitive EGs by qPCR and confirmed specific upregulation of S100a7a, Olfr624, and Gm4868 genes in AKR/J mice whole brain. Therefore, our data provide the first report of genetic changes regulated by LDR in the mouse whole brain, which may affect several aspects of brain function.

• Radiation Oncology Journal
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• 제31권1호
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• pp.12-17
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• 2013

Purpose: Parotid gland can be considered as a risk organ in whole brain radiotherapy (WBRT). The purpose of this study is to evaluate the parotid gland sparing effect of computed tomography (CT)-based WBRT compared to 2-dimensional plan with conventional field margin. Materials and Methods: From January 2008 to April 2011, 53 patients underwent WBRT using CT-based simulation. Bilateral two-field arrangement was used and the prescribed dose was 30 Gy in 10 fractions. We compared the parotid dose between 2 radiotherapy plans using different lower field margins: conventional field to the lower level of the atlas (CF) and modified field fitted to the brain tissue (MF). Results: Averages of mean parotid dose of the 2 protocols with CF and MF were 17.4 Gy and 8.7 Gy, respectively (p < 0.001). Mean parotid dose of both glands ${\geq}20$ Gy were observed in 15 (28.3%) for CF and in 0 (0.0%) for MF. The whole brain percentage volumes receiving >98% of prescribed dose were 99.7% for CF and 99.5% for MF. Conclusion: Compared to WBRT with CF, CT-based lower field margin modification is a simple and effective technique for sparing the parotid gland, while providing similar dose coverage of the whole brain.

• Radiation Oncology Journal
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• 제1권1호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.911-915
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• 2014

Aim: This study was to evaluate the effect of whole brain radiation (WBRT) combined with stereotactic radiotherapy (SRS) versus stereotactic radiotherapy alone for patients with brain metastases using a meta-analysis. Materials and Methods: We searched PubMed, EMBASE, Cochrane Library from their inception up to October 2013. Randomized controlled trials involving whole brain radiation combined with stereotactic radiotherapy versus stereotactic radiotherapy alone for brain metastases were included. Statistical analyses were performed using RevMan5.2 software. Results: Four randomized controlled trials including 903 patients were included. The meta-analysis showed statistically significant lowering of the local recurrence rate (OR=0.29, 95%CI: 0.17~0.49), new brain metastasis rate (OR=0.45, 95%CI: 0.28~0.71) and symptomatic late neurologic radiation toxicity rate (OR=3.92, 95%CI: 1.37~11.20) in the combined group. No statistically significant difference existed in the 1-year survival rate (OR=0.78, 95%CI: 0.60~1.03). Conclusions: The results indicate that whole brain radiotherapy combined with stereotactic radiotherapy has advantages in local recurrence and new brain metastasis rates, but stereotactic radiotherapy alone is associated with better neurological function. However, as the samples included were not large, more high-quality, large-sample size studies are necessary for confirmation.

• 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.

• 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.

• 대한방사선치료학회지
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• 제17권1호
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• pp.9-17
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• 2005

목적 : 방사선치료에 있어 치료부위내의 균등한 선량분포는 환자의 치료성적 및 장해를 좌우하는 매우 중요한 인자이다. 이러한 치료부위내의 균등한 선량분포를 얻기 위해 사용하는 여러 가지 방법 중 간단한 Field-in-Field Technique의 유용성을 평가하고 다양한 크기의 전뇌(whole brain)치료 환자에게 적용가능성을 알아보고자 한다. 대상 및 방법 : 전뇌(whole brain)의 일반적인 치료기법인 대향2문조사와 Field-in-Field Technique을 적용했을 때의 선량분포도를 비교하기 위하여 phantom(acryl 16 cm spheral phantom)을 대상으로 치료계획을 수립하였으며, 선량분포평가를 위하여 저감도필름(X-Omat V-film)과 열형광선량계(TLD)를 사용하여 측정하였다. 또한 다양한 두께의 환자20명(대, 중, 소 및 소아-각각 5명)을 대상으로 Field-in-Field Technique의 적용가능성을 평가 하였다 결과 : 전뇌(whole brain)치료에 대향2문조사와 Field-in-Field Technique을 적용한 경우 각각의 치료부위내의 선량분포 및 DVH를 비교한 결과, Field-in-Field Technique을 사용한 경우 고선량(high dose)영역을 $3{\sim}4\%$이하로 줄일 수 있었고, 저감도필름(X-Omat V-film)과 열형광선량계(TLD)에 의한 측정결과 또한 유사한 수치를 얻을 수 있었다. 이러한 Field-in-Field Technique을 다양한 두께의 환자에게 동일하게 적용해도 선량분포의 변화는 $1{\sim}2\%$로 나타났다. 결론 : 전뇌(whole brain)치료에 Field-in-Field Technique를 이용하여 치료계획을 수립하여 적용하면 치료부위내의 균등한 선량분포를 얻을 수 있으므로 추가적인 치료가 필요한 경우 선량합성이 용이하여 쉽게 치료계획을 수립할 수 있었다. 그리고 균등한 선량분포를 얻기 위해 사용하는 wedge filter 및 3D compensator 의 역할을 대체 할 수 있으며, 방사선 치료 시 고선량 영역으로 인해 발생되는 장해를 최소화할 수 있을 것으로 사료된다.