Brain and Spinal Cord Tumours
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Childhood Brain Tumours
Pituitary Tumours
Primary CNS Lymphoma
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Neuro-oncology (specialty)

Information Patients and the Public (15 links)

Information for Health Professionals / Researchers (24 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Erdis E
A rare metastatic region of cervix cancer; the brain.
J Pak Med Assoc. 2014; 64(1):89-90 [PubMed] Related Publications
Cervical cancer is a frequent malignancy of the females. It still remains a leading cause of cancer-related death in women world wide. Cervical cancers do not always spread, but those that do most often spread to the lungs, liver, bladder, and vagina. We report a 67-year-old woman with squamous cell carcinoma of cervix that could not receive chemo-radio therapy due to mesenteric involvement. A 25 mm mass was detected in the magnetic resonance examination which was performed due to persistent headache. Diffusion magnetic resonance revealed non-contrasted mass consistent with metastases. The patient received palliative radiotherapy at 3000 cGy. Brain scans can be beneficial for metastasis detection if there is presence of significant symptoms at cervical cancer.

Related: Cervical Cancer

Chinot OL, Wick W, Mason W, et al.
Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma.
N Engl J Med. 2014; 370(8):709-22 [PubMed] Related Publications
BACKGROUND: Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma.
METHODS: We randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival.
RESULTS: A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%).
CONCLUSIONS: The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. (Funded by F. Hoffmann-La Roche; number, NCT00943826.).

Related: Angiogenesis Inhibitors Dacarbazine Bevacizumab (Avastin) Temozolomide

Gilbert MR, Dignam JJ, Armstrong TS, et al.
A randomized trial of bevacizumab for newly diagnosed glioblastoma.
N Engl J Med. 2014; 370(8):699-708 [PubMed] Related Publications
BACKGROUND: Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known.
METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab.
RESULTS: A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group.
CONCLUSIONS: First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target. (Funded by the National Cancer Institute; number, NCT00884741.).

Related: Angiogenesis Inhibitors Dacarbazine Bevacizumab (Avastin) Temozolomide

Sethi RV, Giantsoudi D, Raiford M, et al.
Patterns of failure after proton therapy in medulloblastoma; linear energy transfer distributions and relative biological effectiveness associations for relapses.
Int J Radiat Oncol Biol Phys. 2014; 88(3):655-63 [PubMed] Related Publications
PURPOSE: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence.
METHODS AND MATERIALS: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions.
RESULTS: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence.
CONCLUSIONS: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.

Related: Childhood Brain Tumours Childhood Brain Tumors Childhood Medulloblastoma / PNET

Akhavan-Sigari R, Gaab MR, Rohde V, et al.
Expression of PDGFR-α, EGFR and c-MET in spinal chordoma: a series of 52 patients.
Anticancer Res. 2014; 34(2):623-30 [PubMed] Related Publications
AIM: To investigate the expression of platelet-derived growth factor (PDGF) receptor-A (PDGFRα), epidermal growth factor receptor (EGFR) and c-Met in spinal chordoma. To the authors' knowledge, little is known regarding the prognostic significance of receptor tyrosine kinase in spinal chordoma.
MATERIALS AND METHODS: Using immunohistochemical techniques, the authors investigated PDGFR-α, EGFR and c-MET expression in 52 primary and 104 recurrent lesions, and compared these data with clinicopathological parameters.
RESULTS: PDGFR-α, EGFR and c-MET were found to be expressed in 75.0%, 83% and 77% of primary, and in 97.0% of recurrent lesions in all investigated receptor tyrosine kinases. Higher PDGFR-α and c-MET expression was found to be correlated with younger patient age. Lesions with a higher expression of PDGFR-α demonstrated significantly higher EGFR scores in both primary and recurrent lesions compared to those with lower PDGFR-α expression. In recurrent lesions, higher c-MET expression was found to be associated with significantly better prognosis than those with lower c-MET expression (p=0.033). Lesions with a higher level of PDGFR-α expression were found to have significantly poorer prognosis than those with lower PDGFR-α expression (p=0.024). Those patients with lower EGFR expression were found to have significantly better prognosis than those with higher EGFR expression (p=0.005).
CONCLUSION: In the current study, c-MET expression in patients with spinal chordoma was found to be correlated with a younger patient age and a favorable prognosis. Patients with a higher level of PDGFR-α and EGFR expression were found to have a significantly poorer prognosis than those with lower PDGFR-α and EGFR expression.

Related: PDGFRA gene EGFR

Lee Titsworth W, Murad GJ, Hoh BL, Rahman M
Fighting fire with fire: the revival of thermotherapy for gliomas.
Anticancer Res. 2014; 34(2):565-74 [PubMed] Related Publications
In 1891, an orthopedic surgeon in New York noted the disappearance of an inoperable sarcoma in a patient after a febrile illness. This observation resulted in experiments assessing the utility of heat therapy or thermotherapy for the treatment of cancer. While it initially fell from favor, thermotherapy has recently made a resurgence, sparking investigations into its anticancer properties. This therapy is especially attractive for glioblastoma multiforme (GBM) which is difficult to target due to the blood-brain barrier and recalcitrant to treatment. Here we briefly review the history of thermotherapy and then more methodically present the current literature as it relates to central nervous system malignancies. Recent developments show that heat is preferentially cytotoxic to tumor cells and induces cellular pathways which result in apoptotic and non-apoptotic death. Techniques to induce hyperthermia include regional hyperthermia by water bath, focused ultrasound, radiofrequency microwaves, laser-induced interstitial thermotherapy, and magnetic energy. The recent revival of these therapeutic approaches and their preliminary outcomes in the treatment of GBM is reviewed. From bacterial toxins to infusion of magnetic nanoparticles, hyperthermia has the potential to be an effective and easy-to-execute adjuvant therapy for GBM. Hyperthermia for GBM is a promising therapy as part of a growing armamentarium for malignant glioma treatment.

Zhao L, Wu W, Corso JJ
Semi-automatic brain tumor segmentation by constrained MRFs using structural trajectories.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):567-75 [PubMed] Related Publications
Quantifying volume and growth of a brain tumor is a primary prognostic measure and hence has received much attention in the medical imaging community. Most methods have sought a fully automatic segmentation, but the variability in shape and appearance of brain tumor has limited their success and further adoption in the clinic. In reaction, we present a semi-automatic brain tumor segmentation framework for multi-channel magnetic resonance (MR) images. This framework does not require prior model construction and only requires manual labels on one automatically selected slice. All other slices are labeled by an iterative multi-label Markov random field optimization with hard constraints. Structural trajectories-the medical image analog to optical flow and 3D image over-segmentation are used to capture pixel correspondences between consecutive slices for pixel labeling. We show robustness and effectiveness through an evaluation on the 2012 MICCAI BRATS Challenge Dataset; our results indicate superior performance to baselines and demonstrate the utility of the constrained MRF formulation.

Wang H, Yushkevich PA
Multi-atlas segmentation without registration: a supervoxel-based approach.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):535-42 [PubMed] Free Access to Full Article Related Publications
Multi-atlas segmentation is a powerful segmentation technique. It has two components: label transfer that transfers segmentation labels from prelabeled atlases to a novel image and label fusion that combines the label transfer results. For reliable label transfer, most methods assume that the structure of interest to be segmented have localized spatial support across different subjects. Although the technique has been successful for many applications, the strong assumption also limits its applicability. For example, multi-atlas segmentation has not been applied for tumor segmentation because it is difficult to derive reliable label transfer for such applications due to the substantial variation in tumor locations. To address this limitation, we propose a label transfer technique for multi-atlas segmentation. Inspired by the Superparsing work [13], we approach this problem in two steps. Our method first oversegments images into homogeneous regions, called supervoxels. For a voxel in a novel image, to find its correspondence in atlases for label transfer, we first locate supervoxels in atlases that are most similar to the supervoxel the target voxel belongs to. Then, voxel-wise correspondence is found through searching for voxels that have most similar patches to the target voxel within the selected atlas supervoxels. We apply this technique for brain tumor segmentation and show promising results.

Cheng X, Navab N, Ziegler SI, Shi K
Direct parametric image reconstruction of rapid multi-tracer PET.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):155-62 [PubMed] Related Publications
The separation of multiple PET tracers within an overlapped scan based on intrinsic difference of pharmacokinetics is challenging due to the limited SNR of PET measurements and high complexity of fitting models. This study developed a novel direct parametric reconstruction method by integrating a multi-tracer model with reduced number of fitting parameters into image reconstruction. To incorporate the multitracer model, we adopted EM surrogate functions for the optimization of the penalized log-likelihood. The algorithm was validated on realistic simulation phantoms and real rapid [18F]FDG and [18F]FLT PET imaging of mice with lymphoma mouse tumor. Both results have been compared with conventional methods and demonstrated evident improvements for the separation of multiple tracers.

Subbanna NK, Precup D, Collins DL, Arbel T
Hierarchical probabilistic Gabor and MRF segmentation of brain tumours in MRI volumes.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):751-8 [PubMed] Related Publications
In this paper, we present a fully automated hierarchical probabilistic framework for segmenting brain tumours from multispectral human brain magnetic resonance images (MRIs) using multiwindow Gabor filters and an adapted Markov Random Field (MRF) framework. In the first stage, a customised Gabor decomposition is developed, based on the combined-space characteristics of the two classes (tumour and non-tumour) in multispectral brain MRIs in order to optimally separate tumour (including edema) from healthy brain tissues. A Bayesian framework then provides a coarse probabilistic texture-based segmentation of tumours (including edema) whose boundaries are then refined at the voxel level through a modified MRF framework that carefully separates the edema from the main tumour. This customised MRF is not only built on the voxel intensities and class labels as in traditional MRFs, but also models the intensity differences between neighbouring voxels in the likelihood model, along with employing a prior based on local tissue class transition probabilities. The second inference stage is shown to resolve local inhomogeneities and impose a smoothing constraint, while also maintaining the appropriate boundaries as supported by the local intensity difference observations. The method was trained and tested on the publicly available MICCAI 2012 Brain Tumour Segmentation Challenge (BRATS) Database [1] on both synthetic and clinical volumes (low grade and high grade tumours). Our method performs well compared to state-of-the-art techniques, outperforming the results of the top methods in cases of clinical high grade and low grade tumour core segmentation by 40% and 45% respectively.

Ye DH, Zikic D, Glocker B, et al.
Modality propagation: coherent synthesis of subject-specific scans with data-driven regularization.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):606-13 [PubMed] Related Publications
We propose a general database-driven framework for coherent synthesis of subject-specific scans of desired modality, which adopts and generalizes the patch-based label propagation (LP) strategy. While modality synthesis has received increased attention lately, current methods are mainly tailored to specific applications. On the other hand, the LP framework has been extremely successful for certain segmentation tasks, however, so far it has not been used for estimation of entities other than categorical segmentation labels. We approach the synthesis task as a modality propagation, and demonstrate that with certain modifications the LP framework can be generalized to continuous settings providing coherent synthesis of different modalities, beyond segmentation labels. To achieve high-quality estimates we introduce a new data-driven regularization scheme, in which we integrate intermediate estimates within an iterative search-and-synthesis strategy. To efficiently leverage population data and ensure coherent synthesis, we employ a spatio-population search space restriction. In experiments, we demonstrate the quality of synthesis of different MRI signals (T2 and DTI-FA) from a T1 input, and show a novel application of modality synthesis for abnormality detection in multi-channel MRI of brain tumor patients.

Heinrich MP, Jenkinson M, Papiez BW, et al.
Towards realtime multimodal fusion for image-guided interventions using self-similarities.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):187-94 [PubMed] Related Publications
Image-guided interventions often rely on deformable multimodal registration to align pre-treatment and intra-operative scans. There are a number of requirements for automated image registration for this task, such as a robust similarity metric for scans of different modalities with different noise distributions and contrast, an efficient optimisation of the cost function to enable fast registration for this time-sensitive application, and an insensitive choice of registration parameters to avoid delays in practical clinical use. In this work, we build upon the concept of structural image representation for multi-modal similarity. Discriminative descriptors are densely extracted for the multi-modal scans based on the "self-similarity context". An efficient quantised representation is derived that enables very fast computation of point-wise distances between descriptors. A symmetric multi-scale discrete optimisation with diffusion reguIarisation is used to find smooth transformations. The method is evaluated for the registration of 3D ultrasound and MRI brain scans for neurosurgery and demonstrates a significantly reduced registration error (on average 2.1 mm) compared to commonly used similarity metrics and computation times of less than 30 seconds per 3D registration.

Wein W, Ladikos A, Fuerst B, et al.
Global registration of ultrasound to MRI using the LC2 metric for enabling neurosurgical guidance.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):34-41 [PubMed] Related Publications
Automatic and robust registration of pre-operative magnetic resonance imaging (MRI) and intra-operative ultrasound (US) is essential to neurosurgery. We reformulate and extend an approach which uses a Linear Correlation of Linear Combination (LC2)-based similarity metric, yielding a novel algorithm which allows for fully automatic US-MRI registration in the matter of seconds. It is invariant with respect to the unknown and locally varying relationship between US image intensities and both MRI intensity and its gradient. The overall method based on this both recovers global rigid alignment, as well as the parameters of a free-form-deformation (FFD) model. The algorithm is evaluated on 14 clinical neurosurgical cases with tumors, with an average landmark-based error of 2.52 mm for the rigid transformation. In addition, we systematically study the accuracy, precision, and capture range of the algorithm, as well as its sensitivity to different choices of parameters.

Li S, Mattar P, Dixit R, et al.
RAS/ERK signaling controls proneural genetic programs in cortical development and gliomagenesis.
J Neurosci. 2014; 34(6):2169-90 [PubMed] Related Publications
Neural cell fate specification is well understood in the embryonic cerebral cortex, where the proneural genes Neurog2 and Ascl1 are key cell fate determinants. What is less well understood is how cellular diversity is generated in brain tumors. Gliomas and glioneuronal tumors, which are often localized in the cerebrum, are both characterized by a neoplastic glial component, but glioneuronal tumors also have an intermixed neuronal component. A core abnormality in both tumor groups is overactive RAS/ERK signaling, a pro-proliferative signal whose contributions to cell differentiation in oncogenesis are largely unexplored. We found that RAS/ERK activation levels differ in two distinct human tumors associated with constitutively active BRAF. Pilocytic astrocytomas, which contain abnormal glial cells, have higher ERK activation levels than gangliogliomas, which contain abnormal neuronal and glial cells. Using in vivo gain of function and loss of function in the mouse embryonic neocortex, we found that RAS/ERK signals control a proneural genetic switch, inhibiting Neurog2 expression while inducing Ascl1, a competing lineage determinant. Furthermore, we found that RAS/ERK levels control Ascl1's fate specification properties in murine cortical progenitors--at higher RAS/ERK levels, Ascl1(+) progenitors are biased toward proliferative glial programs, initiating astrocytomas, while at moderate RAS/ERK levels, Ascl1 promotes GABAergic neuronal and less glial differentiation, generating glioneuronal tumors. Mechanistically, Ascl1 is phosphorylated by ERK, and ERK phosphoacceptor sites are necessary for Ascl1's GABAergic neuronal and gliogenic potential. RAS/ERK signaling thus acts as a rheostat to influence neural cell fate selection in both normal cortical development and gliomagenesis, controlling Neurog2-Ascl1 expression and Ascl1 function.

Tsivgoulis G, Kontokostas S, Boviatsis E, et al.
Teaching neuroimages: neuromyelitis optica misdiagnosed as spinal cord tumor.
Neurology. 2014; 82(4):e33 [PubMed] Related Publications
A 17-year-old girl presented with acute-onset cervical pain, followed by left arm weakness and gait disturbances. Spinal cord astrocytoma was diagnosed by MRI performed at an outpatient facility (figure, A and B). The patient was admitted to the neurosurgery department to undergo spinal cord biopsy. A second neurologic evaluation indicated neuromyelitis optica (NMO) as the most likely diagnosis, which was confirmed by NMO-immunoglobulin G seropositivity. The patient was treated with rescue plasmapheresis with substantial clinical and radiologic (figure, C) improvement.

Lester SC, Taksler GB, Kuremsky JG, et al.
Clinical and economic outcomes of patients with brain metastases based on symptoms: an argument for routine brain screening of those treated with upfront radiosurgery.
Cancer. 2014; 120(3):433-41 [PubMed] Related Publications
BACKGROUND: Insurers have started to deny reimbursement for routine brain surveillance with magnetic resonance imaging (MRI) after stereotactic radiosurgery (SRS) for brain metastases in favor of symptom-prompted imaging. The authors investigated the clinical and economic impact of symptomatic versus asymptomatic metastases and related these findings to the use of routine brain surveillance.
METHODS: Between January 2000 and December 2010, 442 patients underwent upfront SRS for brain metastases. In total, 127 asymptomatic patients and 315 symptomatic patients were included. Medical records were used to determine the presenting symptoms, distant and local brain failure, retreatment, and need for hospital and rehabilitative care. Cost-of-care estimates were based on Medicare payment rates as of January 2013.
RESULTS: Symptomatic patients had an increased hazard for all-cause mortality (hazard ratio, 1.448) and were more likely to experience neurologic death (42% vs 20%; P < .0001). Relative to asymptomatic patients, symptomatic patients required more craniotomies (43% vs 5%; P < .0001), had more prolonged hospitalization (2 vs 0 days; P < .0001), were more likely to have Radiation Therapy Oncology Group grade 3 and 4 post-treatment symptoms (24% vs 5%; P < .0001), and required $11,957 more on average to manage per patient. Accounting for all-cause mortality rates and the probability of diagnosis at each follow-up period, the authors estimated that insurers would save an average $1326 per patient by covering routine surveillance MRI after SRS to detect asymptomatic metastases.
CONCLUSIONS: Patients who presented with symptomatic brain metastases had worse clinical outcomes and cost more to manage than asymptomatic patients. The current findings argue that routine brain surveillance after radiosurgery has clinical benefits and reduces the cost of care.

Sinha S, Kumar A, Sharma BS
Bifrontal basal interhemispheric approach for midline suprasellar tumors: our experience with forty-eight patients.
Neurol India. 2013 Nov-Dec; 61(6):581-6 [PubMed] Related Publications
INTRODUCTION: Suprasellar lesions present a surgical challenge due to their complex relationship with surrounding neurovascular structures. Of the approaches for these lesions, bifrontal basal interhemispheric approach (BBIA) gives a midline perspective of suprasellar anatomy and has certain advantages over lateral approaches.
MATERIALS AND METHODS: We retrospectively reviewed 48 patients with suprasellar lesions operated over 7 years via BBIA. Patient records, operation notes, radiology, and outpatient files were scrutinized to collect data.
RESULTS: During the study period 48 patients (mean age 33 years, M:F 1.5:1) were operated by this approach. The clinical features included: Visual field deficits in 33 (69%) patients, with 6 of them being blind, diabetes insipidus in 7, growth retardation in 5, and subarachnoid hemorrhage in three patients. Cranopharyngiomas (52%) and meningiomas (16.7%) were the most common pathologies. Dyselectrolytemia (18, 40%) and diabetes insipidus (15, 33%) were the most common complications. Postoperative seizures, meningitis, subdural effusion, and retraction site contusion were seen in 12 (27%), 5 (11%), 4 (9%), and 1 (2.2%) patient, respectively. Three patients died postoperatively and 19 (40%) patients required hormone replacement therapy. Amongst the patients with preoperative visual deficits, 23 (70%) had improvement in visual functions, in six (20%), there was no change and four (8.3%) patients had visual deterioration.
CONCLUSION: BBIA provides a true midline perspective and orientation, and permits complete and safe removal of midline suprasellar lesions in majority of cases. This approach is especially useful in retrochiasmatic tumors and in residual/recurrent tumors providing virgin plane of dissection.

Related: Childhood Brain Tumours Childhood Brain Tumors

Lai JS, Jensen SE, Beaumont JL, et al.
Development of a symptom index for patients with primary brain tumors.
Value Health. 2014 Jan-Feb; 17(1):62-9 [PubMed] Related Publications
OBJECTIVES: This study's primary goals included identifying the highest priority symptoms of patients with advanced brain tumors on treatment, comparing patient priority ratings with those of oncology experts, and constructing a brief symptom index using combined input to assess these symptoms and concerns.
METHODS: Fifty patients with advanced primary brain tumors and 10 physician experts were recruited from the National Comprehensive Cancer Network institutions and community support agencies. By using a 40-item symptom checklist, patients first selected up to 10 of the most important symptoms/concerns to monitor when assessing the value of drug treatment for brain tumors, then nominated up to 5 of the very most important concerns, and finally generated additional symptoms/concerns. By using the same checklist as patients, physicians rated each symptom/concern as disease- or treatment-related.
RESULTS: By using the combined input, a 24-item National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy-Brain Symptom Index (NFBrSI-24) was developed. The NFBrSI-24 showed good internal consistency (α = 0.84), significantly differentiated patients with different levels of functional status (F2,47 = 8.21; P < .001), and demonstrated good convergent validity with the Functional Assessment of Cancer Therapy-General functional, physical, social, emotional, and brain tumor-specific concerns (ρ = 0.59, 0.57, 0.40, 0.35, and 0.50, respectively; Ps < 0.05).
CONCLUSIONS: The NFBrSI-24, an index of the symptoms in advanced brain tumors perceived as most important by both patients and clinicians, improves upon existing measures of brain tumor symptoms through better satisfaction of regulatory requirements for measure development. The findings suggest good reliability and validity, indicating that the NFBrSI-24 is a promising brief assessment of high-priority advanced brain tumor symptoms for research and clinical settings.

Lubanska D, Market-Velker BA, deCarvalho AC, et al.
The cyclin-like protein Spy1 regulates growth and division characteristics of the CD133+ population in human glioma.
Cancer Cell. 2014; 25(1):64-76 [PubMed] Related Publications
The heterogeneity of brain cancers, as most solid tumors, complicates diagnosis and treatment. Identifying and targeting populations of cells driving tumorigenesis is a top priority for the cancer biology field. This is not a trivial task; considerable variance exists in the driving mutations, identifying markers, and evolutionary pressures influencing initiating cells in different individual tumors. Despite this, the ability to self-renew and differentiate must be conserved to reseed a heterogeneous tumor mass. Focusing on one example of a tumor-initiating cell population, we demonstrate that the atypical cyclin-like protein Spy1 plays a role in balancing the division properties of glioma cells with stemness properties. This mechanistic insight may provide new opportunities for therapeutic intervention of brain cancer.

Crisi G, Filice S, Pertinhez TA, et al.
In vivo and ex vivo magnetic resonance spectroscopy in the characterization of hemangioblastoma cyst fluid.
J Comput Assist Tomogr. 2014 Jan-Feb; 38(1):29-32 [PubMed] Related Publications
Peritumoral cyst formation is commonly associated with hemangioblastomas of the central nervous system. Results of a proteomic profiling of hemangioblastoma cyst fluid suggested that cyst formation, whether intratumoral or peritumoral, is a consequence of vascular leakage because protein profiles of cyst fluid and blood serum were similar. To the best of our knowledge, this is the first report of in vivo and ex vivo magnetic resonance spectroscopy analyses of hemangioblastoma cyst fluid that investigates on the mechanism leading to peritumoral cyst formation.

Avraham HK, Jiang S, Fu Y, et al.
Angiopoietin-2 mediates blood-brain barrier impairment and colonization of triple-negative breast cancer cells in brain.
J Pathol. 2014; 232(3):369-81 [PubMed] Related Publications
Although the incidence of breast cancer metastasis (BCM) in brain has increased significantly in triple-negative breast cancer (TNBC), the mechanisms remain elusive. Using in vivo mouse models for BCM in brain, we observed that TNBC cells crossed the blood-brain barrier (BBB), lodged in the brain microvasculature and remained adjacent to brain microvascular endothelial cells (BMECs). Breaching of the BBB in vivo by TNBCs resulted in increased BBB permeability and changes in ZO-1 and claudin-5 tight junction (TJ) protein structures. Angiopoietin-2 expression was elevated in BMECs and was correlated with BBB disruption. Secreted Ang-2 impaired TJ structures and increased BBB permeability. Treatment of mice with the neutralizing Ang-2 peptibody trebananib prevented changes in the BBB integrity and BMEC destabilization, resulting in inhibition of TNBC colonization in brain. Thus, Ang-2 is involved in initial steps of brain metastasis cascade, and inhibitors for Ang-2 may serve as potential therapeutics for brain metastasis.

Hsi AC, Kreisel FH, Frater JL, Nguyen TT
Clinicopathologic features of adult T-cell leukemias/lymphomas at a North American tertiary care medical center: infrequent involvement of the central nervous system.
Am J Surg Pathol. 2014; 38(2):245-56 [PubMed] Related Publications
Human T-cell lymphotropic virus type 1 is associated with adult T-cell leukemia/lymphoma (ATLL). Published series of ATLLs seen at a United States medical institution are rare. We present the features of 4 ATLLs diagnosed at our North American tertiary care medical center from 1990 to 2012. Despite the absence of a history of origin from an endemic region, all our ATLLs demonstrated evidence of human T-cell lymphotropic virus type 1 infection. Central nervous system (CNS) involvement by ATLL was uncommon in our series, and represented only 1.6% (1/64) of all CNS B-cell or T-cell lymphomas diagnosed over a 20+ year period at our institution. Review of the medical literature reveals that the majority of CNS-involved ATLLs present with the lymphoma or acute subtype, and complete remission is difficult to achieve in these cases. CNS involvement frequently occurs with a systemic disease, which carries an aggressive clinical course with poor prognosis. In addition, CNS involvement by ATLL can be the initial presentation or seen with relapsed disease, can be the only site or be associated with other tissue sites of involvement, and may manifest with variable clinical signs/symptoms. Our retrospective study reveals that ATLLs are rare mature T-cell lymphomas in a native North American population, but the clinical and histopathologic features of ATLLs from this nonendemic region are similar to those seen from other endemic regions. Early recognition of these rare ATLLs involving uncommon sites, such as the CNS, will help optimize treatment for these infrequent mature T-cell lymphomas.

Related: Cancer Screening and Early Detection

Brastianos PK, Taylor-Weiner A, Manley PE, et al.
Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas.
Nat Genet. 2014; 46(2):161-5 [PubMed] Related Publications
Craniopharyngiomas are epithelial tumors that typically arise in the suprasellar region of the brain. Patients experience substantial clinical sequelae from both extension of the tumors and therapeutic interventions that damage the optic chiasm, the pituitary stalk and the hypothalamic area. Using whole-exome sequencing, we identified mutations in CTNNB1 (β-catenin) in nearly all adamantinomatous craniopharyngiomas examined (11/12, 92%) and recurrent mutations in BRAF (resulting in p.Val600Glu) in all papillary craniopharyngiomas (3/3, 100%). Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas (36 of 39 tumors) and mutation of CTNNB1 in 96% of adamantinomatous craniopharyngiomas (51 of 53 tumors). The CTNNB1 and BRAF mutations were clonal in each tumor subtype, and we detected no other recurrent mutations or genomic aberrations in either subtype. Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms.

Related: Pituitary Tumors BRAF gene

Cohen GN, Munro JJ, Kirov A, et al.
32P brachytherapy conformal source model RIC-100 for high-dose-rate treatment of superficial disease: Monte Carlo calculations, diode measurements, and clinical implementation.
Int J Radiat Oncol Biol Phys. 2014; 88(3):746-52 [PubMed] Related Publications
PURPOSE: A novel (32)P brachytherapy source has been in use at our institution intraoperatively for temporary radiation therapy of the spinal dura and other localized tumors. We describe the dosimetry and clinical implementation of the source.
METHODS AND MATERIALS: Dosimetric evaluation for the source was done with a complete set of MCNP5 Monte Carlo calculations preceding clinical implementation. In addition, the depth dose curve and dose rate were measured by use of an electron field diode to verify the Monte Carlo calculations. Calibration procedures using the diode in a custom-designed phantom to provide an absolute dose calibration and to check dose uniformity across the source area for each source before treatment were established.
RESULTS: Good agreement was established between the Monte Carlo calculations and diode measurements. Quality assurance measurements results are provided for about 100 sources used to date. Clinical source calibrations were usually within 10% of manufacturer specifications. Procedures for safe handling of the source are described.
DISCUSSION: Clinical considerations for using the source are discussed.

Related: Brachytherapy

Strojnik T, Smigoc T, Lah TT
Prognostic value of erythrocyte sedimentation rate and C-reactive protein in the blood of patients with glioma.
Anticancer Res. 2014; 34(1):339-47 [PubMed] Related Publications
AIM: To determine any correlation between inflammation parameters in blood glioma patients, with some of the established glioma biomarkers and to evaluate the possible prognostic impact of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for patient survival.
PATIENTS AND METHODS: This retrospective study evaluated ESR values in 94 patients and measured CRP values prior to the excision of primary glioma in 165 patients. Overall survival probabilities were determined separately for all patients with glioma in low-grade glioma (LGG), high-grade (HGG) and in glioblastoma multiforme (GBM) using the Kaplan-Meier log-rank test. The correlation between blood ESR and CRP values and between immunohistochemical (IHC) assessment of cluster of differentiation-68 (CD68), cathepsin B and nestin were evaluated.
RESULTS: An ESR above 15 mm/h was significant for poor survival prognosis for patients overall (p<0.001) and in the HGG (p<0.01) and GBM (p<0.04) subgroups. A serum CRP level above 5 mg/l was also identified as prognostic in patients overall (p<0.01), and in the HGG (p=0.02) and GBM (p=0.04) subgroups.
CONCLUSION: Correlations of ESR and serum levels of CRP have been revealed with prognostic tissue biomarkers i.e. cathepsin B, nestin, CD68. Moreover, preoperative measurement of both parameters could be used for survival prognosis in patients with glioma.

Related: Childhood Brain Tumours Childhood Brain Tumors Brain Stem Glioma - Childhood

Pogorzala M, Styczynski J, Wysocki M
Survival and prognostic factors in children with brain tumors: long-term follow-up single center study in Poland.
Anticancer Res. 2014; 34(1):323-6 [PubMed] Related Publications
AIM: Analysis of risk factors for survival in long-term follow-up of children treated at a single pediatric center in Poland.
PATIENTS AND METHODS: Out of 623 children diagnosed with cancer between 1995-2005, 110 were treated for brain tumors and followed-up, with a mean survival of 11.4 years.
RESULTS: Overall 5-year survival in the whole cohort was 60.9±4.7%, while 10-year survival was 58.2±4.7%. No relapse, progression or death occurred after six years from initial diagnosis. Survival was 48.1±9.6% for patients with medulloblastoma and primitive neuroectodermal tumors; 83.3±6.2% for low-grade astrocytoma; 56.6±16.6% for ependymoma, while 0% at 72 months for high-grade glioma. Patients with cerebellar tumors had a survival rate 69.0±7.1% at 10 years. Multivariate analysis showed that factors predicting poor outcome were: grade III-IV tumor, incomplete surgical resection, and complications after surgical resection, while diagnosis of low-grade glioma was the only factor predicting good outcome. Progression of the disease during therapy was an additional independent adverse risk factor for survival.
CONCLUSION: Long-term survival was achieved by 58% of children with brain tumors. Advanced tumor stage, incomplete surgical resection, complications of surgical treatment, and progression of the disease during treatment predicted poor outcome.

Related: Childhood Brain Tumours Childhood Brain Tumors

Nassir M, Roth A, Gasimli K, et al.
Is endometrial cancer really a neurophobic tumor? A case report and review of the literature.
Anticancer Res. 2014; 34(1):249-57 [PubMed] Related Publications
Brain metastases due to endometrial cancer are rare and usually occur in the context of widespread disease. We present a rare case of a 74-year-old woman with recurrent endometrial cancer in terms of a solitary brain lesion two years after initial diagnosis. She was treated with local resection of the brain metastasis and subsequent whole-brain radiotherapy. She then experienced relapse twice, presenting two solitary metastases at two different time points at the same location as at initial diagnosis, but never showed any signs of extracranial widespread disease. The patient has been alive for 13 months after detection of her initial brain metastasis. Despite the identification of some risk factors, there is still very limited knowledge why some patients develop brain metastases as the only sign of distant spread. Our review of the literature revealed that the combination of two treatment modalities yields higher survival rates than single treatment-alone, as was the case in the presented patient. Further case reports, as well as large and prospective studies, may contribute to a better understanding of the etiology and dynamics of this disease and allow better evaluation of treatment options.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Neman J, Termini J, Wilczynski S, et al.
Human breast cancer metastases to the brain display GABAergic properties in the neural niche.
Proc Natl Acad Sci U S A. 2014; 111(3):984-9 [PubMed] Free Access to Full Article Related Publications
Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite.

Related: Breast Cancer

Gerber NU, Mynarek M, von Hoff K, et al.
Recent developments and current concepts in medulloblastoma.
Cancer Treat Rev. 2014; 40(3):356-65 [PubMed] Related Publications
Medulloblastoma is the most common malignant brain tumor of childhood. While prognosis has significantly improved in the last decades with multimodal therapy including surgery, radiotherapy, and chemotherapy, one third of patients still succumb to their disease. Further research is needed to find more efficient treatment strategies for prognostically unfavorable patient groups and to minimize long-term sequelae of tumor treatment. This review gives a summary of the current state of treatment concepts including an outlook on the near future. We describe recent advances in the understanding of molecular mechanisms, their potential impact on risk stratification in upcoming clinical trials, and perspectives for the clinical implementation of targeted therapies.

Related: Childhood Brain Tumours Childhood Brain Tumors Childhood Medulloblastoma / PNET

Due-Tonnessen P, Rasmussen I, Berntsen EM, et al.
Identifying the central sulcus in patients with intra-axial lesions: a multicenter study comparing conventional presurgical MRI to topographical analysis and BOLD-fMRI.
J Comput Assist Tomogr. 2014 Jan-Feb; 38(1):1-8 [PubMed] Related Publications
OBJECTIVES: Identification of eloquent brain areas in patients with intra-axial lesions is important to minimize the risk of neurological deficit. We performed a multicenter study comparing conventional 2-dimensional magnetic resonance imaging (MRI) for identification of the central sulcus to topographical MRI and blood-oxygenation-level-dependent functional MRI (BOLD-fMRI).
METHODS: Seventy-seven unoperated patients with brain lesions were imaged at 1.5 or 3 T. The central sulcus was identified by an experienced neuroradiologist on 2-dimensional MRI, by topographic analysis of 3-dimensional MRI in BrainVoyager, and by BOLD-fMRI analysis in BrainVoyager or SPM5.
RESULTS: The central sulcus in the affected hemisphere was readily identified in a significantly higher percentage of patients by 2-dimensional MRI and topographical analysis (77/77 patients) compared to BOLD-fMRI (57 patients; P < 0.001). The topographical analysis identified a significantly larger portion of the total central sulcus than 2-dimensional MRI (P < 0.05). No differences were found between institutions, histological versus radiological diagnoses, MRI sequence parameters, age, or sex.
CONCLUSIONS: Identification of the central sulcus is best performed using topographical analysis; however, 2-dimensional analysis may suffice for daily routine work.

Related: Childhood Brain Tumours Childhood Brain Tumors

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