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Home > Wellness > Health Library > Childhood Central Nervous System Embryonal Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI]
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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization classification of nervous system tumors.[1,2] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.
Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification.
Disease Overview
Embryonal tumors are a collection of biologically heterogeneous lesions that share the tendency to disseminate throughout the nervous system via cerebrospinal fluid (CSF) pathways. Although there is significant variability, histologically these tumors are grouped together because they are at least partially composed of hyperchromatic cells (blue cell tumors on standard staining) with little cytoplasm, which are densely packed and demonstrate a high degree of mitotic activity. Other histologic and immunohistochemical features, such as the degree of apparent cellular transformation along identifiable cell lineages (ependymal, glial, etc.), can be used to separate these tumors to some degree. However, a convention, which has been accepted by the World Health Organization (WHO), also separates these tumors based on presumed location of origin within the central nervous system (CNS). Molecular studies have substantiated the differences between tumors arising in different areas of the brain and give credence to this classification approach.[4]
The pathologic diagnosis of embryonal tumors is primarily based on histological and immunohistological microscopic features. However, molecular genetic studies are employed increasingly to subclassify embryonal tumors. These molecular genetic findings are now being utilized for risk stratification and treatment planning.[5,6,7,8]
The most recent WHO categorization of embryonal tumors is as follows:[1]
Medulloblastomas are further subdivided, as noted in the Cellular and Molecular Classification of CNS Embryonal Tumors section of this summary.
Pineoblastoma, which in the past was conventionally grouped with embryonal tumors, is now categorized by the WHO as a pineal parenchymal tumor. Given that therapies for pineoblastomas are quite similar to those utilized for embryonal tumors, pineoblastomas are discussed in this summary. A somewhat closely aligned tumor, pineal parenchymal tumor of intermediate differentiation, has recently been identified, but is not considered an embryonal tumor and primarily arises in adults.[1,2]
The prognosis of embryonal tumors and pineoblastomas varies greatly depending on the following:[1,2,9]
It has become increasingly clear, especially for medulloblastomas, that outcome is also related to the molecular characteristics of the tumor, but this has not been definitively shown for other embryonal tumors.[4,7,10,11,12] Overall survival rates range from 40% to 90%, depending on the molecular subtype of the medulloblastoma and possibly other factors, such as extent of dissemination at time of diagnosis and degree of resection. Children who survive 5 years are considered cured of their tumor. Survival rates for other embryonal tumors are generally poorer, ranging from less than 5% to 50% and specifics are discussed within each subgroup in the summary.[13,14,15,16]
Figure 1. Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain. The posterior fossa is the region below the tentorium, which separates the cortex from the cerebellum and essentially denotes the region containing the brain stem, cerebellum, and fourth ventricle.
Embryonal tumors comprise 20% to 25% of primary CNS tumors (malignant brain tumors and pilocytic astrocytomas) arising in children. These tumors occur throughout the pediatric age spectrum but tend to cluster early in life. The incidence of embryonal tumors in children aged 1 to 9 years is fivefold to tenfold higher than is the incidence of embryonal tumors in adults.[17,18]
Medulloblastomas comprise the vast majority of pediatric embryonal tumors and by definition arise in the posterior fossa, where they constitute approximately 40% of all posterior fossa tumors. Other forms of embryonal tumors each make up 2% or less of all childhood brain tumors.
Clinical Features
The clinical features of childhood embryonal tumors depend on the location of the tumor and the age of the child at the time of presentation. Embryonal tumors tend to be quickly growing tumors and are usually diagnosed within 3 months of initial onset of symptoms.[19]
In approximately 80% of children, medulloblastomas arise in the region of the fourth ventricle. Most of the early symptomatology is related to blockage of CSF and resultant hydrocephalus. Children with medulloblastoma are usually diagnosed within 2 to 3 months of onset of symptoms and commonly present with the following:[20]
Twenty percent of patients with medulloblastoma will not have hydrocephalus at the time of diagnosis and are more likely to present initially with cerebellar deficits. For example, more laterally positioned medulloblastomas of the cerebellum may not result in hydrocephalus, and because of their location, are more likely to result in lateralizing cerebellar dysfunction (appendicular ataxia) manifested by unilateral dysmetria, unsteadiness, and weakness of the sixth and seventh nerves on the same side as the tumor. Later, as the tumor grows towards the midline and blocks CSF, the more classical symptoms associated with hydrocephalus become evident.
Cranial nerve findings are less common, except for unilateral or bilateral sixth nerve palsies, which are usually related to hydrocephalus.[20] At times, medulloblastomas will present explosively with the acute onset of lethargy and unconsciousness due to hemorrhage within the tumor.
In infants, the presentation of medulloblastoma is more variable and may include the following:
On examination, there may be bulging of the anterior fontanel due to increased intracranial pressure and abnormal eye movements, including eyes that are deviated downward (the so-called sun setting sign) due to loss of upgaze secondary to compression of the tectum of the midbrain.
Hereditary cancer predisposition syndromes associated with medulloblastoma
A small percentage of medulloblastoma cases arise in the setting of hereditary cancer predisposition syndromes. Syndromes known to be associated with medulloblastoma include the following:
Sometimes medulloblastoma may be the initial manifestation of the presence of germline mutations in these predisposition genes.
Other CNS embryonal tumors
For other embryonal tumors, presentation is also relatively rapid and depends on the location of the tumor in the nervous system. Pineoblastomas often result in hydrocephalus due to blockage of CSF at the third ventricular level and other symptoms related to pressure on the back of the brain stem in the tectal region. Symptoms may include a constellation of abnormalities in eye movements manifested by pupils that react poorly to light but better to accommodation, loss of upgaze, retraction or convergence nystagmus, and lid retraction (Parinaud syndrome). As they grow, these tumors may also cause hemiparesis and ataxia.
Supratentorial lesions, such as CNS neuroblastomas and ganglioneuroblastomas, will result in focal neurologic deficits, such as hemiparesis and visual field loss, depending on which portion of the cerebral cortex is involved. They may also result in seizures and obtundation. Medulloepitheliomas and ependymoblastomas may occur anywhere in the CNS and presentation is variable. Usually there is significant neurologic dysfunction associated with lethargy and vomiting.
Diagnostic and Staging Evaluation
Diagnosis is usually readily made by either magnetic resonance imaging (MRI) or computed tomography scan. MRI is preferable, as the anatomic relationship between the tumor and surrounding brain and tumor dissemination is better visualized.[19]
After diagnosis, evaluation of embryonal tumors is quite similar, essentially independent of the histologic subtype and the location of the tumor. Given the tendency of these tumors to disseminate throughout the CNS early in the course of illness, imaging evaluation of the neuraxis by means of MRI of the entire brain and spine is indicated. Preferably this is done prior to surgery, in order to avoid postoperative artifacts, especially blood. Such imaging can be difficult to interpret and must be performed in at least two planes, with and without the use of contrast enhancement (gadolinium).[34]
Following surgery, imaging of the primary tumor site is indicated to determine the extent of residual disease. In addition, lumbar CSF analysis is performed, if deemed safe. Neuroimaging and CSF evaluation are considered complementary, because as many as 10% of patients will have evidence of free-floating tumor cells in the CSF without clear evidence of leptomeningeal disease on MRI scan.[35] CSF analysis is conventionally done 10 to 21 days following surgery. If CSF is obtained within 10 days of the operation, detection of tumor cells within the spinal fluid is possibly related to the surgical procedure. In most staging systems, if fluid is obtained in the first few days following surgery and found to be positive, the positivity must be confirmed by a subsequent spinal tap to be considered of diagnostic significance. In cases where obtainment of fluid by a lumbar spinal tap is deemed unsafe, ventricular fluid can be obtained; however, it may not to be as sensitive as lumbar fluid assessment.[35]
Because embryonal tumors are rarely metastatic to the bone, bone marrow, or other body sites at the time of diagnosis, studies such as bone marrow aspirates, chest x-rays, or bone scans are not indicated, unless there are symptoms or signs suggesting organ involvement.
Additional diagnostic studies for patients with desmoplastic medulloblastoma
Patients with desmoplastic tumors with extensive nodularity should be carefully evaluated for stigmata of Gorlin syndrome.[25] One report observed that medulloblastoma with extensive nodularity (MBEN) was associated with Gorlin syndrome in 5 of 12 cases.[25] Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is an autosomal dominant disorder in which those affected are predisposed to the development of basal cell carcinomas later in life, especially in skin in the radiation portal. The syndrome can be diagnosed early in life by detection of characteristic dermatological and skeletal features such as keratocysts of the jaw, bifid or fused ribs, macrocephaly, and calcifications of the falx.[25]
Prognostic Factors
Various clinical and biologic parameters have been shown to be associated with the likelihood of disease control of embryonal tumors after treatment.[6] The significance of many of these factors have been shown to be predictive for medulloblastomas, although some are used to assign risk, to some degree, for other embryonal tumors. Parameters that are most frequently utilized to predict outcome include the following:[36,37]
In older studies, the presence of brain stem involvement for children with medulloblastoma was found to be a prognostic factor; it has not been found to be of predictive value in subsequent studies utilizing both radiation and chemotherapy.[34,36]
Extent of CNS disease at diagnosis
Patients with disseminated CNS disease at diagnosis are at highest risk for disease relapse.[35,36,37] Ten percent to 40% of patients with medulloblastoma have CNS dissemination at diagnosis, with infants having the highest incidence and adolescents and adults having the lowest incidence.
CNS primitive neuroectodermal tumors (PNETs) and pineoblastomas may also be disseminated at the time of diagnosis, although the incidence of dissemination may be somewhat less than that of medulloblastomas, with dissemination at diagnosis being documented in approximately 10% to 20% of patients.[13,14] Patients with CNS PNETs and pineoblastomas with disseminated disease at the time of diagnosis have a poor overall survival, with reported survival rates at 5 years ranging from 10% to 30%.[13,14,15,16]
Age at diagnosis
Age younger than 3 years at diagnosis (in the absence of histologic features of extensive nodularity) portends an unfavorable outcome for those with medulloblastoma and, possibly, other embryonal tumors.[38,39,40,41]
Amount of residual disease after definitive surgery
Determination of extent of resection has been supplanted by postoperative MRI measurement of the amount of residual disease after definitive surgery as a predictor of outcome.[34]
In older studies, the extent of resection for medulloblastomas was found to be related to survival.[36,37,42,43] Some studies still utilize the extent of resection after surgery to separate patients into risk groups. In a Children's Oncology Group (COG) study involving over 400 children with nondisseminated medulloblastomas, patients with a subtotal resection did not have a different progression-free survival or overall survival than patients with total or near-total resections.[34] In contrast, a contemporary German HIrnTumor and International Society of Paediatric Oncology (HIT-SIOP) study of 340 children reported that residual disease (>1.5 cm2) connoted a poorer 5-year event-free survival.[44]
In patients with other forms of embryonal tumors, the extent of resection has not been definitively shown to impact survival.[15]
Tumor histopathology
For medulloblastomas, histopathologic features such as large cell variant, anaplasia, and desmoplasia have been shown in retrospective analyses to correlate with outcome.[39,45,46] In prospective studies, immunohistochemical and histopathologic findings have not predicted outcome in children older than 3 years at diagnosis, with the exception of the anaplasia/large cell variant, which has been associated with poorer prognosis.[12,47] Several studies have observed that the histologic finding of desmoplasia, seen in patients aged 3 years and younger with desmoplastic medulloblastoma, especially MBEN, connotes a significantly better prognosis compared with outcome for infants and young children with classic or large cell/anaplastic medulloblastoma.[12,25,38,39,40]; [41][Level of evidence: 2A]
For other embryonal tumors, histologic variations have not been associated with differing outcome.
Biological/molecular tumor cell characteristics
A host of tumor cell characteristics have been associated with prognosis, primarily in children with medulloblastoma, including the following:
Genomic analyses (including RNA gene expression and DNA methylation profiles, as well as DNA sequencing to identify mutations) on both fresh-frozen and formalin-fixed, paraffin-embedded sections have identified molecular subtypes of medulloblastoma.[5,6,7,8,10,11,56,58,59,60,61,62,63,64] These subtypes include those characterized by WNT pathway activation and sonic hedgehog (SHH) pathway activation, as well as additional subgroups characterized by MYC or MYCN alterations and other genomic alterations.[5,6,7,8,10,11,56,58,59,60,61,62,63] Patients whose tumors show WNT pathway activation usually have an excellent prognosis, while patients with SHH pathway activated tumors generally show an intermediate prognosis. Outcome for the remaining patients is less favorable than that for patients with WNT pathway activation. Mutations in medulloblastoma cases are observed in a subtype-specific manner, with CTNNB1 mutations observed in the WNT subtype and with PTCH1, SMO, and SUFU mutations observed in the SHH subtype. The prognostic significance of recurring mutations is closely aligned with that of the molecular subtype with which they are associated.[6,65] At recurrence, the subtype remains unchanged from the original molecular subtype at diagnosis.[66]
Refer to the Biologically/molecularly defined subtypes of medulloblastoma section of this summary for more information on the subtypes of medulloblastoma.
For CNS PNETs, integrative genomic analysis has also identified molecular subtypes with different outcomes. (Refer to the Cellular and Molecular Classification of CNS Embryonal Tumors section for more detailed information.)
Follow-up After Treatment
Relapse in children with embryonal tumors is most likely to occur within the first 18 months of diagnosis.[44,67] Surveillance imaging of the brain and spine is usually undertaken at routine intervals during and after treatment (refer to Table 2). The frequency of such imaging, designed to detect recurrent disease at an early, asymptomatic state, has been arbitrarily determined and has not been shown to clearly influence survival.[68,69,70] Growth hormone replacement therapy has not been shown to increase the likelihood of disease relapse.[40]
By definition, medulloblastomas must arise in the posterior fossa.[1,2] The following five histologic types of medulloblastoma are recognized by the World Health Organization (WHO) classification:[1]
Significant attention has been focused on medulloblastomas that display anaplastic features, including increased nuclear size, marked cytological pleomorphism, numerous mitoses, and apoptotic bodies.[3,4] Using the criteria of anaplasia is subjective because most medulloblastomas have some degree of anaplasia. Foci of anaplasia may appear in tumors with histologic features of both classic and large cell medulloblastomas, and there is significant overlap between the anaplastic and large cell variant.[3,4] One convention is to consider medulloblastomas as anaplastic when anaplasia is diffuse (variably defined as anaplasia occurring in 50% to 80% of the tumor).
The incidence of medulloblastoma with the desmoplastic variant is higher in infants, is less common in children, and increases again in adolescents and adults. The desmoplastic variant subtype is different from MBEN; the nodular variant has an expanded lobular architecture. The nodular subtype occurs almost exclusively in infants and carries an excellent prognosis.[5,6]
Biologically/molecularly defined subtypes of medulloblastoma
Multiple medulloblastoma subtypes have been identified by integrative molecular analysis.[7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22] As of 2012, there was a general consensus that medulloblastoma can be molecularly separated into at least four subtypes; however, it is likely that further subclassification will occur.[20,21,23]
The following four core subtypes of medulloblastoma have been identified:[20,21,24]
The WNT subset is primarily observed in older children, adolescents, and adults and does not show a male predominance. The subset is believed to have brain stem origin, from the embryonal rhombic lip region. Subtype 1 tumors are associated with a very good outcome, especially in individuals with CTNNB1 mutations.[22,25]
Subtype 2 tumors show a bimodal age distribution and are observed primarily in children younger than 3 years and then later in life in older adolescence and adulthood. The tumors are believed to emanate from the external granular layer of the cerebellum. Prognosis for patients with SHH medulloblastoma appears to be negatively affected by other molecular genetic changes, such as chromosome 17p loss, chromosome 3q gain, chromothripsis, p53 amplification, TP53 mutation, and the finding of large cell/anaplastic histology.[21,26] The outcome for patients with SHH medulloblastoma is relatively favorable, primarily in children younger than 3 years and adults. This is likely because of the type of mutation present in the SHH pathway, given that patients with upstream mutations such as PTCH1, PTCH2, and SUFU have a more favorable prognosis than do patients with downstream mutations, such as GLI2.[27] Overall outcome in adolescents and young adults with SHH medulloblastoma is not different from that seen in patients with non-WNT pathway–activated tumors, except for patients with TP53 mutations and downstream SHH pathway mutations. Patients with unfavorable molecular findings have an unfavorable prognosis, with less than 50% of patients surviving after conventional treatment.[24,26,27,28]
Subtype 3 tumors occur throughout childhood and may occur in infants. Males outnumber females in a 2:1 ratio in this medulloblastoma subtype. Patients with subtype 3 tumors have a variable prognosis. Patients with MYC amplification or MYC overexpression have a poor prognosis, with less than 50% of these patients surviving 5 years after diagnosis. This poor prognosis is especially true in children younger than 4 years at the time of diagnosis.[24] However, patients with subtype 3 tumors without MYC amplification or MYC overexpression who are older than 3 years have a prognosis similar to most patients with medulloblastoma, with a 5-year progression-free survival rate greater than 70%.[28]
Subtype 4 tumors occur throughout infancy and childhood and into adulthood. They also predominate in males. The prognosis is better than Subtype 3 tumors but not as good as Subtype 1 tumors. Prognosis for Subtype 4 patients is affected by additional factors such as the presence of metastatic disease and chromosome 17p loss.[20,21]
Optimal ways of identifying the four core medulloblastoma subtypes for clinical use is under active study, and both immunohistochemical methods and methods based on gene expression analysis are under development.[25,29] It is likely that the classification of medulloblastoma into four major subtypes will be altered in the near future. Further subdivision within subgroups based on molecular characteristics is likely, although there is no consensus regarding an alternative classification.[20,23]
Whether the classification for adults with medulloblastoma has similar predictive ability in children is unknown.[21,24] In one study of adult medulloblastoma, MYC oncogene amplifications were rarely observed and tumors with 6q deletion and WNT activation (as measured by nuclear beta-catenin staining) did not share the excellent prognosis seen in pediatric medulloblastomas, although another study did confirm an excellent prognosis for WNT-activated tumors in adults.[21,24]
CNS Primitive Neuroectodermal Tumors (PNETs) and Pineoblastoma
Genome-wide molecular characterization of PNETs and pineoblastomas has demonstrated substantial heterogeneity among these tumors.[30]
Pineoblastoma is histologically similar to medulloblastoma; however, according to the WHO, its histogenesis is linked to the pineocyte (a type of pineal cell).[1]
CNS PNETs generally arise in the cerebrum or suprasellar region, but may arise in the brain stem and spinal cord.[31] According to the 2007 WHO classification, tumors demonstrating areas of distinct neuronal differentiation are termed cerebral neuroblastomas and, if ganglion cells are also present, ganglioneuroblastomas.
Biological subtypes of CNS PNETs
Integrative genomic analysis has been used to molecularly subdivide CNS PNETs, with subtypes defined primarily based on their gene expression profiles. In a study of 142 hemispheric tumors, the following three molecular subsets were identified:[32]
Survival was shortest for Group 1 tumors, although treatment varied among all three groups. Group 3 tumors showed the highest rate of metastatic disease at diagnosis.[32] Loss of INI1 protein expression in the absence of rhabdoid cell morphology has been identified in a small subset of CNS PNETs.[34][Level of evidence: 3iB]
Medulloepithelioma is identified as a histologically discrete tumor within the WHO classification system.[35,36] Medulloepithelioma tumors are rare and tend to arise most commonly in infants and young children. Medulloepitheliomas, which histologically recapitulate the embryonal neural tube, tend to arise supratentorially, primarily intraventricularly but may arise infratentorially, in the cauda, and even extraneural, along nerve roots.[35,36]
Ependymoblastoma is identified as a histologically discrete tumor within the WHO classification system; however, the existence of ependymoblastoma as a discrete entity has been questioned by others.[35] Ependymoblastoma tumors are rare and tend to arise most commonly in infants and young children. Ependymoblastoma is characterized by the presence of true multilayered (or ependymoblastic) rosettes.[37,38] The tumor has a supratentorial predilection, but like medulloepithelioma, it may occur in the spine, especially in the sacrococcygeal region.
Histologically, the tumor shares features with other embryonal tumors and with a rare tumor type, the embryonal tumor with abundant neuropil and true rosettes (ETANTR).[37,38,39,40] The latter entity is characterized by young age at diagnosis (median age of approximately 2 years), primarily supratentorial presentation, poor prognosis, and tumors showing true multilayered/ependymoblastic rosettes within a background of abundant neuropil-like areas.[38,40,41]
In addition to sharing clinical characteristics (i.e., age, primary site, and prognosis), ependymoblastoma and ETANTR show common genomic alterations, including chromosome 2 gain and focal amplification at chromosome band 19q13.42. The latter chromosome region contains a cluster of microRNA coding genes,[42] and its amplification appears to be present in virtually all pediatric embryonal tumors with true multilayered rosettes (i.e., ependymoblastoma and ETANTR).[41,42,43] By contrast, 19q13.42 amplification has not been detected in more than 300 other pediatric brain tumors, suggesting that it may be a useful diagnostic marker for ependymoblastoma and ETANTR.[41]
Staging of Medulloblastoma
Historically, staging was based on an intraoperative evaluation of both the size and extent of the tumor, coupled with postoperative neuroimaging of the brain and spine and cytological evaluation of cerebrospinal fluid (CSF) (the Chang system). Intraoperative evaluation of the extent of the tumor has been supplanted by neuraxis imaging prior to diagnosis and postoperative imaging to determine amount of primary site residual disease. The following tests and procedures are now used for staging:
The tumor extent is defined as:
Postoperative degree of residual disease is designated as:
Since the 1990s, prospective studies have been performed using this staging system to separate patients into average-risk and high-risk medulloblastoma subgroups.[2,3,4]
The presence of diffuse (>50% of the pathologic specimen) histologic anaplasia has been incorporated as an addition to staging systems. If diffuse anaplasia is found, patients with otherwise average-risk disease are up-staged to high-risk disease.
Staging of CNS Primitive Neuroectodermal Tumors (PNETs)
Patients with CNS PNETs are staged in a fashion similar to that used for children with medulloblastoma; however, the patients are not assigned to average-risk and high-risk subgroups for treatment purposes (refer to the Staging of Medulloblastoma section of this summary for more information).
Staging of Medulloepithelioma and Ependymoblastoma
Dissemination of both medulloepitheliomas and ependymoblastomas frequently occurs.[5,6] The tumors are staged in the same way as medulloblastoma; however, the patients are not assigned to average-risk and high-risk subgroups for treatment purposes (refer to the Staging of Medulloblastoma section of this summary for more information).
Staging of Pineoblastoma
Dissemination at the time of diagnosis occurs in 10% to 30% of patients.[7] Because of the location of the tumor, total resections are uncommon, and most patients have only a biopsy or a subtotal resection before postsurgical treatment.[7,8] Staging for children with pineoblastomas is the same as that performed for children with medulloblastoma; however, the patients are not assigned to average-risk and high-risk subgroups for treatment purposes (refer to the Staging of Medulloblastoma section of this summary for more information).[7]
Risk Stratification for Medulloblastoma
Risk stratification is based on neuroradiographic evaluation for disseminated disease, cerebrospinal fluid (CSF) cytological examination, postoperative neuroimaging evaluation for the amount of residual disease, and age of the patient. Patients older than 3 years with medulloblastoma have been stratified into the following two risk groups:
For younger children, in some studies for those younger than 3 years and for others younger than 4 or 5 years, similar separation into average-risk (no dissemination and ≤1.5 cm2 of residual disease) or high-risk (disseminated disease and/or >1.5 cm2 of residual disease) groups has been employed. Histologic findings of desmoplasia have also been used to connote a more favorable risk subgrouping, especially the medulloblastoma with extensive nodularity subgroup.
Assigning a risk group based on extent of resection and disease at diagnosis may not predict treatment outcome. Molecular genetics and histologic factors may be more informative.[4] Although molecular subdivisions will likely change risk characterization in the future, they are not yet used to assign treatment in North American prospective studies.
Treatment Modalities
Surgery is considered a standard part of treatment for histologic confirmation of tumor type and as a means to improve outcome. Total or near-total resections are considered optimal, if they can be performed safely.[1]
Postoperatively, children may have significant neurologic deficits caused by preoperative tumor-related brain injury, hydrocephalus, or surgery-related brain injury.[2][Level of evidence: 3iC] A significant number of patients with medulloblastoma will develop cerebellar mutism syndrome. Symptoms of cerebellar mutism syndrome include the following:
The etiology of cerebellar mutism syndrome remains unclear, although cerebellar vermian damage and/or disruption of cerebellar-cortical tracts has been postulated as the possible cause for the mutism.[3,4]; [5][Level of evidence: 3iC] In two Children's Cancer Group studies evaluating children with both average-risk and high-risk medulloblastoma, the syndrome has been identified in nearly 25% of patients.[4,5,6]; [7][Level of evidence: 3iiiC] Approximately 50% of patients with this syndrome manifest long-term, permanent neurologic and neurocognitive sequelae.[5,7]
Radiation therapy
Radiation therapy to the primary tumor site is usually in the range of 54 Gy to 55.8 Gy. This is usually given with a 1 cm to 2 cm margin around the primary tumor site, preferably by conformal techniques. For all medulloblastomas in children older than 3 or 4 years at diagnosis, craniospinal radiation therapy is given at doses ranging between 23.4 Gy and 36 Gy, depending on risk factors, such as extent of disease at diagnosis. Chemotherapy is routinely administered during and after radiation therapy.
For children younger than 3 years, efforts are made to omit or delay radiation, given the profound impact of radiation at this age. Children of all ages are susceptible to the adverse effects of radiation on brain development. Debilitating effects on neurologic/cognitive development, growth, and endocrine function have been frequently observed, especially in younger children.[8,9,10,11,12] The use of proton-beam therapy to reduce toxicity is under investigation.
Chemotherapy, usually given during and after radiation therapy, is a standard component of treatment for older children with medulloblastoma and other embryonal tumors. Chemotherapy can be used to delay and sometimes obviate the need for radiation therapy in 20% to 40% of children younger than 3 to 4 years with nondisseminated medulloblastoma.[13,14]; [12][Level of evidence: 3iiiC]
Children Older Than 3 Years with Average-Risk Medulloblastoma
Standard treatment options
Standard treatment options for children older than 3 years with newly diagnosed average-risk medulloblastoma include the following:
If deemed feasible, total or near-total removal of the tumor is considered optimal.[1]
Adjuvant therapy
Radiation therapy is usually initiated after surgery with or without concurrent chemotherapy.[15,16,17]
Adjuvant radiation therapy
Adjuvant chemotherapy
Chemotherapy is now a standard component of the treatment of children with average-risk medulloblastoma.
Children Older Than 3 Years with High-Risk Medulloblastoma
Standard treatment options for children older than 3 years who are newly diagnosed with medulloblastoma and have metastatic disease or have had a subtotal resection include the following:
As for those with average-risk disease, attempt at gross-total resection is considered optimal, if deemed feasible.[1] In those with disseminated disease at diagnosis, the degree of resection has not been shown to be an independent predictor of outcome.[30]
In high-risk patients, numerous studies have demonstrated that multimodality therapy improves the duration of disease control and overall disease-free survival (DFS).[29,31] Studies show that approximately 50% to 65% of patients with high-risk disease will experience long-term disease control.[15,29,31,32,33]; [34][Level of evidence: 1iiA]
Treatment options under clinical evaluation
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI website.
Children Aged 3 Years and Younger
Five-year DFS rates for young children with medulloblastoma have ranged between 30% and 70%, with most long-term survivors successfully treated with chemotherapy alone, having nondisseminated, totally resected tumors and histologic evidence of desmoplasia.[13,35,36]
The treatment of children younger than 3 to 4 years with newly diagnosed medulloblastoma continues to evolve. Therapeutic approaches have attempted to delay and, in some cases, avoid the use of craniospinal radiation therapy because of its deleterious effects on the immature nervous system. Results have been variable, and comparison across studies has been difficult because of differences in drug regimens used and the utilization of craniospinal and local boost radiation therapy at the end of chemotherapy or when children reached age 3 years in some studies.
Standard treatment options for children aged 3 years and younger with newly diagnosed medulloblastoma include the following:
If deemed feasible, complete surgical resection of the tumor is the optimal treatment. Surgical resectability is associated with histology, as patients with desmoplastic medulloblastoma or medulloblastoma with extensive nodularity (MBEN) have a higher rate of complete resection than do patients with classic medulloblastoma.[37,38]
Another treatment option for children younger than 3 years at diagnosis is chemotherapy followed by autologous stem cell rescue. Results of trials utilizing higher-dose, marrow-ablative chemotherapeutic regimens supported by stem cell rescue have also demonstrated that a subgroup of patients with medulloblastoma who are younger than 3 years at the time of diagnosis can be treated with chemotherapy alone.[14,47][Level of evidence: 2A]
This study is evaluating chemotherapy as given in the completed COG study COG-99703, which used multiagent chemotherapy followed by thiotepa-based, higher-dose, marrow-ablative chemotherapy and peripheral stem cell rescue, and randomly assigns patients to treatment with or without intravenous high-dose methotrexate.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood medulloblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Children Older Than 3 Years
Standard treatment options for children older than 3 years with newly diagnosed central nervous system primitive neuroectodermal tumor (CNS PNET) include the following:
After surgery, children with CNS PNETs usually receive treatment similar to that received by children with high-risk medulloblastoma.
Adjuvant radiation therapy and chemotherapy
Treatment of children aged 3 years and younger with CNS PNETs is similar to that outlined for children aged 3 years and younger with medulloblastoma. (Refer to the medulloblastoma Children Aged 3 Years and Younger section of this summary for more information).
With the use of chemotherapy alone, outcome has been variable, with survival rates at 5 years ranging between 0% and 50%.[6,7,8]; [9][Level of evidence: 2Di] The addition of craniospinal irradiation to chemotherapy-based regimens may successfully treat some children but with anticipated neurodevelopmental decline.[10][Level of evidence: 2A]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood supratentorial primitive neuroectodermal tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
There are few data on which to base treatment of newly diagnosed medulloepithelioma and ependymoblastoma tumors. Treatment considerations are usually the same as those for children with high-risk medulloblastoma and for children aged 3 years and younger at diagnosis with other embryonal tumors. (Refer to the Children Older Than 3 Years with High-Risk Medulloblastoma and the Children Aged 3 Years and Younger sections of this summary for more information.)
Prognosis is poor, with 5-year survival rates ranging between 0% and 30%.[1,2,3,4]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood ependymoblastoma and childhood medulloepithelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Standard treatment options for children older than 3 years with newly diagnosed pineoblastoma include the following:
Surgery is usually the initial treatment for pineoblastoma for diagnosis.[1] Total and near-total resection is infrequently obtained in pineoblastomas and the impact of the degree of resection on outcome is unknown.[2,3]
The usual postsurgical treatment for pineoblastomas begins with radiation therapy, although some trials have utilized preradiation chemotherapy. The total dose of radiation therapy to the tumor site is 54 Gy to 55.8 Gy using conventional fractionation.[2,3]
For patients with pineoblastoma, a variety of different treatment approaches are under evaluation, including the use of higher doses of chemotherapy following radiation supported by peripheral stem cell rescue and the use of chemotherapy during radiation.
Biopsy is usually performed to diagnose pineoblastoma.
Children aged 3 years and younger with pineoblastoma are usually treated initially with chemotherapy in the hope of delaying, if not obviating, the need for radiation therapy.[5] In children responding to chemotherapy, the timing and amount of radiation therapy required following chemotherapy is unclear. The addition of craniospinal irradiation to chemotherapy-based regimens may successfully treat some children but with anticipated neurodevelopmental decline.[6][Level of evidence: 2A]
High-dose, marrow-ablative chemotherapy with autologous bone marrow rescue or peripheral stem cell rescue has been used with some success in young children.[7][Level of evidence: 2Di]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood pineoblastoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Recurrence of all forms of central nervous system (CNS) embryonal tumors is not uncommon and usually occurs within 36 months of treatment. However, recurrent tumors may develop many years after initial treatment.[1,2] Disease may recur at the primary site or may be disseminated at the time of relapse. Sites of noncontiguous relapse may include the spinal leptomeninges, intracranial sites, and cerebrospinal fluid, in isolation or in any combination, and may be associated with primary tumor relapse.[1,2,3] Extraneural disease relapse may occur but is rare and is seen primarily in patients treated with radiation therapy alone.[4][Level of evidence: 3iiiA]
Studies have found that even in patients with nondisseminated disease at diagnosis, and independent of the dose of radiation therapy or the type of chemotherapy, approximately one-third of patients will relapse at the primary tumor site alone, one-third will relapse at the primary tumor site plus distant sites, and one-third will relapse at distant sites without relapse at the primary site.[1,2,3]
Treatment Options
There are no standard treatment options for recurrent childhood CNS embryonal tumors.
In most children, treatment is palliative and disease control is transient in patients previously treated with radiation therapy and chemotherapy, with over 90% progressing within 12 to 18 months. For young children, predominantly those younger than 3 years at diagnosis who were never treated with radiation therapy, longer-term control with reoperation, radiation therapy, and chemotherapy is possible.[3,5,6,7]
Treatment approaches may include the following:
At the time of relapse, a complete evaluation for extent of recurrence is indicated for all embryonal tumors. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities such as secondary tumors and treatment-related brain necrosis may be clinically indistinguishable from tumor recurrence. The need for surgical intervention must be individualized on the basis of the initial tumor type, the length of time between initial treatment and the reappearance of the lesion, and clinical symptomatology.
Patients with recurrent embryonal tumors who have already received radiation therapy and chemotherapy may be candidates for further radiation therapy depending on the site and dose of previous radiation, including reirradiation at the primary tumor site, focal areas of radiation therapy to sites of disseminated disease, and rarely, craniospinal radiation therapy.[8] In most cases, such therapy is palliative. Stereotactic radiation therapy and/or salvage chemotherapy can also be used (see below).[9]
High-dose chemotherapy with stem cell rescue
For patients who have previously received radiation therapy, higher-dose chemotherapeutic regimens, supported with autologous bone marrow rescue or peripheral stem cell support, have been used with variable results.[6,7,23,24,25,26][Level of evidence: 2A]; [27][Level of evidence: 3iiB]; [28,29][Level of evidence: 3iiiA]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood pineoblastoma, childhood ependymoblastoma, recurrent childhood medulloblastoma, recurrent childhood supratentorial primitive neuroectodermal tumor and childhood medulloepithelioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment of Newly Diagnosed Pineoblastoma
Added Jakacki et al. as reference 1.
Treatment of Recurrent Childhood CNS Embryonal Tumors
Added temozolomide as a chemotherapeutic agent used to treat recurrent central nervous system embryonal tumors (cited Cefalo et al. as reference 18).
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood central nervous system embryonal tumors. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Central Nervous System Embryonal Tumors Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Childhood Central Nervous System Embryonal Tumors Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/types/brain/hp/child-cns-embryonal-treatment-pdq. Accessed <MM/DD/YYYY>.
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.
Contact Us
More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site's Contact Form.
Call 1-800-4-CANCER
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
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The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
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For more information from the NCI, please write to this address:
Search the NCI Web site
The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.
There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.
Find Publications
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).
Last Revised: 2015-08-05
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text:
Thirty years ago, Ray Parker, Jr. got the call that changed his life.
The R&B vocalist-guitarist, previously best known for such hits as "The Other Woman" and "I Still Can't Get Over Loving You," was offered the opportunity to write the theme song for an upcoming Bill Murray-Dan Aykroyd-Harold Ramis comedy. He accepted -- and planted himself in pop culture history.
The film was the 1984 blockbuster "Ghostbusters." And the similarly named song was as big a hit as the movie itself.
"It went to No. 1 or No. 2 in 52 countries around the world," Parker remembers during a recent phone interview. "I like all my songs -- I am not partial to one or the other. But, obviously, the 'Ghostbusters' thing was so past being huge."
It remains his calling card to this day.
"Seven-year-old kids know who I am because of that song," says Parker, who performs Saturday at Yoshi's San Francisco. "That song is still popular with the kids today -- just like Mickey Mouse."
Parker had no clue he had written a song that people would be quoting from 30 years later.
"I had no idea that we were going to be talking about it in the first place -- in the first year," says the 60-year-old Southern California resident. "Just the phrase -- 'Who you gonna call?' -- I would have never thought it would be that popular. That's like 'What's happening?' or 'Hello, how you doing?' or 'Happy birthday' or something. It really caught on."
Of course, "Ghostbusters" is only part of Parker's story. As a solo artist, he scored several top 40 R&B hits in the '80s and early '90s. He's also worked with a who's who of the music industry, including Stevie Wonder, Aretha Franklin and Barry White.
"You learn something different from each person," says Parker, who was recently honored with a star on the Hollywood Walk of Fame. "Even if you're not trying to learn anything -- just being in the room with them and hanging out for a long time, you just pick up different things."
He can now pass on what he's learned to his four sons.
"I tell my kids, if you really want to do it, you have to be aggressive, go out and do it. And don't let anybody tell you that you're not good enough," he says. "I think fear is what stops most people from being successful."
It's been a long time since Parker released his last solo studio record -- 2006's "I'm Free." Yet, that drought should end soon.
"I'm building a new studio at my house," he says. "I'm going to try to get one record per year out. This one record every five or six years is way too slow. I don't like driving to the studios anymore, so I really need one at home."
Details: Parker plays 8 and 10 p.m. Saturday at Yoshi's San Francisco; $29-$39, www.yoshis.com.
ROCK RECITAL: Chester Farrow's life has been filled with two of my all-time favorite things:
Live music and the Oakland A's. And, I list those in no particular order.
The Walnut Creek native was hired to work the scoreboard for the mighty Green and Gold in 1969. He's been getting paid to watch the A's ever since. He also taught broadcast media courses at Monte Vista High School in Danville for more than three decades. Before retiring in 1999, Farrow produced many concerts at the school's theater -- featuring such local talents as Huey Lewis, Journey, Greg Kihn and Joe Satriani.
Once a year, Farrow joins with some former pupils to mount a concert -- dubbed the Rock and Roll Recital. The 16th annual Rock and Roll Recital is set for Thursday at the Village Theatre in Danville. The concert is a showcase for more than 40 guitar students, all under the tutelage of Danville musician Bruce Hock.
"This is such a thrill for the guitar students -- when will they ever have a chance to perform on a big stage?" Farrow says. "The energy is very high, and audiences love the show. The music is great."
Show time is 7 p.m., and tickets are $10 at www.villagetheatreshows.com. The event will also be Webcast live and for free at www.rockandrollrecital.com.
Follow Jim Harrington at Twitter.com/jimthecritic and www.facebook.com/jim.bayareanews.

subset: commoncrawl


text:
The best way to do calculations and figure stuff out.
Soulver helps you do quick calculations and work things out. It's quicker to use than a spreadsheet, and smarter and clearer than a traditional calculator.
You type out your problems as you would on paper, and Soulver calculates your answer as you type. You can do calculations over multiple lines, and use words alongside your numbers so they make sense.
Soulver is great for adding things up, easily doing percentages, and converting things, like currencies.
Use Soulver to play around with numbers, do "back of the envelope" quick calculations, and solve day-to-day problems.
Key Features:
- See all your calculations all the time, and go back and change any of them.
- Use words amid your calculations so your numbers make sense
- Easily do percentages ("$100 - 10%", "30 as a % of 200")
- See a running total of all your lines
- Do easy conversions ("10 USD in Euros, "25 meters in feet")
- Do calculations with stocks ("100 AAPL")
- Connect your lines together using answer tokens.
- Create variables to hold frequently used numbers
- All the standard mathematical functions.
- Support for calculations in binary & hex.
- Save and export your work.
See Soulver in action at Soulver.com
Required OS: not specified
Tags: productivity , numbers , math , shareware , calculator
13 Opinions
After using Soulver almost daily for about a month, it deserves the <3 I gave it. Life isn't all numbers, so why does a calculator have to be? Soulver understands natural English and picks out the necessary information to perform calculations. It even uses English words as constants for subsequent calculations. Results are displayed automatically without hitting the return key, and conversions to decimals, fractions, and even hex and binary happen on the fly.
Definitely watch the videos on the website to see just how intuitive and efficient Soulver is.
Same as frost, never heard of it before the mystery MacZOT deal. Seems cool but haven't needed it yet.
I got this as part of a MacZOT deal before I had even heard of it. Now it's my default calculator. Great stuff.
Page 2 of 2. 13 entries.


text:
Clinical Trial on Alzheimer Disease, Presbycusis and Hearing Aids
The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2007 by Hospices Civils de Lyon.
Recruitment status was Recruiting
Recruitment status was Recruiting
Hospices Civils de Lyon
Information provided by:
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
First received: June 18, 2007
Last updated: NA
Last verified: June 2007
History: No changes posted
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
This is a 12-months' randomized clinical trial that aims at studying the benefit of bilateral hearing aids in hearing impaired patients suffering from a slight to moderate stage Alzheimer disease.
The benefit of this intervention will be studied in the cognitive, behavioural, quality of life and economic fields.
2groups are involved in this trial: Intervention group: 12 months' treatment with active hearing aids, fitted hearing impairment Control group: 6 months' treatment with placebo hearing aids, followed with 6 months' active hearing aids, fitted hearing impairment
Alzheimer Disease
Device: Hearing aids used : PHONAK Savia and Valeo
|Study Type:
|Study Design:
|Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
|Official Title:
|Clinical Trial on Cognitive, Behavioural, Quality of Life and Medico-Economic Benefits of Hearing Aids in Alzheimer Disease Patients Suffering From Presbycusis
Resource links provided by NLM:
Genetics Home Reference related topics: Alzheimer disease nonsyndromic hearing loss
MedlinePlus related topics: Alzheimer's Disease Hearing Aids Hearing Disorders and DeafnessU.S. FDA Resources
Further study details as provided by Hospices Civils de Lyon:
Primary Outcome Measures:
- Cognitive benefit evaluated thanks to the ADAS-Cog scale [ Time Frame: Times of measurements: 0, 6th and 12th month ]
Secondary Outcome Measures:
- Cognitive scales: MMSE, Grober and Buschke, Digit symbol test [ Time Frame: 0, 6th and 12th month ]
- Behavioural scales: IADL, NPI [ Time Frame: 1st week, 3rd 6th 9th and 12th month ]
- Quality of life scales: Zarit scale and ADRQL [ Time Frame: Zarit scale(every 2 months during the study time), ADRQL (0, 6th and 12th month) ]
- Consumption questionnaire [ Time Frame: monthly ]
|Estimated Enrollment:
|Study Start Date:
|May 2007
|Ages Eligible for Study:
|65 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- > 65 year-old
- Medical diagnosis of Alzheimer disease
- No hearing aids in the last 2 years
- Motivated caregiver living with the patient
- Sensorineural hearing loss
Exclusion Criteria:
- Beginning of an anticholinesterasic treatment in the last 6 months
- Change in the anticholinesterasic treatment in the last 2 months
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00488007
Please refer to this study by its ClinicalTrials.gov identifier: NCT00488007
|Contact: Xavier PERROT, MD
|Xavier PERROT
|Lyon, France, 69495
|Contact: Xavier PERROT, MD 0033472666406 firstname.lastname@example.com
|Principal Investigator: Marc BONNEFOY, MD
Sponsors and Collaborators
Hospices Civils de Lyon
|Principal Investigator:
|Marc BONNEFOY, MD
|Hospices Civils de Lyon
More Information
Keywords provided by Hospices Civils de Lyon:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 23, 2016
|ClinicalTrials.gov Identifier:
|NCT00488007 History of Changes
|Other Study ID Numbers:
|Study First Received:
|June 18, 2007
|Last Updated:
|June 18, 2007
|Health Authority:
|France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Keywords provided by Hospices Civils de Lyon:
Alzheimer disease
Cognitive impairment
Sensorineural hearing loss
Hearing aids
Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Hearing Loss, Sensorineural
Hearing Loss
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Signs and Symptoms
ClinicalTrials.gov processed this record on August 23, 2016


text:
5 Moscato Brands You Have To Try
Want to make a super tasty meal for you and your man without spending hours over the stove cooking way too much food? Um, duh. Cue these recipestheyre super quick and practical, so you spend less of your night in the kitchen and more time, ahem, doing other stuff.
If you're in need of a no-fail, one-pot meal idea that's guaranteed to be a hit with your guy, look no further. This savory soup recipe had us at the word "bacon."
PREP: 10 minutes
COOK: 20 minutes
3 bacon strips, diced
1 small onion, chopped
1 clove garlic, minced
3 tablespoons all-purpose flour
1 teaspoon kosher salt
1 teaspoon dried basil
1/2 teaspoon freshly ground pepper
3 cups chicken broth
2 large baked potatoes, peeled and cubed
1 cup half-and-half or light cream
1/2 teaspoon hot pepper sauce
Shredded cheddar cheese (for garnish)
Minced fresh parsley (for garnish)
Cook your bacon in a large saucepan over medium-high heat until crisp, then drain the pan and set the bacon aside. Next, sauté the onion until it feels soft, then add in the garlic and sauté for an additional minute. Stir in the flour, salt, basil and pepper, mixing well, and allow that to cook for about five minutes. Gradually stir in the broth and bring your soup to a boil, stirring for two more minutes. Then, add the potatoes, cream and hot pepper sauce; heat through—but do not boil. Serve the soup into your bowls before garnishing with bacon, cheese and parsley.
23 Bourbon Cocktails You've Got To Try


text:
JAN 23, 2013 - The Nation
A Must Read - Share
On a day when most Americans were focused on the stirring second inaugural address of President Barack Obama – and on the broader majesty of the transference of an election result into a governing mandate – Republican state senators in Virginia hatched an elaborate scheme to rig the electoral system against democracy.
Prevented by an even 20-20 divide in the chamber from gerrymandering Senate districts to favor one party or the other, the Republicans knew that their only opening to draw lines that favored their candidates in this fall's off-year elections would be if at
Read More
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text:
The steelers are cash strapped, your not going to get a big name player in FA for that reason, but you can get a player that might fit in to our system that won't cost to much.
Another words, You'll get a K-Mart Suit, but don't expect an Armani
I do not think Brian Hartline will break the bank. He has a couple of things going against him. One, he doesn't score TD's, and two he is not going to go ahead of any of these free agents. He is going to be way down the pecking order.
Wide receiver
1. Greg Jennings: .
2. Dwayne Bowe: .
3. Mike Wallace:
4. Wes Welker:
5. Danny Amendola:
Steelers 2015 Draft???....Go Freak! As in....
1-Bernardrick McKinney MLB Mississippi State 6 ft 5 250 4.5 40 yard dash


text:
97 Minute Running Time
Genre/Subjects: Action/Adventure, Horror, Sci-Fi
Screens in The Watching Hour Friday, February 8 and Saturday, February 9 at 10pm
The "Tall Man" and his strange little Killer Sphere return for a second round in this sequel to the 1979 cult favorite. Mike Pearson (James LeGros) is still plagued by memories of the Tall Man (Angus Scrimm), an evil mortician who has risen from the grave and bleeds embalming fluid -- and tried to kill him as a boy. Mike has been a patient in a mental institution for the last decade, insisting that the Tall Man is real; he still appears in his dreams 10 years after their first encounter. When Mike changes his tune and says that the undead undertaker was merely a hallucination, he is finally released. However, Mike and his best friend, Reggie (Reggie Bannister), are actually out to find the Tall Man and put an end to his habits of grave-robbing and draining people's bodies with his flying brain-juicer. As they search for the Tall Man, Mike encounters Liz (Paula Irvine), a woman who has also appeared in his dreams, and she claims that she too has been pursued by the Tall Man. Phantasm II was followed by a third installment in 1994, and a fourth in 1998.
DIRECTOR: Don Coscarelli
Screenwriter: Don CoscarelliPrincipal Cast: James LeGros, Reggie Bannister, Angus Scrimm, Paula Irvine
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text:
Fernandes making big impact in the MLS
Former #Seawolves star scored first career MLS goal last week.
#Seawolves play at No. 6 UMBC on must-win Wednesday
Stony Brook needs a win to help America East Championship berth chances
#Seawolves tangle with Vermont on Senior Night Saturday
Stony Brook looking for three critical points against Vermont.
#Seawolves host Hartford Sunday in critical America East match
Stony Brook and Hartford tied in the conference standings.
Stony Brook concludes non-conference schedule at Lehigh Tuesday
#Seawolves are 1-0-1 against Lehigh all-time.
Career Honors
2012: Led the team in goals (9), assists (7), points (25) and shots (50)...started all 18 matches for the Seawolves...led the America East in game winning goals with 5...finished third in the America East in goals, points and assists...named a member of the Top Drawer National Team of the Week...named America East Conference Player of the Week once...converted a penalty kick goal at Villanova (Aug. 28)...assisted on a goal in a 2-0 win over St. Joseph's at the Kentucky Invitational (Sept.9)...named to Kentucky Invitational All-Tournament team...tallied a goal and an assist to help beat Fordham 2-1 (Sept. 14)...scored two goals to beat Buffalo 4-0 (Sept. 16)...after a great weekend with three goals and one assist, Fernandes was named a member of the Top Drawer National Team of the Week as well as America East Conference Player of the Week. (Sept. 17)... scored his third straight game winning goal to top Sacred Heart 2-1 (Sept. 19)...recorded the tieing goal late in the second half in a 1-1 tie at CCSU (Sept. 22)...converted a penalty kick for the 1-0 game winner against Albany (Sept. 29)...extended his point streak to seven games with an assist against Boston University (Oct. 5)...scored the game-winning goal in the 73rd minute against Hartford (Oct. 13)...recorded a goal and an assist in a 5-4 comeback win over Binghamton. (Nov. 3)
2011: Appeared in and started all 20 games...led Stony Brook in scoring with nine goals and seven assists for 20 points...named the America East Midfielder of the Year, first-team All-America East and first-team NSCAA All-Northeast Region...now Stony Brook's all-time Div. I leader in goals scored (22)...succesfully converted penalty kick to goal vs. High Point (Sept. 9)...assisted on game-winning goal vs. Fairleigh Dickinson (Sep. 18)...assisted on a goal vs. Fairfield (Sept. 20)...scored two goals at Temple (Sept. 25)...recorded goal and assisted on the game-winner vs. Vermont (Oct. 7)...converted a penalty kick and assisted on a goal in the win over Binghamton (Oct. 22)...had a goal and an assist in the America East Championship semifinals vs. Albany (Nov. 9)...set the America East Championship record with a five-point performance in Stony Brook's 4-2 title-clinching win over Hartford (Nov. 13)...selected to the All-Tournament team and was named the Most Outstanding Player.
2010: Started 17 games...finished second on the team in goals (6) and points (13)...named the America East Midfielder of the Year and first-team All-America East...scored seven points in one weekend...had a goal on a penalty kick and added an assist in 4-2 win over Central Connecticut State (Sept. 17)...followed up with both of Stony Brook's goals, including the game-winner in the 74th minute, in 2-1 victory vs. Bryant (Sept. 19)...named America East Player of the Week for week ending Sept. 19...named to the College Soccer News National Team of the Week for week ending Sept. 19...named SimplexGrinnell Stony Brook Athlete of the Week for week ending Sept. 19...scored the game-winning goal in 3-2 win over Quinnipiac (Sept. 26)...scored on a penalty kick against Boston University (Oct. 2)...scored the game-winning goal in 2-0 win at Albany (Oct. 9)...named America East Player of the Week on Oct. 11.
2009: Outstanding freshman year...America East Rookie of the Year, second team All-Conference and All-Rookie team selection...led Seawolves with seven goals and 16 points...tied Shane Arikian's '04 Division I program record for goals by a freshman...played in 19 games, starting 17...scored first career goal at St. John's (9/11) on a penalty kick...scored two goals at Evansville (9/20)... three of four goals scored during conference play were game-winners...tallied goals against Binghamton (10/10), Vermont (10/21) and Hartford (10/31)...sealed America East Championship with tally against UMBC (11/12)...two-time America East Rookie of the Week.
High School: A four-year letterwinner at North Babylon High School for coach Michael Cashman...one of the top scorers in Suffolk County...earned first team All-State and All-Region honors...named League III MVP after tallying 14 goals and 20 assist s as a senior...finished high school career with 32 goals and 36 assists... chosen as a U.S. Soccer Developmental Academy U-15/16 Northeast Best XI at midfield...played club soccer for B.W. Gottschee...high school teammate of Antonio Crespi.
Personal: Leonardo Fernandes...born December 23, 1991 in Brazil...son of Carlos, who played professionally in Brazil, and Ana Fernandes...brother of Kaique, Gabriele and Gustavo...majoring in Arts & Sciences.
Career Statistics


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Career credit programs are specialized offerings designed to provide the educational needs of the lifelong learners in our community. Although no college credit will be awarded for these programs, students may earn continuing education units (CEU's) or Continuing Professional Education (CPE). Certificates of completion are awarded for each course listing for continuing education documentation purposes.
Career credit programs are managed by:
Workforce,Economic and Community Development
Phone: 276.656.0260


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With war in Iraq on the horizon, some Muslim Americans worry about the possibility of anti-Islamic backlash in the U.S.
The mosque in Tallahassee was attacked in the wake of Sept. 11, and members want to be sure nothing like that happens this time around. There is certainly a lot of concern and measures are being taken.
The council on American Islamic relations is urging mosques and Muslim leaders to pass out a nine page Muslim Safety Kit.
The kit helps American Muslims deal with hate and discrimination. It teaches them how to respond to bomb threats, check suspicious mail, and to report suspicious activity.
Leon County Sheriff Larry Campbell says that hate crimes against Muslims carry steep penalties in Florida and patrols of local Mosques will be stepped up.
wctv6.com Extended Web Coverage
Who Commits Hate Crimes?
Why Do People Commit Hate Crimes?
What is the Emotional Damage
Source: http://www.apa.org/pubinfo/hate/ (American Psychological Association Web Site)


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Hi - I've got some video files shot with my Canon HF10. These play fine using PS3 Media Server, but what doesnt work is the thumbnail of each clip, so currently we need to guess what we're going to be watching! Anyone know if there's a fix for this?
thanks guys


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The Ultimate Guide to Face Shapes
Oval, square, round or diamond? Identifying which one of the common face shapes you have will help dictate your best haircut and makeup options
Find out what your face shape is now.
Let's say that we solve that little dilemma right now, shall we? Figuring out your face shape (and, best haircut) is really not that complicated (or scary) -- all you need is a mirror, a steady hand, a critical eye and your basic kindergarten knowledge of fundamental shapes. So, what do you say? Are you ready to unlock the mystery of your face shape once and for all and begin to reap the haircut and makeup benefits that finally knowing it will surely bring? Find out which of the face shapes you have here.
SEE NEXT PAGE: How to Identify Your Face Shape
Older comments
Nor the 6th
by brbara_paula_acosta_prez Tuesday, April 30, 2013 at 04:46PM Report as inappropriate
I don't think the 5th question is ok
by brbara_paula_acosta_prez Tuesday, April 30, 2013 at 04:39PM Report as inappropriate
by EricaF123 Friday, February 15, 2013 at 05:44AM Report as inappropriate
My face is very long and I have to be careful with how I wear my hair so it doesn't drag it further. Thanks!
by klfnwf Saturday, December 8, 2012 at 05:20AM Report as inappropriate
I think I have a round face.
by crystal_rangel Monday, June 11, 2012 at 05:54PM Report as inappropriate
thanks! very informative!
by MiSSxLusciouSxLokitA Wednesday, May 30, 2012 at 02:19PM Report as inappropriate
I'm heart shaped
by TBjunkie Tuesday, April 17, 2012 at 12:21AM Report as inappropriate
heart shaped face. very helpful
by bianca_renee_luoni Saturday, March 24, 2012 at 05:44PM Report as inappropriate
I have round face...I wish I liked my shape more! :)
by powerwoman033 Sunday, March 11, 2012 at 08:01PM Report as inappropriate
great info, thanks. I really needed to know.
by coffeechic65 Friday, March 9, 2012 at 11:04AM Report as inappropriate
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Authorities in both Florida and Georgia are on heavy traffic patrols this Christmas.
Georgia troopers say being visible during this travel season is helping save lives.
Drivers in Georgia and Florida are noticing a larger police presence on area highways this year.
Troopers with the Georgia State Patrol hope the added patrols will reduce the number of holiday accidents and deaths.
"Anybody caught drinking and driving are going to pay the ultimate price of going to jail and possibly losing their license," says Anthony Heath of the Georgia State Police.
GSP is expecting a slow travel day on Christmas, but another busy travel day on Friday.
wctv6.com Extended Web Coverage
Holiday Driving Tips
Vehicle Preparation and Packing
Trailers and Caravans
Driver Fatigue
Keep Your Cool
Buckle Up
Share the Road
Source: A compilation of Web Reports contributed to this report.ed to this report.


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Size, it seems, does matter when it comes to the popularity of dogs.
The Amercian Kennel Club has released it's list of most popular dogs in the United States, giving most of its top spots to the massive canines.
"Bigger breeds are making their move," says AKC spokeswoman Lisa Peterson. "The popularity of the pint-sized, portable pooch just gave way to a litter of larger breeds in the Top 10. These predictable, durable, steady breeds, such as Labs and Goldens, are great with kids and offer the whole family more dog to love."
There was some shifting of rankings on the 2012 list as compared with the 2011 list, but none of the most favorites fell out of the Top 10.
The Labrador retriever remained top dog and the bulldog muscled his way into the Top Five, shoving the tiny Yorkshire terrier into sixth place.
San Francisco put its own spin on the list. The AKC identified the city's favorite fives as the Labrador retriever, French bulldog, Golden Retriever, Pembroke Welsh corgi and Bernese mountain dog
Here's the national Top 10 for both years.
1. Labrador retriever
2. German shepherd
3. Golden retriever
4. Beagle
5. Bulldog
6. Yorkshire terrier
7. Boxer
8. Poodle
9. Rottweiler
10. Dachshund
1. Labrador retriever
2. German shepherd
3. Beagle
4. Golden retriever
5. Yorkshire terrier
6. Bulldog
7. Boxer
8. Poodle
9. Dachshund
10. Rottweiler


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Leukemia & Lymphoma
Adult Non-Hodgkin Lymphoma Treatment (PDQ®): Treatment - Patient Information [NCI] - About This PDQ Summary
- General Information About Adult Non-Hodgkin Lymphoma
- Stages of Adult Non-Hodgkin Lymphoma
- Recurrent Adult Non-Hodgkin Lymphoma
- Treatment Option Overview
- Treatment Options for Non-Hodgkin Lymphoma
- To Learn More About Adult Non-Hodgkin Lymphoma
- Changes to This Summary (04 / 25 / 2014)
- About This PDQ Summary
- Get More Information From NCI
About PDQ
Physician Data Query (PDQ) is the National Cancer Institute's (NCI's) comprehensive cancer information database. The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries come in two versions. The health professional versions have detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions have cancer information that is accurate and up to date and most versions are also available in Spanish.
Recommended Related to Non-Hodgkin's Lymphoma
Acute lymphoblastic leukemia (ALL) is a type of blood cancer. Also known as acute lymphocytic leukemia or acute lymphoid leukemia, it is the least common type of leukemia in adults. Here's what you need to know about symptoms, prognosis, survival rates, and treatment for ALL.
Read the Acute Lymphoblastic Leukemia article > >
PDQ is a service of the NCI. The NCI is part of the National Institutes of Health (NIH). NIH is the federal government's center of biomedical research. The PDQ summaries are based on an independent review of the medical literature. They are not policy statements of the NCI or the NIH.
Purpose of This Summary
This PDQ cancer information summary has current information about the treatment of adult non-Hodgkin lymphoma. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.
Reviewers and Updates
Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change.
The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Adult Treatment Editorial Board.
Clinical Trial Information
A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.


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5 Latina Beauty Experts to Follow on Instagram
The black and white trends are already rolling in this year and we are so excited to see what's to come. This geometric shoe offers a new take on traditional black and white, pair with colored jeans to add a really cool contrast.
The zig-zags on this flat give a laid back feel we've been missing all winter long. Jeffrey Campbell's 'Lovins' flat gives us the perfect mix of cover up and sexy to lead into spring.
Lingerie Tips You Need to Know


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Q:�What are foam rollers used for?�A:�A foam roller�a cylinder-shaped log of hard foam�is used like a rolling pin to stretch your tendons, and is a great way to warm up for activity. I find this tool especially good for loosening up hard-to-stretch tissue like the IT (iliotibial) band, which runs down the side of your leg from your hip to your knee. You lie on the roller and pull your body slowly back and forth across the roller. It might be a little uncomfortable while you are doing it, but it feels unbelievably good when you�re done. �Orthopedic surgeon Dr. Vonda Wright, Author of Fitness After 40 Get more expert answers here.Brought to you by: Spry Living
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