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Zhou Y.-H.,University of California at Irvine | Hess K.R.,University of Texas M. D. Anderson Cancer Center | Raj V.R.,University of Arkansas for Medical Sciences | Yu L.,Ziren Research LLC | And 3 more authors.
Biomarker Insights | Year: 2010

Background: Prognosis models established using multiple molecular markers in cancer along with clinical variables should enable prediction of natural disease progression and residual risk faced by patients. In this study, multivariate Cox proportional hazards analyses were done based on overall survival (OS) of 100 glioblastoma multiformes (GBMs, 92 events), 49 anaplastic astrocytomas (AAs, 33 events), 45 gliomas with oligodendroglial features, including anaplastic oligodendroglioma (AO, 13 events) and oligodendraglioma (O, 9 events). The modeling included two clinical variables (patient age and recurrence at the time of sample collection) and the expression variables of 13 genes selected based on their proven biological and/or prognosis functions in gliomas (ABCG2, BMI1, MELK, MSI1, PROM1, CDK4, EGFR, MMP2, VEGFA, PAX6, PTEN, RPS9, and IGFBP2). Gene expression data was a log-transformed ratio of marker and reference (ACTB) mRNA levels quantified using absolute real-time qRT-PCR. Results: Age is positively associated with overall grade (4 for GBM, 3 for AA, 2_1 for AO_O), but lacks significant prognostic value in each grade. Recurrence is an unfavorable prognostic factor for AA, but lacks significant prognostic values for GBM and AO_O. Uni-variate models revealed opposing prognostic effects of ABCG2, MELK, BMI1, PROM1, IGFBP2, PAX6, RPS9, and MSI1 expressions for astrocytic (GBM and AA) and oligodendroglial tumors (AO_O). Multivariate models revealed independent prognostic values for the expressions of MSI1 (unfavorable) in GBM, CDK4 (unfavorable) and MMP2 (favorable) in AA, while IGFBP2 and MELK (unfavorable) in AO_O. With all 13 genes and 2 clinical variables, the model R2 was 14.2% (P = 0.358) for GBM, 45.2% (P = 0.029) for AA, and 62.2% (P = 0.008) for AO_O. Conclusion: The study signifies the challenge in establishing a significant prognosis model for GBM. Our success in establishing prognosis models for AA and AO_O was largely based on identification of a set of genes with independent prognostic values and application of standardized gene expression quantification to allow formation of a large cohort in analysis. © the author(s), publisher and licensee Libertas Academica Ltd.


Ramos A.,Neuroradiology | Hilario A.,Neuroradiology | Lagares A.,Hospital 12 de Octubre | Salvador E.,Neuroradiology | And 2 more authors.
Seminars in Ultrasound, CT and MRI | Year: 2013

Historically, brainstem gliomas have been considered as a single entity. Since the introduction of magnetic resonance (MR) imaging in the late 1980s, these tumors are now regarded as a heterogeneous group of neoplasms with different age of onset, clinical and radiologic presentation, and varying behavior and natural history. This article describes the different subtypes of brainstem gliomas in children and adults. We focus on recent advances in MR such as MR spectroscopy, MR perfusion, and diffusion tensor imaging that often strongly suggest the histopathologic diagnosis of the lesion. © 2013 Elsevier Inc..


Beauchesne P.,Neuro Oncology
The Lancet Oncology | Year: 2010

Neoplastic meningitis consists of diffuse involvement of the leptomeninges by infiltrating cancer cells, and can be caused by systemic or primary CNS tumours, such as solid cancers or lymphoproliferative malignant disease. Neoplastic meningitis is characterised by multifocal neurological signs and symptoms. Thus, careful neurological examination is needed for diagnosis of secondary diffuse involvement. Survival of patients with neoplastic meningitis is short (3-4 months), although some patients have long-lasting remission. Because most patients with neoplastic meningitis have diffuse systemic disease, treatment is typically palliative. However, more aggressive treatments are available to low-risk patients, which could increase survival. Therefore, identification of low-risk patients is important. Intrathecal chemotherapy is currently the main treatment for patients with neoplastic meningitis, but optimum anticancer chemotherapy is being studied. © 2010 Elsevier Ltd.


Gilbert M.,Neuro Oncology | Vogelbaum M.A.,Cleveland Clinic
Journal of Neuro-Oncology | Year: 2010

Atypical (WHO grade II) meningiomas occupy an intermediate risk group between benign (WHO grade I) and anaplastic (WHO grade III) meningiomas. Although grade II meningiomas have traditionally been recognized in only about 5% of cases, after changes in diagnostic criteria with the current 2007 WHO standards, they now comprise approximately 20-35% of all meningiomas. Given the magnitude of this change, much work is now needed to solidify the adoption of these standards, to render inter-observer and inter-institutional comparisons more uniform, and to more carefully define the incidence of grade II histology. However, it is clear that they carry a several-fold increased risk of recurrence, as well as an increased rate of mortality. We will discuss the definition, diagnosis, and treatment of patients with atypical meningioma; review the current phase II cooperative trials; and draw attention to some questions timely for pre-clinical and clinical research. © 2010 Springer Science+Business Media, LLC.


Di Giannatale A.,Neuro Oncology | Morana G.,Neuroradiology Operative Unit | Rossi A.,Neuroradiology Operative Unit | Cama A.,Neurosurgery | And 6 more authors.
Journal of Neuro-Oncology | Year: 2014

Cavernous malformations (CM) are cerebral irradiation-related late complications. Little is known about their natural history and the pathogenetic role of concomitant chemotherapy. We present a retrospective, single-institution study of 108 children affected with medulloblastoma, ependymoma, or germinoma treated with radio- and chemotherapy. The frequency, clinical and radiological presentations, and outcomes were analyzed to investigate the relationship among radiation dose, associated chemotherapy, age, latency and localization of radiation-induced CM. 100 out of 108 children were treated with radiotherapy for primary brain tumor; 34 (27 with medulloblastoma and 7 with other histologies) out of 100 patients developed CM. No significant relationship was found between CM and gender (p = 0.70), age (p = 0.90), use of specific chemotherapy (standard versus high-dose, p = 0.38), methotrexate (p = 0.49), and radiation dose (p = 0.45). However, CM developed more frequently and earlier when radiotherapy was associated with methotrexate (70 % of cases). Radiation-induced CM prevailingly occurred in the cerebral hemispheres (p = 0.0001). Only 3 patients (9 %) were symptomatic with headache. Three patients underwent surgery for intra- or extra-lesional hemorrhage. CM was confirmed by histopathology for all 3 patients. The vast majority of radiation-induced CM is asymptomatic, and macro-hemorrhagic events occur rarely. Concomitant therapy with methotrexate seems to favor their development. We recommend observation for asymptomatic lesions, while surgery should be reserved to symptomatic growth or hemorrhage. © 2014 Springer Science+Business Media New York.

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