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Sample records for brain cancer propagating

  1. Brain cancer spreads

    DEFF Research Database (Denmark)

    Perryman, Lara; Erler, Janine Terra

    2014-01-01

    The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue).......The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue)....

  2. Cube propagation for focal brain atrophy estimation

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru; Sørensen, Lauge; Darkner, Sune

    2013-01-01

    Precise and robust whole brain, ventricle, and hippocampal atrophy measurements are important as they serve as biomarkers for Alzheimer’s disease. They are used as secondary outcomes in drug trials, and they correlate with the cognitive scores. When two successive scans are non-linearly aligned...

  3. Brain cancer treatment

    International Nuclear Information System (INIS)

    Gruszow, S.

    1998-01-01

    As soon as 1936 an American physicist proposed to treat certain forms of cancer by using the nuclear reaction: n + 10 B → 7 Li + 4 He where the alpha particles produced could destroy the DNA of surrounding cells. From 1951 to 1961 62 patients underwent this treatment for brain cancer. The results were unsatisfactory: the neutrons were not energetic enough to enter brain tissues deeply and were accompanied by strongly damaging gamma radiation. In Netherlands an installation using the high flux reactor of Petten has been set up. A highly focused neutron beam of about 10 keV with reduced gamma radiation is produced. The first step is to determine the limit exposure and the maximal permissible concentration of boron. (A.C.)

  4. Brain metastasis from colorectal cancer

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Hirosawa, Tomoichiro; Ogawa, Shinpei; Noguchi, Eiichiro; Takemoto, Kaori; Shirotani, Noriyasu; Kameoka, Shingo

    2007-01-01

    The present study was performed to clarify the clinical characteristics of brain metastasis from colorectal cancer. Five patients with brain metastasis from colorectal cancer treated at our institute between 2001 and 2005 were included in the study. Clinical findings and survival time were determined and an appropriate system for follow-up in such cases was considered. Brain metastasis was found after surgery for colorectal cancer in 4 cases. In addition, colorectal cancer was found after diagnosis of brain metastasis in 1 case. At the time of diagnosis of brain metastasis, all patients had lung metastasis and 3 had liver metastasis. The mean periods between surgery for colorectal cancer and lung and brain metastases were 19.5 and 38.2 months, respectively. In all cases, brain metastasis was diagnosed by imaging after the appearance of neurological symptoms. Brain metastases were multiple in 1 case and focal in 4 cases. We performed gamma knife radiation therapy, and the symptoms disappeared or decreased in all cases. Mean survival time after brain metastasis was 3.0 months. Prognosis after brain metastasis is poor, but gamma knife radiation therapy contributed to patients' quality of life. (author)

  5. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  6. Computer screens and brain cancer

    International Nuclear Information System (INIS)

    Wood, A.W.

    1995-01-01

    Australia, both in the media and at the federal government level, over possible links between screen-based computer use and cancer, brain tumour in particular. The screen emissions assumed to be the sources of the putative hazard are the magnetic fields responsible for horizontal and vertical scanning of the display. Time-varying fluctuations in these magnetic fields induce electrical current flows in exposed tissues. This paper estimates that the induced current densities in the brain of the computer user are up to 1 mA/m 2 (due to the vertical flyback). Corresponding values for other electrical appliances or installations are in general much less than this. The epidemiological literature shows no obvious signs of a sudden increase in brain tumour incidence, but the widespread use of computers is a relatively recent phenomenon. The occupational use of other equipment based on cathode ray tubes (such as TV repair) has a much longer history and has been statistically linked to brain tumour in some studies. A number of factors make this an unreliable indicator of the risk from computer screens, however. 42 refs., 3 tabs., 2 figs

  7. Skull and cerebrospinal fluid effects on microwave radiation propagation in human brain

    Science.gov (United States)

    Ansari, M. A.; Zarei, M.; Akhlaghipour, N.; Niknam, A. R.

    2017-12-01

    The determination of microwave absorption distribution in the human brain is necessary for the detection of brain tumors using thermo-acoustic imaging and for removing them using hyperthermia treatment. In contrast to ionizing radiation, hyperthermia treatment can be applied to remove tumors inside the brain without the concern of including secondary malignancies, which typically form from the neuronal cells of the septum pellucidum. The aim of this study is to determine the microwave absorption distribution in an adult human brain and to study the effects of skull and cerebrospinal fluid on the propagation of microwave radiation inside the brain. To this end, we simulate the microwave absorption distribution in a realistic adult brain model (Colin 27) using the mesh-based Monte Carlo (MMC) method. This is because in spite of there being other numerical methods, the MMC does not require a large memory, even for complicated geometries, and its algorithm is simple and easy to implement with low computational cost. The brain model is constructed using high-resolution (1 mm isotropic voxel) and low noise magnetic resonance imaging (MRI) scans and its volume contains 181×217×181 voxels, covering the brain completely. Using the MMC method, the radiative transport equation is solved and the absorbed microwave energy distribution in different brain regions is obtained without any fracture or anomaly. The simulation results show that the skull and cerebrospinal fluid guide the microwave radiation and suppress its penetration through deep brain compartments as a shielding factor. These results reveal that the MMC can be used to predict the amount of required energy to increase the temperature inside the tumour during hyperthermia treatment. Our results also show why a deep tumour inside an adult human brain cannot be efficiently treated using hyperthermia treatment. Finally, the accuracy of the presented numerical method is verified using the signal flow graph technique.

  8. Nanotherapeutic approaches for brain cancer management.

    Science.gov (United States)

    Saenz del Burgo, Laura; Hernández, Rosa María; Orive, Gorka; Pedraz, Jose Luis

    2014-07-01

    Around the world, cancer remains one of the most important causes of morbidity and mortality. Worldwide, approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed every year. Nanotherapeutic approaches hold tremendous potential for diagnosis and treatment of brain cancer, including the ability to target complex molecular cargoes to the tumor sites and the capacity of crossing the blood-brain barrier and accessing to the brain after systemic administration. A new generation of "smart" nanoparticles has been designed as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic and thermotherapy. This review highlights the latest research, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers. This comprehensive review highlights the latest research results, opportunities and challenges for developing novel nanotherapeutics for treating brain cancers, with a special focus on "smart" nanoparticles as novel targeted delivery devices for new therapies including gene therapy, anti-angiogenic therapy and localized thermotherapy. © 2014.

  9. Characteristics of brain injury induced by shock wave propagation in solids after underwater explosion in rats

    Directory of Open Access Journals (Sweden)

    Xin-ling LI

    2016-09-01

    Full Text Available Objective  To observe the characteristics of rat brain injury induced by shock wave propagation in solids resulting from underwater explosion and explore the related mechanism. Methods  Explosion source outside the simulated ship cabin underwater was detonated for establishing a model of brain injury in rats by shock wave propagation in solid; 72 male SD rats were randomly divided into normal control group (n=8, injury group 1 (600mg RDX paper particle explosion source, n=32, injury group 2 (800mg RDX paper particle explosion source, n=32. The each injury group was randomly divided into 4 subgroups (n=8, 3, 6, 24 and 72h groups. The division plate as a whole and the head of 8 rats in each injury group were measured for the peak value of the solid shock wave, its rising time and the duration time of shock wave propagation in solid. To observe the physiological changes of animals after injury, plasma samples were collected for determination of brain damage markers, NSE and S-100β. All the animals were sacrificed, the right hemisphere of the brain was taken in each group of animals, weighting after baking, and the brain water content was calculated. Pathological examination was performed for left cerebral hemisphere in 24-h group. The normal pyramidal cells in the hippocampal CA1 region were counted. Results  The peak value, rising time and duration time of shock wave propagation on the division plate and head were 1369.74±91.70g, 0.317±0.037ms and 24.85±2.53ms, 26.83±3.09g, 0.901±0.077ms and 104.21±6.26ms respectively in injury group 1, 1850.11±83.86g, 0.184±0.031ms and 35.61±2.66ms, 39.75±3.14g, 0.607±0.069ms and 132.44±7.17ms in injury group 2 (P<0.01. After the injury, there was no abnormality in the anatomy, and brain damage markers NSE, S-100β increased, reached the peak at 24 h, and they were highest in injury group 2 and lowest in control group with a statistically significant difference (P<0.05. The brain water content

  10. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    Directory of Open Access Journals (Sweden)

    D Case

    2016-10-01

    Full Text Available Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on the strains/stresses and pressure gradients and concentrations created in the brain tissue due to propagation of waves produced by the impact through the complex internal structure of the human head. This approach has the potential to expand our understanding of the mechanism of brain injury, and to better assess the risk of delayed neurological disorders for tens of thousands of young athletes throughout the world.

  11. Evaluation of seizure propagation on ictal brain SPECT using statistical parametric mapping in temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Jeon, Tae Joo; Lee, Jong Doo; Kim, Hee Joung; Lee, Byung In; Kim, Ok Joon; Kim, Min Jung; Jeon, Jeong Dong

    1999-01-01

    Ictal brain SPECT has a high diagnostic sensitivity exceeding 90 % in the localization of seizure focus, however, it often shows increased uptake within the extratemporal areas due to early propagation of seizure discharge. This study aimed to evaluate seizure propagation on ictal brian SPECT in patients with temporal lobe epilepsy (TLE) by statistical parametric mapping (SPM). Twenty-one patients (age 27.14 5.79 y) with temporal lobe epilepsy (right in 8, left in 13) who had successful seizure outcome after surgery and nine normal control were included. The data of ictal and interictal brain SPECT of the patients and baseline SPECT of normal control group were analyzed using automatic image registration and SPM96 softwares. The statistical analysis was performed to compare the mean SPECT image of normal group with individual ictal SPECT, and each mean image of the interictal groups of the right or left TLE with individual ictal scans. The t statistic SPM [t] was transformed to SPM [Z] with a threshold of 1.64. The statistical results were displayed and rendered on the reference 3 dimensional MRI images with P value of 0.05 and uncorrected extent threshold p value of 0.5 for SPM [Z]. SPM data demonstrated increased uptake within the epileptic lesion in 19 patients (90.4 %), among them, localized increased uptake confined to the epileptogenic lesion was seen in only 4 (19%) but 15 patients (71.4%) showed hyperperfusion within propagation sites. Bi-temporal hyperperfusion was observed in 11 out of 19 patients (57.9%, 5 in the right and 6 in the left); higher uptake within the lesion than contralateral side in 9, similar activity in 1 and higher uptake within contralateral lobe in one. Extra-temporal hyperperfusion was observed in 8 (2 in the right, 3 in the left, 3 in bilateral); unilateral hyperperfusion within the epileptogenic temporal lobe and extra-temporal area in 4, bi-temporal with extra-temporal hyperperfusion in remaining 4. Ictal brain SPECT is highly

  12. Isolation and propagation of colon cancer stem cells

    NARCIS (Netherlands)

    Prasetyanti, Pramudita R.; Zimberlin, Cheryl; de Sousa E Melo, Felipe; Medema, Jan Paul

    2013-01-01

    The design of tissue culture conditions that faithfully reproduce the characteristics of cells in their native environment remains one of the main challenges of cancer stem cell (CSC) biology. Here we describe a detailed methodology for the isolation and expansion of both human colon CSCs and mouse

  13. Treatment strategies for lung cancer brain metastases

    International Nuclear Information System (INIS)

    Nakade, Masaharu; Kohno, Keijirou; Watanabe, Hiroyoshi

    1997-01-01

    Forty-one patients suffered initial relapses with brain metastasis after surgery for non-small lung cancer at our hospital between 1978 and 1995. These patients were a total of 8.4% of all cases of surgical removal, and had an average relapse period of 8.6 months ± 8.0 months after surgery on the primary lesions. Of these, surgical removal of metastasized lesions was performed on 18 patients (43%), in which the 5-year post-operative survival rate was 35.7%, and the median survival time was good at 28 months. It was found that the survival period was significantly extended in the group whose relapse period was less than one year after surgery on the primary lesions, and in the group who received cranial irradiation post-operatively on the metastasized brain lesion. Following surgery on the metastasized lesion, second relapses occurred in nine patients, and six patients suffered from second relapses in the brain, of which four did not receive cranial irradiation post-operatively. Cases of radiotherapy in patients of 70 years of age or more frequently manifested post-radiotherapy subacute neuropathy. From the above, it is thought that the following procedures should be adopted: Periodic examination for brain metastasis during the 24 months following surgery for non-small cell lung carcinoma for purposes of early detection; in cases where brain metastasis is detected, if no metastasis is identified in other organs, a policy of surgical removal should be adopted where possible; and, in cases of 70 years of age or less following surgery on the metastasized lesion, cranial irradiation should be considered. (author)

  14. Physics of cancer propagation: A game theory perspective

    Directory of Open Access Journals (Sweden)

    Chris Cleveland

    2012-03-01

    Full Text Available This is a theoretical paper which examines at a game theoretical perspective the dynamics of cooperators and cheater cells under metabolic stress conditions and high spatial heterogeneity. Although the ultimate aim of this work is to understand the dynamics of cancer tumor evolution under stress, we use a simple bacterial model to gain fundamental insights into the progression of resistance to drugs under high competition and stress conditions.

  15. Conformity index for brain cancer patients

    International Nuclear Information System (INIS)

    Petkovska, Sonja; Tolevska, Cveta; Kraleva, Slavica; Petreska, Elena

    2010-01-01

    The purpose of this study is to present the level of conformity achieved by using 3D conformal radiotherapy for brain cancer patients. Conformity index is a helpful quantitative tool for assessing (evaluating) the quality of a treatment plan. Treatment plans made for ninety patients with brain tumor are worked on this paper. The patients are in supine position and immobilized with thermoplastic masks for the head. Computed tomography data sets with 5 mm scan thickness are used to create a 3D image. All structures of interest are contoured. In order to obtain an optimal dose distribution, treatment fields are fit around target volume with set-up margins of 7mm in each direction. The conformity index values are between 1.21 and 2.04. Value of 1.8 is exceeded in eighteen cases; nine of them are bigger than 1.9 and only three of them are above 2. The target volume for each of these extreme CI values is ideal covered (between 95% and 105% of the prescribed dose). The most acceptable conformity index value in this paper belongs to the plan with the lowest minimal dose (84.7%). It can be concluded that conformity index is necessary but not sufficient factor for assessing radiation treatment plan conformity. To be able to estimate the acceptability of some treatment plan in daily practice, additional information as minimal, maximal and mean dose into target volume, as well as health tissues coverage must be taken into account.(Author)

  16. Brain abscess mimicking lung cancer metastases; a case report.

    Science.gov (United States)

    Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

    2013-01-01

    A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    Background: Brain metastasis of lung cancer adversely affects overall survival (OS) and quality of life, while peritumoral brain edema is responsible for life-threatening complications. Methods: We retrospectively analyzed the clinicopathological and cerebral radiological data of 575 consecutive...... lung cancer patients with brain metastases. Results: In adenocarcinoma and squamous cell carcinoma, peritumoral brain edema was more pronounced than in small-cell lung cancer (p ... of peritumoral brain edema (p

  18. Parcellation of the Healthy Neonatal Brain into 107 Regions Using Atlas Propagation through Intermediate Time Points in Childhood.

    Science.gov (United States)

    Blesa, Manuel; Serag, Ahmed; Wilkinson, Alastair G; Anblagan, Devasuda; Telford, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Macnaught, Gillian; Semple, Scott I; Bastin, Mark E; Boardman, James P

    2016-01-01

    Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39(+5) weeks, range 37(+2)-41(+6)). An adult brain atlas (SRI24/TZO) was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database), with the final atlas (Edinburgh Neonatal Atlas, ENA33) constructed using the Symmetric Group Normalization (SyGN) method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modeling brain growth during development.

  19. Parcellation of the healthy neonatal brain into 107 regions using atlas propagation through intermediate time points in childhood

    Directory of Open Access Journals (Sweden)

    Manuel eBlesa Cabez

    2016-05-01

    Full Text Available Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39+5 weeks, range 37+2-41+6. An adult brain atlas (SRI24/TZO was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database, with the final atlas (Edinburgh Neonatal Atlas, ENA33 constructed using the Symmetric Group Normalization method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modelling brain growth during development.

  20. The Biology of Breast Cancer in Brain Metastasis

    National Research Council Canada - National Science Library

    Price, Janet

    2001-01-01

    ...% of breast cancer patients and found at autopsy in 20 to 30%. Survival after detection of brain metastases can be short, and the therapy currently available only offers the hope of surviving one year to 20% of patients...

  1. Cyclohexylmethyl Flavonoids Suppress Propagation of Breast Cancer Stem Cells via Downregulation of NANOG

    Directory of Open Access Journals (Sweden)

    Wen-Ying Liao

    2013-01-01

    Full Text Available Breast cancer stem cells (CSCs are highly tumorigenic and possess the capacity to self-renew. Recent studies indicated that pluripotent gene NANOG involves in regulating self-renewal of breast CSCs, and expression of NANOG is correlated with aggressiveness of poorly differentiated breast cancer. We initially confirmed that breast cancer MCF-7 cells expressed NANOG, and overexpression of NANOG enhanced the tumorigenicity of MCF-7 cells and promoted the self-renewal expansion of CD24−/lowCD44+ CSC subpopulation. In contrast, knockdown of NANOG significantly affected the growth of breast CSCs. Utilizing flow cytometry, we identified five cyclohexylmethyl flavonoids that can inhibit propagation of NANOG-positive cells in both breast cancer MCF-7 and MDA-MB231 cells. Among these flavonoids, ugonins J and K were found to be able to induce apoptosis in non-CSC populations and to reduce self-renewal growth of CD24−/lowCD44+ CSC population. Treatment with ugonin J significantly reduced the tumorigenicity of MCF-7 cells and efficiently suppressed formation of mammospheres. This suppression was possibly due to p53 activation and NANOG reduction as either addition of p53 inhibitor or overexpression of NANOG can counteract the suppressive effect of ugonin J. We therefore conclude that cyclohexylmethyl flavonoids can possibly be utilized to suppress the propagation of breast CSCs via reduction of NANOG.

  2. Exposure to magnetic field and brain cancer among child

    International Nuclear Information System (INIS)

    Mir, L.

    2008-01-01

    The risk of childhood brain cancer as a function of magnetic field exposure has been studied less than the risk of leukemia. this updated meta-analysis of thirteen epidemiologic studies thus provides an important contribution to the literature. No increased risk of brain cancer was found, and there were no differences by method of exposure assessment. Doubt remains only for the highest exposure levels, for which very limited data are available. (author)

  3. Relapsing pattern of brain metastasis after brain irradiation in small cell lung cancer

    International Nuclear Information System (INIS)

    Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki; Kono, Koichi; Yoden, Eisaku; Mori, Takeki

    1997-01-01

    Many reports concerning radiation therapy for brain metastasis have been published, and which of the various methods urged by these reports provide optional control is still controversial. According to developing diagnosis of metastasis in CNS, therapeutic problems should be referred. We reviewed 67 patients with small cell lung cancer and brain metastasis who underwent brain irradiation (Ave. 47 Gy/5W), and all 15 patients with brain relapse after the irradiation. Relapsing patterns in this clinical setting were divided into local regrowth in the same lesions and re-metastasis (reseeding) in other regions, by reviewing follow up CT and MRI studies. Total survival among 15 patients with brain relapse and 52 without relapse was longer in the former cases than the later: 1-, and 2-year survival (47/19%, 13/8%) and MST (10.8/5.7 months), from the initial brain irradiation. The concerned significant factors limited in younger age, low value of LDH and improvement of NF. Of the 15 patients with brain relapse, 4 developed local regrowth and 11 did re-metastasis. The period of remission since brain irradiation were 172±94.4 and 393±281 days, respectively. Lower number of brain metastasis and lower value of LDH were shown in re-metastasis patients. At the time of brain relapse, 11 patients had recurrence of carcinomatous meningitis. 4 patients were treated with whole brain re-irradiation. All patients died of cancer, including 12 of relapsing CNS diseases and 3 of primary lesion and hepatic metastasis. Leukoencephalopathy developed in 2 patients. Survival since the brain relapse was 2 to 238 days without significant difference in cases of local regrowth and re-metastasis. According to our data on relapsing pattern of brain metastasis after conventional fractionated brain irradiation with an objective dose of 50 Gy, 75% of brain relapse were re-metastasis, we appreciate this irradiation for initial brain metastasis if limited to the brain. (author)

  4. Contour Propagation Using Feature-Based Deformable Registration for Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yuhan Yang

    2013-01-01

    Full Text Available Accurate target delineation of CT image is a critical step in radiotherapy treatment planning. This paper describes a novel strategy for automatic contour propagation, based on deformable registration, for CT images of lung cancer. The proposed strategy starts with a manual-delineated contour in one slice of a 3D CT image. By means of feature-based deformable registration, the initial contour in other slices of the image can be propagated automatically, and then refined by active contour approach. Three algorithms are employed in the strategy: the Speeded-Up Robust Features (SURF, Thin-Plate Spline (TPS, and an adapted active contour (Snake, used to refine and modify the initial contours. Five pulmonary cancer cases with about 400 slices and 1000 contours have been used to verify the proposed strategy. Experiments demonstrate that the proposed strategy can improve the segmentation performance in the pulmonary CT images. Jaccard similarity (JS mean is about 0.88 and the maximum of Hausdorff distance (HD is about 90%. In addition, delineation time has been considerably reduced. The proposed feature-based deformable registration method in the automatic contour propagation improves the delineation efficiency significantly.

  5. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  6. Value of brain computed tomography in small cell lung cancers

    International Nuclear Information System (INIS)

    Fernet, M.; Breau, J.L.; Goldlust, D.; Israel, L.

    1988-01-01

    88 patients with small cell lung cancer were studied. Brain scans were performed first at initial staging and repeated at regular intervals during the survey. The results confirm the limited value of brain scans in the detection of metastases in neurologically asymptomatic patients [fr

  7. Results of radiotherapy for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

    1987-01-01

    Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation. (author)

  8. Results of radiotherapy for brain metastases from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tatsuno, Ikuro; Tada, Akira; Takanaka, Tsuyoshi; Choto, Shuichi; Watanabe, Kihichiro

    1987-02-01

    Ten patients with brain metastases from lung cancer treated by irradiation between 1982 and 1985 were reviewed. Neurologic improvement by irradiation was obtained in all patients. The median duration of neurologic function control by irradiation and the median survival from the diagnosis of brain metastases were 9 months and 11 months, respectively. General performance status, neurologic function class and the presence or absence of other sites of metastases were important prognostic factors for survival. More than 50 Gy brain irradiation except small cell carcinoma was thought to be necessary to control the brain metastases. CT examinations were useful but limited to evaluate the effectiveness of irradiation.

  9. Brain abscess mimicking brain metastasis in breast cancer

    International Nuclear Information System (INIS)

    Khullar, P.; Datta, N.R.; Wahi, I.K.; Kataria, S.

    2016-01-01

    61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acety- laspartate) ratios of 1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient’s previous history

  10. Brain abscess mimicking brain metastasis in breast cancer.

    Science.gov (United States)

    Khullar, Pooja; Datta, Niloy R; Wahi, Inderjeet Kaur; Kataria, Sabeena

    2016-03-01

    61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acetylaspartate) ratios of ∼1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient's previous history. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  12. Brain metastasis of breast cancer: clinical and radiologic findings

    International Nuclear Information System (INIS)

    An, Jin Kyung; Oh, Ki Keun; Kim, Eun Kyung; Chung, Tae Sub

    2001-01-01

    To analyse the clinical and radiologic findings brain metastasis of breast cancer. Sixty-one of 1399 patients in whom breast cancer was diagnosed between 1983 and 1999 were affected by brain metastasis. Among these 1399, the stage of the breast cancer, in descending order of frequency, was IIA (n=508), I (n=366), IIB (n=247), IIIA (n=189), IIIB (n=45), 0 (n=33) and IV (n=11). The stage of the 61 brain metastases, similarly ordered, was IIB (12.5%), IIA (3.9%), IIIA (3.1%), IIIB (2.2%) and I (0.8%). In all confirmed breast cancers, the age distribution, in descending order of frequency, was 40-49years (n=610), 50-59 (n=301), 30-39 (n=291), 60-69 (n=124), 20-19 (n=41), 70-79 (n=28), and 80-89 (n=4). The age distribution of brain metastasis was 20-29 (14.6%), 30-39 (7.9%), 50-59 (4.6%). 40-49 (2.6%) and 60-69 (1.6%). Imaging findings were available for 35 of the 61 patients affected by brain metastasis, and symptoms from brain among the 35, analysis of the symptoms of this metastasis, the site of the first distant metastasis to an extracranial or cranial organ, the interval from the diagnosis of breast cancer to brain metastasis, the interval from brain metastasis to death, and the difference in survival time between patients with initial and succeeding brain metastasis was undertaken. Brain CT findings were analysed in 29 cases and MRI findings in eight. The most common symptoms were headache and vomiting. Among the 35 brain metastasis patients for whom imaging findings were available, other systemic metastasis occurred in 22. Initial brain metastasis occurred in the remaining 13, and in seven of these there was also coincident organ metastasis, while six showed only brain metastasis, The most frequent intervals from the diagnosis of breast cancer to brain metastasis were 1-2 years(8/35) and 2-3years(8/35). Twenty-six of 35 patients died within one year of brain metastasis. Patients in whom this occurred later survived for longer than those in whom it occurred

  13. Comparison of Back propagation neural network and Back propagation neural network Based Particle Swarm intelligence in Diagnostic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Farahnaz SADOUGHI

    2014-03-01

    Full Text Available Breast cancer is the most commonly diagnosed cancer and the most common cause of death in women all over the world. Use of computer technology supporting breast cancer diagnosing is now widespread and pervasive across a broad range of medical areas. Early diagnosis of this disease can greatly enhance the chances of long-term survival of breast cancer victims. Artificial Neural Networks (ANN as mainly method play important role in early diagnoses breast cancer. This paper studies Levenberg Marquardet Backpropagation (LMBP neural network and Levenberg Marquardet Backpropagation based Particle Swarm Optimization(LMBP-PSO for the diagnosis of breast cancer. The obtained results show that LMBP and LMBP based PSO system provides higher classification efficiency. But LMBP based PSO needs minimum training and testing time. It helps in developing Medical Decision System (MDS for breast cancer diagnosing. It can also be used as secondary observer in clinical decision making.

  14. Plumes of neuronal activity propagate in three dimensions through the nuclear avian brain

    NARCIS (Netherlands)

    Beckers, Gabriël J L; van der Meij, Jacqueline; Lesku, John A.; Rattenborg, Niels C.

    2014-01-01

    Background: In mammals, the slow-oscillations of neuronal membrane potentials (reflected in the electroencephalogram as high-amplitude, slow-waves), which occur during non-rapid eye movement sleep and anesthesia, propagate across the neocortex largely as two-dimensional traveling waves. However, it

  15. Long term imaging of living brain cancer cells

    Science.gov (United States)

    Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

    2018-02-01

    QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

  16. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    .2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain cancer......Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...

  17. Computed tomography in brain metastases of colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuratsu, Jun-ichi; Matsukado, Yasuhiko; Sueyoshi, Nobuyuki [Kumamoto Univ. (Japan). School of Medicine; Nonaka, Nobuhito; Sano, Yoshinori; Itoyama, Yoichi; Miura, Giichi

    1984-10-01

    Metastatic brain tumors from colorectal cancers are relatively rare. In previous reports, the incidence ranged from 3 to 5 percent of all metastatic brain tumors. We report 7 cases of metastatic brain tumors from colorectal cancers. The time interval from the diagnosis of the primary tumors to the brain metastasis was 3 years on the average. Metastasis to the lung and liver were also found in 6 cases at the time of the diagnosis of the brain metastasis. The CEA levels in the serum were highly elevated in all cases. Solitary metastasis was found in all cases; cancers tend to metastasize in the deep area of the cerebrum or cerebellum. On a plain CT scan, tumors were demonstrated as ring-type, with a high-density mass, and ring-like enhancement was seen in 6 cases. Prognosis was very poor in most cases. The median survival time from diagnosis of brain metastasis was 4.5 months in the 2 cases with surgery and 3.5 months in the 4 cases without surgery.

  18. Management of lung cancer brain metastasis: An overview

    Directory of Open Access Journals (Sweden)

    Himanshu Srivastava

    2017-01-01

    Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

  19. Propagation of registration uncertainty during multi-fraction cervical cancer brachytherapy

    Science.gov (United States)

    Amir-Khalili, A.; Hamarneh, G.; Zakariaee, R.; Spadinger, I.; Abugharbieh, R.

    2017-10-01

    Multi-fraction cervical cancer brachytherapy is a form of image-guided radiotherapy that heavily relies on 3D imaging during treatment planning, delivery, and quality control. In this context, deformable image registration can increase the accuracy of dosimetric evaluations, provided that one can account for the uncertainties associated with the registration process. To enable such capability, we propose a mathematical framework that first estimates the registration uncertainty and subsequently propagates the effects of the computed uncertainties from the registration stage through to the visualizations, organ segmentations, and dosimetric evaluations. To ensure the practicality of our proposed framework in real world image-guided radiotherapy contexts, we implemented our technique via a computationally efficient and generalizable algorithm that is compatible with existing deformable image registration software. In our clinical context of fractionated cervical cancer brachytherapy, we perform a retrospective analysis on 37 patients and present evidence that our proposed methodology for computing and propagating registration uncertainties may be beneficial during therapy planning and quality control. Specifically, we quantify and visualize the influence of registration uncertainty on dosimetric analysis during the computation of the total accumulated radiation dose on the bladder wall. We further show how registration uncertainty may be leveraged into enhanced visualizations that depict the quality of the registration and highlight potential deviations from the treatment plan prior to the delivery of radiation treatment. Finally, we show that we can improve the transfer of delineated volumetric organ segmentation labels from one fraction to the next by encoding the computed registration uncertainties into the segmentation labels.

  20. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2013-10-01

    antibodies to the endothelial marker, CD31 (Serotec, Raleigh, NC) followed by Cy3-conjugated secondary antibody ( Jackson Immunoresearch Laboratories...in the brain. Cancer Res 67, 4190-4198, doi:67/9/4190 [pii] 10.1158/0008-5472.CAN-06- 3316 (2007). 7 Percy , D. B. et al. In vivo characterization of

  1. Scalp and skull influence on near infrared photon propagation in the Colin27 brain template.

    Science.gov (United States)

    Strangman, Gary E; Zhang, Quan; Li, Zhi

    2014-01-15

    Near-infrared neuromonitoring (NIN) is based on near-infrared spectroscopy (NIRS) measurements performed through the intact scalp and skull. Despite the important effects of overlying tissue layers on the measurement of brain hemodynamics, the influence of scalp and skull on NIN sensitivity are not well characterized. Using 3555 Monte Carlo simulations, we estimated the sensitivity of individual continuous-wave NIRS measurements to brain activity over the entire adult human head by introducing a small absorption perturbation to brain gray matter and quantifying the influence of scalp and skull thickness on this sensitivity. After segmenting the Colin27 template into five tissue types (scalp, skull, cerebrospinal fluid, gray matter and white matter), the average scalp thickness was 6.9 ± 3.6 mm (range: 3.6-11.2mm), while the average skull thickness was 6.0 ± 1.9 mm (range: 2.5-10.5mm). Mean NIN sensitivity - defined as the partial path length through gray matter divided by the total photon path length - ranged from 0.06 (i.e., 6% of total path length) at a 20mm source-detector separation, to over 0.19 at 50mm separations. NIN sensitivity varied substantially around the head, with occipital pole exhibiting the highest NIRS sensitivity to gray matter, whereas inferior frontal regions had the lowest sensitivity. Increased scalp and skull thickness were strongly associated with decreased sensitivity to brain tissue. Scalp thickness always exhibited a slightly larger effect on sensitivity than skull thickness, but the effect of both varied with SD separation. We quantitatively characterize sensitivity around the head as well as the effects of scalp and skull, which can be used to interpret NIN brain activation studies as well as guide the design, development and optimization of NIRS devices and sensors. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

    International Nuclear Information System (INIS)

    Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie

    2016-01-01

    Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

  3. Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

    Energy Technology Data Exchange (ETDEWEB)

    Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel; Chapman, Shira; Bloch-Shilderman, Eugenia; Grauer, Ettie, E-mail: ettieg@iibr.gov.il

    2016-11-01

    Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. In all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.

  4. No increase in brain cancer rates during period of expanding cell phone use

    Science.gov (United States)

    In a new examination of United States cancer incidence data, investigators at the National Cancer Institute (NCI) reported that incidence trends have remained roughly constant for glioma, the main type of brain cancer hypothesized to be related to cell ph

  5. Gamma knife radiosurgery for metastatic brain tumors from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

    2003-01-01

    The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

  6. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  7. Brain imaging before primary lung cancer resection: a controversial topic.

    Science.gov (United States)

    Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

    2017-01-01

    International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have

  8. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images

    Directory of Open Access Journals (Sweden)

    Suneet Gupta

    2016-01-01

    Full Text Available Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  9. A mathematical theory of shape and neuro-fuzzy methodology-based diagnostic analysis: a comparative study on early detection and treatment planning of brain cancer.

    Science.gov (United States)

    Kar, Subrata; Majumder, D Dutta

    2017-08-01

    Investigation of brain cancer can detect the abnormal growth of tissue in the brain using computed tomography (CT) scans and magnetic resonance (MR) images of patients. The proposed method classifies brain cancer on shape-based feature extraction as either benign or malignant. The authors used input variables such as shape distance (SD) and shape similarity measure (SSM) in fuzzy tools, and used fuzzy rules to evaluate the risk status as an output variable. We presented a classifier neural network system (NNS), namely Levenberg-Marquardt (LM), which is a feed-forward back-propagation learning algorithm used to train the NN for the status of brain cancer, if any, and which achieved satisfactory performance with 100% accuracy. The proposed methodology is divided into three phases. First, we find the region of interest (ROI) in the brain to detect the tumors using CT and MR images. Second, we extract the shape-based features, like SD and SSM, and grade the brain tumors as benign or malignant with the concept of SD function and SSM as shape-based parameters. Third, we classify the brain cancers using neuro-fuzzy tools. In this experiment, we used a 16-sample database with SSM (μ) values and classified the benignancy or malignancy of the brain tumor lesions using the neuro-fuzzy system (NFS). We have developed a fuzzy expert system (FES) and NFS for early detection of brain cancer from CT and MR images. In this experiment, shape-based features, such as SD and SSM, were extracted from the ROI of brain tumor lesions. These shape-based features were considered as input variables and, using fuzzy rules, we were able to evaluate brain cancer risk values for each case. We used an NNS with LM, a feed-forward back-propagation learning algorithm, as a classifier for the diagnosis of brain cancer and achieved satisfactory performance with 100% accuracy. The proposed network was trained with MR image datasets of 16 cases. The 16 cases were fed to the ANN with 2 input neurons, one

  10. Lung cancer brain metastases – the role of neurosurgery

    Directory of Open Access Journals (Sweden)

    V. A. Aleshin

    2016-01-01

    Full Text Available Lung cancer is mostly common occurring oncological disease in the developed countries. Currently lung cancers are subdivided into nonsmall-cell (adenocarcinoma, large-cell, squamous cell and small-cell. The difference in the clinical and morphological picture leads to the necessity of choosing therapeutic approaches to patients of various groups.Lung cancer should be referred to encephalotropic diseases since metastatic lesion of the central nervous system is sufficiently common complication. Successes of complex treatment of primary tumor result in increase of total longlivety currently ther is ageing of patients suffering lung cancer. These factors increase the risk of metastatic lesions of the brain.Interest to the problem of neurosurgical treatment of patients suffering lung cancer is determined by frequency of lesion, varicosity of morphological variants of the disease, requiring various algorithms of treatment and diagnosis.The main role of neurosurgical intervention in cerebral metastases of lung cancer consist in creation of the paled of carrying out combined therapy. Ideally, a neurosurgical operation should be carried out with clearcut observance of oncological principles of ablasty.Adequate comprehensive approach to treatment or patients with cerebral metastases of various forms of lung cancer with the developed of optimal tactics of and stages of treatment would make it possible to increase duration and quality of life of patients.

  11. Radiological Patterns of Brain Metastases in Breast Cancer Patients : A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry

    NARCIS (Netherlands)

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Wuerschmidt, Florian; Fehm, Tanja; Moebus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain

  12. Reconstruction and signal propagation analysis of the Syk signaling network in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Aurélien Naldi

    2017-03-01

    Full Text Available The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology. The spleen tyrosine kinase (Syk protein, a well-characterized key player in immune cell signaling, was surprisingly first shown by our group to exhibit an onco-suppressive function in mammary epithelial cells and corroborated by many other studies, but the molecular mechanisms of this function remain largely unsolved. Based on existing proteomic data, we report here the generation of an interaction-based network of signaling pathways controlled by Syk in breast cancer cells. Pathway enrichment of the Syk targets previously identified by quantitative phospho-proteomics indicated that Syk is engaged in cell adhesion, motility, growth and death. Using the components and interactions of these pathways, we bootstrapped the reconstruction of a comprehensive network covering Syk signaling in breast cancer cells. To generate in silico hypotheses on Syk signaling propagation, we developed a method allowing to rank paths between Syk and its targets. We first annotated the network according to experimental datasets. We then combined shortest path computation with random walk processes to estimate the importance of individual interactions and selected biologically relevant pathways in the network. Molecular and cell biology experiments allowed to distinguish candidate mechanisms that underlie the impact of Syk on the regulation of cortactin and ezrin, both involved in actin-mediated cell adhesion and motility. The Syk network was further completed with the results of our biological validation experiments. The resulting Syk signaling sub-networks can be explored via an online visualization platform.

  13. Cognitive and brain structural changes in a lung cancer population.

    Science.gov (United States)

    Simó, Marta; Root, James C; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Ahles, Tim; Navarro, Arturo; Cardenal, Felipe; Bruna, Jordi; Rodríguez-Fornells, Antoni

    2015-01-01

    No study has examined structural brain changes specifically associated with chemotherapy in a lung cancer population. The aim of this cross-sectional study was to assess differences in brain structure between small-cell lung cancer patients (C+) following chemotherapy, non-small-cell lung cancer patients (C-) before chemotherapy and healthy controls (HC). Twenty-eight small-cell lung cancer patients underwent a neuropsychological assessment and a structural magnetic resonance imaging, including T1-weighted and diffusion tensor imaging to examine gray matter density and white matter (WM) integrity, respectively, 1 month following completion of platinum-based chemotherapy. This group was compared with 20 age and education-matched non-small-cell lung cancer patients before receiving chemotherapy and 20 HC. Both C+ and C- groups exhibited cognitive impairment compared with the HC group. The C+ group performed significantly worse than HC in verbal fluency and visuospatial subtests; C- performed significantly worse than both C+ and HC in verbal memory. Voxel-based morphometry analysis revealed lower gray matter density in the insula and parahippocampal gyrus bilaterally, and left anterior cingulate cortex in C+ compared with HC. Diffusion tensor imaging indices showed focal decreased WM integrity in left cingulum and bilateral inferior longitudinal fasciculus in the C+ group and more widespread decreased integrity in the C- group compared with the HC group. This study demonstrates that lung cancer patients exhibit cognitive impairment before and after chemotherapy. Before the treatment, C- showed verbal memory deficits as well as a widespread WM damage. Following treatment, the C+ group performed exhibited lower visuospatial and verbal fluency abilities, together with structural gray matter and WM differences in bilateral regions integrating the paralimbic system.

  14. Molecular and in vivo characterization of cancer-propagating cells derived from MYCN-dependent medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Zai Ahmad

    Full Text Available Medulloblastoma (MB is the most common malignant pediatric brain tumor. While the pathways that are deregulated in MB remain to be fully characterized, amplification and/or overexpression of the MYCN gene, which is has a critical role in cerebellar development as a regulator of neural progenitor cell fate, has been identified in several MB subgroups. Phenotypically, aberrant expression of MYCN is associated with the large-cell/anaplastic MB variant, which accounts for 5-15% of cases and is associated with aggressive disease and poor clinical outcome. To better understand the role of MYCN in MB in vitro and in vivo and to aid the development of MYCN-targeted therapeutics we established tumor-derived neurosphere cell lines from the GTML (Glt1-tTA/TRE-MYCN-Luc genetically engineered mouse model. A fraction of GTML neurospheres were found to be growth factor independent, expressed CD133 (a marker of neural stem cells, failed to differentiate upon MYCN withdrawal and were highly tumorigenic when orthotopically implanted into the cerebellum. Principal component analyzes using single cell RNA assay data suggested that the clinical candidate aurora-A kinase inhibitor MLN8237 converts GTML neurospheres to resemble non-MYCN expressors. Correlating with this, MLN8237 significantly extended the survival of mice bearing GTML MB allografts. In summary, our results demonstrate that MYCN plays a critical role in expansion and survival of aggressive MB-propagating cells, and establish GTML neurospheres as an important resource for the development of novel therapeutic strategies.

  15. Treatment of brain metastases from primary lung cancer

    International Nuclear Information System (INIS)

    Ryan, Gail F.; Ball, David L.; Smith, Jennifer G.

    1995-01-01

    Purpose: A retrospective study of patients treated at the Peter MacCallum Cancer Institute for brain metastases from primary carcinoma of the lung is presented. Methods and Materials: The medical records of 416 patients with the diagnosis of primary carcinoma of the lung who presented with, or subsequently developed, brain metastases during the period January 1984 to December 1987 were reviewed. Information on a number of factors of potential prognostic significance (sex, age, histology, performance status and interval between diagnosis of the primary and brain metastases) was collected. Details of surgery, radiation and steroid usage were recorded, and any steroid side effects documented. Survival was calculated from the date of diagnosis of brain metastases. Stepwise regression based on Cox's proportional hazards model was used to determine significant prognostic factors affecting survival. Patients with and without steroid side effects were compared using Yate's corrected chi-square test. Results: The overall estimated median survival was only 3.3 months (95% confidence interval 2.9-3.7 months). Only two factors were found to be associated with a significantly improved survival--surgical intervention and good performance status. After taking these two factors into account, the dose of radiation used (< 30 Gy or ≥ 30 Gy) did not influence survival. There was a 3% incidence of gastric bleeding or perforation in patients taking steroids, with a 40% fatality rate. Predisposing factors to gastric side effects were a prior history of peptic ulcer and/or aspirin or nonsteroidal anti-inflammatory drug consumption. Conclusion: Radiation of brain metastases from primary lung cancer results in modest survival benefit. Radiation dose (< 30 Gy or ≥ 30 Gy) is not a significant determinant of survival. Other treatment modifications, such as concurrent radiation and chemotherapy, should be explored. Steroids should be used with caution as fatal side effects can occur

  16. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    OpenAIRE

    Zhou Weihua; Mukherjee Purna; Kiebish Michael A; Markis William T; Mantis John G; Seyfried Thomas N

    2007-01-01

    Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and su...

  17. Monocarboxylate transporters in the brain and in cancer.

    Science.gov (United States)

    Pérez-Escuredo, Jhudit; Van Hée, Vincent F; Sboarina, Martina; Falces, Jorge; Payen, Valéry L; Pellerin, Luc; Sonveaux, Pierre

    2016-10-01

    Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Association of brain cancer with dental x-rays and occupation in Missouri

    International Nuclear Information System (INIS)

    Neuberger, J.S.; Brownson, R.C.; Morantz, R.A.; Chin, T.D.

    1991-01-01

    This investigation of a brain cancer cluster in Missouri used two approaches to investigate associations with potential risk factors. In a case-control study in a rural town, we interviewed surrogates of cases and controls about potential risk factors. We found a statistically significant positive association of brain cancer with reported exposure to dental x-rays. Occupation was not associated with the cluster in the rural town. In a standardized proportional mortality study for the state of Missouri, we calculated the observed and expected proportion of brain cancers by occupation and industry in Missouri decedents. We found that motor vehicle manufacturers, beauty shop workers, managers and administrators, elementary school teachers, and hairdressers and cosmetologists had significantly elevated proportions of brain cancer. Brain tumors are inconsistently associated with occupation in the literature. Further study of brain cancer etiology with respect to dental x-ray exposures seems warranted

  19. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

    OpenAIRE

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

  20. An automatic contour propagation method to follow parotid gland deformation during head-and-neck cancer tomotherapy

    International Nuclear Information System (INIS)

    Faggiano, E; Scalco, E; Rizzo, G; Fiorino, C; Broggi, S; Cattaneo, M; Maggiulli, E; Calandrino, R; Dell'Oca, I; Di Muzio, N

    2011-01-01

    We developed an efficient technique to auto-propagate parotid gland contours from planning kVCT to daily MVCT images of head-and-neck cancer patients treated with helical tomotherapy. The method deformed a 3D surface mesh constructed from manual kVCT contours by B-spline free-form deformation to generate optimal and smooth contours. Deformation was calculated by elastic image registration between kVCT and MVCT images. Data from ten head-and-neck cancer patients were considered and manual contours by three observers were included in both kVCT and MVCT images. A preliminary inter-observer variability analysis demonstrated the importance of contour propagation in tomotherapy application: a high variability was reported in MVCT parotid volume estimation (p = 0.0176, ANOVA test) and a larger uncertainty of MVCT contouring compared with kVCT was demonstrated by DICE and volume variability indices (Wilcoxon signed rank test, p -4 for both indices). The performance analysis of our method showed no significant differences between automatic and manual contours in terms of volumes (p > 0.05, in a multiple comparison Tukey test), center-of-mass distances (p = 0.3043, ANOVA test), DICE values (p = 0.1672, Wilcoxon signed rank test) and average and maximum symmetric distances (p = 0.2043, p = 0.8228 Wilcoxon signed rank tests). Results suggested that our contour propagation method could successfully substitute human contouring on MVCT images.

  1. An automatic contour propagation method to follow parotid gland deformation during head-and-neck cancer tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Faggiano, E; Scalco, E; Rizzo, G [Istituto di Bioimmagini e Fisiologia Molecolare (IBFM), CNR, Milan (Italy); Fiorino, C; Broggi, S; Cattaneo, M; Maggiulli, E; Calandrino, R [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Dell' Oca, I; Di Muzio, N, E-mail: fiorino.claudio@hsr.it [Department of Radiotherapy, San Raffaele Scientific Institute, Milan (Italy)

    2011-02-07

    We developed an efficient technique to auto-propagate parotid gland contours from planning kVCT to daily MVCT images of head-and-neck cancer patients treated with helical tomotherapy. The method deformed a 3D surface mesh constructed from manual kVCT contours by B-spline free-form deformation to generate optimal and smooth contours. Deformation was calculated by elastic image registration between kVCT and MVCT images. Data from ten head-and-neck cancer patients were considered and manual contours by three observers were included in both kVCT and MVCT images. A preliminary inter-observer variability analysis demonstrated the importance of contour propagation in tomotherapy application: a high variability was reported in MVCT parotid volume estimation (p = 0.0176, ANOVA test) and a larger uncertainty of MVCT contouring compared with kVCT was demonstrated by DICE and volume variability indices (Wilcoxon signed rank test, p < 10{sup -4} for both indices). The performance analysis of our method showed no significant differences between automatic and manual contours in terms of volumes (p > 0.05, in a multiple comparison Tukey test), center-of-mass distances (p = 0.3043, ANOVA test), DICE values (p = 0.1672, Wilcoxon signed rank test) and average and maximum symmetric distances (p = 0.2043, p = 0.8228 Wilcoxon signed rank tests). Results suggested that our contour propagation method could successfully substitute human contouring on MVCT images.

  2. CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain

    Directory of Open Access Journals (Sweden)

    Sebastiano Cavallaro

    2013-01-01

    Full Text Available Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC and the pharmacological tools that may be used to interfere with this signaling axis.

  3. Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    Rades, Dirk; Huttenlocher, Stefan; Hornung, Dagmar; Blanck, Oliver; Schild, Steven E; Fischer, Dorothea

    2014-01-01

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1–3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p = 0.59). Age ≤59 years showed a trend towards improved local control on univariate (p = 0.066) and multivariate analysis (p = 0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p = 0.040) and ECOG 0–1 (p = 0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p = 0.039) and performance status (p = 0.028) maintained significance on multivariate analysis. ECOG 0–1 was positively correlated with survival on univariate analysis (p < 0.001); age ≤59 years showed a strong trend (p = 0.054). On multivariate analysis, performance status (p < 0.001) and age (p = 0.041) were significant. In breast cancer patients with few brain metastases, radiosurgery plus whole-brain

  4. Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nagla Abdel Karim

    2015-01-01

    Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

  5. The biochemical, nanomechanical and chemometric signatures of brain cancer

    Science.gov (United States)

    Abramczyk, Halina; Imiela, Anna

    2018-01-01

    % for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

  6. Altered resting brain connectivity in persistent cancer related fatigue

    Directory of Open Access Journals (Sweden)

    Johnson P. Hampson

    2015-01-01

    Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

  7. Intra-operative probe for brain cancer: feasibility study

    Science.gov (United States)

    Vu Thi, M. H.; Charon, Y.; Duval, M. A.; Lefebvre, F.; Menard, L.; Pitre, S.; Pinot, L.; Siebert, R.

    2007-07-01

    The present work aims a new medical probe for surgeons devoted to brain cancers, in particular glioblastoma multiforme. Within the last years, our group has started the development of a new intra-operative beta imaging probe. More recently, we took an alternative approach for the same application: a fluorescence probe. In both cases the purpose is to differentiate normal from tumor brain tissue. In a first step, we developed set-ups capable to measure autofluorescence. They are based on a dedicated epi-fluorescence design and on specific fiber optic probes. Relative signal amplitude, spectral shape and fluorescence lifetime measurements are foreseen to distinguish normal and cancer tissue by analyzing fluorophores like NADH, lipopigments and porphyrines. The autofluorescence spectra are recorded in the 460-640 nm range with a low resolution spectrometer. For lifetime measurements a fast detector (APD) is used together with a TCSPC-carte. Intrinsic wavelength- and time-resolutions are a few nm and 200 ps, respectively. Different samples have been analyzed to validate our new detection system and to allow a first configuration of our medical fluorescence probe. First results from the tissue measurements are shown.

  8. Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

    Directory of Open Access Journals (Sweden)

    Thirugnanam Sivasakthivel

    2013-02-01

    Full Text Available Abstract Background The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs, which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and

  9. (-)1-(Benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.

    Science.gov (United States)

    Knoll, J; Yoneda, F; Knoll, B; Ohde, H; Miklya, I

    1999-12-01

    1. The brain constituents beta-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain ('catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (-)Deprenyl (Selegiline) and (-)1-phenyl-2-propylaminopentane [(-)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property. 2. By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)BPAP] was selected as a potential follower of (-)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain. 3. (-)BPAP significantly enhanced in 0.18 micromol 1(-1) concentration the impulse propagation mediated release of [(3)H]-noradrenaline and [(3)H]-dopamine and in 36 nmol 1(-1) concentration the release of [(3)H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10(-12) - 10(-14) M (-)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of beta-amyloid in 10(-14) M concentration. In rats (-)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 microg kg(-1) s.c. In the shuttle box, (-)BPAP in rats was about 130 times more potent than (-)deprenyl in antagonizing tetrabenazine induced inhibition of performance.

  10. (−)1-(Benzofuran-2-yl)-2-propylaminopentane, [(−)BPAP], a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain

    Science.gov (United States)

    Knoll, Joseph; Yoneda, Fumio; Knoll, Berta; Ohde, Hironori; Miklya, Ildikó

    1999-01-01

    The brain constituents β-phenylethylamine (PEA) and tryptamine enhance the impulse propagation mediated transmitter release (exocytosis) from the catecholaminergic and serotoninergic neurons in the brain (‘catecholaminergic/serotoninergic activity enhancer, CAE/SAE, effect'). (−)Deprenyl (Selegiline) and (−)1-phenyl-2-propylaminopentane [(−)PPAP] are amphetamine derived CAE substances devoid of the catecholamine releasing property.By changing the aromatic ring in PPAP we developed highly potent and selective CAE/SAE substances, structurally unrelated to the amphetamines. Out of 65 newly synthetized compounds, a tryptamine derived structure, (−)1-(benzofuran-2-yl)-2-propylaminopentane [(−)BPAP] was selected as a potential follower of (−)deprenyl in the clinic and as a reference compound for further analysis of the CAE/SAE mechanism in the mammalian brain.(−)BPAP significantly enhanced in 0.18 μmol 1−1 concentration the impulse propagation mediated release of [3H]-noradrenaline and [3H]-dopamine and in 36 nmol 1−1 concentration the release of [3H]-serotonin from the isolated brain stem of rats. The amount of catecholamines and serotonin released from isolated discrete rat brain regions (dopamine from the striatum, substantia nigra and tuberculum olfactorium, noradrenaline from the locus coeruleus and serotonin from the raphe) enhanced significantly in the presence of 10−12–10−14 M (−)BPAP. BPAP protected cultured hippocampal neurons from the neurotoxic effect of β-amyloid in 10−14 M concentration. In rats (−)BPAP significantly enhanced the activity of the catecholaminergic and serotoninergic neurons in the brain 30 min after acute injection of 0.1 μg kg−1 s.c. In the shuttle box, (−)BPAP in rats was about 130 times more potent than (−)deprenyl in antagonizing tetrabenazine induced inhibition of performance. PMID:10588928

  11. Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology.

    Science.gov (United States)

    Azim, Hamdy A; Abdel-Malek, Raafat; Kassem, Loay

    2018-04-01

    Brain metastasis (BM) is a life-threatening event in breast cancer patients. Identifying patients at a high risk for BM can help to adopt screening programs and test preventive interventions. We tried to identify the incidence of BM in different stages and subtypes of breast cancer. We reviewed the clinical records of 2193 consecutive breast cancer patients who presented between January 1999 and December 2010. We explored the incidence of BM in relation to standard clinicopathological factors, and determined the cumulative risk of BM according to the disease stage and phenotype. Of the 2193 included women, 160 (7.3%) developed BM at a median follow-up of 5.8 years. Age younger than 60 years (P = .015), larger tumors (P = .004), lymph node (LN) positivity (P < .001), high tumor grade (P = .012), and HER2 positivity (P < .001) were associated with higher incidence of BM in the whole population. In patients who presented with locoregional disease, 3 factors independently predicted BM: large tumors (hazard ratio [HR], 3.60; 95% confidence interval [CI], 1.54-8.38; P = .003), axillary LN metastasis (HR, 4.03; 95% CI, 1.91-8.52; P < .001), and HER2 positivity (HR, 1.89; 95% CI, 1.0-3.41; P = .049). A Brain Relapse Index was formulated using those 3 factors, with 5-year cumulative incidence of BM of 19.2% in those having the 2 or 3 risk factors versus 2.5% in those with no or 1 risk factor (P < .001). In metastatic patients, 3 factors were associated with higher risk of BM: HER2 positivity (P = .007), shorter relapse-free interval (P < .001), and lung metastasis (P < .001). Disease stage and biological subtypes predict the risk for BM and subsequent treatment outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Late brain metastases from breast cancer: clinical remarks on 11 patients and review of the literature.

    Science.gov (United States)

    Piccirilli, Manolo; Sassun, Tanya Enny; Brogna, Christian; Giangaspero, Felice; Salvati, Maurizio

    2007-01-01

    Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor. Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined 'late metastasis' as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30). Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years). Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the "clonal dominance" theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.

  13. Advances in Diagnosis and Treatment of Brain Metastases from the Primary Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yi LIU

    2013-07-01

    Full Text Available Lung cancer with brain metastasis was 23% to 65%, and is the most common type in brain metastasis tumors with the poor prognosis. At present, diagnosis and treatment of brain metastases from lung carcinoma and its molecular mechanism have become one hot spot of amount researches. Here, we made a systematic review of the progress of the clinical features, diagnosis and treatment of brain metastases from lung and its molecular mechanism.

  14. Application of machine learning on brain cancer multiclass classification

    Science.gov (United States)

    Panca, V.; Rustam, Z.

    2017-07-01

    Classification of brain cancer is a problem of multiclass classification. One approach to solve this problem is by first transforming it into several binary problems. The microarray gene expression dataset has the two main characteristics of medical data: extremely many features (genes) and only a few number of samples. The application of machine learning on microarray gene expression dataset mainly consists of two steps: feature selection and classification. In this paper, the features are selected using a method based on support vector machine recursive feature elimination (SVM-RFE) principle which is improved to solve multiclass classification, called multiple multiclass SVM-RFE. Instead of using only the selected features on a single classifier, this method combines the result of multiple classifiers. The features are divided into subsets and SVM-RFE is used on each subset. Then, the selected features on each subset are put on separate classifiers. This method enhances the feature selection ability of each single SVM-RFE. Twin support vector machine (TWSVM) is used as the method of the classifier to reduce computational complexity. While ordinary SVM finds single optimum hyperplane, the main objective Twin SVM is to find two non-parallel optimum hyperplanes. The experiment on the brain cancer microarray gene expression dataset shows this method could classify 71,4% of the overall test data correctly, using 100 and 1000 genes selected from multiple multiclass SVM-RFE feature selection method. Furthermore, the per class results show that this method could classify data of normal and MD class with 100% accuracy.

  15. Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

    Science.gov (United States)

    Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

    2012-01-01

    The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

  16. Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

    Science.gov (United States)

    Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

    2017-06-01

    Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

    International Nuclear Information System (INIS)

    Viani, Gustavo A; Castilho, Marcus S; Salvajoli, João V; Pellizzon, Antonio Cassio A; Novaes, Paulo E; Guimarães, Flavio S; Conte, Maria A; Fogaroli, Ricardo C

    2007-01-01

    Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001). Our

  18. Mechanisms and Therapy for Cancer Metastasis to the Brain

    Directory of Open Access Journals (Sweden)

    Federica Franchino

    2018-05-01

    Full Text Available Advances in chemotherapy and targeted therapies have improved survival in cancer patients with an increase of the incidence of newly diagnosed brain metastases (BMs. Intracranial metastases are symptomatic in 60–70% of patients. Magnetic resonance imaging (MRI with gadolinium is more sensitive than computed tomography and advanced neuroimaging techniques have been increasingly used in the detection, treatment planning, and follow-up of BM. Apart from the morphological analysis, the most effective tool for characterizing BM is immunohistochemistry. Molecular alterations not always reflect those of the primary tumor. More sophisticated methods of tumor analysis detecting circulating biomarkers in fluids (liquid biopsy, including circulating DNA, circulating tumor cells, and extracellular vesicles, containing tumor DNA and macromolecules (microRNA, have shown promise regarding tumor treatment response and progression. The choice of therapeutic approaches is guided by prognostic scores (Recursive Partitioning Analysis and diagnostic-specific Graded Prognostic Assessment-DS-GPA. The survival benefit of surgical resection seems limited to the subgroup of patients with controlled systemic disease and good performance status. Leptomeningeal disease (LMD can be a complication, especially in posterior fossa metastases undergoing a “piecemeal” resection. Radiosurgery of the resection cavity may offer comparable survival and local control as postoperative whole-brain radiotherapy (WBRT. WBRT alone is now the treatment of choice only for patients with single or multiple BMs not amenable to surgery or radiosurgery, or with poor prognostic factors. To reduce the neurocognitive sequelae of WBRT intensity modulated radiotherapy with hippocampal sparing, and pharmacological approaches (memantine and donepezil have been investigated. In the last decade, a multitude of molecular abnormalities have been discovered. Approximately 33% of patients with non

  19. Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors...

  20. Pesticides and brain cancer linked in orchard farmers of Kashmir.

    Science.gov (United States)

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R; Raina, T H

    2010-10-01

    -related patients. The significantcase/control odds ratio (OR) of 0.28, hospital control SCE OR of 1.1 and family control SCE OR of 1.5, points the finger of suspicion toward the link between pesticides and brain cancer.

  1. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

    OpenAIRE

    Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

    2011-01-01

    We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product b...

  2. Identifying risk factors for brain metastasis in breast cancer patients: Implication for a vigorous surveillance program

    Directory of Open Access Journals (Sweden)

    Lorraine Chow

    2015-10-01

    Conclusion: Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients.

  3. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer.

    Science.gov (United States)

    Papademetriou, Iason T; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers noninvasive delivery of small molecule and biological cancer therapeutics. Local delivery methods enable high dose delivery while avoiding systemic exposure. BBB disruption with focused ultrasound and microbubbles offers local and noninvasive treatment. Clinical trials show the prospects of these technologies and point to challenges for the future.

  4. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer.

    Science.gov (United States)

    Duchnowska, Renata; Loibl, Sibylle; Jassem, Jacek

    2018-06-01

    Approximately 30-50% of advanced HER2-positive breast cancer patients will develop central nervous system (CNS) metastases, with an annual risk of around 10%, and a half of them will die from brain progression. An increased risk of brain metastases is also seen in patients with early HER2-positive breast cancer administered curative therapy. Brain metastases in HER2-positive breast cancer patients usually constitute the first site of recurrence. The administration of anti-HER2 monoclonal antibodies, trastuzumab and pertuzumab, considerably delays the onset of symptomatic brain disease: however, the limited penetration of these compounds into the CNS hinders their efficacy. The small-molecule tyrosine kinase inhibitors of epidermal growth factor receptors family have established activity in HER2-positive breast cancer in both advanced disease and neoadjuvant setting. Favorable physico-chemical properties of these compounds allow them for a more efficient penetration through the blood-brain barrier, and hold the promise for more effective prevention and treatment of brain metastases. In this article we review the role of currently available or investigational HER2 tyrosine kinase inhibitors: lapatinib, neratinib, afatinib and tucatinib in the treatment of brain metastases in HER2-positive breast cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Cancers of the Brain and CNS: Global Patterns and Trends in Incidence.

    Science.gov (United States)

    Mortazavi, S M J; Mortazavi, S A R; Paknahad, M

    2018-03-01

    Miranda-Filho et al. in their recently published paper entitled "Cancers of the brain and CNS: global patterns and trends in incidence" provided a global status report of the geographic and temporal variations in the incidence of brain and CNS cancers in different countries across continents worldwide. While the authors confirm the role of genetic risk factors and ionizing radiation exposures, they claimed that no firm conclusion could be drawn about the role of exposure to non-ionizing radiation. The paper authored by Miranda-Filho et al. not only addresses a challenging issue, it can be considered as a good contribution in the field of brain and CNS cancers. However, our correspondence addresses a basic shortcoming of this paper about the role of electromagnetic fields and cancers and provides evidence showing that exposure to radiofrequency electromagnetic fields (RF-EMFs), at least at high levels and long durations, can increases the risk of cancer.

  6. Prognostic factors for survival and intracerebral control after irradiation for brain metastases from gynecological cancer

    NARCIS (Netherlands)

    Rades, Dirk; Fischer, Dorothea; Veninga, Theo; Stalpers, Lukas J. A.; Schild, Steven E.

    2009-01-01

    The most appropriate treatment for the individual patient with brain metastases from gynecological cancer is unclear. Most of these patients receive whole-brain radiotherapy (WBRT) alone. Prognostic factors predicting the outcomes of these patients may guide the physician to select the appropriate

  7. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    Science.gov (United States)

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.; Fidler, Isaiah J.; Cantley, Lewis C.; Locasale, Jason W.; Weihua, Zhang

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the non-oxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBPs) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis, and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. PMID:25511375

  8. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tarek H. Mouhieddine

    2015-11-01

    Full Text Available Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma and SHSY-5Y (neuroblastoma cell lines.Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence.

  9. Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

    DEFF Research Database (Denmark)

    Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.

    2014-01-01

    The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells...

  10. Brain metastases in lung cancer. Impact of prognostic factors on patient survival

    International Nuclear Information System (INIS)

    Smrdel, U.; Zwitter, M.; Kovac, V.

    2003-01-01

    Background. Brain metastases are common patterns of dissemination in lung cancer patients. In this paper we would like to assess the pattern of brain metastases in lung cancer patients and the impact of prognostic factors on the survival of lung cancer patients with brain metastases. Patients and methods. In the year 1998 there were 974 registered patients with lung cancer in Slovenia, six hundred and fifteen of them were treated at the Institute of Oncology Ljubljana and we analyzed them. Among 615 patients 137 (22.3 %) of them have had brain metastases during a natural course of disease. Results. For 12 patients presenting with solitary brain metastases (most of them were undertaken metastasectomy) median survival was 7.6 months, while in patients with multiple brain metastases the median survival was 2.8 months (p 0.0018). Of the 137 patients 45 (32.8 %) were small cell lung cancer patients, 43 (31.4 %) were adenocarcinoma patients and 19 (13.9 %) were squamous cell carcinoma patients. Patients with performance status (WHO scale) less than 2 had the median survival time 3.7 months while patients with performance status 2 or more had median survival time 2.7 moths (p=0.0448). Conclusions. Patients with solitary brain metastases had better survival comparing with those who had multiple metastases. It is surprisingly that the portion of brain metastases patients with adenocarcinoma is almost equal to those with small-call lung cancer therefore, the prophylactic cranial radiation becomes actual for both groups of patients. The performance status of patients with brain metastases remains very important prognostic factor. (author)

  11. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  12. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    response. e. Correlate imaging findings with histological studies of vascular damage, tumor cell and endothelial cell apoptosis or necrosis and vascular ...phosphatidylserine (PS) is exposed exclusively on tumor vascular endothelium of brain metastases in mouse models. A novel PS-targeting antibody, PGN635... vascular endothelial cells in multi-focal brain metastases throughout the whole mouse brain. Vascular endothelium in normal brain tissues is negative

  13. Integrin Alpha-v and HER2 in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    ZOOM live cell imaging machine (ESSEN Bioscience; Figure 2). c. Interactions of αv integrin and HER2 in breast cancer brain metastases. We found...HCC1954 breast cancer cells. C) Real time live cell imaging of MM2BH cells treated with cilengitide (0, .3, 1, 3, and 10 µg/mL) using IncuCyte ZOOM

  14. Occupational exposure to electromagnetic fields, leukemia and brain cancer: update of two meta-analysis

    International Nuclear Information System (INIS)

    Anon.

    2008-01-01

    This new meta-analysis found a slight increase in the risk of brain cancer and of leukemia in populations occupationally exposed to electromagnetic fields. it does not, however, support the hypothesis that electromagnetic fields have an effect on these cancers. (author)

  15. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    International Nuclear Information System (INIS)

    Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

    2009-01-01

    The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BK Ca ) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BK Ca channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BK Ca channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BK Ca channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BK Ca channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BK Ca channel expression in breast cancer metastatic to brain and the mechanism of its

  16. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  17. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC Registry

    Directory of Open Access Journals (Sweden)

    Elena Laakmann

    2016-09-01

    Full Text Available Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT and magnetic resonance imaging (MRI scans of 300 breast cancer patients with brain metastases (BMs were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC in Germany. Patients with positive estrogen (ER, progesterone (PR, or human epidermal growth factor receptor 2 (HER2 statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001. Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021, whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038. The localization of Brain metastases (BMs was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025. A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012. Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment.

  18. Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

    International Nuclear Information System (INIS)

    Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli

    2012-01-01

    Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  19. Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ostrom, Quinn T. [Department of Anthropology, Case Western Reserve University, Cleveland, OH (United States); McCulloh, Christopher [Case Western Reserve University School of Medicine, Cleveland, OH (United States); Chen, Yanwen; Devine, Karen; Wolinsky, Yingli, E-mail: qto@case.edu [Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH (United States)

    2012-02-28

    Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  20. Family history of cancer in benign brain tumor subtypes versus gliomas

    Directory of Open Access Journals (Sweden)

    Quinn eOstrom

    2012-02-01

    Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  1. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets

    Directory of Open Access Journals (Sweden)

    Nitesh Rohatgi

    2018-01-01

    Full Text Available Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10–16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

  2. The factors that have an impact on the development of brain metastasis in the patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Adem Dayan

    2012-01-01

    Conclusions: As the prognostic and predictive factors showing the development of brain metastasis in breast cancer patients may be identified, follow-up also including the brain is important in order to take preventive measures.

  3. Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

    Science.gov (United States)

    Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

    2015-08-01

    Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Taurine-modified Ru(ii)-complex targets cancerous brain cells for photodynamic therapy.

    Science.gov (United States)

    Du, Enming; Hu, Xunwu; Roy, Sona; Wang, Peng; Deasy, Kieran; Mochizuki, Toshiaki; Zhang, Ye

    2017-05-30

    The precision and efficacy of photodynamic therapy (PDT) is essential for the treatment of brain tumors because the cancer cells are within or adjacent to the delicate nervous system. Taurine is an abundant amino acid in the brain that serves the central nervous system (CNS). A taurine-modified polypyridyl Ru-complex was shown to have optimized intracellular affinity in cancer cells through accumulation in lysosomes. Symmetrical modification of this Ru-complex by multiple taurine molecules enhanced the efficiency of molecular emission with boosted generation of reactive oxygen species. These characteristic features make the taurine-modified Ru-complex a potentially effective photosensitizer for PDT of target cancer cells, with outstanding efficacy in cancerous brain cells.

  5. A case of leukoencephalopathy caused by radiation and chemotherapy for brain metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Shigeru; Sonoo, Hiroshi; Nomura, Tsunehisa; Ohkubo, Sumiko; Yamamoto, Yutaka; Tanaka, Katsuhiro; Kurebayashi, Junichi; Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2002-08-01

    A case of treatment-related leukoencephalopathy is presented. A patient with breast cancer metastasis to the brain, liver, bone and distant lymph nodes was treated with whole brain radiation and docetaxcel. Eleven months after radiation, magnetic resonance imaging showed diffuse leukoencephalopathy. Twenty-two months after radiation, the patient had gait disturbance, parkinsonism, dementia and urinary incontinence. From this experience, stereotactic radiosurgery such as cyber knife and gamma knife therapy, representing a new modality for delivering intense focal radiation, should be come preferred techniques for treating patients with brain metastases, to avoid the potential cognitive side effects of fractionated whole-brain radiotherapy. (author)

  6. Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy

    Directory of Open Access Journals (Sweden)

    Wu S

    2016-12-01

    Full Text Available San-Gang Wu,1,* Jia-Yuan Sun,2,* Qin Tong,3 Feng-Yan Li,2 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 3Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China *These authors contributed equally to this work Objective: The objectives of this study were to describe the distribution of brain metastases (BM in breast cancer patients and investigate the risk factors for perihippocampal metastases (PHM. Patients and methods: Retrospective analysis of the clinicopathological characteristics and patterns of BM was performed. Associations between clinicopathological characteristics and PHM (the hippocampus plus 5 mm margin were evaluated using logistic regression analyses. Results: A total of 1,356 brain metastatic lesions were identified in 192 patients. Patients with 1–3 BM, 4–9 BM, and ≥10 BM accounted for 63.0%, 18.8%, and 18.2%, respectively. There were only 7 (3.6% patients with hippocampal metastases (HM and 14 (7.3% patients with PHM. On logistic regression, the number of BM was an independent risk factor for PHM. Patients with ≥10 BM had a significantly higher risk of PHM compared with those with <10 BM. Breast cancer subtype (BCS was not associated with PHM. The number of BM was significantly correlated with various BCSs. Patients with hormone receptor (HR+/human epidermal growth factor receptor 2 (HER2+, HR-/HER2+, and HR-/HER2- subtypes had a higher probability of ≥10 BM, relative to patients with an HR+/HER2- subtype. Conclusion: Our study suggests that a low incidence of PHM may be acceptable to perform hippocampal-sparing whole-brain radiation therapy for breast cancer patients

  7. Trends in brain cancer mortality among U.S. Gulf War veterans: 21 year follow-up.

    Science.gov (United States)

    Barth, Shannon K; Dursa, Erin K; Bossarte, Robert M; Schneiderman, Aaron I

    2017-10-01

    Previous mortality studies of U.S. Gulf War veterans through 2000 and 2004 have shown an increased risk of brain cancer mortality among some deployed individuals. When veterans possibly exposed to environmental contaminants associated with demolition of the Khamisiyah Ammunition Storage Facility at Khamisiyah, Iraq, have been compared to contemporaneously deployed unexposed veterans, the results have suggested increased risk for mortality from brain cancer among the exposed. Brain cancer mortality risk in this cohort has not been updated since 2004. This study analyzes the risk for brain cancer mortality between 1991-2011 through two series of comparisons: U.S. Gulf War deployed and non-deployed veterans from the same era; and veterans possibly exposed to environmental contaminants at Khamisiyah compared to contemporaneously deployed but unexposed U.S. Gulf War veterans. Risk of brain cancer mortality was determined using logistic regression. Life test hazard models were created to plot comparisons of annual hazard rates. Joinpoint regression models were applied to assess trends in hazard rates for brain cancer mortality. U.S. Army veterans possibly exposed at Khamisiyah had similar rates of brain cancer mortality compared to those not possibly exposed; however, veterans possibly exposed had a higher risk of brain cancer in the time period immediately following the Gulf War. Results from these analyses suggest that veterans possibly exposed at Khamisiyah experienced different patterns of brain cancer mortality risk compared to the other groups. Published by Elsevier Ltd.

  8. Insights into brain metastasis in patients with ALK+ lung cancer: is the brain truly a sanctuary?

    Science.gov (United States)

    Toyokawa, Gouji; Seto, Takashi; Takenoyama, Mitsuhiro; Ichinose, Yukito

    2015-12-01

    Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy. Despite the excellent efficacy of ALK inhibitors, resistance to these drugs is inevitably encountered in most ALK-rearranged pts. Cases of resistance are subtyped into three groups, i.e., systemic, oligo, and central nervous system (CNS) types, with the CNS being used to be considered a sanctuary. With regard to the management of CNS lesions in pts with ALK+ NSCLC, a growing body of evidence has gradually demonstrated the intracranial (IC) efficacy of ALK inhibitor (ALKi) in ALK+ NSCLC pts with brain metastases (BMs). Although the efficacy of crizotinib for the CNS lesions remains controversial, a recent retrospective investigation of ALK+ pts with BM enrolled in PROFILE 1005 and PROFILE 1007 demonstrated that crizotinib is associated with a high disease control rate for BM. However, BM comprises the most common site of progressive disease in pts with or without baseline BMs, which is a serious problem for crizotinib. Furthermore, alectinib can be used to achieve strong and long-lasting inhibitory effects on BM. In addition to alectinib, the IC efficacy of other next-generation ALK inhibitors, such as ceritinib, AP26113 and PF-06463922, has been demonstrated. In this article, we review the latest evidence regarding the BM and IC efficacy of ALK inhibitors in pts with ALK+ NSCLC.

  9. Brain cancer and pesticide relationship in orchard farmers of Kashmir

    OpenAIRE

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A. R.

    2010-01-01

    Background: The increasing trend in the incidence of primary malignant brain tumors in orchard farmers and their families in Kashmir. Aim: To determine the relationship between the patients of primary malignant brain tumors and their occupation. Materials and Methods: Retrospectively, case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases), admitted for treatment simultaneously over a period of 4 years from Ja...

  10. MRI of metastatic adenocarcinomas to the brain. Differential diagnosis of colorectal and pulmonary cancer

    International Nuclear Information System (INIS)

    Fukusumi, Akio; Nakagawa, Hiroyuki; Takayama, Katsutoshi

    1998-01-01

    To clarify the characteristic features of MR imagings of metastatic adenocarcinomas to the brain and search for differential points between the lesions from colorectal cancer and those of lung cancer, we evaluated retrospectively intraparenchymal metastatic lesions of 13 colorectal origins and 13 pulmonary origins on MR imagings, compared with resected specimens. Metastatic lesions from colorectal cancer showed marked hypointense solid components on T2WI, which correspond to the dense tumor cells and coagulated necrosis pathologically. Metastatic lesions from lung cancers showed mixed intensity and various components on T2WI, which correspond to various histological components, such as solid tumor cell's nests, hemorrhage, necrosis and cystic fluid collection. Pathological specimens suggested that the low signal intensity on T2WI of MRI derived from concentration of tumor cells and coagulated necrosis including macrophages and lymphocytes. This study may contribute to make the differential diagnosis of metastatic adenocarcinomas to the brain from colorectal and pulmonary cancers. (author)

  11. Brain propagation of transduced α-synuclein involves non-fibrillar protein species and is enhanced in α-synuclein null mice.

    Science.gov (United States)

    Helwig, Michael; Klinkenberg, Michael; Rusconi, Raffaella; Musgrove, Ruth E; Majbour, Nour K; El-Agnaf, Omar M A; Ulusoy, Ayse; Di Monte, Donato A

    2016-03-01

    Aggregation and neuron-to-neuron transmission are attributes of α-synuclein relevant to its pathogenetic role in human synucleinopathies such as Parkinson's disease. Intraparenchymal injections of fibrillar α-synuclein trigger widespread propagation of amyloidogenic protein species via mechanisms that require expression of endogenous α-synuclein and, possibly, its structural corruption by misfolded conformers acting as pathological seeds. Here we describe another paradigm of long-distance brain diffusion of α-synuclein that involves inter-neuronal transfer of monomeric and/or oligomeric species and is independent of recruitment of the endogenous protein. Targeted expression of human α-synuclein was induced in the mouse medulla oblongata through an injection of viral vectors into the vagus nerve. Enhanced levels of intra-neuronal α-synuclein were sufficient to initiate its caudo-rostral diffusion that likely involved at least one synaptic transfer and progressively reached specific brain regions such as the locus coeruleus, dorsal raphae and amygdala in the pons, midbrain and forebrain. Transfer of human α-synuclein was compared in two separate lines of α-synuclein-deficient mice versus their respective wild-type controls and, interestingly, lack of endogenous α-synuclein expression did not counteract diffusion but actually resulted in a more pronounced and advanced propagation of exogenous α-synuclein. Self-interaction of adjacent molecules of human α-synuclein was detected in both wild-type and mutant mice. In the former, interaction of human α-synuclein with mouse α-synuclein was also observed and might have contributed to differences in protein transmission. In wild-type and α-synuclein-deficient mice, accumulation of human α-synuclein within recipient axons in the pons, midbrain and forebrain caused morphological evidence of neuritic pathology. Tissue sections from the medulla oblongata and pons were stained with different antibodies recognizing

  12. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    International Nuclear Information System (INIS)

    Yang, Heekyoung; Yoon, Su Jin; Jin, Juyoun; Choi, Seung Ho; Seol, Ho Jun; Lee, Jung-Il

    2011-01-01

    Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  13. Brain Tumor Trials Collaborative | Center for Cancer Research

    Science.gov (United States)

    Brain Tumor Trials Collaborative In Pursuit of a Cure The mission of the BTTC is to develop and perform state-of-the-art clinical trials in a collaborative and collegial environment, advancing treatments for patients with brain tumors, merging good scientific method with concern for patient well-being and outcome.

  14. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  15. Brain metastasis from male breast cancer treated 12 years ago ...

    African Journals Online (AJOL)

    A month ago, the patient had headache and vomiting complicated by the sudden onset of left hemiplegia. The brain MRI showed a huge right temporal process with a shift of the ... The development of brain metastases has been associated with young age, ... and immunohistochemistry different profiles regardless of gender.

  16. Pneumonia diagnosis in childhood and incidence of leukaemia, lymphoma and brain cancer

    DEFF Research Database (Denmark)

    Søgaard, Kirstine Kobberøe; Farkas, Dóra Körmendiné; Sørensen, Henrik Toft

    2017-01-01

    of pneumonia was a clinical marker of the three most common childhood cancers. DESIGN: Population-based cohort study. SETTING: Denmark, hospital diagnoses, 1994-2013. METHODS: Using national health registries, we compared the observed incidence of leukaemia, lymphoma and brain cancer among 83 935 children...... with a hospital-based pneumonia diagnosis with that expected among children in the general population. We calculated absolute cancer risks and standardised incidence ratios (SIRs) as a measure of relative risk. RESULTS: The cancer SIRs were substantially increased during the first 6 months of follow-up; lymphoid...

  17. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  18. Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study.

    Science.gov (United States)

    Chen, Bihong T; Sethi, Sean K; Jin, Taihao; Patel, Sunita K; Ye, Ningrong; Sun, Can-Lan; Rockne, Russell C; Haacke, E Mark; Root, James C; Saykin, Andrew J; Ahles, Tim A; Holodny, Andrei I; Prakash, Neal; Mortimer, Joanne; Waisman, James; Yuan, Yuan; Somlo, George; Li, Daneng; Yang, Richard; Tan, Heidi; Katheria, Vani; Morrison, Rachel; Hurria, Arti

    2018-05-02

    Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = - 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = - 6.94) compared to the non-TC group (change = - 1.21, p for

  19. NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer

    International Nuclear Information System (INIS)

    Adkins, Chris E.; Nounou, Mohamed I.; Hye, Tanvirul; Mohammad, Afroz S.; Terrell-Hall, Tori; Mohan, Neel K.; Eldon, Michael A.; Hoch, Ute; Lockman, Paul R.

    2015-01-01

    Brain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity. Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively). NKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (>20 ng/g for 168 h) versus conventional irinotecan (>1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals. Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m 2 NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results. The online version of this article (doi:10.1186/s12885-015-1672-4) contains supplementary material, which is available to authorized users

  20. High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats.

    Science.gov (United States)

    Wu, Yingjen Jeffrey; Pagel, Michael A; Muldoon, Leslie L; Fu, Rongwei; Neuwelt, Edward A

    2017-08-01

    Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

    Science.gov (United States)

    Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna; Seyfried, Thomas N

    2010-07-23

    GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  2. Calorie Restriction as an Anti-Invasive Therapy for Malignant Brain Cancer in the VM Mouse

    Directory of Open Access Journals (Sweden)

    Laura M Shelton

    2010-07-01

    Full Text Available GBM (glioblastoma multiforme is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

  3. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

    Directory of Open Access Journals (Sweden)

    Seyfried B

    2009-09-01

    Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  4. Emerging role of brain metastases in the prognosis of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Hambrecht A

    2011-08-01

    Full Text Available Amanda Hambrecht1,2, Rahul Jandial2, Josh Neman21Department of Biology, University of Southern California; 2Department of Neurosurgery, Beckman Research Institute, City of Hope National Cancer Center, CA, USAAbstract: Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors. Keywords: metastasis, breast cancer, blood-brain barrier, epithelial-mesenchymal transition, mesenchymal-epithelial transition

  5. Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

    Directory of Open Access Journals (Sweden)

    Yamamoto D

    2012-09-01

    Full Text Available Daigo Yamamoto,1,3 Satoru Iwase,2 Yu Tsubota,1 Noriko Sueoka,1 Chizuko Yamamoto,3 Kaoru Kitamura,4 Hiroki Odagiri,5 Yoshinori Nagumo61Department of Surgery, Kansai Medical University, Hirakata, Osaka, 2Department of Palliative Medicine, University of Tokyo Hospital, Tokyo, 3Department of Internal Medicine, Seiko Hospital, Neyagawa, Osaka, 4Breast Unit, Nagumo Clinic, Fukuoka, 5Department of Surgery, Hirosaki National Hospital, Hirosaki, 6Breast Unit, Nagumo Clinic, Tokyo, JapanBackground: Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation.Methods: Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed.Results: The median time to disease progression was 86 days. Of five patients, two (40% achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades were hypertension (60%, neuropathy (40%, and proteinuria (20%. No grade 3 toxicity was seen. No intracranial hemorrhage was observed.Conclusion: We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.Keywords: brain, bevacizumab, metastatic breast cancer

  6. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

    Science.gov (United States)

    Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

    2008-11-01

    Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

  7. Role of infectious agents in the carcinogenesis of brain and head and neck cancers

    Directory of Open Access Journals (Sweden)

    Alibek Kenneth

    2013-02-01

    Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

  8. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    Science.gov (United States)

    Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

    2005-05-01

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

  9. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    International Nuclear Information System (INIS)

    Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

    2005-01-01

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment

  10. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kopelman, Raoul [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States)]. E-mail: kopelman@umich.edu; Lee Koo, Yong-Eun [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States); Philbert, Martin [Environmental Health Sciences, niversity of Michigan (United States); Moffat, Bradford A. [Department of Radiology, The University of Michigan (United States); Ramachandra Reddy, G. [Molecular Therapeutics, Inc., Ann Arbor, MI 48104 (United States); McConville, Patrick [Molecular Therapeutics, Inc., Ann Arbor, MI 48104 (United States); Hall, Daniel E. [Department of Radiology, University of Michigan (United States); Chenevert, Thomas L. [Department of Radiology, University of Michigan (United States); Bhojani, Mahaveer Swaroop [Department of Radiation Oncology, University of Michigan (United States); Buck, Sarah M. [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States); Rehemtulla, Alnawaz [Department of Radiation Oncology, University of Michigan (United States); Ross, Brian D. [Department of Radiology, University of Michigan (United States)

    2005-05-15

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

  11. An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-06-01

    Full Text Available Ying Zhang, Huaping Tang, Jun Li, Meng Li Department of Respiration Medicine, Municipal Hospital, Qingdao, People’s Republic of China Abstract: Lung cancer has the highest mortality rate of all cancers world­wide. A total of 70%–75% of all lung cancers are non-small cell lung cancer (NSCLC with two-thirds presenting with locally advanced or metastatic disease at diagnosis. Brain metastasis is one of the most common problems in the management of NSCLC, worsening the prognosis and quality of life of NSCLC patients. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs gefitinib and erlotinib have been tested in patients with NSCLC and brain metastasis. Icotinib is a new type of oral EGFR-TKI. In this report, we describe a patient with lung adenocarcinoma cancer with brain metastases who received icotinib treatment and kept satisfactory health-related quality of life for 1 year. Keywords: EGFR, non-small cell lung cancer, tyrosine kinase inhibitor

  12. CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2-neu-positive breast cancer.

    Science.gov (United States)

    Sengupta, S; Rojas, R; Mahadevan, A; Kasper, E; Jeyapalan, S

    2015-04-01

    Nervous system relapse of patients with advanced HER2-neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood-brain barrier, as combination therapy to treat HER2-neu-positive breast cancer with brain metastases.

  13. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    Picano, Eugenio; Vano, Eliseo; Domenici, Luciano; Bottai, Matteo; Thierry-Chef, Isabelle

    2012-01-01

    According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906), the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of < 200 mSv, but with head exposure which may (in absence of protection) arrive at a head equivalent dose of 1 to 3 Sv after a professional lifetime (corresponding to a brain equivalent dose around 500 mSv). At this point, a systematic assessment of brain (cancer and non-cancer) effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed

  14. Brain cancer incidence trends in relation to cellular telephone use in the United States.

    Science.gov (United States)

    Inskip, Peter D; Hoover, Robert N; Devesa, Susan S

    2010-11-01

    The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. Log-linear models were used to estimate the annual percent change in rates among whites. With the exception of the 20-29-year age group, the trends for 1992-2006 were downward or flat. Among those aged 20-29 years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males. The recent trend in 20-29-year-old women was driven by a rising incidence of frontal lobe cancers. No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones. Frontal lobe cancer rates also rose among 20-29-year-old males, but the increase began earlier than among females and before cell phone use was highly prevalent. Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer.

  15. Prognostic index to identify patients who may not benefit from whole brain radiotherapy for multiple brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Sundaresan, P.; Yeghiaian, R.; Gebski, V.

    2010-01-01

    Full text: Palliative whole brain radiotherapy (WBRT) is often recommended in the management of multiple brain metastases. Allowing for WBRT waiting time, duration of the WBRT course and time to clinical response, it may take 6 weeks from the point of initial assessment for a benefit from WBRT to manifest. Patients who die within 6 weeks ('early death') may not benefit from WBRT and may instead experience a decline in quality of life. This study aimed to develop a prognostic index (PI) that identifies the subset of patients with lung cancer with multiple brain metastases who may not benefit from WBRT because of'early death'. The medical records of patients with lung cancer who had WBRT recommended for multiple brain metastases over a 10-year period were retrospectively reviewed. Patients were classified as either having died within 6 weeks or having lived beyond 6 weeks. Potential prognostic indicators were evaluated for correlation with 'early death'. A PI was constructed by modelling the survival classification to determine the contribution of these factors towards shortened survival. Of the 275 patients recommended WBRT, 64 (23.22%) died within 6 weeks. The main prognostic factor predicting early death was Eastern Cooperative Oncology Group (ECOG) status >2. Patients with a high PI score (>13) were at higher risk of'early death'. Twenty-three per cent of patients died prior to benefit from WBRT. ECOG status was the most predictive for 'early death'. Other factors may also contribute towards a poor outcome. With further refinement and validation, the PI could be a valuable clinical decision tool.

  16. MANGO PROPAGATION

    OpenAIRE

    ALBERTO CARLOS DE QUEIROZ PINTO; VICTOR GALÁN SAÚCO; SISIR KUMAR MITRA; FRANCISCO RICARDO FERREIRA

    2018-01-01

    ABSTRACT This Chapter has the objectives to search, through the review of the available literature, important informations on the evolution of mango propagation regarding theoretical and practical aspects from cellular base of sexual propagation, nursery structures and organizations, substrate compositions and uses, importance of rootstock and scion selections, also it will be described the preparation and transport of the grafts (stem and bud) as well as the main asexual propagation methods...

  17. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    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.

  18. Systematic review of wireless phone use and brain cancer and other head tumors.

    Science.gov (United States)

    Repacholi, Michael H; Lerchl, Alexander; Röösli, Martin; Sienkiewicz, Zenon; Auvinen, Anssi; Breckenkamp, Jürgen; d'Inzeo, Guglielmo; Elliott, Paul; Frei, Patrizia; Heinrich, Sabine; Lagroye, Isabelle; Lahkola, Anna; McCormick, David L; Thomas, Silke; Vecchia, Paolo

    2012-04-01

    We conducted a systematic review of scientific studies to evaluate whether the use of wireless phones is linked to an increased incidence of the brain cancer glioma or other tumors of the head (meningioma, acoustic neuroma, and parotid gland), originating in the areas of the head that most absorb radiofrequency (RF) energy from wireless phones. Epidemiology and in vivo studies were evaluated according to an agreed protocol; quality criteria were used to evaluate the studies for narrative synthesis but not for meta-analyses or pooling of results. The epidemiology study results were heterogeneous, with sparse data on long-term use (≥ 10 years). Meta-analyses of the epidemiology studies showed no statistically significant increase in risk (defined as P brain cancer or other head tumors from wireless phone use. Analyses of the in vivo oncogenicity, tumor promotion, and genotoxicity studies also showed no statistically significant relationship between exposure to RF fields and genotoxic damage to brain cells, or the incidence of brain cancers or other tumors of the head. Assessment of the review results using the Hill criteria did not support a causal relationship between wireless phone use and the incidence of adult cancers in the areas of the head that most absorb RF energy from the use of wireless phones. There are insufficient data to make any determinations about longer-term use (≥ 10 years). © 2011 Wiley Periodicals, Inc.

  19. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  20. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR Staging

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  1. Radiotherapy of brain metastases of a breast cancer: present strategies, technological innovations and biological perspectives

    International Nuclear Information System (INIS)

    Chargari, C.; Vedrine, L.; Bauduceau, O.; Jacob, J.; Fayolle, M.; Chargari, C.; Campana, F.; Pierga, J.Y.; Idrissi, H.R.; Fourquet, A.; Kirova, Y.

    2010-01-01

    The authors propose an overview of strategies which are presently used for the treatment of brain metastases related to a breast cancer. They outline the perspectives and recent developments of encephalic irradiation with new technologies allowing an increased conformation to be obtained, and also in terms of radiosensitization and radioprotection experiences. Short communication

  2. Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.

    Science.gov (United States)

    Xia, Chun-Fang; Zhang, Yufeng; Zhang, Yun; Boado, Ruben J; Pardridge, William M

    2007-12-01

    The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood-brain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin-biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin. Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 microg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin-streptavidin linker. The intravenous administration of the siRNA caused a 69-81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin-biotin technology.

  3. The economic burden of brain metastasis among lung cancer patients in the United States.

    Science.gov (United States)

    Guérin, A; Sasane, M; Dea, K; Zhang, J; Culver, K; Nitulescu, R; Wu, E Q; Macalalad, A R

    2016-01-01

    Brain metastases among lung cancer patients can impair cognitive and functional ability, complicate care, and reduce survival. This study focuses on the economic burden of brain metastasis in lung cancer-direct healthcare costs to payers and indirect costs to patients, payers, and employers-in the US. Retrospective study using claims data from over 60 self-insured Fortune 500 companies across all US census regions (January 1999-March 2013). Adult, non-elderly lung cancer patients with brain metastasis were evaluated over two study periods: (1) pre-diagnosis (≤30 days prior to first observed lung cancer diagnosis to ≤30 days prior to first-observed brain metastasis diagnosis) and (2) post-diagnosis (≤30 days prior to first observed brain metastasis diagnosis to end of continuous eligibility or observation). Healthcare costs to payers and resource utilization, salary loss to patients, disability payouts for payers, and productivity loss to employers. A total of 132 patients were followed for a median of 8.4 and 6.6 months in the pre- and post-diagnosis periods, respectively. At diagnosis of brain metastasis, 21.2% of patients were on leave of absence and 6.1% on long-term disability leave. Substantial differences were observed in the pre- vs post-diagnosis periods. Specifically, patients incurred much greater healthcare utilization in the post-diagnosis period, resulting in $25,579 higher medical costs per-patient-per-6-months (PPP6M). During this period, patients missed significantly more work days, generating an incremental burden of $2853 PPP6M in salary loss for patients, $2557 PPP6M in disability payments for payers, and $4570 PPP6M in productivity loss for employers. Type of primary lung cancer and extent of brain metastasis could not be assessed in the data. The analysis was also limited to patients with comprehensive disability coverage. Development of brain metastasis among lung cancer patients is associated with a substantial economic burden to payers

  4. Patients' experiences and care needs during the diagnostic phase of an Integrated Brain Cancer Pathway

    DEFF Research Database (Denmark)

    Vedelø, Tina Wang; Sørensen, Jens Christian Hedemann; Delmar, Charlotte

    2018-01-01

    of brain cancer, not knowing what to expect and participants' perceptions of the relationship with the health care providers. The analysis revealed that participants were in risk of having unmet information needs and that contextual factors seemed to cause fragmented care that led to feelings...... that the shock of the diagnosis, combined with the multiple symptoms, affect patients' ability to understand information and express needs of care and support. Unmet needs have been reported within this group of patients, however, the experiences and care needs of patients going through the diagnostic phase...... of a standardised Integrated Brain Cancer Pathway have not previously been explored. DESIGN: A Case Study design was used to provide detailed information of the complex needs of patients being diagnosed with a malignant brain tumour. METHODS: Research interviews and direct participant observation of four patients...

  5. Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Chee, R. J.; Bydder, S.; Cameron, F.

    2007-01-01

    Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations

  6. Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

    Science.gov (United States)

    Li, Wei-Ling; Fu, Chang; Xuan, Ang; Shi, Da-Peng; Gao, Yong-Ju; Zhang, Jie; Xu, Jun-Ling

    2015-02-05

    Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  7. Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

    Directory of Open Access Journals (Sweden)

    Wei-Ling Li

    2015-01-01

    Full Text Available Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People′s Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases, squamous cell carcinoma (43 cases, and small-cell carcinoma (25 cases. The whole body 18F-fluorodeoxyglucose (18F-FDG positron emission tomography (PET/computed tomography (CT of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255 was larger than those in the adenocarcinoma group (total voxel value 1217 and squamous cell carcinoma group (total voxel value 1292. Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  8. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  9. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

    Science.gov (United States)

    Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

  10. Pesticides and brain cancer linked in orchard farmers of Kashmir

    OpenAIRE

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A. R.; Raina, T. H.

    2010-01-01

    Background: The atmosphere of valley of Kashmir is ideal for fresh and dry fruit production. Millions of tons of pesticides, insecticides and fungicides (chemicals like chlorpyriphos, mancozeb, captan, dimethoate, phosalone, etc.) are being used by the orchard farmers to spray the plants, fruits and the leaves every year. The increasing trend in the incidence of primary malignant brain tumors in orchard farmers of Kashmir is alarming. Aim: To determine the relationship between the patients of...

  11. Brain metastases in patients who receive trastuzumab-containing chemotherapy for HER2-overexpressing metastatic breast cancer

    International Nuclear Information System (INIS)

    Ono, Makiko; Ando, Masashi; Yunokawa, Mayu

    2009-01-01

    Recently, a high rate of brain metastases has been reported among patients with human epidermal growth factor receptor (HER2)-overexpressing metastatic breast cancer who were treated with trastuzumab. The present study examined risk factors for the development of brain metastasis in patients with HER2-overexpressing breast cancer who were treated with trastuzumab. We retrospectively reviewed 204 patients with HER-2-overexpressing breast cancer who were treated with a trastuzumab-containing regimen between 1999 and 2006. Patients with clinical symptoms were diagnosed as having brain metastases when brain magnetic resonance imaging (MRI) or a computed tomography (CT) scan revealed positive findings for brain metastases. The median follow-up time of this cohort was 53.6 months. Among the patients who received a trastuzumab-containing regimen, 74 patients (36.3%) developed brain metastases. The median survival from the diagnosis of brain metastases was 13.5 months (95% confidence interval [CI], 12.2-14.7 months). The median time interval between the beginning of trastuzumab treatment and the diagnosis of brain metastases was 13.6 months (range, 0.0-45.8 months). Among patients with brain metastases, the median overall survival period was 39 months. A multivariate logistic regression analysis showed that age (≤50 years), recurrent breast cancer, and liver metastases were significant risk factors for the development of brain metastases. Patients with HER2-overexpressing breast cancer treated with trastuzumab had a high incidence of brain metastases (36.3%). Routine screening for brain metastases 1 year after the start of trastuzumab treatment, may be warranted in younger patients (≤50 years) who had recurrent breast cancer with liver metastases. (author)

  12. Nitrates in drinking water and the risk of death from brain cancer: does hardness in drinking water matter?

    Science.gov (United States)

    Ho, Chi-Kung; Yang, Ya-Hui; Yang, Chun-Yuh

    2011-01-01

    The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from brain cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the influence of nitrates on development of brain cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death from brain cancer and exposure to nitrates in drinking water in Taiwan. All brain cancer deaths of Taiwan residents from 2003 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO₃-N), Ca, and Mg in drinking water was obtained from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO₃-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO₃-N exposure level was cancer occurrence was 1.04 (0.85-1.27) for individuals who resided in municipalities served by drinking water with a NO₃-N exposure ≥ 0.38 ppm. No marked effect modification was observed due to Ca and Mg intake via drinking water on brain cancer occurrence.

  13. Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

    Directory of Open Access Journals (Sweden)

    VandenBerg Scott R

    2010-04-01

    Full Text Available Abstract Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3% cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

  14. Nanotech revolution for the anti-cancer drug delivery through blood-brain barrier.

    Science.gov (United States)

    Caraglia, M; De Rosa, G; Salzano, G; Santini, D; Lamberti, M; Sperlongano, P; Lombardi, A; Abbruzzese, A; Addeo, R

    2012-03-01

    Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

  15. MANGO PROPAGATION

    Directory of Open Access Journals (Sweden)

    ALBERTO CARLOS DE QUEIROZ PINTO

    2018-03-01

    Full Text Available ABSTRACT This Chapter has the objectives to search, through the review of the available literature, important informations on the evolution of mango propagation regarding theoretical and practical aspects from cellular base of sexual propagation, nursery structures and organizations, substrate compositions and uses, importance of rootstock and scion selections, also it will be described the preparation and transport of the grafts (stem and bud as well as the main asexual propagation methods their uses and practices. Finally, pattern and quality of graft mangos and their commercialization aspects will be discussed in this Chapter.

  16. Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

    2018-02-01

    Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

  17. Brain cancer and pesticide relationship in orchard farmers of Kashmir.

    Science.gov (United States)

    Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R

    2010-09-01

    The increasing trend in the incidence of primary malignant brain tumors in orchard farmers and their families in Kashmir. To determine the relationship between the patients of primary malignant brain tumors and their occupation. Retrospectively, case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases), admitted for treatment simultaneously over a period of 4 years from January 2005 to December 2008, to the Neurosurgery, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Kashmir, were studied. Follow-up and family interaction was established. Analysis revealed that 90.04% (389 out of 432) patients were orchard farm workers, orchard residents and orchard playing children exposed to the high levels of multiple types of neurotoxic and carcinogenic (chlorpyriphos, dimethoate, mancozeb and captan) chemicals for more than 10 years [relative risk (RR) = 10.6; odds ratio (OR) = >10; 95% confidence interval (CI) = >25-40]. The 9.96% (43 out of 432) patients were not exposed to pesticides. On the other hand, only 19 patients out of 457 controls had recorded history of pesticide exposure and 438 were unrelated to pesticides. Out of 389 patients, 71.7% (279 out of 389) were males and 28.3% (110 out of 389), including six members of three families, were females (one male child). All orchard-related 389 patients had high-grade tumors as compared to the non-pesticide tumors. Mortality in pesticide-exposed tumors was 12%. The higher or upper-normal levels of serum cholinesterase (AChE) were observed in 54.7% (213 out of 389) patients and decreased levels were found in only 45.3% (176 out of 389) orchard-related patients (RR = 19.4; OR = >5; 95% CI = >1-10). Although serum AChE levels were a routine investigation in malignant brain tumors, this was not a routine in other neurological conditions (hospitalized controls). The familial gliomas have shown an emerging trend in the orchard residents of

  18. Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

    International Nuclear Information System (INIS)

    Uchiyama, Bine; Satoh, Ken; Saijo, Yasuo

    1998-01-01

    Forty patients with metastatic brain tumors from primary lung cancer underwent radiosurgery (γ-knife). We retrospectively compared their prior treatment history, number of metastatic foci, and performance status, to evaluate the effects of, and indications for, γ-knife therapy. After both the primary and the metastatic tumors were controlled, performance status could be used as an index in the choice of γ-knife therapy. Our results demonstrate that repeated γ-knife radiosurgeries prolonged survival time. Gamma-knife radiosurgery improves quality of life and prognosis of patients with metastatic brain tumors. (author)

  19. Boron-neutron capture therapy for incurable cancer and inoperable brain tumors

    International Nuclear Information System (INIS)

    Hatanaka, Hiroshi

    1993-01-01

    Recent advances in cancer diagnosis and treatment have not yet improved the survival rate of patients with cancers of the brain, liver, etc. In these organs, an extirpation of the organ, which can be done for stomach, breast, cervix, lung, etc. is not allowed, and this fact is the cause of poor therapeutic results. Boron-neutron capture therapy (BNCT) utilizes the nuclear reaction which will take place between the boron-10 (loaded in the cancer cells artificially) and the thermal neutrons (delivered by reactors). The secondary radiations, helium and lithium hit the cancer cell itself and cause the death of the cancer cell while sparing the surrounding normal cells. BNCT is now being tried also by Oda of Kyoto University (9 cases) and by Nakagawa of Tokushima University (7 cases). It has been tried by Mishima (Kobe University) on 12 skin melanoma patients, proving satisfactory local control of the melanomas. Mercaptoundecahydrododecaborate (BHS) and boronophenylalanine (BPA) have been tried for brain tumors and for melanoma. For cancers of the liver and abdominal viscerae, antibody to the tumor specific antigen has been considered a good carrier of boron-10. Surgeons Takahashi, Fujii, Fujii, Yanagie, and Sekiguchi and immunologist Nariuchi of Tokyo University have been involved in the research and have obtained encouraging results in animals. Hatanaka has been proving good effect of BNCT upon giant cerebral arteriovenous malformation (AVM) and skull base meningioma. These diseases, although pathologically benign, have posed difficult problems in neurosurgery. It will be exciting good news to the patients. In conclusion, BNCT appears to be a good means to treat difficult lesions in the brain and other organs which defy sophisticated modern therapeutic means. (author)

  20. Neuropsychological profiles of breast cancer and brain tumor cohorts in Northeast Ontario, Canada.

    Science.gov (United States)

    Mariani, Matias; Collins, Mark William Glister

    2018-05-17

    As developments in cancer treatment have improved outcomes, research has increasingly focused on the role of cancer-related cognitive impairment (CRCI) in quality of life for cancer survivors. Impairment profiles have been heterogeneous across studies, necessitating the study of these effects across different cohorts. The purpose of this preliminary study is to compare the memory profiles of Northeast Ontario breast and CNS cancer patients, as there is no literature which exists for profiling CRCI within this largely rural region. Sixty-three outpatients with breast cancer (n = 32) or CNS tumors (n = 30) at the Northeast Cancer Centre in Sudbury, Canada, were administered a neuropsychological test battery as part of their clinical examination. Domains measured within this study included attention and concentration, processing speed, motor function, language skills, verbal and visual memory, and executive functioning. Participants with brain tumors scored poorer on most neuropsychological measures than participants with breast cancer. Initial verbal memory for individuals with breast cancer was lower than delayed recall and recognition trials. Trial 1 performance for this group was also negatively correlated with self-reported anxiety scores. Consistent with the literature, participants with breast cancer obtained higher scores on most test measures than participants with CNC tumors. Breast cancer participants had lower verbal memory scores on initial trials compared to delayed recall, potentially due to relationships with anxiety and attention. Further research into this cohort will strive to gain greater understanding of the patterns of deficits experienced and how these may inform individuals with cancer in other regions.

  1. Exposure to magnetic field and brain cancer among child; Exposition au champ magnetique et cancer du cerveau chez l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Mir, L

    2008-09-15

    The risk of childhood brain cancer as a function of magnetic field exposure has been studied less than the risk of leukemia. this updated meta-analysis of thirteen epidemiologic studies thus provides an important contribution to the literature. No increased risk of brain cancer was found, and there were no differences by method of exposure assessment. Doubt remains only for the highest exposure levels, for which very limited data are available. (author)

  2. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  3. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer - brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  4. The PSA−/lo prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration

    Science.gov (United States)

    Qin, Jichao; Liu, Xin; Laffin, Brian; Chen, Xin; Choy, Grace; Jeter, Collene; Calhoun-Davis, Tammy; Li, Hangwen; Palapattu, Ganesh S.; Pang, Shen; Lin, Kevin; Huang, Jiaoti; Ivanov, Ivan; Li, Wei; Suraneni, Mahipal V.; Tang, Dean G.

    2012-01-01

    SUMMARY Prostate cancer (PCa) is heterogeneous and contains both differentiated and undifferentiated tumor cells, but the relative functional contribution of these two cell populations remains unclear. Here we report distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (PSA+) and low (PSA−/lo) levels of the differentiation marker PSA. PSA−/lo PCa cells are quiescent and refractory to stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity. They preferentially express stem cell genes and can undergo asymmetric cell division generating PSA+ cells. Importantly, PSA−/lo PCa cells can initiate robust tumor development and resist androgen ablation in castrated hosts, and harbor highly tumorigenic castration-resistant PCa cells that can be prospectively enriched using ALDH+CD44+α2β1+ phenotype. In contrast, PSA+ PCa cells possess more limited tumor-propagating capacity, undergo symmetric division and are sensitive to castration. Together, our study suggests PSA−/lo cells may represent a critical source of castration-resistant PCa cells. PMID:22560078

  5. Inclusion of brain in FDG PET/CT scanning techniques in cancer patients: Does it obviate the need for dedicated brain imaging?

    International Nuclear Information System (INIS)

    Purandare, Nilendu C.

    2011-01-01

    Metastases to the brain can affect about 10-20% cancer patients. Rising incidence of brain metastases in recent years is related to improved survival rates as a result of advances in cancer therapy and development of more sensitive diagnostic imaging techniques. In patients with extracranial malignancies detection of brain metastases is very important in deciding further diagnostic procedures, planning therapeutic strategies and also to ascertain prognosis. Computerized tomography (CT) and magnetic resonance imaging (MRI) are the modalities which have been traditionally used to assess metastatic disease to the central nervous system. It is generally accepted that MRI (contrast enhanced) is superior to CT scan (contrast enhanced) in the diagnosis of brain metastases. An inherently better soft tissue contrast resolution, stronger contrast enhancement, lack of bone artifacts and partial volume effects and direct multiplanar imaging enables MRI to pick up smaller sized as well as more number of metastases than a CT scan

  6. Migration Phenotype of Brain-Cancer Cells Predicts Patient Outcomes

    Directory of Open Access Journals (Sweden)

    Chris L. Smith

    2016-06-01

    Full Text Available Glioblastoma multiforme is a heterogeneous and infiltrative cancer with dismal prognosis. Studying the migratory behavior of tumor-derived cell populations can be informative, but it places a high premium on the precision of in vitro methods and the relevance of in vivo conditions. In particular, the analysis of 2D cell migration may not reflect invasion into 3D extracellular matrices in vivo. Here, we describe a method that allows time-resolved studies of primary cell migration with single-cell resolution on a fibrillar surface that closely mimics in vivo 3D migration. We used this platform to screen 14 patient-derived glioblastoma samples. We observed that the migratory phenotype of a subset of cells in response to platelet-derived growth factor was highly predictive of tumor location and recurrence in the clinic. Therefore, migratory phenotypic classifiers analyzed at the single-cell level in a patient-specific way can provide high diagnostic and prognostic value for invasive cancers.

  7. The views of patients with brain cancer about palliative care: a qualitative study.

    Science.gov (United States)

    Vierhout, M; Daniels, M; Mazzotta, P; Vlahos, J; Mason, W P; Bernstein, M

    2017-12-01

    Palliative care, a specialty aimed at providing optimal care to patients with life-limiting and chronic conditions, has several benefits. Although palliative care is appropriate for neurosurgical conditions, including brain cancer, few studies have examined the views of brain cancer patients about palliative care. We aimed to explore the thoughts of brain cancer patients about palliative care, their opinions about early palliative care, and their preferred care setting. Semi-structured interviews and the qualitative research methodologies of grounded theory were used to explore perceptions of palliative care on the part of 39 brain cancer outpatients. Seven overarching actions emerged: ■Patients would prefer to receive palliative care in the home.■Increased time with caregivers and family are the main appeals of home care.■Patients express dissatisfaction with brief and superficial interactions with health care providers.■Patients believe that palliative care can contribute to their emotional well-being.■Patients are open to palliative care if they believe that it will not diminish optimism.■There is a preconceived idea that palliative care is directly linked to active dying, and that supposed link generates fear in some patients.■Patients prefer to be educated about palliative care as an option early in their illness, even if they are fearful of it. Overall, when educated about the true meaning of palliative care, most patients express interest in accessing palliative care services. Although the level of fear concerning palliative care varies in patients, most recognize the associated benefits.

  8. Brain cancer incidence trends in relation to cellular telephone use in the United States

    OpenAIRE

    Inskip, Peter D.; Hoover, Robert N.; Devesa, Susan S.

    2010-01-01

    The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this i...

  9. Brain metastasis from ovarian cancer: case report and review of the literature.

    Science.gov (United States)

    Hu, Xi-Quan; Imitola, Jaime; Kim, Ryan Y; Mahta, Ali; Kesari, Santosh

    2012-06-01

    We present an 80-year-old lady with a history of ovarian cancer, who manifested with seizure and left upper extremity weakness. The imaging revealed a multilobulated mass within right parietal lobe. She underwent surgical resection and the pathology was compatible with metastasis from ovarian adenocarcinoma. She received a whole brain radiation therapy and she has been in remission for more than 2 years.

  10. Selection of optimal treatment scheme for brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Dong Mingxin; Zhao Tong; Huang Jingzi; Yu Shukun; Ma Yan; Tian Zhongcheng; Jin Xiangshun; Quan Jizhong; Liu Jin; Wang Dongxu

    2006-01-01

    Objective: To select the optimal treatment scheme for brain metastases of non-small cell lung cancers (NSCLCs). Methods: Seventy-two NSCLC cases diagnosesd by pathology with brain metastases were randomly classified into three groups, Group I, 24 cases with whole brain conventional external fractioned irradiation of D T 36-41 Gy/4-5 w, Group II, 22 eases with y-knife treatment plus whole brain conventional external fractioned irradiation, and Group III, 26 cases with γ-knife plus whole brain conventional external fractioned irradiation in combination with chemotherapy of Vm-26. The surrounding area of tumor was strictly covered with 50% para-central-dosal curve in γ-knife treatment (D T 16-25 Gy with a mean of 16 Gy). The muirleaf collimator was selected according to the volume of tumors. Chemotherapy of Vm-26 (60 mg/m 2 d1-3) was applied during the treatment with whole brain conventional external fractioned irradiation (D T 19-29 Gy/2-3 w), 21 days in a period, 2 periods in total. Results: The median survival time was estimated to be 6.0 months (ranged from 1.2 to 19.0 months) in the Group I, 9.2 months (4.4-30 months) in the Group II, and 10.8 months (5.2-42.2 months) in the Group III. The 1-year and 2-year survival rates were 34.6% and 12.6% , 62.2% and 30.2%, and 70.8% and 35.6% respectively in Group I, Group II, and Group III, respectively. Conclusion: For brain metastases of NSCLC, γ-knife plus whole brain conventional external fractioned irradiation combined with treatment of Vm-26 had a significantly beneficial influence on improvement of the local control and 1-year and 2-year survival. There was no complaint about the side-effects of the treatment. (authors)

  11. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

    Science.gov (United States)

    Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

    2012-01-01

    We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

  12. An evaluation of an automated 4D-CT contour propagation tool to define an internal gross tumour volume for lung cancer radiotherapy

    International Nuclear Information System (INIS)

    Gaede, Stewart; Olsthoorn, Jason; Louie, Alexander V.; Palma, David; Yu, Edward; Yaremko, Brian; Ahmad, Belal; Chen, Jeff; Bzdusek, Karl; Rodrigues, George

    2011-01-01

    Background and purpose: To evaluate an automated 4D-CT contouring propagation tool by its impact on the inter- and intra-physician variability in lung tumour delineation. Materials and methods: In a previous study, six radiation oncologists contoured the gross tumour volume (GTV) and nodes on 10 phases of the 4D-CT dataset of 10 lung cancer patients to examine the intra- and inter-physician variability. In this study, a model-based deformable image registration algorithm was used to propagate the GTV and nodes on each phase of the same 4D-CT datasets. A blind review of the contours was performed by each physician and edited. Inter- and intra-physician variability for both the manual and automated methods was assessed by calculating the centroid motion of the GTV using the Pearson correlation coefficient and the variability in the internal gross tumour volume (IGTV) overlap using the Dice similarity coefficient (DSC). Results: The time for manual delineation was (42.7 ± 18.6) min versus (17.7 ± 5.4) min when the propagation tool was used. A significant improvement in the mean Pearson correlation coefficient was also observed. There was a significant decrease in mean DSC in only 1 out of 10 primary IGTVs and 2 out of 10 nodal IGTVs. Intra-physician variability was not significantly impacted (DSC > 0.742). Conclusions: Automated 4D-CT propagation tools can significantly decrease the IGTV delineation time without significantly decreasing the inter- and intra-physician variability.

  13. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  14. The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

    Directory of Open Access Journals (Sweden)

    Kimmelman Jonathan

    2007-11-01

    Full Text Available Abstract Background Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations. Methods We interviewed 29 individuals – 7 patients dying of a malignant brain tumor and 22 loved ones. One-on-one interviews were conducted according to a pre-designed interview guide. A combination of open-ended questions, as well as clinical scenarios was presented to participants in order to understand what is meaningful and valuable to them when determining treatment options and management approaches. The results were analyzed, coded, and interpreted using qualitative analytic techniques in order to arrive at several common overarching themes. Results Seven major themes were identified. In general, respondents were united in viewing brain cancer as unique amongst malignancies, due in large part to the premium placed on mental competence and cognitive functioning. Importantly, participants found their experiences, however difficult, led to the discovery of inner strength and resilience. Responses were usually framed within an interpersonal context, and participants were generally grateful for the opportunity to speak about their experiences. Attitudes towards religion, spirituality, and euthanasia were also probed. Conclusion Several important themes underlie the experiences of brain cancer patients and their caregivers. It is important to consider these when managing these patients and to respect not only their autonomy but also the complex interpersonal toll that a malignant diagnosis can have.

  15. Microwave beamforming for non-invasive patient-specific hyperthermia treatment of pediatric brain cancer

    International Nuclear Information System (INIS)

    Burfeindt, Matthew J; Zastrow, Earl; Hagness, Susan C; Van Veen, Barry D; Medow, Joshua E

    2011-01-01

    We present a numerical study of an array-based microwave beamforming approach for non-invasive hyperthermia treatment of pediatric brain tumors. The transmit beamformer is designed to achieve localized heating-that is, to achieve constructive interference and selective absorption of the transmitted electromagnetic waves at the desired focus location in the brain while achieving destructive interference elsewhere. The design process takes into account patient-specific and target-specific propagation characteristics at 1 GHz. We evaluate the effectiveness of the beamforming approach using finite-difference time-domain simulations of two MRI-derived child head models from the Virtual Family (IT'IS Foundation). Microwave power deposition and the resulting steady-state thermal distribution are calculated for each of several randomly chosen focus locations. We also explore the robustness of the design to mismatch between the assumed and actual dielectric properties of the patient. Lastly, we demonstrate the ability of the beamformer to suppress hot spots caused by pockets of cerebrospinal fluid (CSF) in the brain. Our results show that microwave beamforming has the potential to create localized heating zones in the head models for focus locations that are not surrounded by large amounts of CSF. These promising results suggest that the technique warrants further investigation and development.

  16. Prognostic factors of HER2-positive breast cancer patients who develop brain metastasis: a multicenter retrospective analysis.

    Science.gov (United States)

    Hayashi, Naoki; Niikura, Naoki; Masuda, Norikazu; Takashima, Seiki; Nakamura, Rikiya; Watanabe, Ken-ichi; Kanbayashi, Chizuko; Ishida, Mayumi; Hozumi, Yasuo; Tsuneizumi, Michiko; Kondo, Naoto; Naito, Yoichi; Honda, Yayoi; Matsui, Akira; Fujisawa, Tomomi; Oshitanai, Risa; Yasojima, Hiroyuki; Yamauchi, Hideko; Saji, Shigehira; Iwata, Hiroji

    2015-01-01

    The clinical course and prognostic factors of HER2-positive breast cancer patients with brain metastases are not well known because of the relatively small population. The aim of this study was to determine prognostic factors associated with HER2-positive patients who develop brain metastases. This retrospective study assessed the largest dataset to date of 432 HER2-positive patients who were diagnosed with brain metastases from 24 institutions of the Japan Clinical Oncology Group, Breast Cancer Study Group. The median age of the 432 patients was 54 years (range, 20-86 years). Of the patients, 162 patients (37.5 %) had ER-positive/HER2-positive (ER+HER2+) breast cancer, and 270 (62.5 %) had ER-negative/HER2-positive (ER-HER2+) breast cancer. The median brain metastasis-free survival period from primary breast cancer was 33.5 months in both groups. The median survival after developing brain metastasis was 16.5 and 11.5 months in the ER+HER2+ and ER-HER2+ groups, respectively, (p = 0.117). Patients with >3 brain metastases had significantly shorter overall survival in both ER+HER2+ (p developing brain metastases was not associated with survival duration after developing brain metastases (p = 0.571). However, patients treated with both trastuzumab and lapatinib after developing metastasis had significantly longer survival than patients treated with trastuzumab alone, lapatinib alone, or no HER2-targeting agent (p brain metastases, regardless of the use of trastuzumab before developing brain metastasis, treatment with both trastuzumab and lapatinib might improve survival.

  17. Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting

    International Nuclear Information System (INIS)

    Lekic, Mirko; Kovac, Viljem; Triller, Nadja; Knez, Lea; Sadikov, Aleksander; Cufer, Tanja

    2012-01-01

    Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis. All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana. We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4–6 cycles of

  18. Brain tumour stem cells: implications for cancer therapy and regenerative medicine.

    Science.gov (United States)

    Sanchez-Martin, Manuel

    2008-09-01

    The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.

  19. Uterine cervical cancer with brain metastasis as the initial site of presentation.

    Science.gov (United States)

    Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

    2015-07-01

    Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

  20. Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

    Science.gov (United States)

    Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

    Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

  1. Monte Carlo calculations on efficiency of boron neutron capture therapy for brain cancer

    International Nuclear Information System (INIS)

    Awadalla, Galaleldin Mohamed Suliman

    2015-11-01

    The search for ways to treat cancer has led to many different treatments, including surgery, chemotherapy, and radiation therapy. Among these treatments, boron neutron capture therapy (BNCT) has shown promising results. BNCT is a radiotherapy treatment modality that has been proposed to treat brain cancer. In this technique, cancerous cells are being injected with 1 0B and irradiated by thermal neutrons to increase the probability of 1 0B (n, a)7 L i reaction to occur. This reaction can potentially deliver a high radiation dose sufficient to kill cancer cells by concentrating boron in them. The short rang of 1 0B (n, a) 7 L i reaction limits the damage to only cancerous cells without affecting healthy tissues. The effectiveness and safety of radiotherapy are dependent on the radiation dose delivered to the tumor and healthy tissues. In this thesis, after reviewing the basics and working principles of boron neutron capture therapy (BNCT), monte Carlo simulations were carried out to model a thermal neutron source suitable for BNCT and to examine the performance of proposed model when used to irradiate a sample of boron containing both 1 0B and 1 1B isotopes. MCNP5 code was used to examine the modeled neutron source through different shielding materials. The results were presented, analyzed and discussed at the end of the work. (author)

  2. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

    2015-10-01

    The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: A case report

    Directory of Open Access Journals (Sweden)

    Wen-Chih Liu

    2012-05-01

    Full Text Available A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient’s neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.

  4. Brain Metastases from Breast Cancer and Response to Treatment with Eribulin: A Case Series

    Directory of Open Access Journals (Sweden)

    Alex Y. Chang

    2015-01-01

    Full Text Available Brain metastases are common in patients with advanced breast cancer (BC, causing considerable morbidity and mortality. Eribulin is a microtubule dynamics inhibitor approved for treating certain patients with metastatic BC, previously treated with an anthracycline and a taxane. In the 301 phase 3 study in 1102 women with advanced BC, eribulin and capecitabine treatments did not differ for co-primary endpoints (overall survival [OS]: 15.9 vs 14.5 months, P = 0.056; progression-free survival [PFS]: 4.1 vs 4.2 months, P = 0.30. Here, we report outcomes for six patients (eribulin, n = 3; capecitabine, n = 3 who had received treatment for brain metastases from BC (BCBM at baseline. All eribulin-treated patients experienced brain lesion shrinkage at some point during treatment, compared with one capecitabine-treated patient. Fewer patients in study 301 developed new BCBM with eribulin (13/544, 2.4% compared with capecitabine (25/546, 4.6%. Eribulin does not cross the healthy blood–brain barrier (BBB, but could have the potential to do so after cranial radiation therapy. Capecitabine may cross the BBB and has demonstrated activity in BCBM. Data from these patients and previous cases suggest that further investigation of eribulin for BCBM may be warranted.

  5. A delayed radiation necrosis of the brain in a patient with maxillary cancer

    International Nuclear Information System (INIS)

    Koike, Satoshi; Ogawa, Akihiro; Uno, Kinya; Okushi, Ikuyo; Inatsuki, Shinichi

    1987-01-01

    A 63-year-old male with maxillary cancer (T 4 N 0 M 0 ), who had been treated initially with 50 Gy of radiotherapy and 95 mg of Pepleomycin by intraarterial administration, was treated with 60 Gy of internal irradiation of Cesium source for the residual tumor. Furthermore, radical operation was performed to eradicate the tumor. A low density area (LDA) in the right temporal to occipital lobe of the brain was found by CT examination, when patient suffered from mental disturbance one year and 8 months postoperatively. Because a definite mass lesion could not be identified in the LDA, brain metastasis was ruled out. Patient was treated with a conservative medication using Glyceol, and his symptoms were successfully improved. (author)

  6. Next Generation Sequencing As an Aid to Diagnosis and Treatment of an Unusual Pediatric Brain Cancer

    Directory of Open Access Journals (Sweden)

    John Glod

    2014-07-01

    Full Text Available Classification of pediatric brain tumors with unusual histologic and clinical features may be a diagnostic challenge to the pathologist. We present a case of a 12-year-old girl with a primary intracranial tumor. The tumor classification was not certain initially, and the site of origin and clinical behavior were unusual. Genomic characterization of the tumor using a Clinical Laboratory Improvement Amendment (CLIA-certified next-generation sequencing assay assisted in the diagnosis and translated into patient benefit, albeit transient. Our case argues that next generation sequencing may play a role in the pathological classification of pediatric brain cancers and guiding targeted therapy, supporting additional studies of genetically targeted therapeutics.

  7. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Ge, Xiao-hui; Liu, Miao-ling; Lin, Qiang; Ren, Xiao-cang; Liu, Yue-e; Chen, Xue-ji; Wang, Dong-ying; Wang, Yong-qiang; Cao, Bin; Li, Zhi-gang

    2013-01-01

    Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ 2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ 2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ 2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent

  8. BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

    Science.gov (United States)

    Zavitsanos, Peter J; Wazer, David E; Hepel, Jaroslaw T; Wang, Yihong; Singh, Kamaljeet; Leonard, Kara L

    2018-05-18

    Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5/6 or EGFR) was performed for BRCA patients who developed BM and their matched controls. We analyzed 60 patients: 20 BRCA and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA patients and 97% for BRCA controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA patients. All 3 BRCA1 patients who developed BM were of a basal-type triple negative phenotype. Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors.

  9. Incidental findings on brain Magnetic Resonance Imaging in long-term survivors of breast cancer treated with adjuvant chemotherapy.

    Science.gov (United States)

    Koppelmans, Vincent; Schagen, Sanne B; Poels, Mariëlle M F; Boogerd, Willem; Seynaeve, Caroline; van der Lugt, Aad; Breteler, Monique M B

    2011-11-01

    Incidental brain findings defined as previously undetected abnormalities of potential clinical relevance that are unexpectedly discovered at brain imaging and are unrelated to the purpose of the examination are common in the general population. Because it is unclear whether the prevalence of incidental findings in breast cancer patients treated with chemotherapy is different to that in the general population, we compared the prevalence in breast cancer survivors treated with chemotherapy to that in a population-based sample of women without a history of any cancer. Structural brain MRI (1.5T) was performed in 191 female CMF (Cyclophosphamide, Methotrexate, 5-Fluorouracil) chemotherapy-exposed breast cancer survivors. A reference group of 1590 women without a history of cancer was sampled from a population-based cohort study. All participants were aged 50 to 80 years. Five trained reviewers recorded the brain abnormalities. Two experienced neuro-radiologists reviewed the incidental findings. The cancer survivors had completed chemotherapy on average 21 years before. Of the 191 subjects, 2.6% had an aneurysm and 3.7% had a meningioma. The prevalence of meningiomas and aneurysms was not different between the groups. The prevalence of pituitary macro adenomas in the breast cancer survivors (1.6%) was higher than that in the reference group (0.1%) (OR=23.7; 95% CI 2.3-245.8). Contrary to commonly held opinions, we did not observe an increased prevalence of meningiomas in cancer survivors. Breast cancer survivors previously treated with chemotherapy are more likely to develop pituitary adenomas than persons without a history of cancer and chemotherapy treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. [Timing of Brain Radiation Therapy Impacts Outcomes in Patients with 
Non-small Cell Lung Cancer Who Develop Brain Metastases].

    Science.gov (United States)

    Wang, Yang; Fang, Jian; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Ma, Xiangjuan; Han, Jindi; Chen, Xiaoling; Tian, Guangming; Wu, Di; Han, Sen; Long, Jieran

    2016-08-20

    Radiotherapy combined with chemotherapy or molecular targeted therapy remains the standard of treatment for brain metastases from non-small cell lung cancer (NSCLC). The aim of this study is to determine if the deferral of brain radiotherapy impacts patient outcomes. Between May 2003 and December 2015, a total of 198 patients with brain metastases from NSCLC who received both brain radiotherapy and systemic therapy (chemotherapy or targeted therapy) were identified. The rate of grade 3-4 adverse reactions related to chemotherapy and radiotherapy had no significant difference between two groups. 127 patients received concurrent brain radiotherapy and systemic therapy, and 71 patients received deferred brain radiotherapy after at least two cycles of chemotherapy or targeted therapy. Disease specific-graded prognostic assessment was similar in early radiotherapy group and deferred radiotherapy group. Median overall survival (OS) was longer in early radiotherapy group compared to deferred radiotherapy group (17.9 months vs 12.6 months; P=0.038). Progression free survival (PFS) was also improved in patients receiving early radiotherapy compared to those receiving deferred radiotherapy (4.0 months vs 3.0 months; Pbrain metastases as any line therapy improved the OS (20.0 months vs 10.7 months; Pbrain radiotherapy may resulted in inferior OS in patients with NSCLC who develop brain metastases. A prospective multi-central randomized study is imminently needed.

  11. Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients.

    Science.gov (United States)

    Srivastava, Geetika; Rana, Vishal; Wallace, Suzy; Taylor, Sarah; Debnam, Matthew; Feng, Lei; Suki, Dima; Karp, Daniel; Stewart, David; Oh, Yun

    2009-03-01

    Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). The underlying risk of ICH from NSCLC brain metastases is low, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. Two thousand one hundred forty-three patients with metastatic NSCLC registering from January 1998 to September 2005 were followed till March 2006. Seven hundred seventy-six patients with and 1,367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. The incidence of ICH seemed to be higher in those with brain metastasis compared with those without brain metastases, in whom they occurred as result of cerebrovascular accidents. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and had been free of anticoagulation. Most of the brain metastasis-associated ICH's were asymptomatic, detected during increased radiologic surveillance. The rates of symptomatic ICH, or other cerebrovascular accidents in general were similar and not significantly different between the two groups. In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared with those without, but was very low in both groups without a statistically significant difference. These data suggest a minimal risk of clinically significant ICH for NSCLC

  12. Ancestral trees for modeling stem cell lineages genetically rather than functionally: understanding mutation accumulation and distinguishing the restrictive cancer stem cell propagation theory and the unrestricted cell propagation theory of human tumorigenesis.

    Science.gov (United States)

    Shibata, Darryl K; Kern, Scott E

    2008-01-01

    Cancer stem cells either could be rare or common in tumors, constituting the major distinction between the two fundamentally opposed theoretical models of tumor progression: A newer and restrictive stem cell propagation model, in which the stem cells are a small and special minority of the tumor cells, and a standard older model, an unrestricted cell proliferation theory, in which many or most tumor cells are capable of indefinite generations of cell division. Stem cells of tumors are difficult to quantitate using functional assays, and the validity of the most common assays is seriously questioned. Nonetheless, stem cells are an essential component of any tumorigenesis model. Alternative approaches to studying tumor stem cells should be explored. Cell populations can be conceived of as having a genealogy, a relationship of cells to their ancestral lineage, from the zygote to the adult cells or neoplasms. Models using ancestral trees thus offer an anatomic and genetic means to "observe" stem cells independent of artificial conditions. Ancestral trees broaden our attention backward along a lineage, to the zygote stage, and thereby add insight into how the mutations of tumors accumulate. It is possible that a large fraction of mutations in a tumor originate from normal, endogenous, replication errors (nearly all being passenger mutations) occurring prior to the emergence of the first transformed cell. Trees can be constructed from experimental measurements - molecular clocks - of real human tissues and tumors. Detailed analysis of single-cell methylation patterns, heritable yet slightly plastic, now can provide this information in the necessary depth. Trees based on observations of molecular clocks may help us to distinguish between competing theories regarding the proliferative properties among cells of actual human tumors, to observe subtle and difficult phenomena such as the extinction of stem lineages, and to address the origins and rates of mutations in various

  13. Neuro emotional technique effects on brain physiology in cancer patients with traumatic stress symptoms: preliminary findings.

    Science.gov (United States)

    Monti, Daniel A; Tobia, Anna; Stoner, Marie; Wintering, Nancy; Matthews, Michael; He, Xiao-Song; Doucet, Gaelle; Chervoneva, Inna; Tracy, Joseph I; Newberg, Andrew B

    2017-08-01

    The purpose of this study was to characterize the neurophysiological and clinical effects that may result from the neuro emotional technique (NET) in patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that self-regulatory processing of traumatic memories would be observable as physiological changes in key brain areas after undergoing the NET intervention and that these changes would be associated with improvement of traumatic stress symptoms. We enrolled 23 participants with a prior cancer diagnosis who expressed a distressing cancer-related memory that was associated with traumatic stress symptoms of at least 6 months in duration. Participants were randomized to either the NET intervention or a waitlist control condition. To evaluate the primary outcome of neurophysiological effects, all participants received functional magnetic resonance imaging (fMRI) during the auditory presentation of both a neutral stimulus and a description of the specific traumatic event. Pre/post-comparisons were performed between the traumatic and neutral condition, within and between groups. Psychological measures included the Impact of Event Scale (IES), State Trait Anxiety Index (STAI), Brief Symptom Inventory (BSI)-18, and Posttraumatic Cognitions Inventory (PTCI). The initial fMRI scans in both groups showed significant increases in the bilateral parahippocampus and brainstem. After NET, reactivity in the parahippocampus, brainstem, anterior cingulate, and insula was significantly decreased during the traumatic stimulus. Likewise, participants receiving the NET intervention had significant reductions (p stress as measured by the IES and PTCI. This study is an initial step towards understanding mechanistic features of the NET intervention. Specifically, brain regions involved with traumatic memories and distress such as the brainstem, insula, anterior cingulate gyrus, and parahippocampus had significantly reduced activity after the NET

  14. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    Directory of Open Access Journals (Sweden)

    M. Suzuki

    2014-01-01

    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  15. Synergistic tumor microenvironment targeting and blood-brain barrier penetration via a pH-responsive dual-ligand strategy for enhanced breast cancer and brain metastasis therapy.

    Science.gov (United States)

    Li, Man; Shi, Kairong; Tang, Xian; Wei, Jiaojie; Cun, Xingli; Long, Yang; Zhang, Zhirong; He, Qin

    2018-05-22

    Cancer associated fibroblasts (CAFs) which shape the tumor microenvironment (TME) and the presence of blood brain barrier (BBB) remain great challenges in targeting breast cancer and its brain metastasis. Herein, we reported a strategy using PTX-loaded liposome co-modified with acid-cleavable folic acid (FA) and BBB transmigrating cell penetrating peptide dNP2 peptide (cFd-Lip/PTX) for enhanced delivery to orthotopic breast cancer and its brain metastasis. Compared with single ligand or non-cleavable Fd modified liposomes, cFd-Lip exhibited synergistic TME targeting and BBB transmigration. Moreover, upon arrival at the TME, the acid-cleavable cFd-Lip/PTX showed sensitive cleavage of FA, which reduced the hindrance effect and maximized the function of both FA and dNP2 peptide. Consequently, efficient targeting of folate receptor (FR)-positive tumor cells and FR-negative CAFs was achieved, leading to enhanced anti-tumor activity. This strategy provides a feasible approach to the cascade targeting of TME and BBB transmigration in orthotopic and metastatic cancer treatment. Copyright © 2018. Published by Elsevier Inc.

  16. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  17. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  18. Exploring the Support Needs of Family Caregivers of Patients with Brain Cancer Using the CSNAT: A Comparative Study with Other Cancer Groups.

    Science.gov (United States)

    Aoun, Samar M; Deas, Kathleen; Howting, Denise; Lee, Gabriel

    2015-01-01

    A substantial burden is placed on family caregivers of patients diagnosed with brain cancers. Despite this, the support needs of the caregivers are often under-recognised and not addressed adequately in current routine and patient centred clinical care. The Carer Support Needs Assessment Tool (CSNAT) is a validated instrument designed to systematically identify and address caregiver needs [corrected]. It has been trialled in an Australian palliative care community setting using a stepped wedge cluster design involving 322 family carers of terminally ill patients. The current article reports on a subset from this trial, 29 caregivers of patients with primary brain cancer, and compares their profile and outcomes to those of other cancer groups. Caregiver strain was assessed using the Family Appraisal of Caregiving Questionnaire, caregiver physical and mental wellbeing using SF12 and caregiver workload using a questionnaire on support with activities of daily living (ADL). In comparison to caregivers of patients with all other cancers, the primary brain cancer group had significantly higher levels of caregiver strain, lower levels of mental wellbeing and a higher level of ADL workload. Their physical wellness also deteriorated significantly over time. An action plan approach led to practical solutions for addressing highlighted concerns. Four themes evolved from the family caregivers' feedback interviews: The extremely challenging caregiver experience with brain cancer; the systematic and practical approach of the CSNAT during rapid changes; connection with health professionals, feeling acknowledged and empowered; and timely advice and assurance of support during the caregiving journey. This preliminary study has demonstrated that the CSNAT provides a practical and useful tool for assessing the support needs of family caregivers of patients with brain cancer and has provided the basis for a larger scale, longitudinal study that allows a more detailed characterisation

  19. Population-based outcomes after brain radiotherapy in patients with brain metastases from breast cancer in the Pre-Trastuzumab and Trastuzumab eras

    International Nuclear Information System (INIS)

    Karam, Irene; Hamilton, Sarah; Nichol, Alan; Woods, Ryan; Speers, Caroline; Kennecke, Hagen; Tyldesley, Scott

    2013-01-01

    To evaluate the survival of patients with human epidermal growth factor receptor 2 (HER2) positive and negative metastatic breast cancer irradiated for brain metastases before and after the availability of trastuzumab (T). Women diagnosed with brain metastasis from breast cancer in two eras between 2000 and 2007 (T-era, n = 441) and 1986 to 1992 (PreT-era, n = 307), treated with whole brain radiotherapy (RT) were identified. In the T-era, HER2 testing was part of routine clinical practice, and in the preT-era 128/307 (42%) cases had HER2 testing performed retrospectively on tissue microarrays. Overall survival (OS) was estimated using the Kaplan-Meier method and comparisons between eras used log-rank tests. In the preT- and T-era cohorts, the rate of HER2 positivity was 40% (176/441) and 26% (33/128) (p < 0.001). The median time from diagnosis to brain RT was longer in the preT-era (3.3 years versus 2.3 years, p < 0.001). Survival after brain RT was improved in the T-era compared to the preT-era (1-year OS 26% versus 12%, p < 0.001). The 1-year OS rate for HER2 negative patients was 20% in both eras (p = 0.97). Among HER2 positive patients, the 1-year OS in the preT-era was 5% compared to 40% in the T-era (p < 0.001). Distinct from patients with HER2 negative disease in whom no difference in survival after brain RT was observed over time, patients with HER2 positive brain metastases experienced significantly improved survival subsequent to the availability of trastuzumab

  20. Analyzing the evolution of young people's brain cancer mortality in Spanish provinces.

    Science.gov (United States)

    Ugarte, M D; Adin, A; Goicoa, T; López-Abente, G

    2015-06-01

    To analyze the spatio-temporal evolution of brain cancer relative mortality risks in young population (under 20 years of age) in Spanish provinces during the period 1986-2010. A new and flexible conditional autoregressive spatio-temporal model with two levels of spatial aggregation was used. Brain cancer relative mortality risks in young population in Spanish provinces decreased during the last years, although a clear increase was observed during the 1990s. The global geographical pattern emphasized a high relative mortality risk in Navarre and a low relative mortality risk in Madrid. Although there is a specific Autonomous Region-time interaction effect on the relative mortality risks this effect is weak in the final estimates when compared to the global spatial and temporal effects. Differences in mortality between regions and over time may be caused by the increase in survival rates, the differences in treatment or the availability of diagnostic tools. The increase in relative risks observed in the 1990s was probably due to improved diagnostics with computerized axial tomography and magnetic resonance imaging techniques. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The Vitamin D Receptor (VDR Gene Polymorphisms in Turkish Brain Cancer Patients

    Directory of Open Access Journals (Sweden)

    Bahar Toptaş

    2013-01-01

    Full Text Available Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP. Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9% compared with controls (2.5%, and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

  2. Beam propagation

    International Nuclear Information System (INIS)

    Hermansson, B.R.

    1989-01-01

    The main part of this thesis consists of 15 published papers, in which the numerical Beam Propagating Method (BPM) is investigated, verified and used in a number of applications. In the introduction a derivation of the nonlinear Schroedinger equation is presented to connect the beginning of the soliton papers with Maxwell's equations including a nonlinear polarization. This thesis focuses on the wide use of the BPM for numerical simulations of propagating light and particle beams through different types of structures such as waveguides, fibers, tapers, Y-junctions, laser arrays and crystalline solids. We verify the BPM in the above listed problems against other numerical methods for example the Finite-element Method, perturbation methods and Runge-Kutta integration. Further, the BPM is shown to be a simple and effective way to numerically set up the Green's function in matrix form for periodic structures. The Green's function matrix can then be diagonalized with matrix methods yielding the eigensolutions of the structure. The BPM inherent transverse periodicity can be untied, if desired, by for example including an absorptive refractive index at the computational window edges. The interaction of two first-order soliton pulses is strongly dependent on the phase relationship between the individual solitons. When optical phase shift keying is used in coherent one-carrier wavelength communication, the fiber attenuation will suppress or delay the nonlinear instability. (orig.)

  3. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  4. Recurrently Mutated Genes Differ between Leptomeningeal and Solid Lung Cancer Brain Metastases.

    Science.gov (United States)

    Li, Yingmei; Liu, Boxiang; Connolly, Ian David; Kakusa, Bina Wasunga; Pan, Wenying; Nagpal, Seema; Montgomery, Stephen B; Hayden Gephart, Melanie

    2018-03-29

    When compared with solid brain metastases from NSCLC, leptomeningeal disease (LMD) has unique growth patterns and is rapidly fatal. Patients with LMD do not undergo surgical resection, limiting the tissue available for scientific research. In this study we performed whole exome sequencing on eight samples of LMD to identify somatic mutations and compared the results with those for 26 solid brain metastases. We found that taste 2 receptor member 31 gene (TAS2R31) and phosphodiesterase 4D interacting protein gene (PDE4DIP) were recurrently mutated among LMD samples, suggesting involvement in LMD progression. Together with a retrospective review of the charts of an additional 44 patients with NSCLC LMD, we discovered a surprisingly low number of KRAS mutations (n = 4 [7.7%]) but a high number of EGFR mutations (n = 33 [63.5%]). The median interval for development of LMD from NSCLC was shorter in patients with mutant EGFR (16.3 months) than in patients with wild-type EGFR (23.9 months) (p = 0.017). Targeted analysis of recurrent mutations thus presents a useful complement to the existing diagnostic tool kit, and correlations of EGFR in LMD and KRAS in solid metastases suggest that molecular distinctions or systemic treatment pressure underpin the differences in growth patterns within the brain. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  5. Occupational risk factors for brain cancer: a population-based case-control study in Iowa.

    Science.gov (United States)

    Zheng, T; Cantor, K P; Zhang, Y; Keim, S; Lynch, C F

    2001-04-01

    A number of occupations and industries have been inconsistently associated with the risk of brain cancer. To further explore possible relationships, we conducted a population-based case-control study of brain glioma in the state of Iowa, involving 375 histologically confirmed incident cases and 2434 population-based controls. Among men, the industries and/or occupations that had a significantly increased risk for employment of more than 10 years included roofing, siding, and sheet metalworking; newspaper work; rubber and plastics products, particularly tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of durable goods, grain, and field beans; cleaning and building service occupations; miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who worked in plumbing, heating, and air conditioning; electrical services; gasoline service stations; and military occupations also experienced a significantly increased risk. Among women, significant excess risk was observed for occupations in agricultural services and farming, apparel and textile products, electrical and electronic equipment manufacturing, various retail sales, record-keeping, and restaurant service. Workers in industries with a potential for gasoline or motor exhaust exposures experienced a non-significant excess risk of brain glioma.

  6. MRI findings of radiation encephalopathy of brain stem after radiotherapy for nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Liang Changhong; Li Guoye; Huang Biao; Huang Meiping; Zheng Junhui; Tan Shaoheng; Zeng Qiongxin

    1998-01-01

    Purpose: To study MRI findings and clinical manifestation of radiation encephalopathy (RE) of brain stem. Methods: MRI findings and clinical symptoms in 51 patients with RE of brain stem after radiotherapy for nasopharyngeal cancer were reviewed. Results: Clinical symptoms included number weakness or paralysis in the limbs and symptoms of damaged cranial nerves. All lesions appeared hypo- or iso-intense on spin echo(SE) T 1 -weighted images and inhomogeneous and mixed hyper- and iso-intense on Turbo spin echo (TSE) T 2 -weighted images. The lesions were located in mesencephalon, pons, medulla, basilar part of pons, basilar part of pons and medulla oblongata in 2,7,3,9 and 30 patients respectively. The enhancement patterns included irregular rings in 39 patients, spotty in 3 and no enhancement in 9 patients. Mass effect was minimal in all patients. On follow-up MRI, the lesions disappeared in 4 patients, did not change in size and shape in 8 patients and enlarged in 2 patients. Conclusion: MRI could demonstrate the characteristic findings of RE of brain stem. MRI findings sometimes are not consistent with the clinical symptoms

  7. Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

    Science.gov (United States)

    Xu, Xiang; Chan, Kannie W Y; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T; van Zijl, Peter C M

    2015-12-01

    Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. © 2015 Wiley Periodicals, Inc.

  8. Dynamic Glucose Enhanced (DGE) MRI for Combined Imaging of Blood Brain Barrier Break Down and Increased Blood Volume in Brain Cancer

    Science.gov (United States)

    Xu, Xiang; Chan, Kannie WY; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T.; van Zijl, Peter C.M.

    2015-01-01

    Purpose Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Methods Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. Results DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared to contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (pblood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. PMID:26404120

  9. A nomogram for predicting survival in patients with breast cancer brain metastasis.

    Science.gov (United States)

    Huang, Zhou; Sun, Bing; Wu, Shikai; Meng, Xiangying; Cong, Yang; Shen, Ge; Song, Santai

    2018-05-01

    Brain metastasis (BM) is common in patients with breast cancer. Predicting patient survival is critical for the clinical management of breast cancer brain metastasis (BCBM). The present study was designed to develop and evaluate a prognostic model for patients with newly diagnosed BCBM. Based on the clinical data of patients with BCBM treated in the Affiliated Hospital of Academy of Military Medical Sciences (Beijing, China) between 2002 and 2014, a nomogram was developed to predict survival using proportional hazards regression analysis. The model was validated internally by bootstrapping, and the concordance index (c-index) was calculated. A calibration curve and c-index were used to evaluate discriminatory and predictive ability, in order to compare the nomogram with widely used models, including recursive partitioning analysis (RPA), graded prognostic assessment (GPA) and breast-graded prognostic assessment (Breast-GPA). A total of 411 patients with BCBM were included in the development of this predictive model. The median overall survival time was 14.1 months. Statistically significant predictors for patient survival included biological subtype, Karnofsky performance score, leptomeningeal metastasis, extracranial metastasis, the number of brain metastases and disease-free survival. A nomogram for predicting 1- and 2-year overall survival rates was constructed, which exhibited good accuracy in predicting overall survival with a concordance index of 0.735. This model outperformed RPA, GPA and Breast-GPA, based on the comparisons of the c-indexes. The nomogram constructed based on a multiple factor analysis was able to more accurately predict the individual survival probability of patients with BCBM, compared with existing models.

  10. Biomimetic brain tumor niche regulates glioblastoma cells towards a cancer stem cell phenotype.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Chen, Pin-Yuan

    2018-05-01

    Glioblastoma (GBM) is the most malignant primary brain tumor and contains tumorigenic cancer stem cells (CSCs), which support the progression of tumor growth. The selection of CSCs and facilitation of the brain tumor niches may assist the development of novel therapeutics for GBM. Herein, hydrogel materials composed of agarose and hydroxypropyl methyl cellulose (HMC) in different concentrations were established and compared to emulate brain tumor niches and CSC microenvironments within a label-free system. Human GBM cell line, U-87 MG, was cultured on a series of HMC-agarose based culture system. Cell aggregation and spheroids formation were investigated after 4 days of culture, and 2.5% HMC-agarose based culture system demonstrated the largest spheroids number and size. Moreover, CD133 marker expression of GBM cells after 6 days of culture in 2.5% HMC-agarose based culture system was 60%, relatively higher than the control group at only 15%. Additionally, cells on 2.5% HMC-agarose based culture system show the highest chemoresistance, even at the high dose of 500 µM temozolomide for 72 h, the live cell ratio was still > 80%. Furthermore, the results also indicate that the expression of ABCG2 gene was up-regulated after culture in 2.5% HMC-agarose based culture system. Therefore, our results demonstrated that biomimetic brain tumor microenvironment may regulate GBM cells towards the CSC phenotype and expression of CSC characteristics. The microenvironment selection and spheroids formation in HMC-agarose based culture system may provide a label-free CSC selection strategy and drug testing model for future biomedical applications.

  11. Brain Cancer—Patient Version

    Science.gov (United States)

    Brain cancer refers to growths of malignant cells in tissues of the brain. Tumors that start in the brain are called primary brain tumors. Tumors that spread to the brain are called metastatic brain tumors. Start here to find information on brain cancer treatment, research, and statistics.

  12. CPT-11/bevacizumab for the treatment of refractory brain metastases in patients with HER2–neu-positive breast cancer

    Science.gov (United States)

    Sengupta, S.; Rojas, R.; Mahadevan, A.; Kasper, E.; Jeyapalan, S.

    2015-01-01

    Nervous system relapse of patients with advanced HER2–neu-positive breast cancer is an increasing problem, with one-third of women developing brain metastases. Standard therapies using steroids, surgery and radiotherapy do not provide a lasting response. We evaluated CPT-11 and bevacizumab, which can both cross the blood–brain barrier, as combination therapy to treat HER2–neu-positive breast cancer with brain metastases. PMID:26634139

  13. Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

    Science.gov (United States)

    Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

    2016-09-01

    To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study.

    Science.gov (United States)

    Zeng, Yingchun; Cheng, Andy S K; Song, Ting; Sheng, Xiujie; Zhang, Yang; Liu, Xiangyu; Chan, Chetwyn C H

    2017-11-28

    Subjective cognitive impairment can be a significant and prevalent problem for gynaecological cancer survivors. The aims of this study were to assess subjective cognitive functioning in gynaecological cancer survivors after primary cancer treatment, and to investigate the impact of cancer treatment on brain structural networks and its association with subjective cognitive impairment. This was a cross-sectional survey using a self-reported questionnaire by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to assess subjective cognitive functioning, and applying DTI (diffusion tensor imaging) and graph theoretical analyses to investigate brain structural networks after primary cancer treatment. A total of 158 patients with gynaecological cancer (mean age, 45.86 years) and 130 age-matched non-cancer controls (mean age, 44.55 years) were assessed. Patients reported significantly greater subjective cognitive functioning on the FACT-Cog total score and two subscales of perceived cognitive impairment and perceived cognitive ability (all p values impairment (r = -0.388, p = 0.034). When compared with non-cancer controls, a considerable proportion of gynaecological cancer survivors may exhibit subjective cognitive impairment. This study provides the first evidence of brain structural network alteration in gynaecological cancer patients at post-treatment, and offers novel insights regarding the possible neurobiological mechanism of cancer-related cognitive impairment (CRCI) in gynaecological cancer patients. As primary cancer treatment can result in a more random organisation of structural brain networks, this may reduce brain functional specificity and segregation, and have implications for cognitive impairment. Future prospective and longitudinal studies are needed to build upon the study findings in order to assess potentially relevant clinical and psychosocial variables and brain network measures, so as to more accurately understand the

  15. Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965).

    NARCIS (Netherlands)

    Dziadziuszko, R; Ardizzoni, A.; Postmus, P.E.; Smit, E.F.; Price, A; Debruyne, C.; Legrand, C; Giaccone, G.

    2003-01-01

    This study was performed to evaluate the activity of single-agent temozolomide in two groups of chemotherapy-naive non-small cell lung cancer (NSCLC) patients, with (12 patients) and without (13 patients) brain metastases (BM). Patients in both groups were treated with temozolomide 200 mg/m(2)/day,

  16. Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

    Science.gov (United States)

    Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.

    2012-01-01

    Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748

  17. Brain responses to erotic and other emotional stimuli in breast cancer survivors with and without distress about low sexual desire: a preliminary fMRI study.

    Science.gov (United States)

    Versace, Francesco; Engelmann, Jeffrey M; Jackson, Edward F; Slapin, Aurelija; Cortese, Kristin M; Bevers, Therese B; Schover, Leslie R

    2013-12-01

    Many breast cancer survivors report a loss of sexual desire and arousability, consonant with the new DSM-V category of female sexual interest/arousal disorder. The cause of decreased sexual desire and pleasure after treatment for cancer is unknown. One possibility is that cancer, or treatment for cancer, damages brain circuits that are involved in reward-seeking. To test the hypothesis that brain reward systems are involved in decreased sexual desire in breast cancer survivors, we used functional magnetic resonance imaging (fMRI) to compare brain responses to erotica and other emotional stimuli in two groups of women previously treated for breast cancer with chemotherapy: those who were distressed about a perceived loss of sexual desire and those who may have had low desire, but were not distressed about it. Women distressed about their desire had reduced brain responses to erotica in the anterior cingulate and dorsolateral prefrontal cortex, which are part of the brain reward system. This study is the first to demonstrate, in cancer survivors, that problems with sexual desire/arousability are associated with blunted brain responses to erotica in reward systems. Future research is necessary to determine whether brain responses differ as a result of chemotherapy, hormone therapy, and menopausal status. This may contribute to the development of new, evidence-based interventions for one of the most prevalent and enduring side effects of cancer treatment.

  18. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Derek; Zhang, Rui, E-mail: rzhang@marybird.com [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States); Sanders, Mary [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Newhauser, Wayne [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States)

    2015-04-13

    Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

  19. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    Directory of Open Access Journals (Sweden)

    Derek Freund

    2015-04-01

    Full Text Available Cancer of the brain and central nervous system (CNS is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT compared to passively scattered proton therapy (PSPT and intensity modulated proton therapy (IMPT. Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

  20. Systemic treatment after whole-brain radiotherapy may improve survival in RPA class II/III breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Ma, Jinli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Chen, Xingxing; Guo, Xiaomao; Chen, Jiayi

    2013-09-01

    Whole brain radiotherapy (WBRT) is the most widely used treatment for brain metastasis (BM), especially for patients with multiple intracranial lesions. The purpose of this study was to examine the efficacy of systemic treatments following WBRT in breast cancer patients with BM who had different clinical characteristics, based on the classification of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) and the breast cancer-specific Graded Prognostic Assessment (Breast-GPA). One hundred and one breast cancer patients with BM treated between 2006 and 2010 were analyzed. The median interval between breast cancer diagnosis and identification of BM in the triple-negative patients was shorter than in the luminal A subtype (26 vs. 36 months, respectively; P = 0.021). Univariate analysis indicated that age at BM diagnosis, Karnofsky performance status/recursive partitioning analysis (KPS/RPA) classes, number of BMs, primary tumor control, extracranial metastases and systemic treatment following WBRT were significant prognostic factors for overall survival (OS) (P RPA classes and systemic treatments following WBRT remained the significant prognostic factors for OS. For RPA class I, the median survival with and without systemic treatments following WBRT was 25 and 22 months, respectively (P = 0.819), while for RPA class II/III systemic treatments significantly improved OS from 7 and 2 months to 11 and 5 months, respectively (P RPA class II/III patients.

  1. Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy

    NARCIS (Netherlands)

    Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert

    2017-01-01

    Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore

  2. Using the 60Co source to assess the dose received by risky organs during a cancer brain treatment

    International Nuclear Information System (INIS)

    Faik Ouahab, Z.; Jehouani, A.; Ghassoun, J.; Senhou, N.; Mouhssine, D.; Groetz, J.E.

    2010-01-01

    Summary of an investigation of exposures associated with brain cancer treatment for a child in order to determine the level of doses received by the different organs at risk during the treatment. Measurements have been performed at the vicinity of a cobalto therapy apparatus. Then, cumulative doses in each organ have been compared to admitted doses with respect to the organ

  3. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

    International Nuclear Information System (INIS)

    Xu Zhiyuan; Marko, Nicholas F.; Chao, Sam T.; Angelov, Lilyana; Vogelbaum, Michael A.; Suh, John H.; Barnett, Gene H.; Weil, Robert J.

    2012-01-01

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2− breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2− lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2− and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  4. Brain Injury After Proton Therapy or Carbon Ion Therapy for Head-and-Neck Cancer and Skull Base Tumors

    International Nuclear Information System (INIS)

    Miyawaki, Daisuke; Murakami, Masao; Demizu, Yusuke; Sasaki, Ryohei; Niwa, Yasue; Terashima, Kazuki; Nishimura, Hideki; Hishikawa, Yoshio; Sugimura, Kazuro

    2009-01-01

    Purpose: To assess the incidence of early delayed or late morbidity of Brain after particle therapy for skull base tumors and head-and-neck cancers. Methods and Materials: Between May 2001 and December 2005, 59 patients with cancerous invasion of the skull base were treated with proton or carbon ion therapy at the Hyogo Ion Beam Medical Center. Adverse events were assessed according to the magnetic resonance imaging findings (late effects of normal tissue-subjective, objective, management, analytic [LENT-SOMA]) and symptoms (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0). Dose-volume histograms were used to analyze the relationship between the dose and volume of the irradiated brain and the occurrence of brain injury. The median follow-up time was 33 months. Results: Of the 48 patients treated with proton therapy and 11 patients treated with carbon ion radiotherapy, 8 (17%) and 7 (64%), respectively, developed radiation-induced brain changes (RIBCs) on magnetic resonance imaging (LENT-SOMA Grade 1-3). Four patients (7%) had some clinical symptoms, such as vertigo and headache (CTCAE Grade 2) or epilepsy (CTCAE Grade 3). The actuarial occurrence rate of RIBCs at 2 and 3 years was 20% and 39%, respectively, with a significant difference in the incidence between the proton and carbon ion radiotherapy groups. The dose-volume histogram analyses revealed significant differences between Brain lobes with and without RIBCs in the actuarial volume of brain lobes receiving high doses. Conclusion: Particle therapies produced minimal symptomatic brain toxicities, but sequential evaluation with magnetic resonance imaging detected a greater incidence of RIBCs. Significant differences were observed in the irradiated brain volume between Brain lobes with and without RIBCs.

  5. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Rades, Dirk; Nadrowitz, Roger; Buchmann, Inga; Meller, Birgit; Hunold, Peter; Noack, Frank; Schild, Steven E.

    2010-01-01

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m 2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m 2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m 2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ( 123 I-Erbi) on scintigraphy; 123 I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  6. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    Energy Technology Data Exchange (ETDEWEB)

    Rades, Dirk; Nadrowitz, Roger [Dept. of Radiation Oncology, Univ. of Luebeck (Germany); Buchmann, Inga; Meller, Birgit [Section of Nuclear Medicine, Univ. of Luebeck (Germany); Hunold, Peter [Dept. of Radiology, Univ. of Luebeck (Germany); Noack, Frank [Inst. of Pathology, Univ. of Luebeck (Germany); Schild, Steven E. [Dept. of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2010-08-15

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m{sup 2} cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m{sup 2} cetuximab (cold antibody) were given. Weekly doses of 250 mg/m{sup 2} cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab ({sup 123}I-Erbi) on scintigraphy; {sup 123}I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  7. EG-17SUV420-MEDIATED HETEROCHROMATIN CHANGES IN PEDIATRIC BRAIN CANCERS

    Science.gov (United States)

    Van Meter, Timothy E.; Terry, Jocelyn; Rockwell, Nathan; Goggin, Sarah; Nethala, Priya; Khan, Asadullah

    2014-01-01

    Silencing mechanisms play a role in genomic stability by maintaining condensed, non-active regions of the genome. SUV420 enzymes contain a SET domain conferring methyltransferase activity toward histones. The Histone H4 lysine 20 trimethylation (H4K20me3) mark maintained by SUV420H2 is associated with heterochromatin formation and gene silencing, whereas the dimethylated mark (H4K20me2) is associated with DNA repair. In studies of epigenetic factors in large patient cohorts with ependymoma, it was found that SUV420H2 expression was lost or diminished in patients with reciprocal increases in prognostic markers such as hTERT. To better understand the normal function of Suv4-20H1/H2 enzyme in neural progenitors, and pathological changes in cancers, a variety of differentiation paradigms were used. The NT2D1 neurally restricted cell line, and BGO1V and H9 human embryonic stem cells (ESCs), and differentiated progeny, were used alongside tumors to better understand enzyme targets and functional outcomes (e.g.,lineage, differentiation, regional chromatin modifications). Lineage stages were verified with stage-specific markers by immunofluorescence and qPCR. Suv4-20 H1 and H2 were present in ESCs and neural progenitors and decreased thereafter. RNAi knockdown of SUV420 enzymes led to decreased H4K20 methylation in cancer cells. DNA methylation microarrays and ChIP-PCR suggest 1) that SUV420 is not regulated by DNA methylation in ependymomas; 2) that active chromatin marks such as H3K4 dimethylation are enriched near the transcriptional start site in the SUV420H2 gene, and 3) that hTERT is hyper-methylated at specific CpG islands and histones in a tumor sub-group-specific manner. This data supports the hypothesis that Suv4-20H2 is highly active in progenitor cells and functionally lost in some brain cancers. These studies begin to elucidate coincident mechanisms of gene silencing active in neural progenitors that may be altered in a subset of pediatric brain cancers.

  8. Brain Functional Connectivity in Small Cell Lung Cancer Population after Chemotherapy Treatment: an ICA fMRI Study

    Science.gov (United States)

    Bromis, K.; Kakkos, I.; Gkiatis, K.; Karanasiou, I. S.; Matsopoulos, G. K.

    2017-11-01

    Previous neurocognitive assessments in Small Cell Lung Cancer (SCLC) population, highlight the presence of neurocognitive impairments (mainly in attention processing and executive functioning) in this type of cancer. The majority of these studies, associate these deficits with the Prophylactic Cranial Irradiation (PCI) that patients undergo in order to avoid brain metastasis. However, there is not much evidence exploring cognitive impairments induced by chemotherapy in SCLC patients. For this reason, we aimed to investigate the underlying processes that may potentially affect cognition by examining brain functional connectivity in nineteen SCLC patients after chemotherapy treatment, while additionally including fourteen healthy participants as control group. Independent Component Analysis (ICA) is a functional connectivity measure aiming to unravel the temporal correlation between brain regions, which are called brain networks. We focused on two brain networks related to the aforementioned cognitive functions, the Default Mode Network (DMN) and the Task-Positive Network (TPN). Permutation tests were performed between the two groups to assess the differences and control for familywise errors in the statistical parametric maps. ICA analysis showed functional connectivity disruptions within both of the investigated networks. These results, propose a detrimental effect of chemotherapy on brain functioning in the SCLC population.

  9. Do mobile phones cause brain cancer? and what should be done about it?

    International Nuclear Information System (INIS)

    Maclean, I.; Jones, S.

    2000-01-01

    Full text: The explosive growth in the use of mobile phones has led concerns that there might be as-yet-undiscovered effects on human health arising from the use of mobile phones. Many concerns have centred around the possibility that use of mobile phones may cause brain cancer. The Australian Communications Authority (ACA) regulates telecommunications and radiocommunications in Australia, has significant consumer protection responsibilities. The ACA exercises its functions through a range of legislative methods including standards, one of which relates to human exposure to electromagnetic radiation from mobile phones. The rationale for the standard will be discussed, including a brief account of the medical and physical basis for the limits set in the standard. There will also be an account of how physics can inform community debate on this issue, including the approaches adopted by the ACA

  10. Brain Tumor’s Radioresistance: The Neighborhood Helps | Center for Cancer Research

    Science.gov (United States)

    Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. The primary treatment for GBM is radiation therapy. Unfortunately, while some patients initially respond, the vast majority of GBM patients fail radiotherapy, and the tumor usually grows back within two years. To gain a better understanding of the biological basis for GBM resistance to radiation, researchers initially studied GBM cell lines in vitro. In recent years, the focus has been on so-called tumor stem-like cells (TSCs), which are thought to be responsible for driving and maintaining tumor growth. To the researchers’ surprise, TSCs grown in vitro did not have the same ability to resist radiation as TSCs in the GBM tumors.

  11. Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

    Science.gov (United States)

    Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

    2018-01-01

    Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Psychometric validation of the functional assessment of cancer therapy--brain (FACT-Br) for assessing quality of life in patients with brain metastases.

    Science.gov (United States)

    Thavarajah, Nemica; Bedard, Gillian; Zhang, Liying; Cella, David; Beaumont, Jennifer L; Tsao, May; Barnes, Elizabeth; Danjoux, Cyril; Sahgal, Arjun; Soliman, Hany; Chow, Edward

    2014-04-01

    This study aimed to test the reliability, psychometric, and clinical validity of the use of the Functional Assessment of Cancer Therapy--Brain (FACT-Br) in patients with brain metastases. Patients with brain metastases were interviewed using the FACT-Br (including the FACT-general) 1 week prior to treatment. All patients completed a follow-up assessment 1 month post-treatment. Patients with a good performance status and receiving stereotactic radiosurgery completed an additional 1 week follow-up assessment after the initial baseline interview to assess test-retest reliability. Forty patients had complete 1 month follow-up data. Ten of these patients also completed the 1 week follow-up assessment from baseline. The median Karnofsky performance status of patients was 80 and the median age was 64 years. All subscales of the FACT-Br were found to be conceptually related (except for two correlations) using the following subscales: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), FACT-G total score, brain cancer subscale (BrC), and the FACT-Br total score. All FACT-Br scores demonstrated excellent reliability, except for the SWB scale which revealed good reliability. The FACT-Br scores showed no significant change in the quality of life (QoL) of patients from baseline to 1 month follow-up. The use of the combined FACT-G and FACT-Br Subscale to assess QoL specifically in patients with brain metastases has successfully undergone psychometric validation. Future clinical trials should use the FACT-G and FACT-Br Subscale to assess QoL in this patient population.

  13. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

    Institute of Scientific and Technical Information of China (English)

    Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

    2004-01-01

    AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS <70 (P<0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

  14. Outcomes of aggressive treatment in esophageal cancer patients with synchronous solitary brain metastasis.

    Science.gov (United States)

    Onal, Cem; Akkus Yildirim, Berna; Guler, Ozan Cem

    2017-07-01

    The aim of the present study was to investigate the outcomes of esophageal cancer (EC) patients with isolated synchronous brain oligometastasis (oligo-BM) treated with chemoradiotherapy (CRT) of the primary site and localized treatment of the BM with surgery, radiotherapy (RT) or radiosurgery. Of 125 EC patients investigated, seven patients (6%) had solitary BM. Six patients were diagnosed prior to, and one patient was diagnosed during, treatment. All patients were treated with neoadjuvant chemotherapy and whole-brain RT (WBRT) for BM. All but one patient received definitive CRT with a median RT dose of 50.4 Gy using conventional fractionation RT. The median age at diagnosis was 59 years (range, 48-77 years). Six patients succumbed to mortality, and one continued to receive systemic chemotherapy at the last visit. The median survival time of the patients was 18.9 months (range, 10.0-27.2 months). Median time to progression after completion of the treatments was 8 months (range, 3-9 months). Two patients had progression of the primary tumor, and one patient had progression of the BM. The neurological status of three patients with BM who were identified during the staging work-up did not deteriorate as a consequence of WBRT. In conclusion, the present study has demonstrated that aggressive treatment of the primary tumor and oligo-BM in patients with EC may prolong the survival time.

  15. Relative significance of surgery and radiotherapy in treatment of brain metastases of lung cancer

    International Nuclear Information System (INIS)

    Yamashita, Junkoh; Ohtsuka, Sinichi; Yamasaki, Toshiki; Gi, Hidefuku; Ha, Young-Soo; Handa, Hajime

    1983-01-01

    One hundred and sixteen cases of brain metastases of lung cancer were retrospectively analysed with special reference to the relative significance of surgery and radiotherapy. The median survival time from diagnosis of brain metastases was 1.2 months in 27 cases without treatment, 2.5 months in 51 cases treated by surgery alone, 4.2 months in 31 cases treated by radiotherapy alone and 6.5 months in 7 cases treated by surgery and radiotherapy. The survival rate in patients treated by radiotherapy was significantly better than in those not treated by radiotherapy. However, the effect of surgery was not significant in prolongation of survival time. On the other hand, the rate of improvement in neurological symptoms assessed at one month after the initiation of treatment was 80.9% in 47 cases treated by surgery and 19.4 % in 31 cases treated by radiotherapy. The result suggested that surgery is superior to radiotherapy in alleviating neurological symptoms. It is important to understand the nature of effect of each treatment. A better result will be anticipated by proper selection or combination of these treatments. (author)

  16. Temporal Change in Brain Natriuretic Peptide After Radiotherapy for Thoracic Esophageal Cancer

    International Nuclear Information System (INIS)

    Jingu, Keiichi; Nemoto, Kenji; Kaneta, Tomohiro; Oikawa, Minako; Ogawa, Yoshihiro; Ariga, Hisanori; Takeda, Ken; Sakayauchi, Toru; Fujimoto, Keisuke; Narazaki, Kakutaro; Takai, Yoshihiro; Nakata, Eiko; Fukuda, Hiroshi; Takahashi, Shoki; Yamada, Shogo

    2007-01-01

    Purpose: To investigate the relationships of plasma levels of brain natriuretic peptide (BNP) with abnormal 18 F-fluorodeoxyglucose (FDG) accumulation in the myocardium corresponding to irradiated fields and temporal changes in BNP, which is used as an index of heart remodeling, after radiotherapy for the mediastinum. Materials and Methods: Brain natriuretic peptide concentrations were measured before and after radiotherapy for thoracic esophageal cancer, and the change in BNP concentration after radiotherapy was investigated. Moreover, FDG accumulation in the myocardium was investigated in patients who had undergone FDG positron emission tomography less than 14 days before or after measurement of BNP concentration, and the Mann-Whitney U test was used to detect significant difference between BNP concentrations in patients with and without abnormal FDG accumulation corresponding to the irradiated field. Results: There was significant difference between the levels of BNP in patients without abnormal FDG accumulation in the irradiated myocardium and in patients with abnormal FDG accumulation (p 24 months after radiotherapy group were significantly higher than the levels in the before radiotherapy group, immediately after radiotherapy group, 1-2 months after radiotherapy group, and control group. Conclusions: The level of BNP was significantly increased more than 9 months after the start of radiotherapy and was significantly higher in patients who had high FDG accumulation corresponding to the irradiated field. The results of this study indicate that BNP concentration might be an early indicator of radiation-induced myocardial damage

  17. Correlation of neurocognitive function and brain parenchyma volumes in children surviving cancer

    Science.gov (United States)

    Reddick, Wilburn E.; White, Holly A.; Glass, John O.; Mulhern, Raymond K.

    2002-04-01

    This research builds on our hypothesis that white matter damage and associated neurocognitive symptoms, in children treated for cancer with cranial spinal irradiation, spans a continuum of severity that can be reliably probed using non-invasive MR technology. Quantitative volumetric assessments of MR imaging and psychological assessments were obtained in 40 long-term survivors of malignant brain tumors treated with cranial irradiation. Neurocognitive assessments included a test of intellect (Wechsler Intelligence Test for Children, Wechsler Adult Intelligence Scale), attention (Conner's Continuous Performance Test), and memory (California Verbal Learning Test). One-sample t-tests were conducted to evaluate test performance of survivors against age-adjusted scores from the test norms; these analyses revealed significant impairments in all apriori selected measures of intelligence, attention, and memory. Partial correlation analyses were performed to assess the relationships between brain tissues volumes (normal appearing white matter (NAWM), gray matter, and CSF) and neurocognitive function. Global intelligence (r = 0.32, p = 0.05) and global attentional (r = 0.49, p attentional deficits, whereas overall parenchyma loss, as reflected by increased CSF and decreased white matter, is associated with memory-related deficits.

  18. Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Seung Yeun; Kim, Hye Ryun; Cho, Byoung Chul; Lee, Chang Geol; Suh, Chang Ok [Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chang, Jong Hee [Dept. of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2017-06-15

    To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ± boost (WBRT ± boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). The WBRT ± boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ± boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ≥42.3 Gy compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

  19. Altered intrinsic brain activity after chemotherapy in patients with gastric cancer: A preliminary study

    International Nuclear Information System (INIS)

    Kim, Hyun Gi; Shin, Na-Young; Bak, Yunjin; Lim, Soo Mee; Kim, Kyung Ran; Jung, Young-Chul; Han, Kyunghwa; Lee, Seung-Koo

    2017-01-01

    To characterize the pattern of altered intrinsic brain activity in gastric cancer patients after chemotherapy (CTx). Patients before and after CTx (n = 14) and control subjects (n = 11) underwent resting-state functional MRI (rsfMRI) at baseline and 3 months after CTx. Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF) were calculated and compared between the groups using the two-sample t test. Correlation analysis was also performed between rsfMRI values (i.e., ReHo, ALFF, and fALFF) and neuropsychological test results. Patients showed poor performance in verbal memory and executive function and decreased rsfMRI values in the frontal areas even before CTx and showed decreased attention/working memory and executive function after CTx compared to the control subjects. In direct comparison of values before and after CTx, there were no significant differences in neuropsychological test scores, but decreased rsfMRI values were observed at the frontal lobes and right cerebellar region. Among rsfMRI values, lower ALFF in the left inferior frontal gyrus was significantly associated with poor performance of the executive function test. We observed decreased attention/working memory and executive function that corresponded to the decline of frontal region activation in gastric cancer patients who underwent CTx. (orig.)

  20. Altered intrinsic brain activity after chemotherapy in patients with gastric cancer: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Gi [Ajou University Medical Center, Department of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); Shin, Na-Young [Ewha Womans University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Bak, Yunjin; Lim, Soo Mee [Ewha Womans University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Kyung Ran; Jung, Young-Chul [Yonsei University College of Medicine, Department of Psychiatry, Seoul (Korea, Republic of); Han, Kyunghwa; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of)

    2017-07-15

    To characterize the pattern of altered intrinsic brain activity in gastric cancer patients after chemotherapy (CTx). Patients before and after CTx (n = 14) and control subjects (n = 11) underwent resting-state functional MRI (rsfMRI) at baseline and 3 months after CTx. Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF) were calculated and compared between the groups using the two-sample t test. Correlation analysis was also performed between rsfMRI values (i.e., ReHo, ALFF, and fALFF) and neuropsychological test results. Patients showed poor performance in verbal memory and executive function and decreased rsfMRI values in the frontal areas even before CTx and showed decreased attention/working memory and executive function after CTx compared to the control subjects. In direct comparison of values before and after CTx, there were no significant differences in neuropsychological test scores, but decreased rsfMRI values were observed at the frontal lobes and right cerebellar region. Among rsfMRI values, lower ALFF in the left inferior frontal gyrus was significantly associated with poor performance of the executive function test. We observed decreased attention/working memory and executive function that corresponded to the decline of frontal region activation in gastric cancer patients who underwent CTx. (orig.)

  1. Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Lind, Joline S.W.; Lagerwaard, Frank J.; Smit, Egbert F.; Senan, Suresh

    2009-01-01

    Purpose: Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Methods and Materials: Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. Results: A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. Conclusion: WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.

  2. Effects of Chemotherapy on the Brain in Women With Newly Diagnosed Early-Stage Breast Cancer

    Science.gov (United States)

    2017-11-21

    Breast Cancer; Chemotherapeutic Agent Toxicity; Cognitive/Functional Effects; Fatigue; Long-term Effects Secondary to Cancer Therapy in Adults; Neurotoxicity; Psychosocial Effects of Cancer and Its Treatment

  3. Has the incidence of brain cancer risen in Australia since the introduction of mobile phones 29 years ago?

    Science.gov (United States)

    Chapman, Simon; Azizi, Lamiae; Luo, Qingwei; Sitas, Freddy

    2016-06-01

    Mobile phone use in Australia has increased rapidly since its introduction in 1987 with whole population usage being 94% by 2014. We explored the popularly hypothesised association between brain cancer incidence and mobile phone use. Using national cancer registration data, we examined age and gender specific incidence rates of 19,858 male and 14,222 females diagnosed with brain cancer in Australia between 1982 and 2012, and mobile phone usage data from 1987 to 2012. We modelled expected age specific rates (20-39, 40-59, 60-69, 70-84 years), based on published reports of relative risks (RR) of 1.5 in ever-users of mobile phones, and RR of 2.5 in a proportion of 'heavy users' (19% of all users), assuming a 10-year lag period between use and incidence. Age adjusted brain cancer incidence rates (20-84 years, per 100,000) have risen slightly in males (p0.05) and are higher in males 8.7 (CI=8.1-9.3) than in females, 5.8 (CI=5.3-6.3). Assuming a causal RR of 1.5 and 10-year lag period, the expected incidence rate in males in 2012 would be 11.7 (11-12.4) and in females 7.7 (CI=7.2-8.3), both pmobile phones. Modelled expected incidence rates were higher in all age groups in comparison to what was observed. Assuming a causal RR of 2.5 among 'heavy users' gave 2038 expected cases in all age groups. This is an ecological trends analysis, with no data on individual mobile phone use and outcome. The observed stability of brain cancer incidence in Australia between 1982 and 2012 in all age groups except in those over 70 years compared to increasing modelled expected estimates, suggests that the observed increases in brain cancer incidence in the older age group are unlikely to be related to mobile phone use. Rather, we hypothesize that the observed increases in brain cancer incidence in Australia are related to the advent of improved diagnostic procedures when computed tomography and related imaging technologies were introduced in the early 1980s. Copyright © 2016 Elsevier Ltd

  4. Signal propagation along the axon.

    Science.gov (United States)

    Rama, Sylvain; Zbili, Mickaël; Debanne, Dominique

    2018-03-08

    Axons link distant brain regions and are usually considered as simple transmission cables in which reliable propagation occurs once an action potential has been generated. Safe propagation of action potentials relies on specific ion channel expression at strategic points of the axon such as nodes of Ranvier or axonal branch points. However, while action potentials are generally considered as the quantum of neuronal information, their signaling is not entirely digital. In fact, both their shape and their conduction speed have been shown to be modulated by activity, leading to regulations of synaptic latency and synaptic strength. We report here newly identified mechanisms of (1) safe spike propagation along the axon, (2) compartmentalization of action potential shape in the axon, (3) analog modulation of spike-evoked synaptic transmission and (4) alteration in conduction time after persistent regulation of axon morphology in central neurons. We discuss the contribution of these regulations in information processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Longitudinal MRI evaluation of intracranial development and vascular characteristics of breast cancer brain metastases in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heling Zhou

    Full Text Available Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34% of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV showed that rCBV of brain metastases was significantly lower (mean= 0.89±0.03 than that of contralateral normal brain (mean= 1.00±0.03; p<0.005. Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05. The rCBV data were concordant with histological analysis of microvascular density (MVD. Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value.

  6. Pharmacologic inhibition of MLK3 kinase activity blocks the in vitro migratory capacity of breast cancer cells but has no effect on breast cancer brain metastasis in a mouse xenograft model.

    Directory of Open Access Journals (Sweden)

    Kun Hyoe Rhoo

    Full Text Available Brain metastasis of breast cancer is an important clinical problem, with few therapeutic options and a poor prognosis. Recent data have implicated mixed lineage kinase 3 (MLK3 in controlling the in vitro migratory capacity of breast cancer cells, as well as the metastasis of MDA-MB-231 breast cancer cells from the mammary fat pad to distant lymph nodes in a mouse xenograft model. We therefore set out to test whether MLK3 plays a role in brain metastasis of breast cancer cells. To address this question, we used a novel, brain penetrant, MLK3 inhibitor, URMC099. URMC099 efficiently inhibited the migration of breast cancer cells in an in vitro cell monolayer wounding assay, and an in vitro transwell migration assay, but had no effect on in vitro cell growth. We also tested the effect of URMC099 on tumor formation in a mouse xenograft model of breast cancer brain metastasis. This analysis showed that URMC099 had no effect on the either the frequency or size of breast cancer brain metastases. We conclude that pharmacologic inhibition of MLK3 by URMC099 can reduce the in vitro migratory capacity of breast cancer cells, but that it has no effect on either the frequency or size of breast cancer brain metastases, in a mouse xenograft model.

  7. Targeting metastatic breast cancer with ANG1005, a novel peptide-paclitaxel conjugate that crosses the blood-brain-barrier (BBB

    Directory of Open Access Journals (Sweden)

    Fei Li

    2017-03-01

    Full Text Available We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate, ANG1005, in treating brain metastatic breast cancer. These results were presented by Dr. Tang at the recent annual meeting of the European Society for Medical Oncology (ESMO 2016 Congress. This development heralds an important step forward towards the development of effective chemotherapeutic agents, which can cross the blood-brain-barrier and effectively treat and prevent the brain metastatic cancers.

  8. Compact point-detection fluorescence spectroscopy system for quantifying intrinsic fluorescence redox ratio in brain cancer diagnostics

    Science.gov (United States)

    Liu, Quan; Grant, Gerald; Li, Jianjun; Zhang, Yan; Hu, Fangyao; Li, Shuqin; Wilson, Christy; Chen, Kui; Bigner, Darell; Vo-Dinh, Tuan

    2011-03-01

    We report the development of a compact point-detection fluorescence spectroscopy system and two data analysis methods to quantify the intrinsic fluorescence redox ratio and diagnose brain cancer in an orthotopic brain tumor rat model. Our system employs one compact cw diode laser (407 nm) to excite two primary endogenous fluorophores, reduced nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. The spectra were first analyzed using a spectral filtering modulation method developed previously to derive the intrinsic fluorescence redox ratio, which has the advantages of insensitivty to optical coupling and rapid data acquisition and analysis. This method represents a convenient and rapid alternative for achieving intrinsic fluorescence-based redox measurements as compared to those complicated model-based methods. It is worth noting that the method can also extract total hemoglobin concentration at the same time but only if the emission path length of fluorescence light, which depends on the illumination and collection geometry of the optical probe, is long enough so that the effect of absorption on fluorescence intensity due to hemoglobin is significant. Then a multivariate method was used to statistically classify normal tissues and tumors. Although the first method offers quantitative tissue metabolism information, the second method provides high overall classification accuracy. The two methods provide complementary capabilities for understanding cancer development and noninvasively diagnosing brain cancer. The results of our study suggest that this portable system can be potentially used to demarcate the elusive boundary between a brain tumor and the surrounding normal tissue during surgical resection.

  9. [A case of rectal cancer with brain metastasis successfully treated with combined modality therapy - a case report].

    Science.gov (United States)

    Nishimura, Junya; Noda, Eiji; Kitayama, Kishu; Nomura, Shinya; Teraoka, Hitoshi; Nishino, Hiroji; Hirakawa, Kosei

    2014-11-01

    The authors report their experience in a patient with brain metastasis from rectal cancer who has survived without recurrence after multidisciplinary treatment. A 60-year-old man presented to the Department of Neurosurgery with the primary complaint of spasm of the left side of the face. Examination revealed a tumor 2 cm in diameter in the right frontal lobe. The tumor was suspected to be metastatic, and brain metastasis from rectal cancer was diagnosed. The brain tumor was removed by a neurosurgeon, and the patient was transferred to the Department of Surgery. Removal of the primary lesion in the rectum was attempted, but only colostomy could be performed due to extensive anterior invasion. Postoperatively, 5 courses of capecitabine and oxaliplatin (XELOX) + bevacizumab were administered. The rectal tumor shrank in size, while another mass, suspected to be a lung metastasis, remained unchanged. Therefore, a second surgery on the rectum was scheduled, and abdominoperineal resection of the rectum and lateral lymphadenectomy were performed. Postoperatively, 4 courses of XE LOX therapy were administered. The patient is currently alive without recurrence at 1 year after surgery. Treatment (including timing) for brain metastasis from rectal cancer has not been established and prognosis is poor. However, multidisciplinary treatment may provide the possibility of cure.

  10. Ultrasound imaging-guided intracardiac injection to develop a mouse model of breast cancer brain metastases followed by longitudinal MRI.

    Science.gov (United States)

    Zhou, Heling; Zhao, Dawen

    2014-03-06

    Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 months. It is critical to have suitable animal models to mimic the hemodynamic spread of the metastatic cells in the clinical scenario. Here, we are introducing the use of small animal ultrasound imaging to guide an accurate injection of brain tropical breast cancer cells into the left ventricle of athymic nude mice. Longitudinal MRI is used to assessing intracranial initiation and growth of brain metastases. Ultrasound-guided intracardiac injection ensures not only an accurate injection and hereby a higher successful rate but also significantly decreased mortality rate, as compared to our previous manual procedure. In vivo high resolution MRI allows the visualization of hyperintense multifocal lesions, as small as 310 µm in diameter on T2-weighted images at 3 weeks post injection. Follow-up MRI reveals intracranial tumor growth and increased number of metastases that distribute throughout the whole brain.

  11. Vascular targeting of LIGHT normalizes blood vessels in primary brain cancer and induces intratumoural high endothelial venules.

    Science.gov (United States)

    He, Bo; Jabouille, Arnaud; Steri, Veronica; Johansson-Percival, Anna; Michael, Iacovos P; Kotamraju, Venkata Ramana; Junckerstorff, Reimar; Nowak, Anna K; Hamzah, Juliana; Lee, Gabriel; Bergers, Gabriele; Ganss, Ruth

    2018-06-01

    High-grade brain cancer such as glioblastoma (GBM) remains an incurable disease. A common feature of GBM is the angiogenic vasculature, which can be targeted with selected peptides for payload delivery. We assessed the ability of micelle-tagged, vascular homing peptides RGR, CGKRK and NGR to specifically bind to blood vessels in syngeneic orthotopic GBM models. By using the peptide CGKRK to deliver the tumour necrosis factor (TNF) superfamily member LIGHT (also known as TNF superfamily member 14; TNFSF14) to angiogenic tumour vessels, we have generated a reagent that normalizes the brain cancer vasculature by inducing pericyte contractility and re-establishing endothelial barrier integrity. LIGHT-mediated vascular remodelling also activates endothelia and induces intratumoural high endothelial venules (HEVs), which are specialized blood vessels for lymphocyte infiltration. Combining CGKRK-LIGHT with anti-vascular endothelial growth factor and checkpoint blockade amplified HEV frequency and T-cell accumulation in GBM, which is often sparsely infiltrated by immune effector cells, and reduced tumour burden. Furthermore, CGKRK and RGR peptides strongly bound to blood vessels in freshly resected human GBM, demonstrating shared peptide-binding activities in mouse and human primary brain tumour vessels. Thus, peptide-mediated LIGHT targeting is a highly translatable approach in primary brain cancer to reduce vascular leakiness and enhance immunotherapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, Michael A.; Kelly, Paul J. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Pinnell, Nancy E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Claus, Elizabeth B. [Harvard Medical School, Boston, MA (United States); Department of Neurosurgery, Brigham and Women' s Hospital, Boston, MA (United States); Yale University School of Medicine, New Haven, CT (United States); Lee, Eudocia Q. [Harvard Medical School, Boston, MA (United States); Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Center, Boston, MA (United States); Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Arvold, Nils D. [Harvard Radiation Oncology Program, Boston, MA (United States); Lin, Nancy U. [Harvard Medical School, Boston, MA (United States); Department of Medical Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2012-07-15

    Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

  13. Brain cancer associated with environmental lead exposure: evidence from implementation of a National Petrol-Lead Phase-Out Program (PLPOP) in Taiwan between 1979 and 2007.

    Science.gov (United States)

    Wu, Wei-Te; Lin, Yu-Jen; Liou, Saou-Hsing; Yang, Chun-Yuh; Cheng, Kuang-Fu; Tsai, Perng-Jy; Wu, Trong-Neng

    2012-04-01

    In 1981, a Petrol-Lead Phase-Out Program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. The national brain cancer incidence data was obtained from the Taiwan National Cancer Registry. Age standardized incidence rates were calculated based on the 2000 WHO world standard population, and gasoline consumption data was obtained from the Bureau of Energy. The differences in the trend tests for age-standardized incidence rates of brain cancer between high, median, low, and small PLEA were analyzed. A significant increase was found from small to high PLEA in age-standardized incidence rates of brain cancer. By taking six possible confounders into account, the age-standardized incidence rates for brain cancer were highly correlated with the median and high PLEA by reference to the small PLEA. After being adjusted for a number of relevant confounders, it could be concluded that high PLEA might result in an increase in the incidence rate of brain cancer resulting from high lead exposures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  15. Automatic contour propagation using deformable image registration to determine delivered dose to spinal cord in head-and-neck cancer radiotherapy

    Science.gov (United States)

    Yeap, P. L.; Noble, D. J.; Harrison, K.; Bates, A. M.; Burnet, N. G.; Jena, R.; Romanchikova, M.; Sutcliffe, M. P. F.; Thomas, S. J.; Barnett, G. C.; Benson, R. J.; Jefferies, S. J.; Parker, M. A.

    2017-08-01

    To determine delivered dose to the spinal cord, a technique has been developed to propagate manual contours from kilovoltage computed-tomography (kVCT) scans for treatment planning to megavoltage computed-tomography (MVCT) guidance scans. The technique uses the Elastix software to perform intensity-based deformable image registration of each kVCT scan to the associated MVCT scans. The registration transform is then applied to contours of the spinal cord drawn manually on the kVCT scan, to obtain contour positions on the MVCT scans. Different registration strategies have been investigated, with performance evaluated by comparing the resulting auto-contours with manual contours, drawn by oncologists. The comparison metrics include the conformity index (CI), and the distance between centres (DBC). With optimised registration, auto-contours generally agree well with manual contours. Considering all 30 MVCT scans for each of three patients, the median CI is 0.759 +/- 0.003 , and the median DBC is (0.87 +/- 0.01 ) mm. An intra-observer comparison for the same scans gives a median CI of 0.820 +/- 0.002 and a DBC of (0.64 +/- 0.01 ) mm. Good levels of conformity are also obtained when auto-contours are compared with manual contours from one observer for a single MVCT scan for each of 30 patients, and when they are compared with manual contours from six observers for two MVCT scans for each of three patients. Using the auto-contours to estimate organ position at treatment time, a preliminary study of 33 patients who underwent radiotherapy for head-and-neck cancers indicates good agreement between planned and delivered dose to the spinal cord.

  16. Automatic contour propagation using deformable image registration to determine delivered dose to spinal cord in head-and-neck cancer radiotherapy.

    Science.gov (United States)

    Yeap, P L; Noble, D J; Harrison, K; Bates, A M; Burnet, N G; Jena, R; Romanchikova, M; Sutcliffe, M P F; Thomas, S J; Barnett, G C; Benson, R J; Jefferies, S J; Parker, M A

    2017-07-12

    To determine delivered dose to the spinal cord, a technique has been developed to propagate manual contours from kilovoltage computed-tomography (kVCT) scans for treatment planning to megavoltage computed-tomography (MVCT) guidance scans. The technique uses the Elastix software to perform intensity-based deformable image registration of each kVCT scan to the associated MVCT scans. The registration transform is then applied to contours of the spinal cord drawn manually on the kVCT scan, to obtain contour positions on the MVCT scans. Different registration strategies have been investigated, with performance evaluated by comparing the resulting auto-contours with manual contours, drawn by oncologists. The comparison metrics include the conformity index (CI), and the distance between centres (DBC). With optimised registration, auto-contours generally agree well with manual contours. Considering all 30 MVCT scans for each of three patients, the median CI is [Formula: see text], and the median DBC is ([Formula: see text]) mm. An intra-observer comparison for the same scans gives a median CI of [Formula: see text] and a DBC of ([Formula: see text]) mm. Good levels of conformity are also obtained when auto-contours are compared with manual contours from one observer for a single MVCT scan for each of 30 patients, and when they are compared with manual contours from six observers for two MVCT scans for each of three patients. Using the auto-contours to estimate organ position at treatment time, a preliminary study of 33 patients who underwent radiotherapy for head-and-neck cancers indicates good agreement between planned and delivered dose to the spinal cord.

  17. Enhanced brain disposition and effects of Δ9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice.

    Directory of Open Access Journals (Sweden)

    Adena S Spiro

    Full Text Available The ABC transporters P-glycoprotein (P-gp, Abcb1 and breast cancer resistance protein (Bcrp, Abcg2 regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9-tetrahydrocannabinol (THC has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT mice. Abcb1a/b (-/-, Abcg2 (-/- and wild-type (WT mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (-/- and Abcg2 (-/- mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (-/- mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis.

  18. Clinical characteristics and treatment outcomes of patients with colorectal cancer who develop brain metastasis: a single institution experience.

    Science.gov (United States)

    Fountzilas, Christos; Chang, Katherine; Hernandez, Brian; Michalek, Joel; Crownover, Richard; Floyd, John; Mahalingam, Devalingam

    2017-02-01

    The development of brain metastasis (BM) in patients with colorectal cancer (CRC) is a rare and late event. We sought to investigate the clinical characteristics, disease course and safety using biologic agents in our patients with CRC who develop brain metastases. A retrospective review of patients with CRC with brain metastases treated at our institution from 01/2005-01/2015 was performed. Survival analysis was performed using the Kaplan-Meier method. Forty patients were included in the analysis. Median age was 55.5 years, 67.5% were males, and 28% had a KRAS mutation. Twenty-four percent were treatment-naive at the time of BM diagnosis. Patients had a median of two brain lesions. Sixty-five percent of the patients were treated with radiotherapy alone, 22.5% had both surgical resection and brain radiotherapy. Median overall survival was 3.2 months after development of BM. Overall survival was longer in patients who received combined modality local therapy compared to patients treated with surgical resection or radiotherapy alone. Patients who received systemic treatment incorporating biologics following development of BM had a median overall survival of 18.6 months. Overall, the administration of biologic agents was safe and well tolerated. In summary, BM is an uncommon and late event in the natural history of metastatic CRC. The ability to deliver combined-modality local brain therapy as well as availability of more systemic therapy options appear to lead to improved outcomes.

  19. Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer.

    Science.gov (United States)

    Kaul, David; Angelidis, Alexander; Budach, Volker; Ghadjar, Pirus; Kufeld, Markus; Badakhshi, Harun

    2015-11-26

    Our purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). We performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis. The median follow-up time of the surviving patients was 14 months. The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months. Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant. The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis. The ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic

  20. Part two: Error propagation

    International Nuclear Information System (INIS)

    Picard, R.R.

    1989-01-01

    Topics covered in this chapter include a discussion of exact results as related to nuclear materials management and accounting in nuclear facilities; propagation of error for a single measured value; propagation of error for several measured values; error propagation for materials balances; and an application of error propagation to an example of uranium hexafluoride conversion process

  1. Clinical Outcome in Gamma Knife Radiosurgery for Metastatic Brain Tumors from the Primary Breast Cancer : Prognostic Factors in Local Treatment Failure and Survival

    OpenAIRE

    Choi, Seung Won; Kwon, Do Hoon; Kim, Chang Jin

    2013-01-01

    Objective Brain metastases in primary breast cancer patients are considerable sources of morbidity and mortality. Gamma knife radiosurgery (GKRS) has gained popularity as an up-front therapy in treating such metastases over traditional radiation therapy due to better neurocognitive function preservation. The aim of this study was to clarify the prognostic factors for local tumor control and survival in radiosurgery for brain metastases from primary breast cancer. Methods From March 2001 to Ma...

  2. Correlates of objectively measured sedentary behavior in cancer patients with brain metastases: an application of the theory of planned behavior.

    Science.gov (United States)

    Lowe, Sonya S; Danielson, Brita; Beaumont, Crystal; Watanabe, Sharon M; Baracos, Vickie E; Courneya, Kerry S

    2015-07-01

    The aim of this study is to examine the demographic, medical, and social-cognitive correlates of objectively measured sedentary behavior in advanced cancer patients with brain metastases. Advanced cancer patients diagnosed with brain metastases, aged 18 years or older, cognitively intact, and with palliative performance scale greater than 30%, were recruited from a Rapid Access Palliative Radiotherapy Program multidisciplinary brain metastases clinic. A cross-sectional survey interview assessed the theory of planned behavior variables and medical and demographic information. Participants wore activPAL™ (PAL Technologies Ltd, Glasgow, United Kingdom) accelerometers recording time spent supine, sitting, standing, and stepping during 7 days encompassing palliative whole brain radiotherapy treatments. Thirty-one patients were recruited. Correlates of median time spent supine or sitting in hours per day were instrumental attitude (i.e., perceived benefits) of physical activity (r = -0.42; p = 0.030) and affective attitude (i.e., perceived enjoyment) of physical activity (r = -0.43; p = 0.024). Moreover, participants who sat or were supine for greater than 20.7 h per day reported significantly lower instrumental attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.051) and affective attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.041). Finally, participants who were older than 60 years of age spent more time sitting or being supine. Instrumental attitude and affective attitude were the strongest correlates of objectively measured sedentary behavior. This information could inform intervention studies to increase physical activity in advanced cancer patients with brain metastases. Copyright © 2014 John Wiley & Sons, Ltd.

  3. Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

    Science.gov (United States)

    2015-12-01

    empirical method was developed to simulate photon transport in tissue based on the acquired medical images of an individual patient (CT and MRI ) with... MRI , etc. In the current work we have developed a fast voxel based empirical approach which can estimate photon fluence in the brain and evaluate...These tools provide the capability to develop and optimize treatment plans for optimal release of pharmaceuticals to metastatic breast cancer in the

  4. Role of prophylactic brain irradiation in limited stage small cell lung cancer: clinical, neuropsychologic, and CT sequelae

    International Nuclear Information System (INIS)

    Laukkanen, E.; Klonoff, H.; Allan, B.; Graeb, D.; Murray, N.

    1988-01-01

    Ninety-four patients with limited stage small cell lung cancer treated between 1981 and 1985 with a regimen including prophylactic brain irradiation (PBI) after combination chemotherapy were assessed for compliance with PBI, brain relapse, and neurologic morbidity. Seventy-seven percent of patients had PBI and of these, 22% developed brain metastases after a median time of 11 months post treatment. The brain was the apparent unique initial site of relapse in 10% of PBI cases but more commonly brain relapse was preceded or accompanied by failure at other sites, especially the chest. Brain metastases were the greatest cause of morbidity in 50% of PBI failures. Twelve of 14 PBI patients alive 2 years after treatment had oncologic, neurologic, and neuropsychological evaluation, and brain CT. All long-term survivors were capable of self care and none fulfilled diagnostic criteria for dementia, with three borderline cases. One third had pretreatment neurologic dysfunction and two thirds post treatment neurologic symptoms, most commonly recent memory loss. Fifty percent had subtle motor findings. Intellectual functioning was at the 38th percentile with most patients having an unskilled occupational history. Neuropsychologic impairment ratings were borderline in three cases and definitely impaired in seven cases. CT scans showed brain atrophy in all cases with mild progression in those having a pre-treatment baseline. Periventricular and subcortical low density lesions identical to the CT appearance of subcortical arteriosclerotic encephalopathy were seen in 82% of posttreatment CT studies, and lacunar infarcts in 54%. Neuropsychologic impairment scores and the extent of CT periventricular low density lesions were strongly associated

  5. The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

    Science.gov (United States)

    DENG, YANMING; FENG, WEINENG; WU, JING; CHEN, ZECHENG; TANG, YICONG; ZHANG, HUA; LIANG, JIANMIAO; XIAN, HAIBING; ZHANG, SHUNDA

    2014-01-01

    It has been demonstrated that erlotinib is effective in treating patients with brain metastasis from non-small-cell lung cancer. However, the number of studies determining the erlotinib concentration in these patients is limited. The purpose of this study was to measure the concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung carcinoma. Six patients were treated with the standard recommended daily dose of erlotinib (150 mg) for 4 weeks. All the patients had previously received chemotherapy, but no brain radiotherapy. At the end of the treatment period, blood plasma and cerebrospinal fluid samples were collected and the erlotinib concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The average erlotinib concentration in the blood plasma and the cerebrospinal fluid was 717.7±459.7 and 23.7±13.4 ng/ml, respectively. The blood-brain barrier permeation rate of erlotinib was found to be 4.4±3.2%. In patients with partial response (PR), stable disease (SD) and progressive disease (PD), the average concentrations of erlotinib in the cerebrospinal fluid were 35.5±19.0, 19.1±8.7 and 16.4±5.9 ng/ml, respectively. In addition, the efficacy rate of erlotinib for metastatic brain lesions was 33.3%, increasing to 50% in patients with EGFR mutations. However, erlotinib appeared to be ineffective in cases with wild-type EGFR. In conclusion, a relatively high concentration of erlotinib was detected in the cerebrospinal fluid of patients with brain metastases from non-small-cell lung cancer. Thus, erlotinib may be considered as a treatment option for this patient population. PMID:24649318

  6. Prognostic factors and multidisciplinary treatment modalities for brain metastases from colorectal cancer: analysis of 93 patients

    International Nuclear Information System (INIS)

    Gu, Xiao-Dong; Cai, Yan-Tao; Zhou, Yi-Ming; Li, Zhen-Yang; Xiang, Jian-Bin; Chen, Zong-You

    2015-01-01

    The purpose of this study was to review patient characteristics and evaluate the potential factors affecting prognosis in cases of brain metastasis (BM) from colorectal cancer (CRC). We retrospectively reviewed 93 cases of BM from CRC in our hospital. Patient demographics, neurologic symptoms, and location and number of BMs were recorded. Factors analyzed included: age; sex; Karnofsky performance score; number of BMs; presence of extracranial metastases; dimensions; location of tumors; treatment modalities. The overall 1- and 2-year survival rates were 27.7 and 9.9 %. On multivariate analysis, the number of BMs, extracranial metastases and the initial treatment modalities were found to be independent prognostic factors for overall survival. Patients treated with surgical resection followed by WBRT or SRS had an improved prognosis relative to those treated with surgery alone (P = 0.02 and P = 0.02, respectively). No significance difference in survival rate was found between patients treated with SRS alone or SRS plus WBRT (P = 0.11). Surgical resection of BMs from CRC in selected patients may help prolong survival. Additional radiotherapy following surgery is valuable in improving prognosis. Extracranial metastasis, multiple BM lesions and initial non operation can be considered as independent factors associated with poor prognosis

  7. Cancer/testis antigens and gametogenesis: a review and "brain-storming" session

    Directory of Open Access Journals (Sweden)

    Erenpreisa Jekaterina

    2005-02-01

    Full Text Available Abstract Genes expressed both in normal testis and in malignancies (Cancer/ Testis associated genes – CTA have become the most extensively studied antigen group in the field of tumour immunology. Despite this, many fundamentally important questions remain unanswered: what is the connection between germ-cell specific genes and tumours? Is the expression of these genes yet another proof for the importance of genome destabilisation in the process of tumorigenesis?, or maybe activation of these genes is not quite random but instead related to some programme giving tumours a survival advantage? This review collates most of the recent information available about CTAs expression, function, and regulation. The data suggests a programme related to ontogenesis, mostly to gametogenesis. In the "brain-storming" part, facts in conflict with the hypothesis of random CTA gene activation are discussed. We propose a programme borrowed from organisms phylogenetically much older than humans, which existed before the differentiation of sexes. It is a programme that has served as a life cycle with prominent ploidy changes, and from which, as we know, the germ-cell ploidy cycle – meiosis – has evolved. Further work may show whether this hypothesis can lead to a novel anti-tumour strategy.

  8. Analyzing collaboration networks and developmental patterns of nano-enabled drug delivery (NEDD for brain cancer

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2015-07-01

    Full Text Available The rapid development of new and emerging science & technologies (NESTs brings unprecedented challenges, but also opportunities. In this paper, we use bibliometric and social network analyses, at country, institution, and individual levels, to explore the patterns of scientific networking for a key nano area – nano-enabled drug delivery (NEDD. NEDD has successfully been used clinically to modulate drug release and to target particular diseased tissues. The data for this research come from a global compilation of research publication information on NEDD directed at brain cancer. We derive a family of indicators that address multiple facets of research collaboration and knowledge transfer patterns. Results show that: (1 international cooperation is increasing, but networking characteristics change over time; (2 highly productive institutions also lead in influence, as measured by citation to their work, with American institutes leading; (3 research collaboration is dominated by local relationships, with interesting information available from authorship patterns that go well beyond journal impact factors. Results offer useful technical intelligence to help researchers identify potential collaborators and to help inform R&D management and science & innovation policy for such nanotechnologies.

  9. Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

    Science.gov (United States)

    Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

    2018-04-01

    This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

  10. Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

    Science.gov (United States)

    Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

    2018-01-01

    Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

  11. Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

    2016-09-01

    We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

  12. Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells.

    Science.gov (United States)

    Chang, Jiang; Paillard, Archibald; Passirani, Catherine; Morille, Marie; Benoit, Jean-Pierre; Betbeder, Didier; Garcion, Emmanuel

    2012-06-01

    Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells. NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors. While slightly modifying size (80 to 90 nm) and zeta potential (-44 to -32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs in vitro. Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.

  13. Whole-brain radiotherapy with 20 Gy in 5 fractions for brain metastases in patients with cancer of unknown primary (CUP)

    International Nuclear Information System (INIS)

    Rades, D.; Bohlen, G.; Dunst, J.; Lohynska, R.; Veninga, T.; Stalpers, L.J.A.; Schild, S.E.

    2007-01-01

    Background: Whole brain radiotherapy (WBRT) is the most common treatment for brain metastases. Survival of patients with cancer of unknown primary (CUP) presenting with brain metastases is extremely poor. A radiation program with a short overall treatment time (short-course RT) would be preferable to longer programs if it provides similar outcomes. This study compares short-course RT with 20 Gy in 5 fractions (5 x 4 Gy) given over 5 days to longer programs in CUP patients. Patients and Methods: Data regarding 101 CUP patients who received either short course WBRT (n = 34) with 5 x 4 Gy or long-course WBRT (n = 67) with 10 x 3 Gy given over 2 weeks or 20 x 2 Gy given over 4 weeks for brain metastases were analyzed retrospectively. Six additional potential prognostic factors were investigated: age, gender, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, RPA-(Recursive Partitioning Analysis-)class. Results: On univariate analysis, the radiation program was not associated with survival (p = 0.88) nor intracerebral control (p = 0.36). Improved survival was associated with KPS ≥ 70 (p < 0.001), absence of extracranial metastases (p < 0.001), and RPA-class 1 (p < 0.001). On multivariate analyses, KPS (risk ratio [RR]: 4.55; p < 0.001), extracranial metastases (RR: 1.70; p = 0.018), and RPA-class (RR: 2.86; p < 0.001) maintained significance. On univariate analysis, KPS (p < 0.001) and RPA-class (p < 0.001) were significantly associated with intracerebral control. On multivariate analyses, KPS (RR: 2.72; p < 0.001) and RPA-class (RR: 2.09; p < 0.001) remained significant. Conclusion: Short-course WBRT with 5 x 4 Gy provided similar intracerebral control and survival as longer programs for the treatment of brain metastases in CUP patients. 5 x 4 Gy appears preferable because it is more convenient for patients. (orig.)

  14. Validation of the RTOG recursive partitioning analysis (RPA) classification for small-cell lung cancer-only brain metastases

    International Nuclear Information System (INIS)

    Videtic, Gregory M.M.; Adelstein, David J.; Mekhail, Tarek M.; Rice, Thomas W.; Stevens, Glen H.J.; Lee, S.-Y.; Suh, John H.

    2007-01-01

    Purpose: Radiation Therapy Oncology Group (RTOG) developed a prognostic classification based on a recursive partitioning analysis (RPA) of patient pretreatment characteristics from three completed brain metastases randomized trials. Clinical trials for patients with brain metastases generally exclude small-cell lung cancer (SCLC) cases. We hypothesize that the RPA classes are valid in the setting of SCLC brain metastases. Methods and Materials: A retrospective review of 154 SCLC patients with brain metastases treated between April 1983 and May 2005 was performed. RPA criteria used for class assignment were Karnofsky performance status (KPS), primary tumor status (PT), presence of extracranial metastases (ED), and age. Results: Median survival was 4.9 months, with 4 patients (2.6%) alive at analysis. Median follow-up was 4.7 months (range, 0.3-40.3 months). Median age was 65 (range, 42-85 years). Median KPS was 70 (range, 40-100). Number of patients with controlled PT and no ED was 20 (13%) and with ED, 27 (18%); without controlled PT and ED, 34 (22%) and with ED, 73 (47%). RPA class distribution was: Class I: 8 (5%); Class II: 96 (62%); Class III: 51 (33%). Median survivals (in months) by RPA class were: Class I: 8.6; Class II: 4.2; Class III: 2.3 (p = 0.0023). Conclusions: Survivals for SCLC-only brain metastases replicate the results from the RTOG RPA classification. These classes are therefore valid for brain metastases from SCLC, support the inclusion of SCLC patients in future brain metastases trials, and may also serve as a basis for historical comparisons

  15. Proteotranscriptomic Profiling of 231-BR Breast Cancer Cells: Identification of Potential Biomarkers and Therapeutic Targets for Brain Metastasis*

    Science.gov (United States)

    Dun, Matthew D.; Chalkley, Robert J.; Faulkner, Sam; Keene, Sheridan; Avery-Kiejda, Kelly A.; Scott, Rodney J.; Falkenby, Lasse G.; Cairns, Murray J.; Larsen, Martin R.; Bradshaw, Ralph A.; Hondermarck, Hubert

    2015-01-01

    Brain metastases are a devastating consequence of cancer and currently there are no specific biomarkers or therapeutic targets for risk prediction, diagnosis, and treatment. Here the proteome of the brain metastatic breast cancer cell line 231-BR has been compared with that of the parental cell line MDA-MB-231, which is also metastatic but has no organ selectivity. Using SILAC and nanoLC-MS/MS, 1957 proteins were identified in reciprocal labeling experiments and 1584 were quantified in the two cell lines. A total of 152 proteins were confidently determined to be up- or down-regulated by more than twofold in 231-BR. Of note, 112/152 proteins were decreased as compared with only 40/152 that were increased, suggesting that down-regulation of specific proteins is an important part of the mechanism underlying the ability of breast cancer cells to metastasize to the brain. When matched against transcriptomic data, 43% of individual protein changes were associated with corresponding changes in mRNA, indicating that the transcript level is a limited predictor of protein level. In addition, differential miRNA analyses showed that most miRNA changes in 231-BR were up- (36/45) as compared with down-regulations (9/45). Pathway analysis revealed that proteome changes were mostly related to cell signaling and cell cycle, metabolism and extracellular matrix remodeling. The major protein changes in 231-BR were confirmed by parallel reaction monitoring mass spectrometry and consisted in increases (by more than fivefold) in the matrix metalloproteinase-1, ephrin-B1, stomatin, myc target-1, and decreases (by more than 10-fold) in transglutaminase-2, the S100 calcium-binding protein A4, and l-plastin. The clinicopathological significance of these major proteomic changes to predict the occurrence of brain metastases, and their potential value as therapeutic targets, warrants further investigation. PMID:26041846

  16. Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain

    Directory of Open Access Journals (Sweden)

    Anna Koumarianou

    2016-01-01

    Full Text Available Patients with HER2-positive breast cancer and brain metastases have limited treatment options, and, as a result of their poor performance status and worse prognosis, they are underrepresented in clinical trials. Not surprisingly, these patients may not be fit enough to receive any active treatment and are offered supportive therapy. BRCA2 mutations are reported to be rarely associated with HER2-overexpressing advanced breast cancer and even more rarely with brain metastases at diagnosis. We report on a BRCA2-positive breast cancer patient with metastatic disease in multiple sites, including the brain, and poor performance status who exhibited an extraordinary clinical and imaging response to the novel anti-HER2 therapy pertuzumab after multiple lines of therapy including anti-HER2 targeting. To our knowledge, the clinicopathologic and therapeutic characteristics of this patient point to a unique case and an urgent need for further investigation of pertuzumab in patients with brain metastases.

  17. The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

    International Nuclear Information System (INIS)

    Niwinska, Anna; Tacikowska, Malgorzata; Murawska, Magdalena

    2010-01-01

    Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

  18. Validity of Three Recently Proposed Prognostic Grading Indexes for Breast Cancer Patients With Radiosurgically Treated Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Masaaki, E-mail: BCD06275@nifty.com [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Tokyo Women' s Medical University Medical Center E, Tokyo (Japan); Kawabe, Takuya [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto (Japan); Higuchi, Yoshinori [Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba (Japan); Sato, Yasunori [Clinical Research Center, Chiba University Graduate School of Medicine, Chiba (Japan); Barfod, Bierta E. [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan); Kasuya, Hidetoshi [Department of Neurosurgery, Tokyo Women' s Medical University Medical Center E, Tokyo (Japan); Urakawa, Yoichi [Katsuta Hospital Mito GammaHouse, Hitachi-naka (Japan)

    2012-12-01

    Purpose: We tested the validity of 3 recently proposed prognostic indexes for breast cancer patients with brain metastases (METs) treated radiosurgically. The 3 indexes are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), New Breast Cancer (NBC)-Recursive Partitioning Analysis (RPA), and our index, sub-classification of RPA class II patients into 3 sub-classes (RPA class II-a, II-b and II-c) based on Karnofsky performance status, tumor number, original tumor status, and non-brain METs. Methods and Materials: This was an institutional review board-approved, retrospective cohort study using our database of 269 consecutive female breast cancer patients (mean age, 55 years; range, 26-86 years) who underwent Gamma Knife radiosurgery (GKRS) alone, without whole-brain radiation therapy, for brain METs during the 15-year period between 1996 and 2011. The Kaplan-Meier method was used to estimate the absolute risk of each event. Results: Kaplan-Meier plots of our patient series showed statistically significant survival differences among patients stratified into 3, 4, or 5 groups based on the 3 systems (P<.001). However, the mean survival time (MST) differences between some pairs of groups failed to reach statistical significance with all 3 systems. Thus, we attempted to regrade our 269 breast cancer patients into 3 groups by modifying our aforementioned index along with the original RPA class I and III, (ie, RPA I+II-a, II-b, and II-c+III). There were statistically significant MST differences among these 3 groups without overlap of 95% confidence intervals (CIs) between any 2 pairs of groups: 18.4 (95% CI = 14.0-29.5) months in I+II-a, 9.2 in II-b (95% CI = 6.8-12.9, P<.001 vs I+II-a) and 5.0 in II-c+III (95% CI = 4.2-6.8, P<.001 vs II-b). Conclusions: As none of the new grading systems, DS-GPS, BC-RPA and our system, was applicable to our set of radiosurgically treated patients for comparing survivals after GKRS, we slightly modified our system for breast cancer

  19. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial

    OpenAIRE

    Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl

    2016-01-01

    Summary Background Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. Methods The Quality of Life a...

  20. Occupational exposure to electromagnetic fields, leukemia and brain cancer: update of two meta-analysis; Exposition professionnelle aux champs electromagnetiques, leucemie et cancer du cerveau: mise a jour de deux meta-analyses

    Energy Technology Data Exchange (ETDEWEB)

    Anon

    2008-11-15

    This new meta-analysis found a slight increase in the risk of brain cancer and of leukemia in populations occupationally exposed to electromagnetic fields. it does not, however, support the hypothesis that electromagnetic fields have an effect on these cancers. (author)

  1. [Brain metastasis from breast cancer: who?, when? and special considerations about the role of technology in neurosurgery].

    Science.gov (United States)

    Dutertre, Guillaume; Pouit, Bruno

    2011-04-01

    Questions about both the place and the role of surgery on brain metastasis from breast cancer are arising more and more frequently in practice due to the increase of brain metastasis in patients suffering from a form of cancer recognized as one of the most recurrent cancers in adults but also one of the most sensitive to general treatments of the systemic disease. With improvements in anaesthesia, in surgical instruments, and in global care, neurosurgery has taken advantage of new techniques such as pre- and even per-operative imagery and also neuronavigation. These techniques enable radical and effective surgical intervention with a high level of safety for the patient, making neurosurgery perfectly competitive with other therapeutic modalities, particularly on functional grounds. As for symptomatic treatments or other anti-metastasis treatments, most situations allow a reflection on the global therapeutic strategy which can be adapted to individual cases depending on the patient's general prognosis. In developing this global therapeutic strategy, surgical treatment is still as relevant as ever.

  2. BRAIN METASTASES OF GERM CELL TUMORS. THE RUSSIAN CANCER RESEARCH CENTER'S EXPERIENCE

    Directory of Open Access Journals (Sweden)

    A. A. Tryakin

    2014-07-01

    Full Text Available This paper analyzes the experience in treating 20 patients with nonseminomatous germ cell tumors metastasizing to the brain. It presents brain metastasis-associated factors: multiple lung metastases; IGCCCG poor prognosis; and a baseline human chorionic gonadotropin level of > 50000 mIU/ml. The authors have identified a group to be screened for brain metastasis, which includes patients with intermediate/poor prognosis and multiple lung metastases. Long-term survival was achieved in 45 % of patients with baseline brain damage and in 22 % of those with metastases revealed after first-line chemotherapy. The positive prognostic factors associated with long-term survival were a single brain lesion, no neurological symptoms, and achievement of clinical complete personse in the brain.

  3. Benefit of brain prophylactic irradiation in patients suffering from a small-cell bronchial cancer: retrospective study on 289 cases

    International Nuclear Information System (INIS)

    Assouline, A.; Tai, P.; Jancewicz, M.; Joseph, K.; Krzisch, C.; Yu, E.

    2011-01-01

    The authors report a study which aimed at determining the benefit of a brain prophylactic irradiation for patients suffering from a localized small-cell bronchial cancer and in partial response to the local-regional treatment of their disease. A retrospective analysis has been performed on a set of 289 patients who had been treated by chemo-radiotherapy with or without brain prophylactic irradiation between 1981 and 2007. Data are discussed in terms of remission level, survival with respect to the level of response to the local-regional treatment. Depending on this response level the irradiation increases or not the probability of global survival, or the probability of specific survival. Short communication

  4. Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy

    Directory of Open Access Journals (Sweden)

    Donna H. Murrell

    2015-06-01

    Full Text Available OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB, which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2+ breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2 were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105 across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05; interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001. Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05 in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2+ breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

  5. Image Guided Radiation Therapy Using Synthetic Computed Tomography Images in Brain Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Price, Ryan G. [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan (United States); Kim, Joshua P.; Zheng, Weili [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Chetty, Indrin J. [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan (United States); Glide-Hurst, Carri, E-mail: churst2@hfhs.org [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan (United States)

    2016-07-15

    Purpose: The development of synthetic computed tomography (CT) (synCT) derived from magnetic resonance (MR) images supports MR-only treatment planning. We evaluated the accuracy of synCT and synCT-generated digitally reconstructed radiographs (DRRs) relative to CT and determined their performance for image guided radiation therapy (IGRT). Methods and Materials: Magnetic resonance simulation (MR-SIM) and CT simulation (CT-SIM) images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images (n=37) were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism. Results: Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4 ± 0.5 mm (range, −0.6 to 1.6 mm), 0.0 ± 0.5 mm (range, −0.9 to 1.2 mm), and 0.1 ± 0.3 mm (range, −0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6 ± 0.4 mm (range, −0.2 to 1.6 mm), 0.2 ± 0.4 mm (range, −0.3 to 1.2 mm), and 0.2 ± 0

  6. Image Guided Radiation Therapy Using Synthetic Computed Tomography Images in Brain Cancer

    International Nuclear Information System (INIS)

    Price, Ryan G.; Kim, Joshua P.; Zheng, Weili; Chetty, Indrin J.; Glide-Hurst, Carri

    2016-01-01

    Purpose: The development of synthetic computed tomography (CT) (synCT) derived from magnetic resonance (MR) images supports MR-only treatment planning. We evaluated the accuracy of synCT and synCT-generated digitally reconstructed radiographs (DRRs) relative to CT and determined their performance for image guided radiation therapy (IGRT). Methods and Materials: Magnetic resonance simulation (MR-SIM) and CT simulation (CT-SIM) images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images (n=37) were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism. Results: Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4 ± 0.5 mm (range, −0.6 to 1.6 mm), 0.0 ± 0.5 mm (range, −0.9 to 1.2 mm), and 0.1 ± 0.3 mm (range, −0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6 ± 0.4 mm (range, −0.2 to 1.6 mm), 0.2 ± 0.4 mm (range, −0.3 to 1.2 mm), and 0.2 ± 0

  7. Evaluation of Biomarkers Predictive of Benefit from the PD-1 Inhibitor MK-3475 in Patients with Non-Small Cell Lung Cancer and Brain Metastases

    Science.gov (United States)

    2017-07-01

    Small Cell Lung Cancer and Brain Metastases PRINCIPAL INVESTIGATOR: Sarah B. Goldberg, MD CONTRACTING ORGANIZATION: Yale University New Haven, CT...benefit in patients with non- small cell lung cancer (NSCLC). However, the overall response rate is only 20-30% and there is no clearly-defined...9. Appendices……………………………………………………………14 4 1. INTRODUCTION: Lung cancer is the leading cause of cancer death in the United States, resulting in more

  8. Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

    Science.gov (United States)

    Shiroishi, Mark S.; Gupta, Vikash; Bigjahan, Bavrina; Cen, Steven Y.; Rashid, Faisal; Hwang, Darryl H.; Lerner, Alexander; Boyko, Orest B.; Liu, Chia-Shang Jason; Law, Meng; Thompson, Paul M.; Jahanshad, Neda

    2017-11-01

    Background: Increases in cancer survival have made understanding the basis of cancer-related cognitive impairment (CRCI) more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors with small sample sizes; little is known about other non-CNS cancers. However, there is a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI. Objective: Evaluate brain cortical structural differences in those with non-CNS cancers using clinically-indicated MRIs. Design: Cross-sectional Patients: Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs. Methods: Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C. Results: Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 LCa was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple ROIs primarily within the frontal and temporal lobes for all comparisons. Limitations: Several limitations were apparent including a small sample size that precluded adjustment for other covariates. Conclusions: Our preliminary results suggest that various types of non-CNS cancers, both with and without chemotherapy, may result in brain structural abnormalities. Also, there is a wealth of untapped clinical MRIs that could be used for future CRCI studies.

  9. Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

    Science.gov (United States)

    Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

    2014-01-06

    Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

  10. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

    Science.gov (United States)

    Freedman, Rachel A; Gelman, Rebecca S; Wefel, Jeffrey S; Melisko, Michelle E; Hess, Kenneth R; Connolly, Roisin M; Van Poznak, Catherine H; Niravath, Polly A; Puhalla, Shannon L; Ibrahim, Nuhad; Blackwell, Kimberly L; Moy, Beverly; Herold, Christina; Liu, Minetta C; Lowe, Alarice; Agar, Nathalie Y R; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F; Krop, Ian E; Wolff, Antonio C; Winer, Eric P; Lin, Nancy U

    2016-03-20

    Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥ 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients

  11. Adult Brain Cancer in the U.S. Black Population: A Surveillance, Epidemiology, and End Results (SEER) Analysis of Incidence, Survival, and Trends

    OpenAIRE

    Gabriel, Abigail; Batey, Jason; Capogreco, Joseph; Kimball, David; Walters, Andy; Tubbs, R. Shane; Loukas, Marios

    2014-01-01

    Background Despite much epidemiological research on brain cancer in the United States, the etiology for the various subtypes remains elusive. The black population in the United States currently experiences lower incidence but higher survival rates when compared to other races. Thus, the aim of this study is to analyze the trends in incidence and survival for the 6 most common primary brain tumors in the black population of the United States. Material/Methods The Surveillance, Epidemiology, an...

  12. Outcome and prognostic factors in single brain metastases from small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bernhardt, Denise; Koenig, Laila [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Adeberg, Sebastian; Debus, Juergen [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Bozorgmehr, Farastuk; Thomas, Michael; Steins, Martin [Heidelberg University, Department of Thoracic Oncology, Thoraxklinik, Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Opfermann, Nils; Hoerner-Rieber, Juliane; Rieken, Stefan [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Kappes, Jutta [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); Unterberg, Andreas [University Hospital Heidelberg, Department of Neurosurgery, INF 400, Heidelberg (Germany); Herth, Felix [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Heussel, Claus Peter [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology, Heidelberg (Germany); Warth, Arne [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (DE); Heidelberg University, Institute of Pathology, Heidelberg (DE)

    2018-02-15

    Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response

  13. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  14. (64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients.

    Science.gov (United States)

    Kurihara, Hiroaki; Hamada, Akinobu; Yoshida, Masayuki; Shimma, Schuichi; Hashimoto, Jun; Yonemori, Kan; Tani, Hitomi; Miyakita, Yasuji; Kanayama, Yousuke; Wada, Yasuhiro; Kodaira, Makoto; Yunokawa, Mayu; Yamamoto, Harukaze; Shimizu, Chikako; Takahashi, Kazuhiro; Watanabe, Yasuyoshi; Fujiwara, Yasuhiro; Tamura, Kenji

    2015-01-01

    The purpose of this study was to determine whether brain metastases from HER2-positive breast cancer could be detected noninvasively using positron emission tomography (PET) with (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-trastuzumab. PET was performed on five patients with brain metastases from HER2-positive breast cancer, at 24 or 48 h after the injection of approximately 130 MBq of the probe (64)Cu-DOTA-trastuzumab. Radioactivity in metastatic brain tumors was evaluated based on PET images in five patients. Autoradiography, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were performed in one surgical case to confirm HER2 specificity of (64)Cu-DOTA-trastuzumab. Metastatic brain lesions could be visualized by (64)Cu-DOTA-trastuzumab PET in all of five cases, which might indicated that trastuzumab passes through the blood-brain barrier (BBB). The HER2 specificity of (64)Cu-DOTA-trastuzumab was demonstrated in one patient by autoradiography, immunohistochemistry, and LC-MS/MS. Cu-DOTA-trastuzumab PET could be a potential noninvasive procedure for serial identification of metastatic brain lesions in patients with HER2-positive breast cancer. UMIN000004170.

  15. Trajectories of Symptom Clusters, Performance Status, and Quality of Life During Concurrent Chemoradiotherapy in Patients With High-Grade Brain Cancers.

    Science.gov (United States)

    Kim, Sang-Hee; Byun, Youngsoon

    Symptom clusters must be identified in patients with high-grade brain cancers for effective symptom management during cancer-related therapy. The aims of this study were to identify symptom clusters in patients with high-grade brain cancers and to determine the relationship of each cluster with the performance status and quality of life (QOL) during concurrent chemoradiotherapy (CCRT). Symptoms were assessed using the Memorial Symptom Assessment Scale, and the performance status was evaluated using the Karnofsky Performance Scale. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General. This prospective longitudinal survey was conducted before CCRT and at 2 to 3 weeks and 4 to 6 weeks after the initiation of CCRT. A total of 51 patients with newly diagnosed primary malignant brain cancer were included. Six symptom clusters were identified, and 2 symptom clusters were present at each time point (ie, "negative emotion" and "neurocognitive" clusters before CCRT, "negative emotion and decreased vitality" and "gastrointestinal and decreased sensory" clusters at 2-3 weeks, and "body image and decreased vitality" and "gastrointestinal" clusters at 4-6 weeks). The symptom clusters at each time point demonstrated a significant relationship with the performance status or QOL. Differences were observed in symptom clusters in patients with high-grade brain cancers during CCRT. In addition, the symptom clusters were correlated with the performance status and QOL of patients, and these effects could change during CCRT. The results of this study will provide suggestions for interventions to treat or prevent symptom clusters in patients with high-grade brain cancer during CCRT.

  16. External radiation of brain metastases from renal carcinoma: a retrospective study of 119 patients from the M. D. Anderson Cancer Center

    International Nuclear Information System (INIS)

    Wronski, Marek; Maor, Moshe H.; Davis, Brian J.; Sawaya, Raymond; Levin, Victor A.

    1997-01-01

    Purpose: Approximately 10% of patients with metastatic renal cell carcinoma are diagnosed with brain metastases. Most of these patients receive palliative radiotherapy and die of progressive brain metastatic disease. This retrospective study examines the M. D. Anderson Cancer Center experience with such patients who received only whole brain radiation therapy (WBRT). Methods and Materials: Records of 200 patients with brain metastases from renal carcinoma who were treated at M. D. Anderson Cancer Center between 1976 and 1993 were reviewed. Of these patients, 119 received WBRT only and constitute the basis of this study. Different prognostic factors were analyzed. Results: Overall median survival time from diagnosis of the brain metastases was 4.4 months. Multiple brain tumors were treated in 70 patients (58.8%) who had a survival of 3.0 months compared with 4.4 months for patients having a single brain metastasis (p = 0.043). Among 117 patients the causes of death were neurologic in 90 (76%), systemic cancer in 19 (16%), and unknown in 9 (8%). Survival rates at 6 months, 1 year, and 2 years, were 33.6, 16.8, and 5.9%, respectively. Patients in whom brain metastases were diagnosed synchronously with a renal primary (n = 24) had a median survival time of 3.4 months compared with 3.2 months for those 95 who were diagnosed metachronously (p < 0.79, NS). In the Cox multivariate analysis of 13 possible prognostic factors, only a single brain metastasis (p = 0.0329), lack of distant metastases at the time of diagnosis (p = 0.0056), and tumor diameter ≤ 2 cm (p < 0.0016) were statistically significant. Conclusion: These unsatisfactory results with WBRT suggest that more aggressive approaches, such as surgery or radiosurgery should be applied whenever possible

  17. Childhood CT scans linked to leukemia and brain cancer later in life

    Science.gov (United States)

    Children and young adults scanned multiple times by computed tomography (CT), a commonly used diagnostic tool, have a small increased risk of leukemia and brain tumors in the decade following their first scan.

  18. Combining Whole-Brain Radiotherapy with Gefitinib/Erlotinib for Brain Metastases from Non-Small-Cell Lung Cancer: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mao-hua Zheng

    2016-01-01

    Full Text Available Background. To comprehensively assess the efficacy and safety of whole-brain radiotherapy (WBRT combined with gefitinib/erlotinib for treatment of brain metastases (BM from non-small-cell lung cancer (NSCLC. Methods. Databases including PubMed, EMBASE.com, Web of Science, and Cochrane Library were searched from inception to April 12, 2015. Studies on randomized controlled trials (RCTs and case-control trials comparing WBRT combined with gefitinib/erlotinib versus WBRT alone for BM from NSCLC were included. Literature selection, data extraction, and quality assessment were performed independently by two trained reviewers. RevMan 5.3 software was used to analyze data. Results. A total of 7 trials involving 622 patients were included. Compared with WBRT alone or WBRT plus chemotherapy, WBRT plus gefitinib/erlotinib could significantly improve response rate (OR = 2.16, 95% CI: 1.35–3.47; P=0.001, remission rate of central nervous system (OR = 6.06, 95% CI: 2.57–14.29; P<0.0001, disease control rate (OR = 3.34, 95% CI: 1.84–6.07; P<0.0001, overall survival (HR = 0.72, 95% CI: 0.58–0.89; P=0.002, and 1-year survival rate (OR = 2.43, 95% CI: 1.51–3.91; P=0.0002. In adverse events (III-IV, statistically significant differences were not found, except for rash (OR = 7.96, 95% CI: 2.02–31.34; P=0.003 and myelosuppression (OR = 0.19, 95% CI: 0.07–0.51; P=0.0010. Conclusions. WBRT plus gefitinib/erlotinib was superior to WBRT alone and well tolerated in patients with BM from NSCLC.

  19. Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients With Breast Cancer and Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Sperduto, Paul W., E-mail: psperduto@mropa.com [University of Minnesota Gamma Knife, Minneapolis Radiation Oncology, Minneapolis, MN (United States); Kased, Norbert [Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA (United States); Roberge, David [Radiation Oncology, McGill University Health Center, Montreal, QC (Canada); Xu Zhiyuan [Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Shanley, Ryan [Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Luo, Xianghua [Masonic Cancer Center, University of Minnesota, Minneapolis, MN (United States); Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN (United States); Sneed, Penny K. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, CA (United States); Chao, Samuel T. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Weil, Robert J. [Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Suh, John [Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Bhatt, Amit [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Jensen, Ashley W.; Brown, Paul D. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Shih, Helen A. [Massachusetts General Hospital, Department of Radiation Oncology, Harvard Medical School, Boston, MA (United States); Kirkpatrick, John [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Gaspar, Laurie E. [Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO (United States); Fiveash, John B. [Radiation Oncology, University of Alabama Medical Center at Birmingham, Birmingham, AL (United States); and others

    2012-04-01

    Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

  20. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  1. A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Larsen, Pia Bükmann; Kümler, Iben; Nielsen, Dorte Lisbet

    2013-01-01

    Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies in the treatm......, it is still not evident which HER2-targeting agent should be preferred when brain metastases occur. The choice of chemotherapy to accompany the blockade is not obvious and we do not know if dual is better than single blockade. Further clinical trials are urgently needed....

  2. Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study.

    Science.gov (United States)

    Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

    2016-01-01

    The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects. NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software. Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (Pbrain signal transduction pathways, and the hypometabolism regions (the left superior parietal lobule, bilateral inferior parietal lobule and left fusiform gyrus) lied in dorsal attention network and visuospatial function areas. The changes of brain glucose metabolism exist in NSCLC patients prior to oncotherapy, which might be attributed to lung-cancer related visceral sympathetic activation and decrease of dorsal attention network function.

  3. SFRO booklets - The radiotherapy of cancers: of anal canal (Anus), brain, mediastinum, pancreas, lung, prostate, rectum, breast, upper aero-digestive tract (ENT cancers), cervix, endometrium (cervical cancers), and bladder for a better understanding of radiotherapy, sarcoma radiotherapy - To better understand your treatment

    International Nuclear Information System (INIS)

    Leroy, Thomas; Mornex, Francoise; Peiffert, Didier; Thariat, Juliette; Faivre, Jean-Christophe; Huguet, Florence; Vendrely, Veronique; Barillot, Isabelle; Janoray, Guillaume; Bibault, Jean-Emmanuel; Antoni, Delphine; Crehange, Gilles; Meillan, Nicolas; Pichon, Baptiste; Biau, Julian; Pointreau, Yoann; Mirabel, Xavier; Leysalle, Axel; Claren, Audrey; Cartier, Lysian; Chand, Mari-Eve; Jacob, Julian; Renard-Oldrini, Sophie; Le Pechoux, Cecile; Ducassou, Anne; Moureau-Zabotto, Laurence; Lagrange, Jean Leon; Molina, Sarah

    2016-07-01

    This document gathers several booklets which, for different types of cancers, propose information regarding the anatomy and location of the cancer, its diagnosis, possible treatments, secondary effects during treatment, some practical advices, issues related to the post-treatment period, associations and other resources which can be useful for patient information, and a glossary of the main terms used for this cancer and its treatment. Cancer types are anal canal (Anus), brain, mediastinum, pancreas, lung, prostate, rectum, breast, upper aero-digestive tract (ENT cancers), cervix, endometrium (cervical cancers), and bladder cancers

  4. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M., E-mail: lhalasz@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan [Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2013-02-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  5. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    International Nuclear Information System (INIS)

    Halasz, Lia M.; Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan; Punglia, Rinaa S.

    2013-01-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  6. Controlling micro- and nano-environment of tumor and stem cells for novel research and therapy of brain cancer

    Science.gov (United States)

    Smith, Christopher Lloyd

    The use of modern technologies in cancer research has engendered a great deal of excitement. Many of these advanced approaches involve in-depth mathematical analyses of the inner working of cells, via genomic and proteomic analyses. However these techniques may not be ideal for the study of complex cell phenotypes and behaviors. This dissertation explores cancer and potential therapies through phenotypic analysis of cell behaviors, an alternative approach. We employ this experimental framework to study brain cancer (glioma), a particularly formidable example of this diverse ailment. Through the application of micro- and nanotechnology, we carefully control the surrounding environments of cells to understand their responses to various cues and to manipulate their behaviors. Subsequently we obtain clinically relevant information that allows better understanding of glioma, and enhancement of potential therapies. We first aim to address brain tumor dispersal, through analysis of cell migration. Utilizing nanometer-scale topographic models of the extracellular matrix, we study the migratory response of glioma cells to various stimuli in vitro. Second, we implement knowledge gained from these investigations to define characteristics of tumor progression in patients, and to develop treatments inhibiting cell migration. Next we use microfluidic and nanotopographic models to study the behaviors of stem cells in vitro. Here we attempt to improve their abilities to deliver therapeutic proteins to cancer, an innovative treatment approach. We analyze the multi-step process by which adipose-derived stem cells naturally home to tumor sites, and identify numerous environmental perturbations to enhance this behavior. Finally, we attempt to demonstrate that these cell culture-based manipulations can enhance the localization of adipose stem cells to glioma in vivo using animal models. Throughout this work we utilize environmental cues to analyze and induce particular behaviors in

  7. Modelling the gluon propagator

    Energy Technology Data Exchange (ETDEWEB)

    Leinweber, D.B.; Parrinello, C.; Skullerud, J.I.; Williams, A.G

    1999-03-01

    Scaling of the Landau gauge gluon propagator calculated at {beta} = 6.0 and at {beta} = 6.2 is demonstrated. A variety of functional forms for the gluon propagator calculated on a large (32{sup 3} x 64) lattice at {beta} = 6.0 are investigated.

  8. Sound propagation in cities

    NARCIS (Netherlands)

    Salomons, E.; Polinder, H.; Lohman, W.; Zhou, H.; Borst, H.

    2009-01-01

    A new engineering model for sound propagation in cities is presented. The model is based on numerical and experimental studies of sound propagation between street canyons. Multiple reflections in the source canyon and the receiver canyon are taken into account in an efficient way, while weak

  9. Predictors of quality of life and survival following Gamma Knife surgery for lung cancer brain metastases: a prospective study.

    Science.gov (United States)

    Bragstad, Sidsel; Flatebø, Marianne; Natvig, Gerd Karin; Eide, Geir Egil; Skeie, Geir Olve; Behbahani, Maziar; Pedersen, Paal-Henning; Enger, Per Øyvind; Skeie, Bente Sandvei

    2017-08-18

    OBJECTIVE Lung cancer (LC) patients who develop brain metastases (BMs) have a poor prognosis. Estimations of survival and risk of treatment-related deterioration in quality of life (QOL) are important when deciding on treatment. Although we know of several prognostic factors for LC patients with BMs, the role of QOL has not been established. Authors of this study set out to evaluate changes in QOL following Gamma Knife surgery (GKS) for BMs in LC patients and QOL as a prognostic factor for survival. METHODS Forty-four of 48 consecutive LC patients with BMs underwent GKS in the period from May 2010 to September 2011, and their QOL was prospectively assessed before and 1, 3, 6, 9, and 12 months after GKS by using the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire. A mixed linear regression model was used to identify potential predictive factors for QOL and to assess the effect of GKS and the disease course on QOL at follow-up. RESULTS Mean QOL as measured by the brain cancer subscale (BRCS) of the FACT-BR remained stable from baseline (score 53.0) up to 12 months post-GKS (57.1; p = 0.624). The BRCS score improved for 32 patients (72.3%) with a total BM volume ≤ 5 cm 3 . Mean improvement in these patients was 0.45 points each month of follow-up, compared to a decline of 0.50 points each month despite GKS treatment in patients with BM volumes > 5 cm 3 (p = 0.04). Asymptomatic BMs (p = 0.01), a lower recursive partitioning analysis (RPA) classification (p = 0.04), and a higher Karnofsky Performance Scale (KPS) score (p Knife surgery is a safe and effective therapeutic modality that improves QOL for LC patients with a BM volume ≤ 5 cm 3 at treatment. Careful follow-up and salvage therapy on demand seem to prevent worsening of QOL due to relapse of BMs.

  10. Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

    International Nuclear Information System (INIS)

    Bubb, Robbin S.; Komaki, Ritsuko; Hachiya, Tsutomu; Milas, Ivan; Ro, Jae Y.; Langford, Lauren; Sawaya, Raymond; Putnam, Joe B.; Allen, Pamela; Cox, James D.; McDonnell, Timothy J.; Brock, William; Hong, Waun K.; Roth, Jack A.; Milas, Luka

    2002-01-01

    Purpose: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar. Methods and Materials: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis. Results: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p=0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p=0.04), and these patients had a higher rate of nonbrain distant metastases (p=0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p=0.01). There was a positive correlation in the expression of Ki-67 (p=0.02) (r 2 =0.1608), as well as p53 (p 2 =0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive. Conclusion: Differences in biomarker expression between the

  11. Problem Solving and Emotional Distress Among Brain and Breast Cancer Survivors

    Science.gov (United States)

    2007-03-30

    with cancer and their families. Cancer, 74, 2071-2078. Lazarus , R. S., & Folkman , S. (1984). Stress, appraisal, and coping. New York: Springer...being able to access post-treatment rehabilitative care (Eversley et al., 2005). Social Problem Solving Lazarus and Folkman’s stress appraisal...International Neuropsychological Sociology, 9(7), 967-982. Archibald, Y . M., Lunn, D., Ruttan, L. A., MacDonald, D. R., Del Maestro, R. F., Barr, H

  12. Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

    NARCIS (Netherlands)

    A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

    2011-01-01

    textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive

  13. Outcomes of social support programs in brain cancer survivors in an Australian community cohort: a prospective study

    Directory of Open Access Journals (Sweden)

    Khan F

    2013-03-01

    Full Text Available This study evaluated the impact of social support programs on improving cancer related disability, neuro-cognitive dysfunction and enhancing participation (quality of life (QoL, social reintegration in brain tumour (BT survivors. Participants (n=43 were recruited prospectively following definitive treatment in the community. Each BT survivor received an individualised social support program which comprised: face-to-face interview for education/counselling plus peer support program or community education/counselling sessions. The assessments were at baseline (T1, 6-week (T2 and 6-month (T3 post-intervention using validated questionnaires: depression anxiety stress scale (DASS, functional independence measure (FIM, perceived impact problem profile (PIPP, cancer rehabilitation evaluation system–short form (CARES-SF, a cancer survivor unmet needs measure (CaSUN, McGill quality of life questionnaire (MQOL and Brief COPE. Participants’ mean age was 53 years (range 31–72 years, the majority were female (72%; median time since BT diagnosis was 2.3 years and almost half (47% had high grade tumours. At T2, participants reported higher emotional well-being (DASS ‘anxiety’ and ‘stress’ subscales, p<0.05; FIM ‘cognition’ subscale, p<0.01, improved function (FIM ‘motor’ subscale, p<0.01 and higher QoL (CARES-SF ‘global’ score, p<0.05; MQOL ‘physical symptom’ subscale, p<0.05. At the T3 follow-up, most of these effects were maintained. The intervention effect for BT specific coping strategies emerged for the Brief COPE ‘self-distraction’ and ‘behavioural disengagement’ domains, (p<0.05 for both. There were no adverse effects reported. A post-treatment social support program can improve physical and cognitive function and enhancing overall QoL of BT survivors. Social support programs need further evaluation and should be encouraged by clinicians within cancer rehabilitative services.

  14. The role of brain/behavioural systems in prediction of quality of life and coping strategies in cancer patients

    Directory of Open Access Journals (Sweden)

    Shala Jangi Goujeh Biglou

    2014-03-01

    Full Text Available Background: It seems that individual differences in personality characteristics are implicated in the incidence and progress of physical diseases and socio-psychological consequences. However, there are a few studies about the role of personality in the prediction of socio-psychological consequences of cancer. The aim of this research was to survey the role of personality in the prediction of socio-psychosocial factors: quality of life and coping strategies. Methods: This research was a descriptive-correlational study in which the sample included fifty cancer patients who were selected through convenience sampling method. To assess the personality differences, quality of life and coping strategies, the Carver and White (1994 BIS/BAS Scales, SF-12 Health Survey and Coping Inventory for Stressful Situation (CISS were used, respectively. The data were analysed by SPSS software using Pearson correlation coefficient and stepwise regression. Results: The findings showed that Both BIS and BAS systems could predict the quality of life (P<0.001, BIS system could explain the emotion-oriented coping strategy (P<0.05 and avoidance-oriented coping stratesy (P<0.01 and BAS system could explain the problem-oriented coping strategy (P<0.001. Conclusion: The findings of this study showed that brain/behavioural systems can predict the quality of life and coping strategies in cancer patients. The identification of these systems in cancer patients can help recognize the persons that are under the risk of poor quality of life or have a higher chance of using inconsistent coping strategies, and execute preventive measures about them.

  15. Radiotherapy for asymptomatic brain metastasis in epidermal growth factor receptor mutant non-small cell lung cancer without prior tyrosine kinase inhibitors treatment: a retrospective clinical study

    International Nuclear Information System (INIS)

    Liu, SongRan; Qiu, Bo; Chen, LiKun; Wang, Fang; Liang, Ying; Cai, PeiQiang; Zhang, Li; Chen, ZhaoLin; Liu, ShiLiang; Liu, MengZhong; Liu, Hui

    2015-01-01

    Non-small cell lung cancer (NSCLC) with brain metastasis (BM) harboring an epidermal growth factor receptor (EGFR) mutation shows good response to tyrosine kinase inhibitors (TKIs). This study is to assess the appropriate timing of brain radiotherapy (RT) for asymptomatic BM in EGFR mutant NSCLC patients. There were 628 patients diagnosed with EGFR mutant NSCLC between October 2005 and December 2011. Treatment outcomes had been retrospectively evaluated in 96 patients with asymptomatic BM without prior TKI treatment. 39 patients received first-line brain RT, 23 patients received delayed brain RT, and 34 patients did not receive brain RT. With a median follow-up of 26 months, the 2-year OS was 40.6 %. Univariate analyses revealed that ECOG performance status (p = 0.006), other distant metastases (p = 0.002) and first line systemic treatment (p = 0.032) were significantly associated with overall survival (OS). Multivariate analyses revealed that other sites of distant metastases (p = 0.030) were prognostic factor. The timing of brain RT was not significantly related to OS (p = 0.246). The 2-year BM progression-free survival (PFS) was 26.9 %. Brain RT as first-line therapy failed to demonstrate a significant association with BM PFS (p = 0.643). First-line brain RT failed to improve long-term survival in TKI-naïve EGFR mutant NSCLC patients with asymptomatic BM. Prospective studies are needed to validate these clinical findings

  16. Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy

    NARCIS (Netherlands)

    Koppelmans, Vincent; de Ruiter, Michiel B.; van der Lijn, Fedde; Boogerd, Willem; Seynaeve, Caroline; van der Lugt, Aad; Vrooman, Henri; Niessen, Wiro J.; Breteler, Monique M. B.; Schagen, Sanne B.

    2012-01-01

    A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. Results of these studies indicate local gray matter volume decrease and an increase in white matter

  17. Preliminary analysis of proton magnetic resonance 1D spectra of cerebrospinal fluid and brain cancer extracts

    International Nuclear Information System (INIS)

    Toczylowska, B.; Jozwik, A.; Kierul, K.; Matysiak, Z.; Sidor, M.; Wojcik, J.

    1999-01-01

    In series of cerebrospinal fluid samples from 25 patients proton spectra of magnetic resonance were measured. The spectra were measured also for series of brain tumor tissue extracts received from another 25 patients. This paper presents an attempt to apply statistical methods of image recognition for spectra analysis of the two measured series

  18. Brain Connectivity and Neuropsychological Functioning in Recently Treated Testicular Cancer Patients

    DEFF Research Database (Denmark)

    Amidi, Ali; Agerbæk, Mads; Leemans, Alexander

    neuropsychological functioning. Cisplatin-based chemotherapy has well-known neurotoxic side effects and neural populations such as progenitor cells, oligodendrocytes, and hippocampal neurons are exceptionally vulnerable to even small concentrations of cisplatin. The aim of the present study was to investigate...... the possible adverse effects of BEP on brain white matter connectivity and neuropsychological functioning in recently treated men with TC....

  19. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline.

    Science.gov (United States)

    Ramakrishna, Naren; Temin, Sarah; Chandarlapaty, Sarat; Crews, Jennie R; Davidson, Nancy E; Esteva, Francisco J; Giordano, Sharon H; Gonzalez-Angulo, Ana M; Kirshner, Jeffrey J; Krop, Ian; Levinson, Jennifer; Modi, Shanu; Patt, Debra A; Perez, Edith A; Perlmutter, Jane; Winer, Eric P; Lin, Nancy U

    2014-07-01

    To provide formal expert consensus-based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus-based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations. No studies or existing guidelines met the systematic review criteria; therefore, ASCO conducted a formal expert consensus-based process. Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. Clinicians should not perform routine magnetic resonance imaging (MRI) to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. © 2014 by American Society of Clinical Oncology.

  20. Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumor propagation in vitro.

    Science.gov (United States)

    Henriquez, Nico V; Forshew, Tim; Tatevossian, Ruth; Ellis, Matthew; Richard-Loendt, Angela; Rogers, Hazel; Jacques, Thomas S; Reitboeck, Pablo Garcia; Pearce, Kerra; Sheer, Denise; Grundy, Richard G; Brandner, Sebastian

    2013-09-15

    Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor. ©2013 AACR.

  1. Mobile phones, cordless phones and rates of brain tumors in different age groups in the Swedish National Inpatient Register and the Swedish Cancer Register during 1998-2015.

    Directory of Open Access Journals (Sweden)

    Lennart Hardell

    Full Text Available We used the Swedish Inpatient Register (IPR to analyze rates of brain tumors of unknown type (D43 during 1998-2015. Average Annual Percentage Change (AAPC per 100,000 increased with +2.06%, 95% confidence interval (CI +1.27, +2.86% in both genders combined. A joinpoint was found in 2007 with Annual Percentage Change (APC 1998-2007 of +0.16%, 95% CI -0.94, +1.28%, and 2007-2015 of +4.24%, 95% CI +2.87, +5.63%. Highest AAPC was found in the age group 20-39 years. In the Swedish Cancer Register the age-standardized incidence rate per 100,000 increased for brain tumors, ICD-code 193.0, during 1998-2015 with AAPC in men +0.49%, 95% CI +0.05, +0.94%, and in women +0.33%, 95% CI -0.29, +0.45%. The cases with brain tumor of unknown type lack morphological examination. Brain tumor diagnosis was based on cytology/histopathology in 83% for men and in 87% for women in 1980. This frequency increased to 90% in men and 88% in women in 2015. During the same time period CT and MRI imaging techniques were introduced and morphology is not always necessary for diagnosis. If all brain tumors based on clinical diagnosis with CT or MRI had been reported to the Cancer Register the frequency of diagnoses based on cytology/histology would have decreased in the register. The results indicate underreporting of brain tumor cases to the Cancer Register. The real incidence would be higher. Thus, incidence trends based on the Cancer Register should be used with caution. Use of wireless phones should be considered in relation to the change of incidence rates.

  2. Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

    Directory of Open Access Journals (Sweden)

    Anja Kafka

    2014-06-01

    Full Text Available The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1, Dishevelled-3 (DVL3, E-cadherin (CDH1 and beta-catenin (CTNNB1. Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR/loss of heterozygosity (LOH. Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p = 0.0001. Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC were significantly associated to CDH1 LOH (p = 0.001. Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

  3. SU-E-J-90: MRI-Based Treatment Simulation and Patient Setup for Radiation Therapy of Brain Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Y [UCLA School of Medicine, Los Angeles, AA (United States); Cao, M; Han, F; Santhanam, A; Neylon, J; Gomez, C; Kaprealian, T; Sheng, K; Agazaryan, N; Low, D; Hu, P

    2014-06-01

    Purpose: Traditional radiation therapy of cancer is heavily dependent on CT. CT provides excellent depiction of the bones but lacks good soft tissue contrast, which makes contouring difficult. Often, MRIs are fused with CT to take advantage of its superior soft tissue contrast. Such an approach has drawbacks. It is desirable to perform treatment simulation entirely based on MRI. To achieve MR-based simulation for radiation therapy, bone imaging is an important challenge because of the low MR signal intensity from bone due to its ultra-short T2 and T1, which presents difficulty for both dose calculation and patient setup in terms of digitally reconstructed radiograph (DRR) generation. Current solutions will either require manual bone contouring or multiple MR scans. We present a technique to generate DRR using MRI with an Ultra Short Echo Time (UTE) sequence which is applicable to both OBI and ExacTrac 2D patient setup. Methods: Seven brain cancer patients were scanned at 1.5 Tesla using a radial UTE sequence. The sequence acquires two images at two different echo times. The two images were processed using in-house software. The resultant bone images were subsequently loaded into commercial systems to generate DRRs. Simulation and patient clinical on-board images were used to evaluate 2D patient setup with MRI-DRRs. Results: The majority bones are well visualized in all patients. The fused image of patient CT with the MR bone image demonstrates the accuracy of automatic bone identification using our technique. The generated DRR is of good quality. Accuracy of 2D patient setup by using MRI-DRR is comparable to CT-based 2D patient setup. Conclusion: This study shows the potential of DRR generation with single MR sequence. Further work will be needed on MR sequence development and post-processing procedure to achieve robust MR bone imaging for other human sites in addition to brain.

  4. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  5. Cancer: brain-regulated biphasic stress response induces cell growth or cell death to adapt to psychological stressors.

    Science.gov (United States)

    Thomas, Charles; Bhatia, Shruti

    2014-01-01

    According to Indian Vedic philosophy, a human being contains 3 major bodies: (1) the matter body--brain, organs, and senses; (2) the mental body--mind, individual consciousness, intellect, and ego; and (3) the soul or causal body--universal consciousness. The third, which is located in the heart according to all spiritual traditions and recent scientific literature, can be seen as the information body that contains all memories. The mental body, which can interface with the matter and information bodies, can be seen as a field of immaterial energy that can carry, regulate, and strengthen all information (eg, thoughts or emotions) both positively and negatively. This body of information may store ancestral and/or autobiographical memories: unconscious memories from inner traumas--inner information (Ii) or samskaras in Vedic philosophy--and conscious memories from outer traumas--outer information (Io). These conscious and unconscious memories can be seen as potential psychological stressors. Resonance between Ii and Io may induce active conflicts if resistance occurs in the mental body; this conflict may cause specific metabolic activity in the brain and a stress response in the physical body, which permits adjustment to psychological stressors. The brainregulated stress response may be biphasic: cell death or growth induced by adrenergic molecular pathways during the conflict's unresolved phase and reversion to cell growth or death induced by cholinergic molecular pathways during the conflict's resolved phase. Case studies and data mining from PubMed suggest that this concept complies with the principles of holistic medicine and the scientific literature supporting its benefits. We suggest that the evolution of cancer can be seen as a biphasic stress response regulated by the brain to adapt to psychological stressors, which produce imbalance among the physical, mental, and information bodies.

  6. A Numerical Investigation of the Time Reversal Mirror Technique for Trans-skull Brain Cancer Ultrasound Surgery

    Directory of Open Access Journals (Sweden)

    H. Zahedmanesh

    2007-06-01

    Full Text Available Introduction: The medical applications of ultrasound on human brain are highly limited by the phase and amplitude aberrations induced by the heterogeneities of the skull. However, it has been shown that time reversing coupled with amplitude compensation can overcome these aberrations. In this work, a model for 2D simulation of the time reversal mirror technique is proposed to study the possibility of targeting any point within the brain without the need for craniotomy and to calculate the acoustic pressure field and the resulting temperature distribution within the skull and brain during a High Intensity Focused Ultrasound (HIFU transcranial therapy. Materials and Methods: To overcome the sensitivity of the wave pattern to the heterogeneous geometry of the skull, a real MRI derived 2D model is constructed. The model should include the real geometry of brain and skull. The model should also include the couplant medium which has the responsibility of coupling the transducer to the skull for the penetration of ultrasound. The clinical substance used as the couplant is water. The acoustic and thermal parameters are derived from the references. Next, the wave propagation through the skull is computed based on the Helmholtz equation, with a 2D finite element analysis. The acoustic simulation is combined with a 2D thermal diffusion analysis based on Pennes Bioheat equation and the temperature elevation inside the skull and brain is computed. The numerical simulations were performed using the FEMLAB 3.2 software on a PC having 8 GB RAM and a 2.4 MHz dual CPU. Results: It is seen that the ultrasonic waves are exactly focalized at the location where the hydrophone has been previously implanted. There is no penetration into the sinuses and the waves are reflected from their surface because of the high discrepancy between the speed of sound in bone and air.  Under the focal pressure of 2.5 MPa and after 4 seconds of sonication the temperature at the focus

  7. Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer.

    Science.gov (United States)

    Tsai, Yi-Fang; Tseng, Ling-Ming; Hsu, Chih-Yi; Yang, Muh-Hwa; Chiu, Jen-Hwey; Shyr, Yi-Ming

    2017-01-01

    There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples. The results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS. Our study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in

  8. Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

    Directory of Open Access Journals (Sweden)

    Poujol Sylvain

    2010-06-01

    Full Text Available Abstract Background Since 1999, patients presenting with brain metastases (BM from breast cancer (BC are treated in our institution with a carmustine (BCNU - methotrexate (MTX combination. We report here our clinical experience regarding this combination. Patients and Methods Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity. Results 50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5. Median number of cycles was 3 (1-20. There were 11 objective responses (23% [95%CI 12-37] among 48 evaluable patients. Median progression-free survival and overall survival (OS were 4.2 (95%CI: 2.8-5.3 and 6.9 (4.2-10.7 months respectively, with a one-year OS rate of 32% (20-46. Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1 and 0.96 (0.57-1.66 respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis. Conclusions This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.

  9. Database for propagation models

    Science.gov (United States)

    Kantak, Anil V.

    1991-07-01

    A propagation researcher or a systems engineer who intends to use the results of a propagation experiment is generally faced with various database tasks such as the selection of the computer software, the hardware, and the writing of the programs to pass the data through the models of interest. This task is repeated every time a new experiment is conducted or the same experiment is carried out at a different location generating different data. Thus the users of this data have to spend a considerable portion of their time learning how to implement the computer hardware and the software towards the desired end. This situation may be facilitated considerably if an easily accessible propagation database is created that has all the accepted (standardized) propagation phenomena models approved by the propagation research community. Also, the handling of data will become easier for the user. Such a database construction can only stimulate the growth of the propagation research it if is available to all the researchers, so that the results of the experiment conducted by one researcher can be examined independently by another, without different hardware and software being used. The database may be made flexible so that the researchers need not be confined only to the contents of the database. Another way in which the database may help the researchers is by the fact that they will not have to document the software and hardware tools used in their research since the propagation research community will know the database already. The following sections show a possible database construction, as well as properties of the database for the propagation research.

  10. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    Science.gov (United States)

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary.

  11. SU-F-303-12: Implementation of MR-Only Simulation for Brain Cancer: A Virtual Clinical Trial

    International Nuclear Information System (INIS)

    Glide-Hurst, C; Zheng, W; Kim, J; Wen, N; Chetty, I J

    2015-01-01

    Purpose: To perform a retrospective virtual clinical trial using an MR-only workflow for a variety of brain cancer cases by incorporating novel imaging sequences, tissue segmentation using phase images, and an innovative synthetic CT (synCT) solution. Methods: Ten patients (16 lesions) were evaluated using a 1.0T MR-SIM including UTE-DIXON imaging (TE = 0.144/3.4/6.9ms). Bone-enhanced images were generated from DIXON-water/fat and inverted UTE. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating intersection and Dice similarity coefficients (DSC) using CT-SIM as ground truth. SynCTs were generated using voxel-based weighted summation incorporating T2, FLAIR, UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized HU differences between synCT and CT-SIM. Dose was recalculated on synCTs; differences were quantified using planar gamma analysis (2%/2 mm dose difference/distance to agreement) at isocenter. Digitally reconstructed radiographs (DRRs) were compared. Results: On average, air maps intersected 80.8 ±5.5% (range: 71.8–88.8%) between MR-SIM and CT-SIM yielding DSCs of 0.78 ± 0.04 (range: 0.70–0.83). Whole-brain MAE between synCT and CT-SIM was 160.7±8.8 HU, with the largest uncertainty arising from bone (MAE = 423.3±33.2 HU). Gamma analysis revealed pass rates of 99.4 ± 0.04% between synCT and CT-SIM for the cohort. Dose volume histogram analysis revealed that synCT tended to yield slightly higher doses. Organs at risk such as the chiasm and optic nerves were most sensitive due to their proximities to air/bone interfaces. DRRs generated via synCT and CT-SIM were within clinical tolerances. Conclusion: Our approach for MR-only simulation for brain cancer treatment planning yielded clinically acceptable results relative to the CT-based benchmark. While slight dose differences were observed, reoptimization of treatment plans and improved image registration can address

  12. An Institutional Retrospective Analysis of 93 Patients with Brain Metastases from Breast Cancer: Treatment Outcomes, Diagnosis-Specific Prognostic Factors

    Directory of Open Access Journals (Sweden)

    Delphine Antoni

    2012-12-01

    Full Text Available To evaluate the prognostic factors and indexes of a series of 93 patients with breast cancer and brain metastases (BM in a single institution. Treatment outcomes were evaluated according to the major prognostic indexes (RPA, BSBM, GPA scores and breast cancer subtypes. Independent prognostic factors for overall survival (OS were identified. The median OS values according to GPA 0–1, 1.5–2, 2.5–3 and 3.5–4, were 4.5, 9.5, 14.2 and 19.1 months, respectively (p < 0.0001 and according to genetic subtypes, they were 5, 14.2, 16.5 and 17.1 months for basal-like, luminal A and B and HER, respectively (p = 0.04. Using multivariate analysis, we established a new grading system using the six factors that were identified as indicators of longer survival: age under 60 (p = 0.001, high KPS (p = 0.007, primary tumor control (p = 0.05, low number of extracranial metastases and BM (p = 0.01 and 0.0002, respectively and triple negative subtype (p = 0.002. Three groups with significantly different median survival times were identified: 4.1, 9.5 and 26.3 months, respectively (p < 0.0001. Our new grading system shows that prognostic indexes could be improved by using more levels of classification and confirms the strength of biological prognostic factors.

  13. Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

    International Nuclear Information System (INIS)

    Gong Linlin; Wang, Q.I.; Zhao Lujun; Yuan Zhiyong; Li Ruijian; Wang Ping

    2013-01-01

    Purpose: The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed. Methods and Materials: One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases. Results: The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy. Conclusions: Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

  14. Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non-Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial

    International Nuclear Information System (INIS)

    Mehta, Minesh P.; Shapiro, William R.; Phan, See C.; Gervais, Radj; Carrie, Christian; Chabot, Pierre; Patchell, Roy A.; Glantz, Michael J.; Recht, Lawrence; Langer, Corey; Sur, Ranjan K.; Roa, Wilson H.; Mahe, Marc A.; Fortin, Andre; Nieder, Carsten; Meyers, Christina A.; Smith, Jennifer A.; Miller, Richard A.; Renschler, Markus F.

    2009-01-01

    Purpose: To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. Methods and Materials: In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Results: Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. Conclusion: In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable

  15. Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1).

    Science.gov (United States)

    Kort, Anita; Durmus, Selvi; Sparidans, Rolf W; Wagenaar, Els; Beijnen, Jos H; Schinkel, Alfred H

    2015-07-01

    Regorafenib is a novel multikinase inhibitor, currently approved for the treatment of metastasized colorectal cancer and advanced gastrointestinal stromal tumors. We investigated whether regorafenib is a substrate for the multidrug efflux transporters ABCG2 and ABCB1 and whether oral availability, brain and testis accumulation of regorafenib and its active metabolites are influenced by these transporters. We used in vitro transport assays to assess human (h)ABCB1- or hABCG2- or murine (m)Abcg2-mediated active transport at high and low concentrations of regorafenib. To study the single and combined roles of Abcg2 and Abcb1a/1b in oral regorafenib disposition and the impact of Cyp3a-mediated metabolism, we used appropriate knockout mouse strains. Regorafenib was transported well by mAbcg2 and hABCG2 and modestly by hABCB1 in vitro. Abcg2 and to a lesser extent Abcb1a/1b limited brain and testis accumulation of regorafenib and metabolite M2 (brain only) in mice. Regorafenib oral availability was not increased in Abcg2(-/-);Abcb1a/1b(-/-) mice. Up till 2 h, metabolite M5 was undetectable in plasma and organs. Brain and testis accumulation of regorafenib and brain accumulation of metabolite M2 are restricted by Abcg2 and Abcb1a/1b. Inhibition of these transporters may be of clinical relevance for patients with brain (micro)metastases positioned behind an intact blood-brain barrier.

  16. Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

    Science.gov (United States)

    2010-10-01

    Barry AM, MacKenzie LT, Mikulis DJ, Palmieri D, Bronder JL, Steeg PS, Yoneda T, MacDonald IC, Chambers AF, Rutt BK, Foster PJ: In vivo MRI of cancer...Fransisco, CA). Caspase-3 was immunoprecipitated from cell lysates in the presence of protease inhibitors (Roche complete Mini tablet , EDTA-free and 2

  17. Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression.

    Science.gov (United States)

    Jehn, C F; Becker, B; Flath, B; Nogai, H; Vuong, L; Schmid, P; Lüftner, D

    2015-10-15

    Increased IL-6 and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. The objective was to assess the influence of BDNF and IL-6 on cognitive function and depression in patients with cancer. Serum BDNF and plasma IL-6 were measured in patients with metastatic cancer. Diagnosis of depression was established according to DSM-IV criteria. Cognitive function was assessed by the Verbal Learning and Memory Test (VLMT). A total of 59 patients were recruited in this study. Only IL-6 levels were significantly elevated in patients with clinical depression (35.7 vs. 6.9 pg/ml; pBDNF levels (p=0.16). Patients with clinical depression showed significant impairment of short-term memory (STM) (24.4 vs. 37.5; p=0.01), but not of long-term memory (LTM) (3.9 vs. 2.8; p=0.3). STM was dependent on the level of BDNF and younger age (b=0.60; p=0.001; b= -0.63; p=0.003, respectively). IL-6 was not only strongly associated with depression, but was an independent predictor of BDNF level as well (b= -0.50; p=0.01). LTM was associated only with a good KPS (b=0.47; p=0.037). Hemoglobin levels and the prior number of chemotherapy lines were not predictive of memory performance. Low BDNF is associated with cognitive impairment, STM, in patients with cancer, however no influence on depression could be found. IL-6 is strongly associated with depression and an independent predictor of BDNF levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Metastasis of Pregnancy-Associated Breast Cancer (Suspected to Be Hereditary Breast and Ovarian Cancer to the Brain, Diagnosed at 18 Weeks’ Gestation: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Tomohiro Okuda

    2016-01-01

    Full Text Available We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC. A 35-year-old woman (gravida 2, para 0-1-0-1 underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]. The patient refused adjuvant therapy because of the risk of infertility. After 4 years, she became pregnant naturally. At 18 weeks’ gestation, she experienced aphasia and dyslexia due to brain metastasis. The pregnancy was terminated at 21 weeks’ gestation after thorough counseling. Her family history, young-onset disease, and histopathological findings suggested HBOC. She declined genetic testing for BRCA1/2, though genetic counseling was provided. In cases of pregnancy-related breast cancer, consideration must be given to whether the pregnancy should be continued and to posttreatment fertility. HBOC should also be considered. Genetic counseling should be provided and the patient should be checked for the BRCA mutation, as it is meaningful for the future of any potential children. Genetic counseling should be provided even if the cancer is advanced or recurrent.

  19. A Comparative Study of Personality Traits and Brain Behavioral activation Systems and Inhibition in Women with Cancer, Cardiovascular Diseases and Normal Women

    Directory of Open Access Journals (Sweden)

    Sohrab Amiri

    2017-04-01

    Full Text Available Background and Objectives: Chronic diseases are among the most important causes of mortality. The aim of the current study was to compare the Brain/behavioral systems and Dark personality traits of Machiavellianism, narcissism, and psychopathy in cancer, cardiovascular female patients and normal women. Methods: In this study, 60 individuals were selected using available sampling in three groups of 20 cancer patients, cardiovascular patients, and normal subjects. Finally, in order to test the goals and hypotheses of the research, the participants were studied based on Behavioral Activation System and Behavioral Inhibition System, and Dark Triad traits. Data analysis was performed using multivariate ANOVA, univariate ANOVA and post-hoc tests. Results: In this study, there was a significant difference among the three groups in Brain/behavioral systems and traits of Machiavellianism, narcissism, and psychopathy, so that the cancer and cardiovascular patients had higher score in dark triad traits compared to normal individuals. Also, the cancer patients had a higher score in Machiavellianism trait compared to the cardiovascular patients. In the brain/behavioral systems, cardiovascular and cancer patients had higher score in behavioral inhibition system (BIS component compared to the normal individuals in the of behavioral inhibition system (BIS. Also, in the reward seeking subscale of behavioral activation system (BAS-f, cancer patients had a higher score compared to cardiovascular patients, which was significantly different. Conclusion: The results of this study indicated that cancer and cardiovascular patients, have greater extent of social disgusting personality traits as well as behavioral inhibition system as anxiety-predisposing factor.

  20. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  1. The use and impact of quality of life assessment tools in clinical care settings for cancer patients, with a particular emphasis on brain cancer: insights from a systematic review and stakeholder consultations.

    Science.gov (United States)

    King, Sarah; Exley, Josephine; Parks, Sarah; Ball, Sarah; Bienkowska-Gibbs, Teresa; MacLure, Calum; Harte, Emma; Stewart, Katherine; Larkin, Jody; Bottomley, Andrew; Marjanovic, Sonja

    2016-09-01

    Patient-reported data are playing an increasing role in health care. In oncology, data from quality of life (QoL) assessment tools may be particularly important for those with limited survival prospects, where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting, particularly those with brain cancer. It also examines facilitators and challenges, and provides implications for policy and practice. We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit. The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient-physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address. Our findings suggest that the use of QoL tools in cancer patients may improve patient-physician communication and have the potential to improve care, but the tools are not currently widely used in clinical practice (in brain cancer nor some other cancer contexts) although they are in clinical trials. There is a need for further research and stakeholder engagement on how QoL tools can achieve most impact across cancer and patient contexts. There is also a need for policy, health professional, research and patient communities to strengthen information exchange and debate, support awareness raising and provide training on tool design, use and interpretation.

  2. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial.

    Science.gov (United States)

    Yang, Jin-Ji; Zhou, Caicun; Huang, Yisheng; Feng, Jifeng; Lu, Sun; Song, Yong; Huang, Cheng; Wu, Gang; Zhang, Li; Cheng, Ying; Hu, Chengping; Chen, Gongyan; Zhang, Li; Liu, Xiaoqing; Yan, Hong Hong; Tan, Fen Lai; Zhong, Wenzhao; Wu, Yi-Long

    2017-09-01

    For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China. Eligible participants were patients with NSCLC with EGFR mutations, who were naive to treatment with EGFR-TKIs or radiotherapy, and had at least three metastatic brain lesions. We randomly assigned participants (1:1) to either icotinib 125 mg orally (three times per day) or WBI (30 Gy in ten fractions of 3 Gy) plus concurrent or sequential chemotherapy for 4-6 cycles, until unacceptable adverse events or intracranial disease progression occurred. The randomisation was done by the Chinese Thoracic Oncology Group with a web-based allocation system applying the Pocock and Simon minimisation method; groups were stratified by EGFR gene mutation status, treatment line (first line or second line), brain metastases only versus both intracranial and extracranial metastases, and presence or absence of symptoms of intracranial hypertension. Clinicians and patients were not masked to treatment assignment, but individuals involved in the data analysis did not participate in the treatments and were thus masked to allocation. Patients receiving icotinib who had intracranial progression only were switched to WBI plus either icotinib or chemotherapy until further progression; those receiving icotinib who had extracranial progression only were switched to icotinib plus chemotherapy. Patients receiving WBI who progressed were switched to icotinib until further progression. Icotinib could be continued beyond progression if a clinical benefit

  3. Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases.

    Science.gov (United States)

    Yamamoto, Masaaki; Serizawa, Toru; Sato, Yasunori; Kawabe, Takuya; Higuchi, Yoshinori; Nagano, Osamu; Barfod, Bierta E; Ono, Junichi; Kasuya, Hidetoshi; Urakawa, Yoichi

    2013-02-01

    We tested the validity of two prognostic indices for stereotactic radiosurgically (SRS)-treated patients with brain metastases (BMs) from five major original cancer categories. The two indices are Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) and our Modified Recursive Partitioning Analysis (RPA). Forty-six hundred and eight BM patients underwent gamma knife SRS during the 1998-2011 period. Primary cancer categories were non-small cell lung cancer (NSCLC, 2827 patients), small cell lung cancer (SCLC, 460), gastro-intestinal cancer (GIC, 582), breast cancer (BC, 547) and renal cell cancer (RCC, 192). There were statistically significant survival differences among patients stratified into four groups based on the DS-GPA systems (p failed to reach statistical significance with this system. There were, however, statistically significant MST differences (p < 0.001) among the three groups without overlapping of 95 % CIs between any two pairs of groups with the Modified RPA system in all five categories. The DS-GPA system is applicable to our set of patients with NSCLC only. However, the Modified RPA system was shown to be applicable to patients with five primary cancer categories. This index should be considered when designing future clinical trials involving BM patients.

  4. Mobile phone use and risk of brain neoplasms and other cancers: prospective study.

    Science.gov (United States)

    Benson, Victoria S; Pirie, Kirstin; Schüz, Joachim; Reeves, Gillian K; Beral, Valerie; Green, Jane

    2013-06-01

    Results from some retrospective studies suggest a possible increased risk of glioma and acoustic neuroma in users of mobile phones. The relation between mobile phone use and incidence of intracranial central nervous system (CNS) tumours and other cancers was examined in 791,710 middle-aged women in a UK prospective cohort, the Million Women Study. Cox regression models were used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Women reported mobile phone use in 1999 to 2005 and again in 2009. During 7 years' follow-up, 51,680 incident invasive cancers and 1,261 incident intracranial CNS tumours occurred. Risk among ever vs never users of mobile phones was not increased for all intracranial CNS tumours (RR = 1.01, 95% CI = 0.90-1.14, P = 0.82), for specified CNS tumour types nor for cancer at 18 other specified sites. For long-term users compared with never users, there was no appreciable association for glioma (10+ years: RR = 0.78, 95% CI = 0.55-1.10, P = 0.16) or meningioma (10+ years: RR = 1.10, 95% CI = 0.66-1.84, P = 0.71). For acoustic neuroma, there was an increase in risk with long term use vs never use (10+ years: RR = 2.46, 95% CI = 1.07-5.64, P = 0.03), the risk increasing with duration of use (trend among users, P = 0.03). In this large prospective study, mobile phone use was not associated with increased incidence of glioma, meningioma or non-CNS cancers.

  5. Delivery of Nanotethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

    Science.gov (United States)

    2016-12-01

    transport in tissue based on the acquired medical images of an individual patient (CT and MRI ) with sufficient accuracy and at accelerated rates for...anatomical and physiological information provided by imaging modalities such as CT, Ultrasound, PET, MRI , etc. In the current work we have developed a...capability to develop and optimize treatment plans for optimal release of pharmaceuticals in the treatment of cancer. Future work will test and

  6. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Harris, Sunit; Chan, Michael D.; Lovato, James F.; Ellis, Thomas L.; Tatter, Stephen B.; Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P.

    2012-01-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10–24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients’ ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

  7. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Sunit [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Chan, Michael D., E-mail: mchan@wfubmc.edu [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Lovato, James F. [Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University, Winston-Salem, North Carolina (United States); Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P. [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States)

    2012-05-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

  8. Hemoglobins, Hemorphins, and 11p15.5 Chromosomal Region in Cancer Biology and İmmunity with Special Emphasis for Brain Tumors.

    Science.gov (United States)

    Altinoz, Meric Adil; Elmaci, Ilhan; Ince, Bahri; Ozpinar, Aysel; Sav, Aydin Murat

    2016-05-01

    In systemic cancers, increased hemolysis leads to extracellular hemoglobin (HB), and experimental studies have shown its provoking role on tumor growth and metastasis. However, investigations have shown that HB chains presented by tumor vascular pericytes or serum protein complexes of HB could also induce antitumor immunity, which may be harnessed to treat refractory cancers and brain tumors. Mounting recent evidence shows that expression of HBs is not restricted to erythrocytes and that HBs exist in the cells of lung and kidney, in macrophages, and in neurons and glia of the central nervous system (CNS). HBs mediate coping with hypoxia and free radical stress in normal and tumor cells, and they are increased in certain tumors including breast, lung, colon, and squamous cell cancers. Recent studies showed HBs in meningioma, in the cyst fluid of craniopharyngioma, in the cerebrospinal fluid (CSF) of pediatric patients with posterior fossa tumors, and in glioblastoma cell lines. Hemorphins, abundant brain peptides formed via HB-chain cleavage, exert opioid activity and antiproliferative and immunomodifier effects. Hence mutations in HBs may modify brain tumorigenesis via influencing hemorphins and perturbing regulations of immune surveillance and cell growth in the neuroectodermal tissues. The β-globin gene cluster resides in the chromosome region 11p15.5, harboring important immunity genes and IGF2, H19, PHLDA2/TSSC3, TRIM3, and SLC22A18 genes associated with cancers and gliomas. 11p15.5 is a prominent region subject to epigenetic regulation. Thus the β-globin loci may exert haplotypal interactions with these. Some clues support this theory. It is well established that iron load induces liver cancer in thalassemia major; however iron load-independent associations also exist. Enhanced rates of hematologic malignancies are associated with HB Lepore, association of hemoglobin E with cholangiocarcinoma, and enhanced gastric cancer rates in the thalassemia trait. In

  9. Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

    International Nuclear Information System (INIS)

    Le Scodan, Romuald; Jouanneau, Ludivine; Massard, Christophe; Gutierrez, Maya; Kirova, Youlia; Cherel, Pascal; Gachet, Julie; Labib, Alain; Mouret-Fourme, Emmanuelle

    2011-01-01

    To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC). We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated. The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83). In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control

  10. Propagation of waves

    CERN Document Server

    David, P

    2013-01-01

    Propagation of Waves focuses on the wave propagation around the earth, which is influenced by its curvature, surface irregularities, and by passage through atmospheric layers that may be refracting, absorbing, or ionized. This book begins by outlining the behavior of waves in the various media and at their interfaces, which simplifies the basic phenomena, such as absorption, refraction, reflection, and interference. Applications to the case of the terrestrial sphere are also discussed as a natural generalization. Following the deliberation on the diffraction of the "ground? wave around the ear

  11. Concurrent radiotherapy and fotemustine for brain metastases of non small cell cancer of the lung

    International Nuclear Information System (INIS)

    Pignon, T.; Ruggieri, S.; Orabona, P.; Muracciole, X.; Juin, P.; Astoul, P.; Vialette, J.P.; Boutin, C.

    1994-01-01

    The radiotherapy is the most employed in the treatment of cerebral metastases, even if results are deceptive. The tests with chemotherapy are not better and the nitrosoureas remain the most employed drugs. The fotemustin is a new one which can give good results for bearing cerebral metastases patients's response. The associations radiotherapy and chemotherapy are developing to potentiate radiotherapy action but are still a little studied in the cases of cerebral metastases; that is why we choose to treat in an open study the patients bearers of cerebral metastases in lungs cancers with no little cells. 18 refs

  12. High-Resolution Longitudinal Screening with Magnetic Resonance Imaging in a Murine Brain Cancer Model

    Directory of Open Access Journals (Sweden)

    Nicholas A. Bock

    2003-11-01

    Full Text Available One of the main limitations of intracranial models of diseases is our present inability to monitor and evaluate the intracranial compartment noninvasively over time. Therefore, there is a growing need for imaging modalities that provide thorough neuropathological evaluations of xenograft and transgenic models of intracranial pathology. In this study, we have established protocols for multiple-mouse magnetic resonance imaging (MRI to follow the growth and behavior of intracranial xenografts of gliomas longitudinally. We successfully obtained weekly images on 16 mice for a total of 5 weeks on a 7-T multiple-mouse MRI. T2- and Ti-weighted imaging with gadolinium enhancement of vascularity was used to detect tumor margins, tumor size, and growth. These experiments, using 3D whole brain images obtained in four mice at once, demonstrate the feasibility of obtaining repeat radiological images in intracranial tumor models and suggest that MRI should be incorporated as a research modality for the investigation of intracranial pathobiology.

  13. Magnetic resonance imaging for radiotherapy planning of brain cancer patients using immobilization and surface coils

    Science.gov (United States)

    Hanvey, S.; Glegg, M.; Foster, J.

    2009-09-01

    This study investigated the compatibility of a head and neck immobilization device with magnetic resonance imaging (MRI). The immobilization device is used to position a patient in the same way as when receiving a computed tomography (CT) scan for radiotherapy planning and radiation treatment. The advantage of using immobilization in MR is improved accuracy in CT/MR image registration enabling greater confidence in the delineation of structures. The main practical difficulty in using an immobilization device in MRI is that physical constraints make their use incompatible with head imaging coils. Within this paper we describe a method for MR imaging of the brain which allows the use of head and neck immobilization devices. By a series of image quality tests we obtained the same or better image quality as a multi-channel head coil.

  14. Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

    International Nuclear Information System (INIS)

    Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

    2014-01-01

    Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective

  15. Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial.

    Science.gov (United States)

    Choi, Clara Y H; Wakelee, Heather A; Neal, Joel W; Pinder-Schenck, Mary C; Yu, Hsiang-Hsuan Michael; Chang, Steven D; Adler, John R; Modlin, Leslie A; Harsh, Griffith R; Soltys, Scott G

    2017-09-01

    To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days. From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS. The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Non-small cell lung cancer brain metastasis screening in the era of positron emission tomography-CT staging: Current practice and outcomes.

    Science.gov (United States)

    Diaz, Mauricio E; Debowski, Maciej; Hukins, Craig; Fielding, David; Fong, Kwun M; Bettington, Catherine S

    2018-05-10

    Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non-small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT). We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET-CT to stage extra-cranial disease. BMS was defined as dedicated brain imaging with contrast-enhanced computed tomography (CE-CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits. A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE-CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non-brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N-stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T-stage (P = 0.001), N-Stage (P < 0.001) and overall stage (P < 0.001). Non-small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system. © 2018 The Royal Australian and New Zealand College of Radiologists.

  17. Incidence, symptoms, treatment, and prognosis in 113 patients with brain/meningeal metastasis from breast cancer. Screening in accordance with hormone receptor and HER2/neu

    International Nuclear Information System (INIS)

    Kan, Norimichi; Takada, Masayasu; Kuwata, Katsuya

    2009-01-01

    In 113 of 422 patients with metastatic/recurrent breast cancer (MBC who were treated in our hospital after 2001, brain/meningeal metastasis was detected. In 240 patients who died, the overall incidence of brain/meningeal metastasis was 36.3% (n=87). With respect to hormone receptor (HR) and HER2 presence, metastasis was detected in 32 (58.2%) of 55 patients showing HR(-) and HER2(+), 17 (39.5%) of 43 patients showing HR(-) and HER2(-), 19 (31.5%) of 54 patients showing HR(+) and HER2(+), and 17 (20%) of 85 patients showing HR(+) and HER2(-) (brain metastasis was detected in 2 of 3 patients in whom HR or HER2 was unclear); the incidence was significantly higher in HR(-) or HER2(+) patients. Of our series including surviving patients, asymptomatic brain metastasis was detected using contrast-enhanced MRI in 24 HER2(+) patients. In the above 113 patients, the median survival time (MST) after diagnosis was 10 months. However, it was 17 months in 24 patients who underwent screening. For treatment, whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) mainly with a gamma knife was performed. During a follow-up of more than 12 months, 1 to 4 sessions of treatment (mean: 2.39, median: 2) were required. In 50% of the patients, both WBRT and SRS were performed. There were no HR- or HER2- related differences in survival after brain metastasis. However, the MST was 34 months in 7 patients in whom the 1st relapse site involved the brain. In the future, the usefulness of early treatment via brain metastasis screening should be reviewed in HR(-) and HER2(+) patients. (author)

  18. Brain Cancer—Health Professional Version

    Science.gov (United States)

    Cancers of the brain and spinal cord include anaplastic astrocytomas and glioblastomas, meningiomas, pituitary tumors, schwannomas, ependymomas, and sarcomas. Find evidence-based information on brain cancer treatment, research, genetics, and statistics.

  19. Propagation environments [Chapter 4

    Science.gov (United States)

    Douglass F. Jacobs; Thomas D. Landis; Tara Luna

    2009-01-01

    An understanding of all factors influencing plant growth in a nursery environment is needed for the successful growth and production of high-quality container plants. Propagation structures modify the atmospheric conditions of temperature, light, and relative humidity. Native plant nurseries are different from typical horticultural nurseries because plants must be...

  20. Uncertainty Propagation in OMFIT

    Science.gov (United States)

    Smith, Sterling; Meneghini, Orso; Sung, Choongki

    2017-10-01

    A rigorous comparison of power balance fluxes and turbulent model fluxes requires the propagation of uncertainties in the kinetic profiles and their derivatives. Making extensive use of the python uncertainties package, the OMFIT framework has been used to propagate covariant uncertainties to provide an uncertainty in the power balance calculation from the ONETWO code, as well as through the turbulent fluxes calculated by the TGLF code. The covariant uncertainties arise from fitting 1D (constant on flux surface) density and temperature profiles and associated random errors with parameterized functions such as a modified tanh. The power balance and model fluxes can then be compared with quantification of the uncertainties. No effort is made at propagating systematic errors. A case study will be shown for the effects of resonant magnetic perturbations on the kinetic profiles and fluxes at the top of the pedestal. A separate attempt at modeling the random errors with Monte Carlo sampling will be compared to the method of propagating the fitting function parameter covariant uncertainties. Work supported by US DOE under DE-FC02-04ER54698, DE-FG2-95ER-54309, DE-SC 0012656.

  1. The Weinberg propagators

    International Nuclear Information System (INIS)

    Dvoeglazov, V.V.

    1997-01-01

    An analog of the j = 1/2 Feynman-Dyson propagator is presented in the framework of the j = 1 Weinberg's theory. The basis for this construction is the concept of the Weinberg field as a system of four field functions differing by parity and by dual transformations. (orig.)

  2. UWB Propagation through Walls

    Czech Academy of Sciences Publication Activity Database

    Schejbal, V.; Bezoušek, P.; Čermák, D.; NĚMEC, Z.; Fišer, Ondřej; Hájek, M.

    2006-01-01

    Roč. 15, č. 1 (2006), s. 17-24 ISSN 1210-2512 R&D Projects: GA MPO(CZ) FT-TA2/030 Institutional research plan: CEZ:AV0Z30420517 Keywords : Ultra wide band * UWB antennas * UWB propagation * multipath effects Subject RIV: JB - Sensors, Measurment, Regulation

  3. Tropical Cyclone Propagation

    National Research Council Canada - National Science Library

    Gray, William

    1994-01-01

    This paper discusses the question of tropical cyclone propagation or why the average tropical cyclone moves 1-2 m/s faster and usually 10-20 deg to the left of its surrounding (or 5-7 deg radius) deep layer (850-300 mb) steering current...

  4. Analysis of outcome in patients irradiated for brain metastases of lung (no oatcell) cancer

    International Nuclear Information System (INIS)

    Lione, Marcelo; Tissera, Norberto

    2004-01-01

    Purpose: To correlate our findings with those of the international literature and identify the factors related to survival. Material and methods: Fifty patients with central nervous system metastases of non-small cell lung cancer were evaluated. Holocranial radiotherapy was performed with a daily dose of 1.8 Gy and a total dose of 50.4 Gy. Results: Overall survival of all patients at 6 months, 1 year and 2 years was 37%, 27% and 5% respectively. Mean survival was 5 months; 9 months for the group with a favorable outcome and 4 months for the group with an unfavorable outcome. Conclusion: The results are similar to those published in the international literature. Factors that relate to survival are: age, performance status, and the presence or absence of metastases in other sites. (author)

  5. Correlation between quantitative HER-2 protein expression and risk for brain metastases in HER-2+ advanced breast cancer patients receiving trastuzumab-containing therapy.

    Science.gov (United States)

    Duchnowska, Renata; Biernat, Wojciech; Szostakiewicz, Barbara; Sperinde, Jeff; Piette, Fanny; Haddad, Mojgan; Paquet, Agnes; Lie, Yolanda; Czartoryska-Arłukowicz, Bogumiła; Wysocki, Piotr; Jankowski, Tomasz; Radecka, Barbara; Foszczynska-Kłoda, Małgorzata; Litwiniuk, Maria; Debska, Sylwia; Weidler, Jodi; Huang, Weidong; Buyse, Marc; Bates, Michael; Jassem, Jacek

    2012-01-01

    Patients with human epidermal growth factor receptor (HER)-2+ breast cancer are at particularly high risk for brain metastases; however, the biological basis is not fully understood. Using a novel HER-2 assay, we investigated the correlation between quantitative HER-2 expression in primary breast cancers and the time to brain metastasis (TTBM) in HER-2+ advanced breast cancer patients treated with trastuzumab. The study group included 142 consecutive patients who were administered trastuzumab-based therapy for HER-2+ metastatic breast cancer. HER-2/neu gene copy number was quantified as the HER-2/centromeric probe for chromosome 17 (CEP17) ratio by central laboratory fluorescence in situ hybridization (FISH). HER-2 protein was quantified as total HER-2 protein expression (H2T) by the HERmark® assay (Monogram Biosciences, Inc., South San Francisco, CA) in formalin-fixed, paraffin-embedded tumor samples. HER-2 variables were correlated with clinical features and TTBM was measured from the initiation of trastuzumab-containing therapy. A higher H2T level (continuous variable) was correlated with shorter TTBM, whereas HER-2 amplification by FISH and a continuous HER-2/CEP17 ratio were not predictive (p = .013, .28, and .25, respectively). In the subset of patients that was centrally determined by FISH to be HER-2+, an above-the-median H2T level was significantly associated with a shorter TTBM (hazard ratio, [HR], 2.4; p = .005), whereas this was not true for the median HER-2/CEP17 ratio by FISH (p = .4). Correlation between a continuous H2T level and TTBM was confirmed on multivariate analysis (HR, 3.3; p = .024). These data reveal a strong relationship between the quantitative HER-2 protein expression level and the risk for brain relapse in HER-2+ advanced breast cancer patients. Consequently, quantitative assessment of HER-2 protein expression may inform and facilitate refinements in therapeutic treatment strategies for selected subpopulations of patients in this

  6. Power Burst Reactor Facility as an epithermal neutron source for brain cancer therapy

    International Nuclear Information System (INIS)

    Wheeler, F.J.

    1986-01-01

    The Power Burst Facility (PBF) reactor is considered for modification to provide an intense, clean source of intermediate-energy (epithermal) neutrons desirable for clinical studies of neutron capture therapy (NCT) for malignant tumors. The modifications include partial replacement of the reflector, installation of a neutron-moderating, shifting region, additional shielding, and penetration of the present concrete shield with a collimating (and optionally) filtering region. The studies have indicated that the reactor, after these modifications, will be safely operable at full power (28 MW) within the acceptable limits of the plant protection systems. The neutron beam exiting from the collimator port is predicted to be of sufficient intensity (approx.10 10 neutrons/cm 2 -s) to provide therapeutic doses in very short irradiation times. The beam would be relatively free of undesirable fast neutrons, thermal neutrons and gamma rays. The calculated neutron energy spectrum and associated gamma rays in the beam were provided as input in simulation studies that used a computer model of a patient with a brain tumor to determine predicted dose rates to the tumor and healthy tissue. The results of this conceptual study indicate an intense, clean beam of epithermal neutrons for NCT clinical trials is attainable in the PBF facility with properly engineered design modifications. 9 refs., 11 figs., 3 tabs

  7. [18F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood–brain barrier

    International Nuclear Information System (INIS)

    Wanek, Thomas; Traxl, Alexander; Bankstahl, Jens P.; Bankstahl, Marion; Sauberer, Michael; Langer, Oliver; Kuntner, Claudia

    2015-01-01

    Introduction: Transport of 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) by the multidrug efflux transporters P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) at the blood–brain barrier (BBB) may confound the interpretation of [ 18 F]FDG brain PET data. Aim of this study was to assess the influence of ABCB1 and ABCG2 at the BBB on brain distribution of [ 18 F]FDG in vivo by performing [ 18 F]FDG PET scans in wild-type and transporter knockout mice and by evaluating changes in [ 18 F]FDG brain distribution after transporter inhibition. Methods: Dynamic small-animal PET experiments (60 min) were performed with [ 18 F]FDG in groups of wild-type and transporter knockout mice (Abcb1a/b (−/−) , Abcg2 (−/−) and Abcb1a/b (−/−) Abcg2 (−/−) ) and in wild-type rats without and with i.v. pretreatment with the known ABCB1 inhibitor tariquidar (15 mg/kg, given at 2 h before PET). Blood was sampled from animals from the orbital sinus vein at the end of the PET scans and measured in a gamma counter. Brain uptake of [ 18 F]FDG was expressed as the brain-to-blood radioactivity concentration ratio in the last PET time frame (K b,brain ). Results: K b,brain values of [ 18 F]FDG were not significantly different between different mouse types both without and with tariquidar pretreatment. The blood-to-brain transfer rate constant of [ 18 F]FDG was significantly lower in tariquidar-treated as compared with vehicle-treated rats (0.350 ± 0.025 mL/min/g versus 0.416 ± 0.024 mL/min/g, p = 0.026, paired t-test) but K b,brain values were not significantly different between both rat groups. Conclusion: Our results show that [ 18 F]FDG is not transported by Abcb1 at the mouse and rat BBB in vivo. In addition we found no evidence for Abcg2 transport of [ 18 F]FDG at the mouse BBB. Advances in knowledge and implications for patient care: Our findings imply that functional activity of ABCB1 and ABCG2 at the BBB does not need to be taken into account when

  8. Laser-Neuron Interaction with Femtosecond Beat-Modulated 800-1200 nm Photon Beams, as the Treatment of Brain Cancer Tissue. Laser Neurophysics

    Science.gov (United States)

    Stefan, V. Alexander

    2011-03-01

    I propose a novel mechanism for the brain cancer tissue treatment: nonlinear interaction of ultrashort pulses of beat-photon, (ω1 -- ω2) , or double-photon, (ω1 +ω2) , beams with the cancer tissue. The multiphoton scattering is described via photon diffusion equation. The open-scull cerebral tissue can be irradiated with the beat-modulated photon pulses with the laser irradiances in the range of a few mW/cm2 , and repetition rate of a few 100s Hz generated in the beat-wave driven free electron laser. V. Stefan, B. I. Cohen, and C. Joshi, Nonlinear Mixing of Electromagnetic Waves in PlasmasScience 27 January 1989: V. Alexander Stefan, Genomic Medical Physics: A New Physics in the Making, (S-U-Press, 2008).} This highly accurate cancer tissue ablation removal may prove to be an efficient method for the treatment of brain cancer. Work supported in part by Nikola Tesla Laboratories (Stefan University), La Jolla, CA.

  9. Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors

    DEFF Research Database (Denmark)

    Cheung, Wang; Darfler, Marlene M; Alvarez, Hector

    2008-01-01

    BACKGROUND: Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset ...... their overexpression in IPMNs. CONCLUSION: Global proteomics analysis using the Liquid Tissue workflow is a feasible approach for unbiased biomarker discovery in limited archival material, particularly applicable to precursor lesions of cancer......., and mass spectrometry to conduct a global proteomic analysis of an intraductal papillary mucinous neoplasm (IPMN). Tissue microarrays comprised of 38 IPMNs were used for validation of candidate proteins. RESULTS: The proteomic analysis of the IPMN Liquid Tissue lysate resulted in identification of 1......,534 peptides corresponding to 523 unique proteins. A subset of 25 proteins was identified that had previously been reported as upregulated in pancreatic cancer. Immunohistochemical analysis for two of these, deleted in malignant brain tumors 1 (DMBT1) and tissue transglutaminase 2 (TGM2), confirmed...

  10. Fatigue during chemoradiotherapy for nasopharyngeal cancer and its relationship to radiation dose distribution in the brain

    International Nuclear Information System (INIS)

    Powell, Ceri; Schick, Ulrike; Morden, James P.; Gulliford, Sarah L.; Miah, Aisha B.; Bhide, Shreerang; Newbold, Kate; Harrington, Kevin J.; Nutting, Chris M.

    2014-01-01

    Background and purpose: Fatigue during head and neck radiotherapy may be related to radiation dose to the central nervous system (CNS). The impact of patient, tumour, and dosimetric variables on acute fatigue was assessed in nasopharyngeal cancer patients undergoing chemoradiotherapy. Material and methods: Radiation dose to the following retrospectively-delineated CNS structures; brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia (BG) and clinical variables were related to incidence of ⩾ grade 2 fatigue in 40 patients. Results: Sixty per cent of patients reported fatigue during and following radiotherapy. Dmean and D2 to the BG and Dmean to the pituitary gland were significantly associated with fatigue during radiation (P < 0.01). Dmean to the cerebellum was associated with fatigue following radiotherapy and at any time (P < 0.01). After adjusting for clinical factors, an association remained between fatigue during radiotherapy and mean dose and D2 to the pituitary gland and BG (P = 0.012, 0.036, 0.009 and 0.018) and mean dose to the cerebellum following radiation and at any time (P = 0.042 and 0.029). Conclusion: Disruption of connections between BG, cerebellum, and higher cortical centres or disruption of pituitary-regulated hormonal balance may be implicated in the pathophysiology of radiation-related fatigue

  11. Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

    Directory of Open Access Journals (Sweden)

    Kenneth A. Schwartz

    2018-02-01

    Full Text Available Survival of glioblastoma multiforme (GBM with the current recommended treatment is poor. Reported median survivals are approximately 8–15 months. Based on recent publications from animal models, combining cancer drugs, radiation, and diet-metabolic treatments may be a new route to better survivals. To investigate this possibility, we have begun a clinical trial that has enrolled 15 subjects using a ketogenic diet (KD as an addition to current standard treatments that include surgery, radiation therapy, and chemotherapy. Of the 15 enrolled, 10 completed the protocol. This perspective describes the challenges and lessons learned during this clinical trial and discusses the critical elements that are essential for investigating treatment with a KD. We also reviewed and compared various types of KDs. We believe that the diet selected should be standardized within individual clinical trials, and more importantly, the patients’ blood should be monitored for glucose and ketones twice daily so that the supervising dietitian can work with the patient and their caregivers to make appropriate changes in the diet. Compliance with the diet is best in highly motivated patients who have excellent home support from a family member or a friend who can help to overcome administrative, physical, and cognition deficiencies associated with the disease. Treatment of GBM using a KD represents a reasonable investigative approach. This perspective summarizes the challenges and lessons learned implementing and continuing KD therapy while the patients are concurrently being treated with radiation and chemotherapy.

  12. Gender, Race, and Survival: A Study in Non-Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

    International Nuclear Information System (INIS)

    Videtic, Gregory M.M.; Reddy, Chandana A.; Chao, Samuel T.; Rice, Thomas W.; Adelstein, David J.; Barnett, Gene H.; Mekhail, Tarek M.; Vogelbaum, Michael A.; Suh, John H.

    2009-01-01

    Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

  13. Propagator of stochastic electrodynamics

    International Nuclear Information System (INIS)

    Cavalleri, G.

    1981-01-01

    The ''elementary propagator'' for the position of a free charged particle subject to the zero-point electromagnetic field with Lorentz-invariant spectral density proportionalω 3 is obtained. The nonstationary process for the position is solved by the stationary process for the acceleration. The dispersion of the position elementary propagator is compared with that of quantum electrodynamics. Finally, the evolution of the probability density is obtained starting from an initial distribution confined in a small volume and with a Gaussian distribution in the velocities. The resulting probability density for the position turns out to be equal, to within radiative corrections, to psipsi* where psi is the Kennard wave packet. If the radiative corrections are retained, the present result is new since the corresponding expression in quantum electrodynamics has not yet been found. Besides preceding quantum electrodynamics for this problem, no renormalization is required in stochastic electrodynamics

  14. Preventing Unofficial Information Propagation

    Science.gov (United States)

    Le, Zhengyi; Ouyang, Yi; Xu, Yurong; Ford, James; Makedon, Fillia

    Digital copies are susceptible to theft and vulnerable to leakage, copying, or manipulation. When someone (or some group), who has stolen, leaked, copied, or manipulated digital documents propagates the documents over the Internet and/or distributes those through physical distribution channels many challenges arise which document holders must overcome in order to mitigate the impact to their privacy or business. This paper focuses on the propagation problem of digital credentials, which may contain sensitive information about a credential holder. Existing work such as access control policies and the Platform for Privacy Preferences (P3P) assumes that qualified or certified credential viewers are honest and reliable. The proposed approach in this paper uses short-lived credentials based on reverse forward secure signatures to remove this assumption and mitigate the damage caused by a dishonest or honest but compromised viewer.

  15. Automatic quality control in clinical (1)H MRSI of brain cancer.

    Science.gov (United States)

    Pedrosa de Barros, Nuno; McKinley, Richard; Knecht, Urspeter; Wiest, Roland; Slotboom, Johannes

    2016-05-01

    MRSI grids frequently show spectra with poor quality, mainly because of the high sensitivity of MRS to field inhomogeneities. These poor quality spectra are prone to quantification and/or interpretation errors that can have a significant impact on the clinical use of spectroscopic data. Therefore, quality control of the spectra should always precede their clinical use. When performed manually, quality assessment of MRSI spectra is not only a tedious and time-consuming task, but is also affected by human subjectivity. Consequently, automatic, fast and reliable methods for spectral quality assessment are of utmost interest. In this article, we present a new random forest-based method for automatic quality assessment of (1)H MRSI brain spectra, which uses a new set of MRS signal features. The random forest classifier was trained on spectra from 40 MRSI grids that were classified as acceptable or non-acceptable by two expert spectroscopists. To account for the effects of intra-rater reliability, each spectrum was rated for quality three times by each rater. The automatic method classified these spectra with an area under the curve (AUC) of 0.976. Furthermore, in the subset of spectra containing only the cases that were classified every time in the same way by the spectroscopists, an AUC of 0.998 was obtained. Feature importance for the classification was also evaluated. Frequency domain skewness and kurtosis, as well as time domain signal-to-noise ratios (SNRs) in the ranges 50-75 ms and 75-100 ms, were the most important features. Given that the method is able to assess a whole MRSI grid faster than a spectroscopist (approximately 3 s versus approximately 3 min), and without loss of accuracy (agreement between classifier trained with just one session and any of the other labelling sessions, 89.88%; agreement between any two labelling sessions, 89.03%), the authors suggest its implementation in the clinical routine. The method presented in this article was implemented

  16. SU-G-JeP2-08: Image-Guided Radiation Therapy Using Synthetic CTs in Brain Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Price, R.G.; Glide-Hurst, C. [Wayne State School of Medicine, Detroit, MI (United States); Henry Ford Health System, Detroit, MI (United States); Kim, J.; Zheng, W.; Chetty, I.J. [Henry Ford Health System, Detroit, MI (United States)

    2016-06-15

    Purpose: Synthetic-CTs(synCTs) are essential for MR-only treatment planning. However, the performance of synCT for IGRT must be carefully assessed. This work evaluated the accuracy of synCT and synCT-generated DRRs and determined their performance for IGRT in brain cancer radiation therapy. Methods: MR-SIM and CT-SIM images were acquired of a novel anthropomorphic phantom and a cohort of 12 patients. SynCTs were generated by combining an ultra-short echo time (UTE) sequence with other MRI datasets using voxel-based weighted summation. For the phantom, DRRs from synCT and CT were compared via bounding box and landmark analysis. Planar (MV/KV) and volumetric (CBCT) IGRT performance were evaluated across several platforms. In patients, retrospective analysis was conducted to register CBCTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system using whole brain and local registration techniques. A semi-automatic registration program was developed and validated to rigidly register planar MV/KV images (n=37) to synCT and CT DRRs. Registration reproducibility was assessed and margin differences were characterized using the van Herk formalism. Results: Bounding box and landmark analysis of phantom synCT DRRs were within 1mm of CT DRRs. Absolute 2D/2D registration shift differences ranged from 0.0–0.7mm for phantom DRRs on all treatment platforms and 0.0–0.4mm for volumetric registrations. For patient planar registrations, mean shift differences were 0.4±0.5mm (range: −0.6–1.6mm), 0.0±0.5mm, (range: −0.9–1.2mm), and 0.1±0.3mm (range: −0.7–0.6mm) for the superior-inferior(S-I), left-right(L–R), and anterior-posterior(A-P) axes, respectively. Mean shift differences in volumetric registrations were 0.6±0.4mm (range: −0.2–1.6mm), 0.2±0.4mm (range: −0.3–1.2mm), and 0.2±0.3mm (range: −0.2–1.2mm) for S-I, L–R, and A–P axes, respectively. CT-SIM and synCT derived margins were within 0.3mm. Conclusion

  17. SU-G-JeP2-08: Image-Guided Radiation Therapy Using Synthetic CTs in Brain Cancer

    International Nuclear Information System (INIS)

    Price, R.G.; Glide-Hurst, C.; Kim, J.; Zheng, W.; Chetty, I.J.

    2016-01-01

    Purpose: Synthetic-CTs(synCTs) are essential for MR-only treatment planning. However, the performance of synCT for IGRT must be carefully assessed. This work evaluated the accuracy of synCT and synCT-generated DRRs and determined their performance for IGRT in brain cancer radiation therapy. Methods: MR-SIM and CT-SIM images were acquired of a novel anthropomorphic phantom and a cohort of 12 patients. SynCTs were generated by combining an ultra-short echo time (UTE) sequence with other MRI datasets using voxel-based weighted summation. For the phantom, DRRs from synCT and CT were compared via bounding box and landmark analysis. Planar (MV/KV) and volumetric (CBCT) IGRT performance were evaluated across several platforms. In patients, retrospective analysis was conducted to register CBCTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system using whole brain and local registration techniques. A semi-automatic registration program was developed and validated to rigidly register planar MV/KV images (n=37) to synCT and CT DRRs. Registration reproducibility was assessed and margin differences were characterized using the van Herk formalism. Results: Bounding box and landmark analysis of phantom synCT DRRs were within 1mm of CT DRRs. Absolute 2D/2D registration shift differences ranged from 0.0–0.7mm for phantom DRRs on all treatment platforms and 0.0–0.4mm for volumetric registrations. For patient planar registrations, mean shift differences were 0.4±0.5mm (range: −0.6–1.6mm), 0.0±0.5mm, (range: −0.9–1.2mm), and 0.1±0.3mm (range: −0.7–0.6mm) for the superior-inferior(S-I), left-right(L–R), and anterior-posterior(A-P) axes, respectively. Mean shift differences in volumetric registrations were 0.6±0.4mm (range: −0.2–1.6mm), 0.2±0.4mm (range: −0.3–1.2mm), and 0.2±0.3mm (range: −0.2–1.2mm) for S-I, L–R, and A–P axes, respectively. CT-SIM and synCT derived margins were within 0.3mm. Conclusion

  18. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.

    Science.gov (United States)

    Cortés, Javier; Rugo, Hope S; Awada, Ahmad; Twelves, Chris; Perez, Edith A; Im, Seock-Ah; Gómez-Pardo, Patricia; Schwartzberg, Lee S; Diéras, Veronique; Yardley, Denise A; Potter, David A; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol; Hoch, Ute; Tagliaferri, Mary; Hannah, Alison L; O'Shaughnessy, Joyce

    2017-09-01

    Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BEACON compared EP with treatment of physician's choice (TPC; eribulin, vinorelbine, gemcitabine, nab-paclitaxel, paclitaxel, ixabepilone, or docetaxel) in patients previously treated with anthracycline, taxane, and capecitabine, including those with treated, stable brain metastases. The primary endpoint, overall survival (OS), was assessed in a pre-defined subgroup of BCBM patients; an exploratory post hoc analysis adjusting for the diagnosis-specific graded prognostic assessment (GPA) index was also conducted. In the trial, 67 BCBM patients were randomized (EP, n = 36; TPC, n = 31). Treatment subgroups were balanced for baseline characteristics and GPA indices. EP was associated with a significant reduction in the risk of death (HR 0.51; P BEACON population, fewer patients on EP experienced grade ≥3 toxicity (50 vs. 70%). The significant improvement in survival in BCBM patients provides encouraging data for EP in this difficult-to-treat subgroup of patients. A phase three trial of EP in BCBM patients is underway (ClinicalTrials.gov NCT02915744).

  19. Stacking denoising auto-encoders in a deep network to segment the brainstem on MRI in brain cancer patients: A clinical study.

    Science.gov (United States)

    Dolz, Jose; Betrouni, Nacim; Quidet, Mathilde; Kharroubi, Dris; Leroy, Henri A; Reyns, Nicolas; Massoptier, Laurent; Vermandel, Maximilien

    2016-09-01

    Delineation of organs at risk (OARs) is a crucial step in surgical and treatment planning in brain cancer, where precise OARs volume delineation is required. However, this task is still often manually performed, which is time-consuming and prone to observer variability. To tackle these issues a deep learning approach based on stacking denoising auto-encoders has been proposed to segment the brainstem on magnetic resonance images in brain cancer context. Additionally to classical features used in machine learning to segment brain structures, two new features are suggested. Four experts participated in this study by segmenting the brainstem on 9 patients who underwent radiosurgery. Analysis of variance on shape and volume similarity metrics indicated that there were significant differences (p<0.05) between the groups of manual annotations and automatic segmentations. Experimental evaluation also showed an overlapping higher than 90% with respect to the ground truth. These results are comparable, and often higher, to those of the state of the art segmentation methods but with a considerably reduction of the segmentation time. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Wave propagation in elastic solids

    CERN Document Server

    Achenbach, Jan

    1984-01-01

    The propagation of mechanical disturbances in solids is of interest in many branches of the physical scienses and engineering. This book aims to present an account of the theory of wave propagation in elastic solids. The material is arranged to present an exposition of the basic concepts of mechanical wave propagation within a one-dimensional setting and a discussion of formal aspects of elastodynamic theory in three dimensions, followed by chapters expounding on typical wave propagation phenomena, such as radiation, reflection, refraction, propagation in waveguides, and diffraction. The treat

  1. Differentiated thyroid cancer (papillary). Brain tumor metastasis as clinical onset. surgical treatment and "1"3"1I. 8 years disease-free

    International Nuclear Information System (INIS)

    Mena, D.; Pena, M.; Alvarez, L.; García del Rio, H.; Bruno, O.

    2015-01-01

    Introduction: The differentiated thyroid cancer is the most common endocrine neoplasia. The major manifestation belongs to the papillary variant (65-90%). The prognosis tends to be very favorable, with a mortality rate of 1.8 % and a disease-free rate up to 10 years of around 90-95 %. The distant metastasis in brain accounts for 0.1-5 %. There are no established protocols for the management of brain metastasis. Therapeutic options are: surgery, stereotactic radiotherapy / radiosurgery, and "1"3"1I. The successful management of this case is an option for brain metastasis from thyroid papillary carcinoma. Case report: A 77 year-old female begins with double vision (diplopia). She underwent twice a surgery for brain tumor with a histopathological report on thyroid papillary tissue. The endocrine evaluation determines euthyroid state except thyroglobulin (TG) 2300 ng/ml. Total thyroidectomy with classic thyroid papillary carcinoma. A diagnostic "1"3"1I scan after surgery shows for first time brain metastasis uptake. The patient receives 25 mCi of "1"3"1I as initial therapeutic dose, and subsequent therapeutic doses (50, 50, 75, 75, 50 mCi) in 2 years, in accordance with the evolution of magnetic resonance, clinic, endocrine lab, hematological analysis, and "1"3"1I scintigraphy, that shows the possible remission of the disease. The follow-up was carried out by means of a clinical control, thyroglobulin values, U.S., "1"3"1I scans, and magnetic resonance. The patient is at the present time over 11 years survival and 8 years disease-free. Discussion: Even though the distant metastasis is not very common in brain and is generally associated with aggressive variants of tumor, our case started with a metastatic brain tumor in an euthyroid patient with no thyroid pathology background and with low-risk post-thyroidectomy criterion. The "1"3"1I scan turned positive in brain metastasis when the patient was thyroidectomized. This detail must be considered important, since it

  2. Evaluation of the P-glycoprotein- and breast cancer resistance protein-mediated brain penetration of 11C-labeled topotecan using small-animal positron emission tomography

    International Nuclear Information System (INIS)

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Kawamura, Kazunori; Hatori, Akiko; Yui, Joji; Nengaki, Nobuki; Ogawa, Masanao; Yoshida, Yuichiro; Wakizaka, Hidekatsu; Yanamoto, Kazuhiko; Fukumura, Toshimitsu; Zhang Mingrong

    2011-01-01

    Introduction: Topotecan (TPT) is a camptothecin derivative and is an anticancer drug working as a topoisomerase-I-specific inhibitor. But TPT cannot penetrate through the blood-brain barrier. In this study, we synthesized a new positron emission tomography (PET) probe, [ 11 C]TPT, to evaluate the P-glycoprotein (Pgp)- and breast cancer resistance protein (BCRP)-mediated brain penetration of [ 11 C]TPT using small-animal PET. Methods: [ 11 C]TPT was synthesized by the reaction of a desmethyl precursor with [ 11 C]CH 3 I. In vitro study using [ 11 C]TPT was carried out in MES-SA and doxorubicin-resistant MES-SA/Dx5 cells in the presence or absence of elacridar, a specific inhibitor for Pgp and BCRP. The biodistribution of [ 11 C]TPT was determined using small-animal PET and the dissection method in mice. Results: The transport of [ 11 C]TPT to the extracellular side was determined in MES-SA/Dx5 cells exhibiting the expressions of Pgp and BCRP at high levels. This transport was inhibited by coincubation with elacridar. In Mdr1a/b -/- Bcrp1 -/- mice, PET results indicated that the brain uptake of [ 11 C]TPT was about two times higher than that in wild-type mice. Similarly, the brain penetration of [ 11 C]TPT in wild-type mice was increased by treatment with elacridar. The radioactivity in the brain of elacridar-treated mice was maintained at a certain level after the injection of [ 11 C]TPT, although the radioactivity in the blood decreased with time. Conclusions: We demonstrated the increase of brain penetration of [ 11 C]TPT by deficiency and inhibition of Pgp and BCRP functions using small-animal PET in mice.

  3. Cancer 'survivor-care': II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment).

    Science.gov (United States)

    Raffa, R B

    2013-08-01

    Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation. © 2013 John Wiley & Sons Ltd.

  4. Temporal scaling in information propagation

    Science.gov (United States)

    Huang, Junming; Li, Chao; Wang, Wen-Qiang; Shen, Hua-Wei; Li, Guojie; Cheng, Xue-Qi

    2014-06-01

    For the study of information propagation, one fundamental problem is uncovering universal laws governing the dynamics of information propagation. This problem, from the microscopic perspective, is formulated as estimating the propagation probability that a piece of information propagates from one individual to another. Such a propagation probability generally depends on two major classes of factors: the intrinsic attractiveness of information and the interactions between individuals. Despite the fact that the temporal effect of attractiveness is widely studied, temporal laws underlying individual interactions remain unclear, causing inaccurate prediction of information propagation on evolving social networks. In this report, we empirically study the dynamics of information propagation, using the dataset from a population-scale social media website. We discover a temporal scaling in information propagation: the probability a message propagates between two individuals decays with the length of time latency since their latest interaction, obeying a power-law rule. Leveraging the scaling law, we further propose a temporal model to estimate future propagation probabilities between individuals, reducing the error rate of information propagation prediction from 6.7% to 2.6% and improving viral marketing with 9.7% incremental customers.

  5. Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke.

    Science.gov (United States)

    Van Kanegan, Michael J; Dunn, Denise E; Kaltenbach, Linda S; Shah, Bijal; He, Dong Ning; McCoy, Daniel D; Yang, Peiying; Peng, Jiangnan; Shen, Li; Du, Lin; Cichewicz, Robert H; Newman, Robert A; Lo, Donald C

    2016-05-12

    We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0-4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.

  6. A functional study of EGFR and Notch signaling in brain cancer stem-like cells from glioblastoma multiforme (Ph.d.)

    DEFF Research Database (Denmark)

    Kristoffersen, Karina

    2013-01-01

    Glioblastoma Multiforme (GBM) is the most common and aggressive brain tumor in adults with a median survival for newly diagnosed GBM patients at less than 1.5 year. Despite intense treatment efforts the vast majority of patients will experience relapse and much research today is therefore searching...... for new molecular and cellular targets that can improve the prognosis for GBM patients. One such target is the brain cancer stem-like cells (bCSC) that are believed to be responsible for tumor initiation, progression, treatment resistance and ultimately relapse. bCSC are identified based...... on their resemblance to normal neural stem cells (NSC) and their tumorigenic potential. Like for NSC, the epidermal growth factor receptor (EGFR) and Notch receptor signaling pathways are believed to be important for the maintenance of bCSC. These pathways as such present promising targets in a future anti-bCSC GBM...

  7. Deleted in Malignant Brain Tumors 1 is a versatile mucin-like molecule likely to play a differential role in digestive tract cancer

    DEFF Research Database (Denmark)

    Mollenhauer, J; Herbertz, S; Helmke, B

    2001-01-01

    Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a candidate tumor suppressor gene for brain, lung, and digestive tract cancer. In particular, alterations of the gene and/or a loss of expression have been observed in gastric, colorectal, and esophageal carcinomas. Initial evidence...... has accumulated that DMBT1 may represent a multifunctional protein. Because the consequences of a loss of DMBT1 function may be different depending on its original function in a particular tissue, we wondered if it is appropriate to assume a uniform role for DMBT1 in digestive tract carcinomas. We...... hypothesized that a systematic characterization of DMBT1 in the human alimentary tract would be useful to improve the understanding of this molecule and its role in digestive tract carcinomas. Our data indicate that the expression pattern and subcellular distribution of DMBT1 in the human alimentary tract...

  8. Bolt beam propagation analysis

    Science.gov (United States)

    Shokair, I. R.

    BOLT (Beam on Laser Technology) is a rocket experiment to demonstrate electron beam propagation on a laser ionized plasma channel across the geomagnetic field in the ion focused regime (IFR). The beam parameters for BOLT are: beam current I(sub b) = 100 Amps, beam energy of 1--1.5 MeV (gamma =3-4), and a Gaussian beam and channel of radii r(sub b) = r(sub c) = 1.5 cm. The N+1 ionization scheme is used to ionize atomic oxygen in the upper atmosphere. This scheme utilizes 130 nm light plus three IR lasers to excite and then ionize atomic oxygen. The limiting factor for the channel strength is the energy of the 130 nm laser, which is assumed to be 1.6 mJ for BOLT. At a fixed laser energy and altitude (fixing the density of atomic oxygen), the range can be varied by adjusting the laser tuning, resulting in a neutralization fraction axial profile of the form: f(z) = f(sub 0) e(exp minus z)/R, where R is the range. In this paper we consider the propagation of the BOLT beam and calculate the range of the electron beam taking into account the fact that the erosion rates (magnetic and inductive) vary with beam length as the beam and channel dynamically respond to sausage and hose instabilities.

  9. Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kuchcinski, Gregory; Duhal, Romain; Lalisse, Maxime; Dumont, Julien; Lopes, Renaud; Pruvo, Jean-Pierre; Leclerc, Xavier; Delmaire, Christine [University of Lille, CHU Lille, Department of Neuroradiology, Lille (France); Le Rhun, Emilie [University of Lille, CHU Lille, Department of Neurosurgery, Lille (France); Oscar Lambret Center, Department of Medical Oncology, Lille (France); Inserm U1192-PRISM-Laboratoire de Proteomique, Reponse Inflammatoire, Spectrometrie de Masse, Lille (France); Cortot, Alexis B. [University of Lille, CHU Lille, Department of Thoracic Oncology, Lille (France); Drumez, Elodie [University of Lille, CHU Lille, Department of Biostatistics, Lille (France)

    2017-09-15

    To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K{sup trans}, k{sub ep}, v{sub e}, v{sub p}) and their early variation (∇K{sup trans}, ∇k{sub ep}, ∇v{sub e}, ∇v{sub p}). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∇K{sup trans}, ∇v{sub e} and ∇v{sub p} were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∇v{sub e} with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∇v{sub e} may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. (orig.)

  10. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    International Nuclear Information System (INIS)

    Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

    2010-01-01

    Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

  11. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    Science.gov (United States)

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  12. EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data

    Directory of Open Access Journals (Sweden)

    Fan Y

    2014-11-01

    Full Text Available Yun Fan,1,2 Xiaoling Xu,3 Conghua Xie4 1Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People's Republic of China; 2Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 3Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China; 4Zhongnan Hospital of Wuhan University, Department of Radiation Oncology, Wuhan, People’s Republic of China Introduction: Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC. The use of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Methods: Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR, disease control rate (DCR, progression-free survival (PFS, overall survival (OS, and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Results: Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group, and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%–57.8% and 75.7% (95% CI: 70.3%–80.5%, respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%; a similar trend was observed for the DCR (94.6% vs 71.3%. The pooled median PFS and OS were 7.4 months (95% CI, 4.9–9.9 and 11.9 months (95% CI, 7.7–16.2, respectively, with longer PFS (12.3 months vs 5.9 months and OS (16.2 months vs

  13. Feasibility of MRI-only treatment planning for proton therapy in brain and prostate cancers: Dose calculation accuracy in substitute CT images

    International Nuclear Information System (INIS)

    Koivula, Lauri

    2016-01-01

    Purpose: Magnetic resonance imaging (MRI) is increasingly used for radiotherapy target delineation, image guidance, and treatment response monitoring. Recent studies have shown that an entire external x-ray radiotherapy treatment planning (RTP) workflow for brain tumor or prostate cancer patients based only on MRI reference images is feasible. This study aims to show that a MRI-only based RTP workflow is also feasible for proton beam therapy plans generated in MRI-based substitute computed tomography (sCT) images of the head and the pelvis. Methods: The sCTs were constructed for ten prostate cancer and ten brain tumor patients primarily by transforming the intensity values of in-phase MR images to Hounsfield units (HUs) with a dual model HU conversion technique to enable heterogeneous tissue representation. HU conversion models for the pelvis were adopted from previous studies, further extended in this study also for head MRI by generating anatomical site-specific conversion models (a new training data set of ten other brain patients). This study also evaluated two other types of simplified sCT: dual bulk density (for bone and water) and homogeneous (water only). For every clinical case, intensity modulated proton therapy (IMPT) plans robustly optimized in standard planning CTs were calculated in sCT for evaluation, and vice versa. Overall dose agreement was evaluated using dose–volume histogram parameters and 3D gamma criteria. Results: In heterogeneous sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and 42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The maximum absolute dose differences relative to CT in the brain tumor clinical target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and 8.9% for homogenous sCT. The corresponding maximum differences in the prostate CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in the head and pelvis passing 1% and 1 mm

  14. Feasibility of MRI-only treatment planning for proton therapy in brain and prostate cancers: Dose calculation accuracy in substitute CT images

    Energy Technology Data Exchange (ETDEWEB)

    Koivula, Lauri [Department of Radiation Oncology, Comprehensive Cancer Center, Helsinki University Central Hospital, P.O. Box 180, Helsinki 00029 HUS (Finland)

    2016-08-15

    Purpose: Magnetic resonance imaging (MRI) is increasingly used for radiotherapy target delineation, image guidance, and treatment response monitoring. Recent studies have shown that an entire external x-ray radiotherapy treatment planning (RTP) workflow for brain tumor or prostate cancer patients based only on MRI reference images is feasible. This study aims to show that a MRI-only based RTP workflow is also feasible for proton beam therapy plans generated in MRI-based substitute computed tomography (sCT) images of the head and the pelvis. Methods: The sCTs were constructed for ten prostate cancer and ten brain tumor patients primarily by transforming the intensity values of in-phase MR images to Hounsfield units (HUs) with a dual model HU conversion technique to enable heterogeneous tissue representation. HU conversion models for the pelvis were adopted from previous studies, further extended in this study also for head MRI by generating anatomical site-specific conversion models (a new training data set of ten other brain patients). This study also evaluated two other types of simplified sCT: dual bulk density (for bone and water) and homogeneous (water only). For every clinical case, intensity modulated proton therapy (IMPT) plans robustly optimized in standard planning CTs were calculated in sCT for evaluation, and vice versa. Overall dose agreement was evaluated using dose–volume histogram parameters and 3D gamma criteria. Results: In heterogeneous sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and 42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The maximum absolute dose differences relative to CT in the brain tumor clinical target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and 8.9% for homogenous sCT. The corresponding maximum differences in the prostate CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in the head and pelvis passing 1% and 1 mm

  15. Mobile phones, cordless phones and rates of brain tumors in different age groups in the Swedish National Inpatient Register and the Swedish Cancer Register during 1998-2015

    OpenAIRE

    Hardell, Lennart; Carlberg, Michael

    2017-01-01

    We used the Swedish Inpatient Register (IPR) to analyze rates of brain tumors of unknown type (D43) during 1998-2015. Average Annual Percentage Change (AAPC) per 100,000 increased with +2.06%, 95% confidence interval (CI) +1.27, +2.86% in both genders combined. A joinpoint was found in 2007 with Annual Percentage Change (APC) 1998-2007 of +0.16%, 95% CI -0.94, +1.28%, and 2007-2015 of +4.24%, 95% CI +2.87, +5.63%. Highest AAPC was found in the age group 20-39 years. In the Swedish Cancer Regi...

  16. Anti-Ma2 antibody related paraneoplastic limbic/brain stem encephalitis associated with breast cancer expressing Ma1, Ma2, and Ma3 mRNAs.

    Science.gov (United States)

    Sahashi, K; Sakai, K; Mano, K; Hirose, G

    2003-09-01

    A 69 year old woman presented with cognitive impairment and supranuclear gaze palsy caused by paraneoplastic limbic/brain stem encephalitis associated with atypical medullary breast carcinoma. The cerebrospinal fluid from the patient harboured an anti-neuronal cell antibody against Ma2 antigen, but not against Ma1 or Ma3 antigen. Despite the antibody being restricted to the Ma2 antigen, the patient's cancer tissue expressed Ma1, Ma2, and Ma3 mRNAs. These results, and the expression of Ma2 mRNA in an atypical medullar breast carcinoma in another patient without paraneoplastic encephalitis, indicate that the induction of anti-Ma2 antibody depends on host immunoreponsiveness and not on the presence of the antigen itself in the cancer.

  17. Questionnaire survey of treatment choice for breast cancer patients with brain metastasis in Japan. Results of a nationwide survey by the task force of the Japanese Breast Cancer Society

    International Nuclear Information System (INIS)

    Matsumoto, Koji; Ando, Masashi; Yamauchi, Chikako

    2009-01-01

    A nationwide survey was performed to investigate the current patterns of care for brain metastasis (BM) from breast cancer in Japan. A total of 351 survey questionnaires were sent to community or academic breast oncologists who were members of the Japanese Breast Cancer Society as of December 2005. The questionnaire consists of 40 multiple choice questions in eight categories. Of 240 institutions sent survey questionnaires, 161 (67.1%) answered; 60% of institutions answered with '<5' patients with BM every year; almost half (83 of 161) screened for BM in asymptomatic patients; surgical resection was rarely performed, as ∼75% of institutions (118 of 160 institutions) answered 'none or one case of surgery per year'; 27% (41 of 154) preferred stereotactic radiosurgery (SRS) over whole-brain radiotherapy (WBRT) as the initial treatment in all cases, although ∼70% (100 of 154) of them answered 'depend on cases'. The preference for SRS over WBRT mainly depends on the impressions of breast oncologists about both safety (late normal tissue damage and dementia in WBRT) and efficacy (better local control by SRS). Eighty-one percent (117 of 144) of institutions did not limit the number of SRS sessions as far as technically applicable. SRS is widely used as the first choice for BM from breast cancer in Japan. Considerable numbers of Japanese breast oncologists prefer SRS over WBRT as the initial treatment for BM. A randomized trial comparing SRS and WBRT is warranted. (author)

  18. Role of Human Breast Cancer Related Protein versus P-Glycoprotein as an Efflux Transporter for Benzylpenicillin: Potential Importance at the Blood-Brain Barrier.

    Directory of Open Access Journals (Sweden)

    Yangfang Li

    Full Text Available While the blood-brain barrier (BBB protects the brain by controlling the access of solutes and toxic substances to brain, it also limits drug entry to treat central nervous system disorders. Many drugs are substrates for ATP-binding cassette (ABC transporters at the BBB that limit their entry into the brain. The role of those transporters in limiting the entry of the widely prescribed therapeutic, benzylpenicillin, has produced conflicting results. This study investigated the possible potential involvement of P-glycoprotein (P-gp and breast cancer resistance protein (BCRP, two ABC transporters, in benzylpenicillin transport at BBB in human using MDCKII cells overexpressing those transporters as well as pharmacological inhibition. MDCKII cells overexpressing human BCRP (MDCKII-BCRP but not those overexpressing human P-gp (MDCKII-MDR cells had reduced [3H]benzylpenicillin uptake. Similarly, inhibiting BCRP increased [3H]benzylpenicillin uptake in MDCKII-BCRP cells, while inhibiting P-gp in MDCKII-MDR cells had no effect on uptake although there was evidence that benzylpenicillin is a substrate for canine P-gp. While inhibiting BCRP affected [3H]benzylpenicillin cell concentrations it did not affect transepithelial flux in MDCKII-BCRP cells. In summary, the results indicate that human BCRP and not human P-gp is involved in benzylpenicillin transport. However, targeting BCRP alone was not sufficient to alter transepithelial flux in MDCKII cells. Whether it would be sufficient to alter blood-to-brain flux at the human BBB remains to be investigated.

  19. Propagators and path integrals

    Energy Technology Data Exchange (ETDEWEB)

    Holten, J.W. van

    1995-08-22

    Path-integral expressions for one-particle propagators in scalar and fermionic field theories are derived, for arbitrary mass. This establishes a direct connection between field theory and specific classical point-particle models. The role of world-line reparametrization invariance of the classical action and the implementation of the corresponding BRST-symmetry in the quantum theory are discussed. The presence of classical world-line supersymmetry is shown to lead to an unwanted doubling of states for massive spin-1/2 particles. The origin of this phenomenon is traced to a `hidden` topological fermionic excitation. A different formulation of the pseudo-classical mechanics using a bosonic representation of {gamma}{sub 5} is shown to remove these extra states at the expense of losing manifest supersymmetry. (orig.).

  20. Curvilinear crack layer propagation

    Science.gov (United States)

    Chudnovsky, Alexander; Chaoui, Kamel; Moet, Abdelsamie

    1987-01-01

    An account is given of an experiment designed to allow observation of the effect of damage orientation on the direction of crack growth in the case of crack layer propagation, using polystyrene as the model material. The direction of crack advance under a given loading condition is noted to be determined by a competition between the tendency of the crack to maintain its current direction and the tendency to follow the orientation of the crazes at its tip. The orientation of the crazes is, on the other hand, determined by the stress field due to the interaction of the crack, the crazes, and the hole. The changes in craze rotation relative to the crack define the active zone rotation.

  1. Atomistics of crack propagation

    International Nuclear Information System (INIS)

    Sieradzki, K.; Dienes, G.J.; Paskin, A.; Massoumzadeh, B.

    1988-01-01

    The molecular dynamic technique is used to investigate static and dynamic aspects of crack extension. The material chosen for this study was the 2D triangular solid with atoms interacting via the Johnson potential. The 2D Johnson solid was chosen for this study since a sharp crack in this material remains stable against dislocation emission up to the critical Griffith load. This behavior allows for a meaningful comparison between the simulation results and continuum energy theorems for crack extension by appropriately defining an effective modulus which accounts for sample size effects and the non-linear elastic behavior of the Johnson solid. Simulation results are presented for the stress fields of moving cracks and these dynamic results are discussed in terms of the dynamic crack propagation theories, of Mott, Eshelby, and Freund

  2. Broadband unidirectional ultrasound propagation

    Science.gov (United States)

    Sinha, Dipen N.; Pantea, Cristian

    2017-12-12

    A passive, linear arrangement of a sonic crystal-based apparatus and method including a 1D sonic crystal, a nonlinear medium, and an acoustic low-pass filter, for permitting unidirectional broadband ultrasound propagation as a collimated beam for underwater, air or other fluid communication, are described. The signal to be transmitted is first used to modulate a high-frequency ultrasonic carrier wave which is directed into the sonic crystal side of the apparatus. The apparatus processes the modulated signal, whereby the original low-frequency signal exits the apparatus as a collimated beam on the side of the apparatus opposite the sonic crystal. The sonic crystal provides a bandpass acoustic filter through which the modulated high-frequency ultrasonic signal passes, and the nonlinear medium demodulates the modulated signal and recovers the low-frequency sound beam. The low-pass filter removes remaining high-frequency components, and contributes to the unidirectional property of the apparatus.

  3. Propagation into an unstable state

    International Nuclear Information System (INIS)

    Dee, G.

    1985-01-01

    We describe propagating front solutions of the equations of motion of pattern-forming systems. We make a number of conjectures concerning the properties of such fronts in connection with pattern selection in these systems. We describe a calculation which can be used to calculate the velocity and state selected by certain types of propagating fronts. We investigate the propagating front solutions of the amplitude equation which provides a valid dynamical description of many pattern-forming systems near onset

  4. What Is Cancer?

    Science.gov (United States)

    ... on the head causes brain cancer or that bad people get cancer. This isn't true! Kids don't do anything wrong to get cancer. But some unhealthy habits, especially cigarette smoking or drinking too much alcohol ...

  5. Epidemiological features of brain tumors

    OpenAIRE

    Živković Nenad; Mihailović Goran; Marković Marko; Berisavac Iva; Spaić Milan

    2013-01-01

    Brain tumors account for 1.4% of all cancers and 2.4% of all cancer-related deaths. The incidence of brain tumors varies and it is higher in developed countries of Western Europe, North America, Australia and New Zealand. In Serbia, according to data from 2009, malignant brain tumors account for 2. 2 of all tumors, and from all cancer­related deaths, 3.2% is caused by malignant brain tumors. According to recent statistical reports, an overall incidence of b...

  6. Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: A Cochrane Review

    International Nuclear Information System (INIS)

    Lester, Jason Francis; MacBeth, Fergus R.; Coles, Bernadette

    2005-01-01

    Purpose: To investigate whether prophylactic cranial irradiation (PCI) has a role in the management of patients with non-small-cell lung cancer (NSCLC) treated with curative intent. Methods and Materials: A search strategy was designed to identify randomized controlled trials (RCTs) comparing PCI with no PCI in NSCLC patients treated with curative intent. The electronic databases MEDLINE, EMBASE, LILACS, and Cancerlit were searched, along with relevant journals, books, and review articles to identify potentially eligible trials. Four RCTs were identified and reviewed. A total of 951 patients were randomized in these RCTs, of whom 833 were evaluable and reported. Forty-two patients with small-cell lung cancer were excluded, leaving 791 patients in total. Because of the small patient numbers and trial heterogeneity, no meta-analysis was attempted. Results: Prophylactic cranial irradiation did significantly reduce the incidence of brain metastases in three trials. No trial reported a survival advantage with PCI over observation. Toxicity data were poorly collected and no quality of life assessments were carried out in any trial. Conclusion: Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit. It was not possible to evaluate whether any radiotherapy regimen is superior, and the effect of PCI on quality of life is not known. There is insufficient evidence to support the use of PCI in clinical practice. Where possible, patients should be offered entry into a clinical trial

  7. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial.

    Science.gov (United States)

    Mulvenna, Paula; Nankivell, Matthew; Barton, Rachael; Faivre-Finn, Corinne; Wilson, Paula; McColl, Elaine; Moore, Barbara; Brisbane, Iona; Ardron, David; Holt, Tanya; Morgan, Sally; Lee, Caroline; Waite, Kathryn; Bayman, Neil; Pugh, Cheryl; Sydes, Benjamin; Stephens, Richard; Parmar, Mahesh K; Langley, Ruth E

    2016-10-22

    Whole brain radiotherapy (WBRT) and dexamethasone are widely used to treat brain metastases from non-small cell lung cancer (NSCLC), although there have been no randomised clinical trials showing that WBRT improves either quality of life or overall survival. Even after treatment with WBRT, the prognosis of this patient group is poor. We aimed to establish whether WBRT could be omitted without a significant effect on survival or quality of life. The Quality of Life after Treatment for Brain Metastases (QUARTZ) study is a non-inferiority, phase 3 randomised trial done at 69 UK and three Australian centres. NSCLC patients with brain metastases unsuitable for surgical resection or stereotactic radiotherapy were randomly assigned (1:1) to optimal supportive care (OSC) including dexamethasone plus WBRT (20 Gy in five daily fractions) or OSC alone (including dexamethasone). The dose of dexamethasone was determined by the patients' symptoms and titrated downwards if symptoms improved. Allocation to treatment group was done by a phone call from the hospital to the Medical Research Council Clinical Trials Unit at University College London using a minimisation programme with a random element and stratification by centre, Karnofsky Performance Status (KPS), gender, status of brain metastases, and the status of primary lung cancer. The primary outcome measure was quality-adjusted life-years (QALYs). QALYs were generated from overall survival and patients' weekly completion of the EQ-5D questionnaire. Treatment with OSC alone was considered non-inferior if it was no more than 7 QALY days worse than treatment with WBRT plus OSC, which required 534 patients (80% power, 5% [one-sided] significance level). Analysis was done by intention to treat for all randomly assigned patients. The trial is registered with ISRCTN, number ISRCTN3826061. Between March 2, 2007, and Aug 29, 2014, 538 patients were recruited from 69 UK and three Australian centres, and were randomly assigned to

  8. Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

    Science.gov (United States)

    Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

    2016-01-19

    Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

  9. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

    International Nuclear Information System (INIS)

    Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

    2016-01-01

    To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2–4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were −12.8 and −24.7 % for Peak, −46.6 and −65.8 % for Slope, −27.9 and −55.5 % for iAUC 60 , and −46.6 and −63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. ClinicalTrials.gov, identifier NCT01281696, registered prospectively on December 24, 2010

  10. Long-Term Survival in Patients With Synchronous, Solitary Brain Metastasis From Non-Small-Cell Lung Cancer Treated With Radiosurgery

    International Nuclear Information System (INIS)

    Flannery, Todd W.; Suntharalingam, Mohan; Regine, William F.; Chin, Lawrence S.; Krasna, Mark J.; Shehata, Michael K.; Edelman, Martin J.; Kremer, Marnie; Patchell, Roy A.; Kwok, Young

    2008-01-01

    Purpose: To report the outcome of patients with synchronous, solitary brain metastasis from non-small-cell lung cancer (NSCLC) treated with gamma knife stereotactic radiosurgery (GKSRS). Patients and Methods: Forty-two patients diagnosed with synchronous, solitary brain metastasis from NSCLC were treated with GKSRS between 1993 and 2006. The median Karnofsky performance status (KPS) was 90. Patients had thoracic Stage I-III disease (American Joint Committee on Cancer 2002 guidelines). Definitive thoracic therapy was delivered to 26/42 (62%) patients; 9 patients underwent chemotherapy and radiation, 12 patients had surgical resection, and 5 patients underwent preoperative chemoradiation and surgical resection. Results: The median overall survival (OS) was 18 months. The 1-, 2-, and 5-year actuarial OS rates were 71.3%, 34.1%, and 21%, respectively. For patients who underwent definitive thoracic therapy, the median OS was 26.4 months compared with 13.1 months for those who had nondefinitive therapy, and the 5-year actuarial OS was 34.6% vs. 0% (p < 0.0001). Median OS was significantly longer for patients with a KPS ≥90 vs. KPS < 90 (27.8 months vs. 13.1 months, p < 0.0001). The prognostic factors significant on multivariate analysis were definitive thoracic therapy (p = 0.020) and KPS (p = 0.001). Conclusions: This is one of the largest series of patients diagnosed with synchronous, solitary brain metastasis from NSCLC treated with GKSRS. Definitive thoracic therapy and KPS significantly impacted OS. The 5-year OS of 21% demonstrates the potential for long-term survival in patients treated with GKSRS; therefore, patients with good KPS should be considered for definitive thoracic therapy

  11. Propagating annular modes

    Science.gov (United States)

    Sheshadri, A.; Plumb, R. A.

    2017-12-01

    The leading "annular mode", defined as the dominant EOF of surface pressure or of zonal mean zonal wind variability, appears as a dipolar structure straddling the mean midlatitude jet and thus seems to describe north-south wobbling of the jet latitude. However, extratropical zonal wind anomalies frequently tend to migrate poleward. This behavior can be described by the first two EOFs, the first (AM1) being the dipolar structure, and the second (AM2) having a tripolar structure centered on the mean jet. Taken in isolation, AM1 thus describes a north-south wobbling of the jet position, while AM2 describes a strengthening and narrowing of the jet. However, despite the fact that they are spatially orthogonal, and their corresponding time series temporally orthogonal, AM1 and AM2 are not independent, but show significant lag-correlations which reveal the propagation. The EOFs are not modes of the underlying dynamical system governing the zonal flow evolution. The true modes can be estimated using principal oscillation pattern (POP) analysis. In the troposphere, the leading POPs manifest themselves as a pair of complex conjugate structures with conjugate eigenvalues thus, in reality, constituting a single, complex, mode that describes propagating anomalies. Even though the principal components associated with the two leading EOFs decay at different rates, each decays faster than the true mode. These facts have implications for eddy feedback and the susceptibility of the mode to external perturbations. If one interprets the annular modes as the modes of the system, then simple theory predicts that the response to steady forcing will usually be dominated by AM1 (with the longest time scale). However, such arguments should really be applied to the true modes. Experiments with a simplified GCM show that climate response to perturbations do not necessarily have AM1 structures. Implications of these results for stratosphere-troposphere interactions are explored. The POP

  12. Propagation of Ion Acoustic Perturbations

    DEFF Research Database (Denmark)

    Pécseli, Hans

    1975-01-01

    Equations describing the propagation of ion acoustic perturbations are considered, using the assumption that the electrons are Boltzman distributed and isothermal at all times. Quasi-neutrality is also considered.......Equations describing the propagation of ion acoustic perturbations are considered, using the assumption that the electrons are Boltzman distributed and isothermal at all times. Quasi-neutrality is also considered....

  13. A phase II study of icotinib and whole-brain radiotherapy in Chinese patients with brain metastases from non-small cell lung cancer.

    Science.gov (United States)

    Fan, Yun; Huang, Zhiyu; Fang, Luo; Miao, Lulu; Gong, Lei; Yu, Haifeng; Yang, Haiyan; Lei, Tao; Mao, Weimin

    2015-09-01

    Icotinib is a new first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. A phase II study was conducted to evaluate the efficacy and safety of icotinib in combination with whole-brain radiotherapy (WBRT) in Chinese NSCLC patients with brain metastases (BMs); the cerebrospinal fluid (CSF)/plasma concentrations of icotinib were also investigated. Eligible patients had BMs from NSCLC, regardless of the EGFR status. Icotinib was administered at 125 mg orally 3 times/day until tumor progression or unacceptable toxicity, concurrently with WBRT (3.0 Gy per day, 5 days per week, to 30 Gy). CSF and plasma samples were collected simultaneously from 10 patients. Icotinib concentrations in the CSF and plasma were measured by high-performance liquid chromatography coupled with tandem mass spectrometry. Twenty patients were enrolled. The median follow-up time was 20.0 months. The overall response rate was 80.0%. The median progression-free survival time was 7.0 months (95% CI 1.2-13.2 months), and the median survival time (MST) was 14.6 months (95% CI 12.5-16.7 months). Of the 18 patients with known EGFR status, the MST was 22.0 months for those with an EGFR mutation and was 7.5 months for those with wild-type EGFR (P = 0.0001). The CSF concentration and penetration rate of icotinib were 11.6 ± 9.1 ng/mL and 1.4 ± 1.1%, respectively. No patient experienced ≥grade 4 toxicity. Icotinib was well tolerated in combination with WBRT and showed efficacy in patients with BMs from NSCLC. This clinical benefit was related to the presence of activating EGFR mutations.

  14. Propagation Engineering in Wireless Communications

    CERN Document Server

    Ghasemi, Abdollah; Ghasemi, Farshid

    2012-01-01

    Wireless communications has seen explosive growth in recent decades, in a realm that is both broad and rapidly expanding to include satellite services, navigational aids, remote sensing, telemetering, audio and video broadcasting, high-speed data communications, mobile radio systems and much more. Propagation Engineering in Wireless Communications deals with the basic principles of radiowaves propagation for frequency bands used in radio-communications, offering descriptions of new achievements and newly developed propagation models. The book bridges the gap between theoretical calculations and approaches, and applied procedures needed for advanced radio links design. The primary objective of this two-volume set is to demonstrate the fundamentals, and to introduce propagation phenomena and mechanisms that engineers are likely to encounter in the design and evaluation of radio links of a given type and operating frequency. Volume one covers basic principles, along with tropospheric and ionospheric propagation,...

  15. Transionospheric propagation predictions

    Science.gov (United States)

    Klobucher, J. A.; Basu, S.; Basu, S.; Bernhardt, P. A.; Davies, K.; Donatelli, D. E.; Fremouw, E. J.; Goodman, J. M.; Hartmann, G. K.; Leitinger, R.

    1979-01-01

    The current status and future prospects of the capability to make transionospheric propagation predictions are addressed, highlighting the effects of the ionized media, which dominate for frequencies below 1 to 3 GHz, depending upon the state of the ionosphere and the elevation angle through the Earth-space path. The primary concerns are the predictions of time delay of signal modulation (group path delay) and of radio wave scintillation. Progress in these areas is strongly tied to knowledge of variable structures in the ionosphere ranging from the large scale (thousands of kilometers in horizontal extent) to the fine scale (kilometer size). Ionospheric variability and the relative importance of various mechanisms responsible for the time histories observed in total electron content (TEC), proportional to signal group delay, and in irregularity formation are discussed in terms of capability to make both short and long term predictions. The data base upon which predictions are made is examined for its adequacy, and the prospects for prediction improvements by more theoretical studies as well as by increasing the available statistical data base are examined.

  16. Dressing the nucleon propagator

    International Nuclear Information System (INIS)

    Fishman, S.; Gersten, A.

    1976-01-01

    The nucleon propagator in the ''nested bubbles'' approximation is analyzed. The approximation is built from the minimal set of diagrams which is needed to maintain the unitarity condition under two-pion production threshold in the two-nucleon Bethe--Salpeter equation. Recursive formulas for subsets of ''nested bubbles'' diagrams calculated in the framework of the pseudoscalar interaction are obtained by the use of dispersion relations. We prove that the sum of all the ''nested bubbles'' diverges. Moreover, the successive iterations are plagued with ghost poles. We prove that the first approximation--which is the so-called chain approximation--has ghost poles for any nonvanishing coupling constant. In an earlier paper we have shown that ghost poles lead to ghost cuts. These cuts are present in the ''nested bubbles.'' Ghost elimination procedures are discussed. Modifications of the ''nested bubbles'' approximation are introduced in order to obtain convergence and in order to eliminate the ghost poles and ghost cuts. In a similar way as in the Lee model, cutoff functions are introduced in order to eliminate the ghost poles. The necessary and sufficient conditions for the absence of ghost poles are formulated and analyzed. The spectral functions of the modified ''nested bubbles'' are analyzed and computed. Finally, we present a theorem, similar in its form to Levinson's theorem in scattering theory, which enables one to compute in a simple way the number of ghost poles

  17. Validation and Development of a Modified Breast Graded Prognostic Assessment As a Tool for Survival in Patients With Breast Cancer and Brain Metastases.

    Science.gov (United States)

    Subbiah, Ishwaria M; Lei, Xiudong; Weinberg, Jeffrey S; Sulman, Erik P; Chavez-MacGregor, Mariana; Tripathy, Debu; Gupta, Rohan; Varma, Ankur; Chouhan, Jay; Guevarra, Richard P; Valero, Vicente; Gilbert, Mark R; Gonzalez-Angulo, Ana M

    2015-07-10

    Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases-a highly relevant clinical variable-is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials. © 2015 by American Society of Clinical Oncology.

  18. Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy.

    Science.gov (United States)

    Saligan, L N; Lukkahatai, N; Holder, G; Walitt, B; Machado-Vieira, R

    2016-12-01

    Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men. Fatigue, as measured by the 13-item Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and plasma neurotrophic factors were collected at baseline (prior to EBRT) and mid-EBRT. Subjects were categorized into fatigue and no fatigue groups using a > 3-point change in FACT-F scores between the two time points. Multiple linear regressions analysed the associations between fatigue and neurotrophic factors. FACT-F scores of 47 subjects decreased from baseline (43.95 ± 1.3) to mid-EBRT (38.36 ± 1.5, P fatigue. SNAPIN levels were associated with fatigue scores (r s = 0.43, P = 0.005) at baseline. A significant decrease of BDNF concentration (P = 0.008) was found in fatigued subjects during EBRT (n = 39). Baseline SNAPIN and decreasing BDNF levels may influence worsening fatigue during EBRT. Further investigations are warranted to confirm their role in the pathophysiology and therapeutics of fatigue.

  19. Cancer Stem Cells in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J., E-mail: christiane.bruns@med.uni-muenchen.de [Department of Surgery, Ludwig Maximilian University of Munich, Klinikum Grosshadern, Marchioninistr. 15, D-81377, Munich (Germany)

    2010-08-19

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  20. Cancer Stem Cells in Pancreatic Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Renner, Andrea; Niess, Hanno; Seeliger, Hendrik; Jauch, Karl-Walter; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer. PMID:24281178

  1. Cancer Stem Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Karl-Walter Jauch

    2010-08-01

    Full Text Available Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs. Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer.

  2. Dike Propagation Near Drifts

    International Nuclear Information System (INIS)

    2002-01-01

    The purpose of this Analysis and Model Report (AMR) supporting the Site Recommendation/License Application (SR/LA) for the Yucca Mountain Project is the development of elementary analyses of the interactions of a hypothetical dike with a repository drift (i.e., tunnel) and with the drift contents at the potential Yucca Mountain repository. This effort is intended to support the analysis of disruptive events for Total System Performance Assessment (TSPA). This AMR supports the Process Model Report (PMR) on disruptive events (CRWMS M and O 2000a). This purpose is documented in the development plan (DP) ''Coordinate Modeling of Dike Propagation Near Drifts Consequences for TSPA-SR/LA'' (CRWMS M and O 2000b). Evaluation of that Development Plan and the work to be conducted to prepare Interim Change Notice (ICN) 1 of this report, which now includes the design option of ''Open'' drifts, indicated that no revision to that DP was needed. These analyses are intended to provide reasonable bounds for a number of expected effects: (1) Temperature changes to the waste package from exposure to magma; (2) The gas flow available to degrade waste containers during the intrusion; (3) Movement of the waste package as it is displaced by the gas, pyroclasts and magma from the intruding dike (the number of packages damaged); (4) Movement of the backfill (Backfill is treated here as a design option); (5) The nature of the mechanics of the dike/drift interaction. These analyses serve two objectives: to provide preliminary analyses needed to support evaluation of the consequences of an intrusive event and to provide a basis for addressing some of the concerns of the Nuclear Regulatory Commission (NRC) expressed in the Igneous Activity Issue Resolution Status Report

  3. Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases

    Science.gov (United States)

    Gelman, Rebecca S.; Wefel, Jeffrey S.; Melisko, Michelle E.; Hess, Kenneth R.; Connolly, Roisin M.; Van Poznak, Catherine H.; Niravath, Polly A.; Puhalla, Shannon L.; Ibrahim, Nuhad; Blackwell, Kimberly L.; Moy, Beverly; Herold, Christina; Liu, Minetta C.; Lowe, Alarice; Agar, Nathalie Y.R.; Ryabin, Nicole; Farooq, Sarah; Lawler, Elizabeth; Rimawi, Mothaffar F.; Krop, Ian E.; Wolff, Antonio C.; Winer, Eric P.; Lin, Nancy U.

    2016-01-01

    Purpose Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2-positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. Patients and Methods Eligible patients were those with HER2-positive brain metastases (≥ 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: ≥50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression—the threshold for success was five of 40 responders. Results Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade ≥ 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. Conclusion Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies

  4. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  5. Laser beam propagation generation and propagation of customized light

    CERN Document Server

    Forbes, Andrew

    2014-01-01

    ""The text is easy to read and is accompanied by beautiful illustrations. It is an excellent book for anyone working in laser beam propagation and an asset for any library.""-Optics & Photonics News, July 2014

  6. Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: Results of phase I dose-escalation study.

    Science.gov (United States)

    Zhou, Lin; He, Jiazhuo; Xiong, Weijie; Liu, Yongmei; Xiang, Jing; Yu, Qin; Liang, Maozhi; Zhou, Xiaojuan; Ding, Zhenyu; Huang, Meijuan; Ren, Li; Zhu, Jiang; Li, Lu; Hou, Mei; Ding, Lieming; Tan, Fenlai; Lu, You

    2016-06-01

    Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are both treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. However, the dose-escalation toxicity and efficacy of combination therapy, and the effect of WBRT on cerebrospinal fluid (CSF) penetration of EGFR-TKIs are still unclear. EGFR-mutated NSCLC patients with brain metastases were enrolled in this study, and the cohorts were constructed with a 3+3 design. The patients received icotinib with escalating doses (125-625mg, tid), and the concurrent WBRT (37.5Gy/15f/3weeks) started a week later. The CSF penetration rates of icotinib were tested before, immediately after, and 4 weeks after WBRT, respectively. Potential toxicities and benefits from dose-escalation treatment were analyzed. Fifteen patients were included in this study, 3 at each dose level from 125mg-375mg and 6 at 500mg with 3 occurred dose-limiting toxicities. The maximal tolerated dose of icotinib was 375mg tid in this combination therapy. There was a significant correlation between icotinib concentration in the CSF and plasma (R(2)=0.599, Picotinib, from 1.2% to 9.7%, reached a maximum at 375mg (median, 6.1%). There was no significant difference for CSF penetration rates among the three test points (median, 4.1% vs. 2.8% vs. 2.8%, P=0.16). The intracranial objective response rate and median intracranial progression free survival are 80% and 18.9 months. WBRT plus concurrent icotinib is well tolerated in EGFR-mutated NSCLC patients with brain metastases, up to an icotinib dose of 375mg tid. The icotinib CSF concentration seemed to have a potential ceiling effect with the dose escalation, and WBRT seemed to have no significant impact on CSF penetration of icotinib till 4 weeks after the treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  8. Reference Data for Standardized Quality of Life Questionnaires in Indian Patients with Brain Metastases from Non-small Cell Lung Cancer: Results from a Prospective Study.

    Science.gov (United States)

    Aggarwal, Jaiprakash; Chakraborty, Santam; Ghosh Laskar, Sarbani; Patil, Vijay M; Prabhash, Kumar; Bhattacharya, Atanu; Noronha, Vanita; Purandare, Nilendu C; Joshi, Amit; Mummudi, Naveen; Arora, Jitendra; Badhe, Rupali

    2017-04-10

    Reference data for European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaires do not include studies from the Indian subcontinent. The objective of the current study was to establish a reference dataset for Indian patients of non-small cell lung cancer (NSCLC) presenting with brain metastases (BM). One hundred forty patients with NSCLC with BM treated between 2012-2015 were registered in a prospective cohort study (CTRI/2013/01/003299). The baseline quality of life was evaluated using the EORTC general quality of life questionnaire QLQ-C30 and lung cancer specific module LC13. Minimum important difference (MID) scores for individual domains of the EORTC QLQ-C30 and LC13 questionnaires were derived (MID = 0.2 x standard deviation) from the reference data for patients with recurrent/metastatic lung cancers. In addition, a systematic review was conducted to identify studies reporting baseline quality of life scores for recurrent/metastatic NSCLC. Scores of several functional as well as symptom scales in the current NSCLC population differed by more than the MID from the baseline mean scores in the reference EORTC population as well as that reported from other studies. Differences in mean score from the EORTC reference data ranged from 6.2 and 9.4 points for the role functioning and cognitive functioning domains. In the symptom scales, the largest differences were observed for the financial difficulties (23.9) scores for the QLQ-C30 and peripheral neuropathy (21.7) for LC13 questionnaires. The current study demonstrates that baseline reference scores need to be established for patients from the Indian subcontinent. The findings from the current study have important implications for studies employing quality of life (QOL) assessment in the Indian NSCLC patient population.

  9. The small-molecule kinase inhibitor D11 counteracts 17-AAG-mediated up-regulation of HSP70 in brain cancer cells.

    Science.gov (United States)

    Schaefer, Susanne; Svenstrup, Tina H; Guerra, Barbara

    2017-01-01

    Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years. Exposure of cancer cells to HSP90 inhibitors, including 17-AAG, has been shown to cause resistance to chemotherapeutic treatment mostly attributable to induction of the heat shock response and increased cellular levels of pro-survival chaperones. In this study, we show that treatment of glioblastoma cells with 17-AAG leads to HSP90 inhibition indicated by loss of stability of the EGFR client protein, and significant increase in HSP70 expression. Conversely, co-treatment with the small-molecule kinase inhibitor D11 leads to suppression of the heat shock response and inhibition of HSF1 transcriptional activity. Beside HSP70, Western blot and differential mRNA expression analysis reveal that combination treatment causes strong down-regulation of the small chaperone protein HSP27. Finally, we demonstrate that incubation of cells with both agents leads to enhanced cytotoxicity and significantly high levels of LC3-II suggesting autophagy induction. Taken together, results reported here support the notion that including D11 in future treatment regimens based on HSP90 inhibition can potentially overcome acquired resistance induced by the heat shock response in brain cancer cells.

  10. Heterogeneous incidence and propagation of spreading depolarizations

    Science.gov (United States)

    Kaufmann, Dan; Theriot, Jeremy J; Zyuzin, Jekaterina; Service, C Austin; Chang, Joshua C; Tang, Y Tanye; Bogdanov, Vladimir B; Multon, Sylvie; Schoenen, Jean; Ju, Y Sungtaek

    2016-01-01

    Spreading depolarizations are implicated in a diverse set of neurologic diseases. They are unusual forms of nervous system activity in that they propagate very slowly and approximately concentrically, apparently not respecting the anatomic, synaptic, functional, or vascular architecture of the brain. However, there is evidence that spreading depolarizations are not truly concentric, isotropic, or homogeneous, either in space or in time. Here we present evidence from KCl-induced spreading depolarizations, in mouse and rat, in vivo and in vitro, showing the great variability that these depolarizations can exhibit. This variability can help inform the mechanistic understanding of spreading depolarizations, and it has implications for their phenomenology in neurologic disease. PMID:27562866

  11. Brain Metastases Treatment Worsens Cognitive Decline

    Science.gov (United States)

    In some patients with cancer that has spread to the brain, whole brain radiation following radiosurgery causes more severe cognitive decline and does not improve survival compared with radiosurgery alone, a new study has found.

  12. Methodologies of Uncertainty Propagation Calculation

    International Nuclear Information System (INIS)

    Chojnacki, Eric

    2002-01-01

    After recalling the theoretical principle and the practical difficulties of the methodologies of uncertainty propagation calculation, the author discussed how to propagate input uncertainties. He said there were two kinds of input uncertainty: - variability: uncertainty due to heterogeneity, - lack of knowledge: uncertainty due to ignorance. It was therefore necessary to use two different propagation methods. He demonstrated this in a simple example which he generalised, treating the variability uncertainty by the probability theory and the lack of knowledge uncertainty by the fuzzy theory. He cautioned, however, against the systematic use of probability theory which may lead to unjustifiable and illegitimate precise answers. Mr Chojnacki's conclusions were that the importance of distinguishing variability and lack of knowledge increased as the problem was getting more and more complex in terms of number of parameters or time steps, and that it was necessary to develop uncertainty propagation methodologies combining probability theory and fuzzy theory

  13. Propagation engineering in wireless communications

    CERN Document Server

    Ghasemi, Abdollah; Ghasemi, Farshid

    2016-01-01

    This book covers the basic principles for understanding radio wave propagation for common frequency bands used in radio-communications. This includes achievements and developments in propagation models for wireless communication. This book is intended to bridge the gap between the theoretical calculations and approaches to the applied procedures needed for radio links design in a proper manner. The authors emphasize propagation engineering by giving fundamental information and explain the use of basic principles together with technical achievements. This new edition includes additional information on radio wave propagation in guided media and technical issues for fiber optics cable networks with several examples and problems. This book also includes a solution manual - with 90 solved examples distributed throughout the chapters - and 158 problems including practical values and assumptions.

  14. Wave propagation in electromagnetic media

    CERN Document Server

    Davis, Julian L

    1990-01-01

    This is the second work of a set of two volumes on the phenomena of wave propagation in nonreacting and reacting media. The first, entitled Wave Propagation in Solids and Fluids (published by Springer-Verlag in 1988), deals with wave phenomena in nonreacting media (solids and fluids). This book is concerned with wave propagation in reacting media-specifically, in electro­ magnetic materials. Since these volumes were designed to be relatively self­ contained, we have taken the liberty of adapting some of the pertinent material, especially in the theory of hyperbolic partial differential equations (concerned with electromagnetic wave propagation), variational methods, and Hamilton-Jacobi theory, to the phenomena of electromagnetic waves. The purpose of this volume is similar to that of the first, except that here we are dealing with electromagnetic waves. We attempt to present a clear and systematic account of the mathematical methods of wave phenomena in electromagnetic materials that will be readily accessi...

  15. Massive propagators in instanton fields

    International Nuclear Information System (INIS)

    Brown, L.S.; Lee, C.

    1978-01-01

    Green's functions for massive spinor and vector particles propagating in a self-dual but otherwise arbitrary non-Abelian gauge field are shown to be completely determined by the corresponding Green's functions of massive scalar particles

  16. Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

    Directory of Open Access Journals (Sweden)

    Nina P Connolly

    -associated microglia- and bone marrow-derived macrophages, and the formation of stem-like cell niches within the tumor. This transgenic rat model may enable detailed interspecies comparisons of fundamental cancer pathways and clinically relevant experimental imaging procedures and interventions that are limited by the smaller size of the mouse brain.

  17. Delayed Development of Brain Abscesses Following Stent-Graft Placement in a Head and Neck Cancer Patient Presenting with Carotid Blowout Syndrome

    International Nuclear Information System (INIS)

    Oweis, Yaseen; Gemmete, Joseph J.; Chaudhary, Neeraj; Pandey, Aditya; Ansari, Sameer

    2011-01-01

    We describe the delayed development of intracranial abscesses following emergent treatment with a covered stent-graft for carotid blowout syndrome (CBS) in a patient with head and neck cancer. The patient presented with hemoptysis and frank arterial bleeding through the tracheostomy site. A self-expandable stent-graft was deployed across a small pseudoaneurysm arising from the right common carotid artery (RCCA) and resulted in immediate hemostasis. Three months later, the patient suffered a recurrent hemorrhage. CT of the neck demonstrated periluminal fluid around the caudal aspect of the stent-graft with intraluminal thrombus and a small pseudoaneurysm. Subsequently, the patient underwent a balloon test occlusion study and endovascular sacrifice of the RCCA and right internal carotid artery. MRI of the brain demonstrated at least four ring-enhancing lesions within the right cerebral hemisphere consistent with intracranial abscesses that resolved with broad-spectrum antibiotic coverage.

  18. Propagation of dynamic measurement uncertainty

    International Nuclear Information System (INIS)

    Hessling, J P

    2011-01-01

    The time-dependent measurement uncertainty has been evaluated in a number of recent publications, starting from a known uncertain dynamic model. This could be defined as the 'downward' propagation of uncertainty from the model to the targeted measurement. The propagation of uncertainty 'upward' from the calibration experiment to a dynamic model traditionally belongs to system identification. The use of different representations (time, frequency, etc) is ubiquitous in dynamic measurement analyses. An expression of uncertainty in dynamic measurements is formulated for the first time in this paper independent of representation, joining upward as well as downward propagation. For applications in metrology, the high quality of the characterization may be prohibitive for any reasonably large and robust model to pass the whiteness test. This test is therefore relaxed by not directly requiring small systematic model errors in comparison to the randomness of the characterization. Instead, the systematic error of the dynamic model is propagated to the uncertainty of the measurand, analogously but differently to how stochastic contributions are propagated. The pass criterion of the model is thereby transferred from the identification to acceptance of the total accumulated uncertainty of the measurand. This increases the relevance of the test of the model as it relates to its final use rather than the quality of the calibration. The propagation of uncertainty hence includes the propagation of systematic model errors. For illustration, the 'upward' propagation of uncertainty is applied to determine if an appliance box is damaged in an earthquake experiment. In this case, relaxation of the whiteness test was required to reach a conclusive result

  19. The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30 in pre-operative patients with brain tumor in China

    Directory of Open Access Journals (Sweden)

    Zhang Hong-ying

    2011-04-01

    Full Text Available Abstract Background Health related quality of life (HRQOL has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0 in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery. Methods The questionnaire EORTC QLQ-C30 (version 3.0 was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery; T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status. Results Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms. Conclusions The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.

  20. Semiclassical propagation of Wigner functions.

    Science.gov (United States)

    Dittrich, T; Gómez, E A; Pachón, L A

    2010-06-07

    We present a comprehensive study of semiclassical phase-space propagation in the Wigner representation, emphasizing numerical applications, in particular as an initial-value representation. Two semiclassical approximation schemes are discussed. The propagator of the Wigner function based on van Vleck's approximation replaces the Liouville propagator by a quantum spot with an oscillatory pattern reflecting the interference between pairs of classical trajectories. Employing phase-space path integration instead, caustics in the quantum spot are resolved in terms of Airy functions. We apply both to two benchmark models of nonlinear molecular potentials, the Morse oscillator and the quartic double well, to test them in standard tasks such as computing autocorrelation functions and propagating coherent states. The performance of semiclassical Wigner propagation is very good even in the presence of marked quantum effects, e.g., in coherent tunneling and in propagating Schrodinger cat states, and of classical chaos in four-dimensional phase space. We suggest options for an effective numerical implementation of our method and for integrating it in Monte-Carlo-Metropolis algorithms suitable for high-dimensional systems.

  1. Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury.

    Directory of Open Access Journals (Sweden)

    Sonia Podvin

    Full Text Available By virtue of its ability to regulate the composition of cerebrospinal fluid (CSF, the choroid plexus (CP is ideally suited to instigate a rapid response to traumatic brain injury (TBI by producing growth regulatory proteins. For example, Esophageal Cancer Related Gene-4 (Ecrg4 is a tumor suppressor gene that encodes a hormone-like peptide called augurin that is present in large concentrations in CP epithelia (CPe. Because augurin is thought to regulate senescence, neuroprogenitor cell growth and differentiation in the CNS, we evaluated the kinetics of Ecrg4 expression and augurin immunoreactivity in CPe after CNS injury. Adult rats were injured with a penetrating cortical lesion and alterations in augurin immunoreactivity were examined by immunohistochemistry. Ecrg4 gene expression was characterized by in situ hybridization. Cell surface augurin was identified histologically by confocal microscopy and biochemically by sub-cellular fractionation. Both Ecrg4 gene expression and augurin protein levels were decreased 24-72 hrs post-injury but restored to uninjured levels by day 7 post-injury. Protein staining in the supraoptic nucleus of the hypothalamus, used as a control brain region, did not show a decrease of auguin immunoreactivity. Ecrg4 gene expression localized to CPe cells, and augurin protein to the CPe ventricular face. Extracellular cell surface tethering of 14 kDa augurin was confirmed by cell surface fractionation of primary human CPe cells in vitro while a 6-8 kDa fragment of augurin was detected in conditioned media, indicating release from the cell surface by proteolytic processing. In rat CSF however, 14 kDa augurin was detected. We hypothesize the initial release and proteolytic processing of augurin participates in the activation phase of injury while sustained Ecrg4 down-regulation is dysinhibitory during the proliferative phase. Accordingly, augurin would play a constitutive inhibitory function in normal CNS while down

  2. Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

    Science.gov (United States)

    Jeong, Hyeonseok S; Choi, Eun Kyoung; Song, In-Uk; Chung, Yong-An; Park, Jong-Sik; Oh, Jin Kyoung

    2017-01-01

    In preparation for 131 I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18 F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18 F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

  3. It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain.

    Science.gov (United States)

    Janssens, Derek H; Lee, Cheng-Yu

    2014-04-01

    During malignant transformation the cells of origin give rise to cancer stem cells which possess the capacity to undergo limitless rounds of self-renewing division, regenerating themselves while producing more tumor cells. Within normal tissues, a limitless self-renewal capacity is unique to the stem cells, which divide asymmetrically to produce more restricted progenitors. Accumulating evidence suggests that misregulation of the self-renewal machinery in stem cell progeny can lead to tumorigenesis, but how it influences the properties of the resulting tumors remains unclear. Studies of the type II neural stem cell (neuroblast) lineages in the Drosophila larval brain have identified a regulatory cascade that promotes commitment to a progenitor cell identity by restricting their response to the self-renewal machinery. Brain tumor (Brat) and Numb initiate this cascade by asymmetrically extinguishing the activity of the self-renewal factors. Subsequently, Earmuff (Erm) and the SWI/SNF complex stably restrict the competence of the progenitor cell to respond to reactivation of self-renewal mechanisms. Together, this cascade programs the progenitor cell to undergo limited rounds of division, generating exclusive differentiated progeny. Here we review how defects in this cascade lead to tumor initiation and how inhibiting the self-renewal mechanisms may be an effective strategy to block CSC expansion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A Neuro-oncologist's Perspective on Management of Brain Metastases in Patients with EGFR Mutant Non-small Cell Lung Cancer.

    Science.gov (United States)

    McGranahan, Tresa; Nagpal, Seema

    2017-04-01

    Management of non-small cell lung cancer (NSCLC) with brain metastasis (BrM) has been revolutionized by identification of molecular subsets that have targetable oncogenes. Historically, survival for NSCLC with symptomatic BrM was weeks to months. Now, many patients are surviving years with limited data to guide treatment decisions. Tumors with activating mutations in epidermal growth factor receptor (EGFRact+) have a higher incidence of BrM, but a longer overall survival. The high response rate of both systemic and BrM EGFRact+ NSCLC to tyrosine kinase inhibitors (TKIs) has led to the rapid incorporation of new therapies but is outpacing evidence-based decisions for BrM in NSCLC. While whole brain radiation therapy (WBRT) was the foundation of management of BrM, extended survival raises concerns for the subacute and late effects radiotherapy. We favor the use of TKIs and delaying the use of WBRT when able. At inevitable disease progression, we consider alternative dosing schedules to increase CNS penetration (such as pulse dosing of erlotinib) or advance to next generation TKI if available. We utilize local control options of surgery or stereotactic radiosurgery (SRS) for symptomatic accessible lesions based on size and edema. At progression despite available TKIs, we use pemetrexed-based platinum doublet chemotherapy or immunotherapy if the tumor has high expression of PDL-1. We reserve the use of WBRT for patients with more than 10 BrM and progression despite TKI and conventional chemotherapy, if performance status is appropriate.

  5. Could new reconstruction CT techniques challenge MRI for the detection of brain metastases in the context of initial lung cancer staging?

    Energy Technology Data Exchange (ETDEWEB)

    Millon, Domitille; Byl, David; Coche, Emmanuel E. [Universite Catholique de Louvain, Department of Radiology and Medical Imaging, Cliniques Universitaires Saint Luc, Brussels (Belgium); Collard, Philippe [Universite Catholique de Louvain, Department of Pneumology, Cliniques Universitaires Saint Luc, Brussels (Belgium); Cambier, Samantha E.; Maanen, Aline G. van [Universite Catholique de Louvain, Statistic Unit, King Albert II Cancer Institute, Brussels (Belgium); Vlassenbroek, Alain [Philips Healthcare, Brussels (Belgium)

    2018-02-15

    To evaluate the diagnostic performance of brain CT images reconstructed with a model-based iterative algorithm performed at usual and reduced dose. 115 patients with histologically proven lung cancer were prospectively included over 15 months. Patients underwent two CT acquisitions at the initial staging, performed on a 256-slice MDCT, at standard (CTDIvol: 41.4 mGy) and half dose (CTDIvol: 20.7 mGy). Both image datasets were reconstructed with filtered back projection (FBP) and iterative model-based reconstruction (IMR) algorithms. Brain MRI was considered as the reference. Two blinded independent readers analysed the images. Ninety-three patients underwent all examinations. At the standard dose, eight patients presented 17 and 15 lesions on IMR and FBP CT images, respectively. At half-dose, seven patients presented 15 and 13 lesions on IMR and FBP CT images, respectively. The test could not highlight any significant difference between the standard dose IMR and the half-dose FBP techniques (p-value = 0.12). MRI showed 46 metastases on 11 patients. Specificity, negative and positive predictive values were calculated (98.9-100 %, 93.6-94.6 %, 75-100 %, respectively, for all CT techniques). No significant difference could be demonstrated between the two CT reconstruction techniques. (orig.)

  6. The process of translation and linguistic validation of the Functional Assessment of Cancer Therapy-Brain quality of life instrument from English to Malayalam: The challenges faced

    Directory of Open Access Journals (Sweden)

    Durgapoorna Menon

    2017-01-01

    Full Text Available Aim: Both brain tumors and their treatments have a major negative impact on the quality of life (QoL. EORTC BN20 and Functional Assessment of Cancer Therapy-Brain (FACT-BR are the most commonly used tools to assess QoL. The FACT-BR is a 23-item questionnaire, especially about the psychosocial aspects of QoL. This paper describes the challenges we faced during the process of translation and validation of the FACT-BR into Malayalam. Methods: We first screened the patients to ensure their mental status was satisfactory and that they could communicate well in both languages. According to the Functional Assessment of Chronic Illness Therapy methodology, there were two forward translations from English to Malayalam by two independent translators, a reconciliation of the two forward translations, a back-translation into English, a review/finalization by a fifth translator, proofreading, and then testing on a small cohort of patients. Results: The whole process of translation was fraught with small and large hurdles – from small technical issues to the gaps in sociocultural norms. The sub item BR 7, due to the lack of an exact equivalent word, had issues that persisted up to the validation phase. The postquestionnaire debriefing interviews confirmed that the translations were well understood and conceptually equivalent to the original English one. Conclusions: Translation of the FACT-BR into Malayalam nearly completely reproduced the concepts of the original English questionnaire, as proved in the subsequent validation process.

  7. Developing Master Keys to Brain Pathology, Cancer and Aging from the Structural Biology of Proteins Controlling Reactive Oxygen Species and DNA Repair

    Science.gov (United States)

    Perry, J. Jefferson P.; Fan, Li; Tainer, John A.

    2007-01-01

    This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to varying extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression. PMID:17174478

  8. Stereotactic Radiosurgery in the Management of Patients With Brain Metastases of Non-Small Cell Lung Cancer: Indications, Decision Tools and Future Directions

    Directory of Open Access Journals (Sweden)

    Dianne Hartgerink

    2018-05-01

    Full Text Available Brain metastases (BM frequently occur in non-small cell lung cancer (NSCLC patients. Most patients with BM have a limited life expectancy, measured in months. Selected patients may experience a very long progression-free survival, for example, patients with a targetable driver mutation. Traditionally, whole-brain radiotherapy (WBRT has been the cornerstone of the treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS. This review discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS.

  9. Seizure characteristics and the use of anti-epileptic drugs in children and young people with brain tumours and epileptic seizures: Analysis of regional paediatric cancer service population.

    Science.gov (United States)

    Pilotto, Chiara; Liu, Jo-Fen; Walker, David A; Whitehouse, William P

    2018-03-21

    Epileptic seizures complicate the management of childhood brain tumours. There are no published standards for clinical practice concerning risk factors, treatment selection or strategies to withdraw treatment with antiepileptic drugs (AED). we undertook a case note review of 120 patients with newly diagnosed brain tumours, referred to a regional paediatric cancer service. data was available on 117/120 (98%) children seizures. A cortical tumour location was associated with the highest risk of seizures (OR: 7.1; CI 95% 2.9-17.3). At a median follow up of 24 months (IQR 25°-75° : 15-48), 22/35 (63%) with seizures, had a single seizure episode, 15/35 (43%) were seizure free (SF) on AEDs, 13/35 (37%) were SF off AEDs, and 7/35 (20%) experienced continuing epileptic seizures. Overall 34/35 (97%) were treated with AEDs after a seizure, of whom 12/35 (35%) withdrew from AED medication, and although 4/35 (12%) had seizure relapse, all were after further acute events. The median duration of AED before withdrawal was 11 months (IQR 25°-75° 5-14 months), and the median follow up after withdrawal was 15 months (IQR 25°-75° 5-34 months). Seizures affect about 1/3rd of children and young people presenting with and being treated for brain tumours particularly when the tumour is in the cerebral cortex. The low risk of recurrent seizures after AED treatment justifies consideration of early withdrawal of AED after seizure control. Copyright © 2018. Published by Elsevier Ltd.

  10. Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition.

    Directory of Open Access Journals (Sweden)

    Stuart J Smith

    Full Text Available INTRODUCTION: Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS. METHODS: CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS: Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS: Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system.

  11. Long-Term Survival of a Patient with Brainstem and Recurrent Brain Metastasis from Stage IV Nonsmall Cell Lung Cancer Treated with Multiple Gamma Knife Radiosurgeries and Craniotomies: A Case Report and Review of the Literature

    Science.gov (United States)

    Lamm, Andrew F.; Elaimy, Ameer L.; Mackay, Alexander R.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.; Taylor, Blake S.; Lamoreaux, Wayne T.

    2012-01-01

    The prognosis of patients diagnosed with stage IV nonsmall cell lung cancer that have brain and brainstem metastasis is very poor, with less than a third surviving a year past their initial date of diagnosis. We present the rare case of a 57-year-old man who is a long-term survivor of brainstem and recurrent brain metastasis, after aggressive treatment. He is now five and a half years out from diagnosis and continues to live a highly functional life without evidence of disease. Four separate Gamma Knife stereotactic radiosurgeries in conjunction with two craniotomies were utilized since his initial diagnosis to treat recurrent brain metastasis while chemoradiation therapy and thoracic surgery were used to treat his primary disease in the right upper lung. In his situation, Gamma Knife radiosurgery proved to be a valuable, safe, and effective tool for the treatment of multiply recurrent brain metastases within critical normal structures. PMID:23056973

  12. Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial.

    Science.gov (United States)

    Churilla, Thomas M; Ballman, Karla V; Brown, Paul D; Twohy, Erin L; Jaeckle, Kurt; Farace, Elana; Cerhan, Jane H; Anderson, S Keith; Carrero, Xiomara W; Garces, Yolanda I; Barker, Fred G; Deming, Richard; Dixon, Jesse G; Burri, Stuart H; Chung, Caroline; Ménard, Cynthia; Stieber, Volker W; Pollock, Bruce E; Galanis, Evanthia; Buckner, Jan C; Asher, Anthony L

    2017-12-01

    To determine whether whole-brain radiation therapy (WBRT) is associated with improved overall survival among non-small cell lung cancer (NSCLC) patients with favorable prognoses at diagnosis. In the N0574 trial, patients with 1 to 3 brain metastases were randomized to receive stereotactic radiosurgery (SRS) or SRS plus WBRT (SRS + WBRT), with a primary endpoint of cognitive deterioration. We calculated diagnosis-specific graded prognostic assessment (DS-GPA) scores for NSCLC patients and evaluated overall survival according to receipt of WBRT and DS-GPA score using 2 separate cut-points (≥2.0 vs <2.0 and ≥2.5 vs <2.5). A total of 126 NSCLC patients were included for analysis, with median follow-up of 14.2 months. Data for DS-GPA calculation were available for 86.3% of all enrolled NSCLC patients. Overall, 50.0% of patients had DS-GPA score ≥2.0, and 23.0% of patients had DS-GPA scores ≥2.5. The SRS and SRS + WBRT groups were well balanced with regard to prognostic factors. The median survival according to receipt of WBRT was 11.3 months (+WBRT) and 17.9 months (-WBRT) for patients with DS-GPA ≥2.0 (favorable prognoses, P=.63; hazard ratio 0.86; 95% confidence interval 0.47-1.59). Median survival was 3.7 months (+WBRT) and 6.6 months (-WBRT) for patients with DS-GPA <2.0 patients (unfavorable prognoses, P=.85; hazard ratio 0.95; 95% confidence interval 0.56-1.62). Outcomes according to the receipt of WBRT and DS-GPA remained similar utilizing DS-GPA ≥2.5 as a cutoff for favorable prognoses. There was no interaction between the continuum of the DS-GPA groups and WBRT on overall survival (P=.53). We observed no significant differences in survival according to receipt of WBRT in favorable-prognosis NSCLC patients. This study further supports the approach of SRS alone in the majority of patients with limited brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Multicriteria plan optimization in the hands of physicians: a pilot study in prostate cancer and brain tumors.

    Science.gov (United States)

    Müller, Birgit S; Shih, Helen A; Efstathiou, Jason A; Bortfeld, Thomas; Craft, David

    2017-11-06

    The purpose of this study was to demonstrate the feasibility of physician driven planning in intensity modulated radiotherapy (IMRT) with a multicriteria optimization (MCO) treatment planning system and template based plan optimization. Exploiting the full planning potential of MCO navigation, this alternative planning approach intends to improve planning efficiency and individual plan quality. Planning was retrospectively performed on 12 brain tumor and 10 post-prostatectomy prostate patients previously treated with MCO-IMRT. For each patient, physicians were provided with a template-based generated Pareto surface of optimal plans to navigate, using the beam angles from the original clinical plans. We compared physician generated plans to clinically delivered plans (created by dosimetrists) in terms of dosimetric differences, physician preferences and planning times. Plan qualities were similar, however physician generated and clinical plans differed in the prioritization of clinical goals. Physician derived prostate plans showed significantly better sparing of the high dose rectum and bladder regions (p(D1) plans indicated higher doses for targets and brainstem (p(D1) plan comparisons physicians preferred the clinical plans more often (brain: 6:3 out of 12, prostate: 2:6 out of 10) (not statistically significant). While times of physician involvement were comparable for prostate planning, the new workflow reduced the average involved time for brain cases by 30%. Planner times were reduced for all cases. Subjective benefits, such as a better understanding of planning situations, were observed by clinicians through the insight into plan optimization and experiencing dosimetric trade-offs. We introduce physician driven planning with MCO for brain and prostate tumors as a feasible planning workflow. The proposed approach standardizes the planning process by utilizing site specific templates and integrates physicians more tightly into treatment planning. Physicians

  14. Complete remission through icotinib treatment in Non-small cell lung cancer epidermal growth factor receptor mutation patient with brain metastasis: A case report

    Directory of Open Access Journals (Sweden)

    Wang Tao

    2016-01-01

    Full Text Available Brain metastasis (BM has been universally recognized as a poor prognostic factor in non-small cell lung cancer (NSCLC. Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have shown efficacy in treating BM with an EGFR mutation. This paper reports a case of BM patient with EGFR-mutated NSCLC. According to the findings, a complete remission (CR of the BM was achieved by icotinib treatment without conducting a radiotherapy, which was followed by a resection of the primary lung cancer lesion and lymph nodes. After one-year follow-up, the disease progressed to liver metastasis and liver lesion biopsy showed a T790M mutation. The patient responded well to the combination treatment of AZD9291 and icotinib after the failure of transcatheter arterial chemoembolization (TACE. This case report suggests that icotinib has a sustainable anticancer response to BM and the combination with icotinib and AZD9291 is effective for liver metastasis with T790M.

  15. Biofabrication of morphology improved cadmium sulfide nanoparticles using Shewanella oneidensis bacterial cells and ionic liquid: For toxicity against brain cancer cell lines.

    Science.gov (United States)

    Wang, Li; Chen, Siyuan; Ding, Yiming; Zhu, Qiang; Zhang, Nijia; Yu, Shuqing

    2018-01-01

    The present work determines the anticancer activity of bio-mediated synthesized cadmium sulfide nanoparticles using the ionic liquid and bacterial cells (Shewanella oneidensis). Bacterial cells have been exposed to be important resources that hold huge potential as ecofriendly, cost-effective, evading toxic of dangerous chemicals and the alternative of conventional physiochemical synthesis. The Shewanella oneidensis is an important kind of metal reducing bacterium, known as its special anaerobic respiratory and sulfate reducing capacity. The crystalline nature, phase purity and surface morphology of biosynthesized cadmium sulfide nanoparticles were analyzed by Fourier transform infrared spectroscopy, X-ray diffraction, Field emission scanning electron microscopy, Energy dispersive spectroscopy and Transmission electron microscopy. The use of imidazolium based ionic liquids as soft templating agent for controlling self-assembly and crystal growth direction of metal sulfide nanoparticles has also advanced as an important method. The microscopic techniques showed that the nanoparticles are designed on the nano form and have an excellent spherical morphology, due to the self-assembled mechanism of ionic liquid assistance. The antitumor efficiency of the cadmium sulfide nanoparticles was investigated against brain cancer cell lines using rat glioma cell lines. The effectively improved nano-crystalline and morphological structure of CdS nanoparticles in the presence of IL exhibit excellent cytotoxicity and dispersion ability on the cell shape is completely spread out showing a nice toxic environment against cancer cells. The cytotoxicity effect of cadmium sulfide nanoparticles was discussed with a diagrammatic representation. Copyright © 2017. Published by Elsevier B.V.

  16. Saturable active efflux by p-glycoprotein and breast cancer resistance protein at the blood-brain barrier leads to nonlinear distribution of elacridar to the central nervous system.

    Science.gov (United States)

    Sane, Ramola; Agarwal, Sagar; Mittapalli, Rajendar K; Elmquist, William F

    2013-04-01

    The study objective was to investigate factors that affect the central nervous system (CNS) distribution of elacridar. Elacridar inhibits transport mediated by P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and has been used to study the influence of transporters on brain distribution of chemotherapeutics. Adequate distribution of elacridar across the blood-brain barrier (BBB) and into the brain parenchyma is necessary to target tumor cells in the brain that overexpress transporters and reside behind an intact BBB. We examined the role of P-gp and Bcrp on brain penetration of elacridar using Friend leukemia virus strain B wild-type, Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) mice. Initially, the mice were administered 2.5 mg/kg of elacridar intravenously, and the plasma and brain concentrations were determined. The brain-to-plasma partition coefficient of elacridar in the wild-type mice was 0.82, as compared with 3.5 in Mdr1a/b(-/-) mice, 6.6 in Bcrp1(-/-) mice, and 15 in Mdr1a/b(-/-)Bcrp1(-/-) mice, indicating that both P-gp and Bcrp limit the brain distribution of elacridar. The four genotypes were then administered increasing doses of elacridar, and the CNS distribution of elacridar was determined. The observed and model predicted maximum brain-to-plasma ratios (Emax) at the highest dose were not significantly different in all genotypes. However, the ED50 was lower for Mdr1a/b(-/-) mice compared with Bcrp1(-/-) mice. These findings correlate with the relative expression of P-gp and Bcrp at the BBB in these mice and demonstrate the quantitative enhancement in elacridar CNS distribution as a function of its dose. Overall, this study provides useful concepts for future applications of elacridar as an adjuvant therapy to improve targeting of chemotherapeutic agents to tumor cells in the brain parenchyma.

  17. Group symmetries and information propagation

    International Nuclear Information System (INIS)

    Draayer, J.P.

    1980-01-01

    Spectroscopy concerns itself with the ways in which the Hamiltonian and other interesting operators defined in few-particle spaces are determined or determine properties of many-particle systems. But the action of the central limit theorem (CLT) filters the transmission of information between source and observed so whether propagating forward from a few-particle defining space, as is usual in theoretical studies, or projecting backward to it from measured things, each is only sensitive to averaged properties of the other. Our concern is with the propagation of spectroscopic information in the presence of good symmetries when filtering action of the CLT is effective. Specifically, we propose to address the question, What propagates and how. We begin with some examples, using both scalar and isospin geometries to illustrate simple propagation. Examples of matrix propagation are studied; contact with standard tensor algebra is established and an algorithm put forward for the expansion of any operator in terms of another set, complete or not; shell-model results for 20 Ne using a realistic interaction and two trace-equivalent forms are presented; and some further challenges are mentioned

  18. Selected Arterial Infusion Chemotherapy Combined with Target Drugs 
for Non-small Cell Lung Cancer with Multiple Brain Metastase

    Directory of Open Access Journals (Sweden)

    Jinduo LI

    2012-05-01

    Full Text Available Background and objective The aim of this study is to evaluate the efficacy of selected arterial infusion chemotherapy in treating non-small cell lung cancer (NSCLC with multiple brain metastases and corresponding factors to influencing prognosis. Methods From September 2008 to October 2011, a total of 31 patients of NSCLC with multiple brain metastases (≥3 received selected incranial, bronchial and corresponding target arterial infusion chemotherapy combined with EGFR-TKIs. Interventional treatment was performed every four weeks, two-six cycles with synchronized or sequential targeted drugs (erlotinib, gefitinib or icotinib. Follow-up CT and MRI were regularly finished at interval of four weeks after two cycles of interventional treatment were finished or during taking targeted drugs in order to evaluate efficacy of the therapy. The procedure was stopped for the tumor disease was worse or the patient could not tolerate the toxity of drugs any longer. Results 31 patients was performed two to six cycles of interventional therapy, 3cycles at average. Response assessment showed that 5 (16.1% patients got a complete response (CR, 7 (22.6% had a partial response (PR, 11 (35.5% had a stable disease (SD and 8 (25.8% had a progressive disease (PD. The objective response rate (ORR was 38.7%, and the disease control rate was 74.2%. The median progression free survival (PFS and overall survival (OS were 13.1 months and 15.1 months. The 6-month survival rate, one-year survival rate and two-year survival rate were 79%, 61.1%, and 31.1%, respectively. The patients’ OS and PFS were influenced by smoking state, tumor pathology, extracranial metastases, period of targeted drug taking and performance status, not by sex, age, before therapy and the total of brain metastases. Conclusion Selected arterial infusion chemotherapy with targeted drugs is one of the most effective and safe treatment to NSCLC with multiple brain metastases. Smoking status, tumor

  19. Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

    Science.gov (United States)

    Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

    2014-11-01

    Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brainpropagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mec