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The Role of Surgery, Radiosurgery and Whole Brain Radiation Therapy in the Management of Patients with Metastatic Brain Tumors  [PDF]
Thomas L. Ellis,Matthew T. Neal,Michael D. Chan
International Journal of Surgical Oncology , 2012, DOI: 10.1155/2012/952345
Abstract: Brain tumors constitute the most common intracranial tumor. Management of brain metastases has become increasingly complex as patients with brain metastases are living longer and more treatment options develop. The goal of this paper is to review the role of stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), and surgery, in isolation and in combination, in the contemporary treatment of brain metastases. Surgery and SRS both offer management options that may help to optimize therapy in selected patients. WBRT is another option but can lead to late toxicity and suboptimal local control in longer term survivors. Improved prognostic indices will be critical for selecting the best therapies. Further prospective trials are necessary to continue to elucidate factors that will help triage patients to the proper brain-directed therapy for their cancer. 1. Introduction Brain metastases are the most common intracranial tumor, arising in 10%–40% of all cancer patients [1, 2] and accounting for up to 170,000 new cases per year in the United States [3]. The observation of rising incidence is most likely related to the aging population, improved systemic treatment for the primary disease, and improved imaging techniques [4]. As a result, brain metastases are an increasing source of morbidity and mortality as well as cognitive impairment at the time of cancer diagnosis [5, 6]. Cancers with a high incidence in the general population (e.g., lung and breast) are the most frequently encountered source of brain metastases, accounting for up to two thirds of new cases [7]. Solid tumors constitute 95% of brain metastases, while leptomeningeal involvement makes up the remaining 5% [8–10]. Approximately 50%–60% of patients with solid tumors present with multiple metastases, while the remaining patients harbor a single mass [1, 11, 12]. The prognosis for patients with brain metastases from any histology is poor overall, with a median survival of only 4–7 months following treatment with WBRT alone [12–22]. For patients harboring a single, surgically amenable lesion, resection followed by WBRT has been found to be favorable to WBRT alone in two of three randomized controlled trials [17, 19, 22]. The local control rates and overall survival for patients with a single metastasis treated either with surgical resection followed by WBRT or with stereotactic radiosurgery (SRS) alone have been found to be similar [18, 19, 22–28]. On the other hand, SRS may yield superior local control rates for radioresistant brain metastases (e.g., from melanoma and renal cell) and
Overall Survival and Related Prognostic Factors in Metastatic Brain Tumors Treated with Whole Brain Radiation Therapy
A.Sh. Yousefi Kashi,B. Mofid,H.R. Mirzaei,P. Azadeh
Research Journal of Medical Sciences , 2012, DOI: 10.3923/rjmsci.2010.213.216
Abstract: Multiple brain metastases are a common health problem, frequently found in patients with cancer. The prognosis, even after treatment with Whole-Brain Radiation Therapy (WBRT) is poor with an average expected survival time of >6 months. To evaluate the prognostic factors associated with overall survival in patients with brain metastasis treated with Whole Brain Radio Therapy (WBRT) and estimate the potential improvement in survival for patients with brain metastases, stratified by Karnofsky Performance Status (KPS), gender, age, number of lesions, primary tumor site, surgery, chemotherapy and radiation doses and fractionation. From January 2007 to May 2010, 54 medical records of patients with diagnosis of brain metastasis, who received WBRT in the shohadaye tajrish in Tehran Iran were analyzed. The most common primary tumor type was breast (22.2%) followed by lung (21.9%), unknown primary (16.6%) and solitary brain metastasis was present in 29.6% of patients. The surgery followed by WBRT was used in 11.1% of patients and 88.9% of others patients were submitted at WBRT alone. About 36 patients (66.7%) received the fractionation schedule of 30 Gy in 10 fractions. The prognostic factors evaluated for overall survival were Karnofsky Performance Status (KPS), gender, age, number of lesions, primary tumor site, surgery, chemotherapy and radiation doses and fractionation. The OS in 1 and 2 years was 15, 3, 5 and 4%, respectively and the median survival time was 3.5 months. In the analysis, the significant prognostic factors associated with better survival were: KPS>70 (p<0.001), neurosurgery (p<0.001), primary tumor site breast (p<0.001) and solitary brain metastasis (p = 0. 01). In this series, the patients with higher perform status or primary tumor site breast or treated with surgery followed by whole brain radiotherapy had better survival. This data suggest that patients with cancer and a single metastasis to the brain may be treated effectively with surgical resection plus radiotherapy. The different gender, age, radiotherapy doses and fractionation schedules did not altered survival.
Differential responses of tumors and normal brain to the combined treatment of 2-DG and radiation in glioablastoma  [cached]
Prasanna Venkatesh,Venkataramana Neelam,Dwarakanath B,Santhosh Vani
Journal of Cancer Research and Therapeutics , 2009,
Abstract: 2-deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, enhances radiation damage selectively in tumor cells by modulating damage response pathways resulting in cell death in vitro and local tumor control. Phase I and II clinical trials in patients with malignant glioma have shown excellent tolerance to a combined treatment of orally administered 2-DG and hypofractionated radiotherapy without any acute toxicity and late radiation damage. Phase III efficacy trials are currently at an advanced stage. Re-exploratory surgery performed in 13 patients due to persistent symptoms of elevated ICP and mass effect at different follow-up periods revealed extensive tumor necrosis with well-preserved normal brain tissue adjoining the tumor included in the treatment volume as revealed by a histological examination. These observations are perhaps the first clinical evidences for differential effects of 2-DG on tumors and normal tissues in conformity with earlier in vitro and in vivo studies in normal and tumor-bearing mice.
Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors
Hemant Sarin
Journal of Translational Medicine , 2009, DOI: 10.1186/1479-5876-7-77
Abstract: Malignant brain tumors consist of high-grade primary brain tumors such as malignant gliomas[1], and metastatic lesions to the brain from peripheral cancers such as lung, breast, renal, gastrointestinal tract, and melanoma[2,3]. Glioblastoma, the highest grade of malignant glioma, is the most common high-grade primary brain tumor in adults[4,5]. Overall, metastatic brain tumors are the most common brain tumors in adults, as 10% to 20% of patients with a malignant peripheral tumor develop brain metastases[2,3,6]. Even though malignant gliomas are generally treated with a combination of surgery, radiotherapy and systemic chemotherapy[7,8], and metastatic brain tumors with a combination of surgery and radiotherapy [9-11], the overall long-term prognosis of patients with these tumors, whether primary or metastatic, remains poor. Patient median survival times typically range between 3 and 16 months [12-16], and the percentage of patients alive at 5 years ranges between 3% and 10%[12,13,16,17]. In the treatment of both malignant gliomas and metastatic brain tumors, surgery and radiotherapy are more effective when used in combination[7-11,18-20]. In the treatment of malignant gliomas, there some minimal additional benefit of systemic chemotherapy[8,15,20-27]; and in the treatment of metastatic brain tumors, it remains unclear as to if there is any additional benefit of systemic chemotherapy[9,10,28-31].Systemic chemotherapy consists of small molecule chemotherapy drugs[8,32] that are drugs of molecular weights (MW) less than 1 kDa and diameters less than 1 to 2 nm. These small molecule chemotherapy drugs include traditional drugs that target the cell cycle, for example, DNA alkylating drugs, and newer investigational drugs that target cell surface receptors and associated pathways, for example, tyrosine kinase inhibitors[8,32]. The ineffectiveness of these chemotherapy drugs in treating malignant brain tumors has been attributed to the blood-brain barrier (BBB) being a sign
USE OF PROTON MAGNETIC RESONANCE SPECTROSCOPIC IMAGING DATA IN PLANNING FOCAL RADIATION THERAPIES FOR BRAIN TUMORS  [cached]
Edward E Graves,Andrea Pirzkall,Tracy R Mcknight,Daniel B Vigneron
Image Analysis and Stereology , 2002, DOI: 10.5566/ias.v21.p69-76
Abstract: Advances in radiation therapy for malignant neoplasms have produced techniques such as Gamma Knife radiosurgery, capable of delivering an ablative dose to a specific, irregular volume of tissue. However, efficient use of these techniques requires the identification of a target volume that will produce the best therapeutic response while sparing surrounding normal brain tissue. Accomplishing this task using conventional computed tomography (CT) and contrast-enhanced magnetic resonance imaging (MRI) techniques has proven difficult because of the difficulties in identifying the effective tumor margin. Magnetic resonance spectroscopic imaging (MRSI) has been shown to offer a clinically-feasible metabolic assessment of the presence and extent of neoplasm that can complement conventional anatomic imaging. This paper reviews current Gamma Knife protocols and MRSI acquisition, reconstruction, and interpretation techniques, and discusses the motivation for including magnetic resonance spectroscopy findings while planning focal radiation therapies. A treatment selection and planning strategy incorporating MRSI is then proposed, which can be used in the future to assess the efficacy of spectroscopy-based therapy planning.
Patient Specification Quality Assurance for Glioblastoma Multiforme Brain Tumors Treated with Intensity Modulated Radiation Therapy  [cached]
H. I. Al-Mohammed
International Journal of Medical Sciences , 2011,
Abstract: The aim of this study was to evaluate the significance of performing patient specification quality assurance for patients diagnosed with glioblastoma multiforme treated with intensity modulated radiation therapy. The study evaluated ten intensity modulated radiation therapy treatment plans using 10 MV beams, a total dose of 60 Gy (2 Gy/fraction, five fractions a week for a total of six weeks treatment). For the quality assurance protocol we used a two-dimensional ionization-chamber array (2D-ARRAY). The results showed a very good agreement between the measured dose and the pretreatment planned dose. All the plans passed >95% gamma criterion with pixels within 5% dose difference and 3 mm distance to agreement. We concluded that using the 2D-ARRAY ion chamber for intensity modulated radiation therapy is an important step for intensity modulated radiation therapy treatment plans, and this study has shown that our treatment planning for intensity modulated radiation therapy is accurately done.
Childhood Brain tumors
Mrs. Rupali A. Patil.,Ritesh Soni
Pharmaceutical Reviews , 2007,
Abstract: Childhood brain tumors are a diverse group of diseases characterized by the abnormal growth of tissue contained within the skull. Brain tumors can be benign (without cancer cells) or malignant (contains cancer cells).The brain controls vital functions such as memory and learning, the senses (hearing, sight, smell, taste, and touch), and emotion.It also controls other parts of the body, including muscles, organs, and blood vessels. Other than leukemia and lymphoma, brain tumors are the most common type of cancer that occurs in children.The articles in this section refer only to tumors that originate in the brain (primary brain tumors). Metastatic brain tumors, which are secondary tumors formed by cancer cells that begin in other parts of the body and spread to the brain, are not included. Brain tumors can occur in both children and adults; however, treatment may be different for adults than for children.
Recent advances in imaging of brain tumors  [cached]
Sanghvi D
Indian Journal of Cancer , 2009,
Abstract: The recent advances in brain tumor imaging offer unique anatomical as well as pathophysiological information that provides new insights on brain tumors, directed at facilitating therapeutic decisions and providing information regarding prognosis. This information is presently utilized in clinical practice for initial diagnosis and noninvasive, preoperative grading of tumors, biopsy planning, surgery, and radiation portal planning, as well as, prognostication. The newer advances described in this review include magnetic resonance (MR) diffusion and diffusion tensor imaging with tractography, perfusion imaging, MR spectroscopy, and functional imaging, using the blood oxygenation level dependent (BOLD) technique. Diffusion tensor MR imaging is the only noninvasive in vivo method for mapping white matter fiber tract trajectories in the human brain. In the current clinical practice, one of the most important indications of diffusion tensor imaging (DTI) is to study the relation of a tumor to the adjacent white matter tracts. Perfusion imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is an exciting new radiological technique for noninvasive evaluation of cerebral hemodynamics, in certain definite clinical settings. Cerebral perfusion imaging describes the passage of blood through the brain′s vascular network. Perfusion imaging, especially with MRI has become an integral component of the complete radiological assessment of brain tumors. MR Spectroscopy (MSR) is the only noninvasive technique capable of measuring chemicals within the body. MRS distinguishes various metabolites on the basis of their slightly different chemical shifts or resonance frequencies. Functional MRI refers to the demonstration of brain function with neuroanatomic localization on a real-time basis. In patient care, functional MR imaging is primarily used in the preoperative evaluation of the relationship of a brain tumor with an eloquent cortex. The next decade will witness further sophistication of these techniques, with data available from larger studies. It is expected that imaging will continue to provide new and unique insights in neuro-oncology, which should hopefully contribute to the better management of patients with brain tumors.
Biomarkers of Pediatric Brain Tumors  [PDF]
Mark D. Russell,Adam M. H. Young,Surya K. Karri
Frontiers in Pediatrics , 2013, DOI: 10.3389/fped.2013.00007
Abstract: Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as cancer antigen (CA) 19-9 and CA 125 facilitate early diagnosis and treatment.
Cell Phones and Brain Tumors  [PDF]
Nezih OKTAR
Journal of Neurological Sciences , 2011,
Abstract: The use of cellular (mobile) phones is widespread all over the world nowadays. Brain is the organ with the highest near-field exposure to microwaves during the use of the mobile phones. I've searched in “Science” magazine about the “cell phones and brain tumor” topics a week ago and have found only one resource which was dated back to 2001 (Cell phone lawsuits face a scientific test. Parascandola M. Science 294:1440-2, 16 Nov 2001)(10). This single source was dealing with the claims of a neurologist who diagnosed a life-threatening brain tumor and he concluded that it was caused by the cell-phone. Evidence that radiation from cell phones increases the risk of brain cancer has not fared well in the court of scientific opinion; is it acceptable in the court of law?...
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