Management Of Brain Tumors Research Articles

Highlights of This Issue

Tumor-targeting monoclonal antibodies represent a major advance in oncology therapy; however, due to their limited brain permeability, mAbs are not generally effective against brain tumors. Conjugation of an anti-HER2 mAb with Angiopep-2, a peptide recognized by LRP1 (low-density lipoprotein receptor-related protein 1), results in ANG4043, which enters brain physiologically, targets HER2+ tumors, and increases survival in mice bearing intracranial tumors. The Angiopep conjugation to mAbs, as well as to previously reported small molecules, is applicable in general to create brain-penetrant therapeutics for brain malignancies and other CNS disorders.Activation of the Hedgehog pathway is a feature of many different types of cancer, including highly lethal brain tumors. Accordingly, small molecules that can antagonize Hedgehog signaling are being developed as new anticancer drugs. Larsen and colleagues demonstrate that mebendazole, a widely used antiparasitic, can inhibit Hedgehog pathway activation by preventing the formation of the primary cilium, a tubulin-based cellular organelle that functions as a signaling hub. The off-label use of mebendazole as a Hedgehog inhibitor provides a promising new option for the management of brain tumors and other tumor types in which Hedgehog activation is prevalent.HSP90 inhibitors simultaneously affect multiple cancer-related proteins; therefore, they have potential use in advanced cancer treatment. However, because HSP90 also functions in normal cells, it is essential to balance efficacy and toxicity to maximize the antitumor potential of HSP90 inhibitors. Ohkubo and colleagues report on the biological activity of TAS-116, a novel, orally active HSP90α and β selective inhibitor. TAS-116 showed antitumor activity without detectable ocular toxicities in a rat model, due to greater TAS-116 distribution in target tumor tissues than in non-target eye tissues. The favorable therapeutic index of TAS-116 thus highlights its therapeutic potential.Treatment options for breast cancer brain metastases are limited and new therapies are needed. Here, Meisen and colleagues discovered the relationship of multifunctional brain angiogenesis inhibitor 1 (BAI1) and nestin expression with breast cancer brain metastases. Higher BAI1 expression is associated with better patient survival and higher nestin expression is significantly correlated with breast cancer lung and brain metastases. The application of 34.5ENVE, a Nestin-targeted oncolytic virus expressing a therapeutic extracellular fragment of BAI1 destroyed breast cancer brain metastases in two different immune-competent murine models of the disease. The results of these studies warrant the clinical investigation of 34.5ENVE for breast cancer brain metastases.

MicroRNA signatures as biomarkers and therapeutic target for CNS embryonal tumors: the pros and the cons.

Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs) in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets.

ED-04 * SURVIVAL RATES AMONG CANADIAN PATIENTS WITH PRIMARY MALIGNANT BRAIN TUMOURS: AN ANALYSIS BASED ON STATISTICS CANADA DATA, 1992-2010

BACKGROUND: There is little information availableon brain tumour survival among the Canadian population. The objective is to investigate patterns of survival among patients with malignant brain tumours in Canada by province/territory, age at diagnosis, histology, and time period. We aim to examine whether outcomes have improved over time and whether they are consistent with those reported in the US. MATERIALS AND METHODS: Data from the Canadian Cancer Registry are available through Statistics Canada. Data on all primary brain tumours diagnosed between 1992-2010 have been requested for analysis. Analysis will be restricted to patients with no previous history of cancer and no subsequent development of second primaries. Survival curves will be estimated where there are at least 20 events to provide precision to the estimates given that these are rare tumours. Overall and stratified survival rates (1, 2, 5 and 10 year) by province/territory, age at diagnosis, histology and time period and 95% confidence intervals will be estimated. Standard Kaplan Meier and Proportional Hazards survival analysis techniques will be performed to calculate survival curves, using SAS software. RESULTS: New information to health care providers and decision makers will be presented. CONCLUSION: These data will provide a pan-Canadian picture of primary malignant brain tumour survival over time; including overall and subgroup estimates which will be compared with published rates from the Central Brain Tumour Registry of the US. Identified areas for improvement will potentially influence brain tumour management.

Medical management of brain tumors and the sequelae of treatment.

Patients with malignant brain tumors are prone to complications that negatively impact their quality of life and sometimes their overall survival as well. Tumors may directly provoke seizures, hypercoagulable states with resultant venous thromboembolism, and mood and cognitive disorders. Antitumor treatments and supportive therapies also produce side effects. In this review, we discuss major aspects of supportive care for patients with malignant brain tumors, with particular attention to management of seizures, venous thromboembolism, corticosteroids and their complications, chemotherapy including bevacizumab, and fatigue, mood, and cognitive dysfunction.

Abstract 3025: HER2/Stat3 signaling mediated radioresistance in U87 glioma cancer cells through suppressed apoptosis and enhanced glycolysis

Abstract GBM is the most common and aggressive malignant primary brain tumor, and the prognosis for GBM patients remains poor. Radiotherapy continues to play a central role in the management of brain tumors. Even though the advances of radiotherapy strategies and techniques, frequent failure of radiotherapy made GBM a disease difficult to be treated. GBM cancer stem cells (CSCs) are reported to be responsible for resistance to chemo- and radiotherapy, and chemotherapy and radiotherapy resistant GBM CSCs have been isolated from GBM. However, the mechanisms of radioresistance of glioma cells are still elucidative. In this study, we investigated the role of HER2-Stat3 signaling pathway in radioresistance using human glioma cell line U87. We found that long-term therapeutic dose of fragmented irradiation induces repopulation of human glioma U87 cells with increased number of CD133+/HER2+ stem-like cells. FIR-surviving CD133+/HER2+ U87 cells have coactivation of HER2 and Stat3 and increased cell proliferation and invasion abilities. More importantly, we found that U87-FIR cells have lower level of mitochondria metabolism and ROS level, and higher mitochondrial membrane potential, while 5Gy single dose radiation induces increased mitochondria function. Furthermore, U87 cell injection derived xenograph tumor also has increased mitochondrial membrane potential and decreased mitochondria function after radiation. These results suggest that the radioresistance of GBM CSCs possibly due to the suppressed apoptosis and enhanced glycolysis mediated by HER2/STAT3 pathway. Citation Format: Lili Qin, Ming Fan, Jian Jian Li. HER2/Stat3 signaling mediated radioresistance in U87 glioma cancer cells through suppressed apoptosis and enhanced glycolysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3025. doi:10.1158/1538-7445.AM2014-3025

O7.08 * ONE-STOP SHOPPING IN BRAIN TUMOR IMAGING: INITIAL EXPERIENCE WITH PET/MR FOR SIMULTANEOUS EVALUATION OF TUMOR METABOLISM, STRUCTURE AND BLOOD VOLUME USING [18F]-FLUOR-ETHYL-THYROSINE PET AND DSC-MRI

AIM: Assessment of amino acid transport using PET tracers such as [18F]-fluor-ethyl-thyrosine (FET) is a valuable supplement to routine contrast enhanced structural MRI in the initial and follow up evaluations of patients with brain tumors. MRI blood volume (BV) imaging using dynamic susceptibility contrast (DSC) has also been shown to give important information about tumor angiogenesis. The aim of the study was to investigate the feasibility of simultaneous imaging of structural MRI, angiogenic activity (BV DSC), and metabolic activity (FET) in a short single session using an integrated PET/MRI scanner. METHODS AND MATERIALS: Twenty-five scans were obtained in 22 referred brain tumor patients. A 20 min static simultaneous PET/MRI (Siemens mMR) acquisition 20 min. p.i. of 200 MBq FET was performed. The MRI protocol included axial FLAIR and post-contrast T1 MPRAGE. For BV imaging the contrast agent (0.1-0.2 ml/kg, Gadovist 1 mmol/ml) was administered using a power injector and BV maps were calculated using dedicated software. Metabolically active tumor volume (FET-vol) was defined in tissue as activity > 1.6 x background activity (B), and metabolic activity, Tmax/B, as maximal tumor activity/B. A low-dose CT scan was obtained for attenuation correction. RESULTS: The PET/MRI scans were well-accepted by patients. Fourteen had high grade glioma (glioblastoma n = 9, oligodendroglioma III n = 4, astrocytoma III n = 1), 7 patients had low grade glioma (ganglioglioma =1, brain stem glioma n = 1, astrocytoma II n = 1, pontine glioma, oligodendroglioma n = 2, unspecified n = 1) and one patients has brain metastasis (malignant melanoma). Five patients had been exposed to anti-angiogenetic chemotherapy (Bevacizumab + irinotecan). Median tumor volume was 1.6 ml (range 0-138 ml). Areas with visually increased BV were observed in 15 of 18 scans with metabolically active tumor tissue. Scans with increased BV had significantly larger median FET-vol (4.1 ml vs 0 ml, p < 0.0005) and median Tmax/B (2.5 vs 1.4, p < 0.005) compared to those with without increased BV. Excluding scans without metabolically active tumor tissue, neither FET-vol nor Tmax/B was different. There was a high variability in the regional signals observed using FLAIR, FET PET, BV, and post-contrast T1, and poor spatial congruence between FET and BV. The fraction of scans with and without increased BV was not related to tumor grade or exposure to Bevacizumab. CONCLUSION: In the clinical management of brain tumors a simultaneous and comprehensive evaluation of structure, metabolism and blood volume is feasible in a short single session FET PET/MRI DSC scan yielding complementary high quality information. This modality may provide valuable insight into tumor biology and increase the overall diagnostic quality, decrease clinical decision time, and increase acceptance of PET imaging with patients and treating clinicians in clinical management and in trials.

Flexible endoscopy for management of intraventricular brain tumors in patients with small ventricles.

Endoscopic surgery is generally withheld in patients with small ventricles due to difficulties in ventricular cannulation and intraventricular manipulation. The effectiveness of flexible endoscopy for management of intraventricular brain tumors in patients with small ventricles was evaluated. Forty-five patients who underwent endoscopic surgery with a flexible endoscope for intraventricular brain tumors were divided into small-ventricle and ventriculomegaly groups according to the frontal and occipital horn ratio (FOR). Retrospective review of these cases was performed and achievement of surgical goals and morbidity were assessed. Among the 45 patients, there were 14 with small ventricles and 31 with ventriculomegaly. In the smallventricle group, targeted tumors were located in the suprasellar region in 12 patients and in the pineal region in 2. In the ventriculomegaly group, tumors were located in the pineal region in 15 patients, in the suprasellar region in 9, in the lateral ventricle in 4, in the midbrain in 2, and in the fourth ventricle in 1. In the small-ventricle group, ventricular cannulation was successful and the surgical goals were accomplished in all patients. In ventriculomegaly group, sampling of the tumor was not diagnostic due to intraoperative hemorrhage in 1 patient. There were no significant differences in the rate of achieving the surgical goals or the morbidity between the 2 groups. Endoscopic surgery using a flexible endoscope is useful for management of intraventricular brain tumors in patients with small ventricles. A flexible endoscope allows excellent maneuverability in introducing the device into the lateral ventricle and manipulating through small ventricles.

Unyielding progress: recent advances in the treatment of central nervous system neoplasms with radiosurgery and radiation therapy.

In the past decade, our understanding of the roles of external beam radiotherapy (EBRT) and stereotactic radiosurgery (SRS) in the management of brain tumors has dramatically improved. To highlight the changes and contemporary treatment approaches, we review the indications and outcomes of ionizing radiation for benign intracranial tumors and brain metastases. For nonfunctioning pituitary adenomas, SRS is able to achieve radiographic tumor control in at least 90 % of cases. The rate of SRS-induced endocrine remission for functioning pituitary adenomas depends on the tumor subtype, but it is generally lower than the rate of radiographic tumor control. The most common complications from pituitary adenoma SRS treatment are hypopituitarism and cranial neuropathies. SRS has become the preferred treatment modality for vestibular schwannomas and skull base meningiomas less than 3 cm in size. Large vestibular schwannomas and meningiomas remain best managed with initial surgical resection or EBRT for surgically ineligible patients. For small to moderately sized brain metastases, there has been a shift toward treatment of newly diagnosed patients with SRS alone due to similar local control rates compared with surgical resection. RCTs have shown combined SRS and whole brain radiation therapy (WBRT) for brain metastases to decrease rates of local and distant intracranial recurrence compared to SRS alone. However, the improved intracranial control comes at the expense of poorer neurocognitive outcomes and without prolonging overall survival. Therefore, WBRT is generally reserved for salvage therapy. While EBRT has been frequently supplanted by SRS for the treatment pituitary adenomas and brain metastases, it still proves useful in selected cases of large lesions which are not amenable to surgical debulking or for those with widespread disease, poor performance status, and short life expectancy. In recent years, the scope of SRS has extended beyond the intracranial space to include extradural and intradural spinal tumors.

English

BACKGROUND AND OBJECTIVE: Pregnant women with brain tumors are uncommon; however pregnancy itself may aggravate the natural history of an intracranial tumor and may even unmask a previously unknown diagnosis. Small studies remain an important source of knowledge and experience and hence this study aims to highlight the major issues and provide an overview to the case of the pregnant patients with brain tumor posted for emergency caesarean section including pre-anaesthetic evaluation, patient counseling per operative management and follow up. PRESENTATION, DIAGNOSIS, MANAGEMENT: A 23years old G2P1L1 lady presented at 41 weeks gestation and was posted for emergency caesarean section, indication being post-dated pregnancy with previous caesarean section. She reported of being diagnosed with a brain tumor 6months back and that she has been suffering from severe headache associated with right sided facial palsy and bilateral hearing loss with severe papilledema. She confessed of her economic constraints because of which she couldn't get operated for so long. Following consultation between the anaesthetist, obstetrician and the neurosurgeon it was decided to proceed with caesarean section followed by V-P shunting under general anaesthesia. Rapid sequence induction and intubation was performed and was maintained with isoflurane, titrated to maintain the stability of mean arterial pressure until extraction. A live 2.6kgs female child was born with apgar scores of 8 and 9 at 1 and 5 mins respectively. Following extraction 10U oxytocin was given intramuscularly and 10U run as infusion in ringers lactate. Intra-operative analgesia was administered after extraction. After completion of caesarean section V-P shunting was performed by the neurosurgeon during which propofol and dexmedetomedine infusions were used. Post-operative period was uneventful. DISCUSSION & CONCLUSION: Anaesthetic management of brain tumor in pregnant women is mainly reliant on doctor's personal experience as no evidence based guidelines are available. General anaesthesia using thiopentone, propofol, fentanyl, dexmedetomedine and titrated dose of isoflurane as used in our case were found to be safe with adequate hemodynamic stability and post-operative pain control. A team

INFORMATION-GUIDED SURGERY USING INTRAOPERATIVE MRI AND FUNCTIONAL MAPPING FOR GLIOMAS.

BACKGROUND: Contemporary technological developments revolutionized surgical management of intraaxial brain tumors. The intraoperative MRI (iMRI) and updated neuronavigation permitted for neurosurgeons to perform tumor resection under precise guidance. Neurophysiological monitoring and brain mapping allows precise localization of the cerebral functions and preservation of the important function during removal of the tumor. Intraoperative histopathological diagnosis allows fast direct investigation for identification of the neoplastic cells. Incorporation of these adjuncts provides for the surgeon an opportunity to perform aggressive glioma resection with minimal risk of neurological morbidity. The present report highlights our experience with information-guided surgical management of gliomas using low magnetic field strength iMRI in the intelligent operating theater with an emphasis on tumor resection rate and outcome. METHODS: From 2000 to 2013, 1234 surgeries for intracranial lesions were performed with the use of intraoperative MRI (iMRI) with low magnetic field strength of 0.3 Tesla, updated neuronavigation, serial intraoperative histopathological investigations, and neurophysiological monitoring (1000 gliomas, 45 cavernous malformations, 34 pituitary tumors, and other tumors). Newly-diagnostic gliomas followed more than one year were 533 cases (8 biopsies, 525 craniotomy) and WHO grade-II, -III, and -IV gliomas resected were 197, 150, and 170 cases, respectively (8 not specified). Adjuvant therapy for grade-II, -III, and IV patients was radiation (RT) and/or ACNU chemotherapy if resection rate were less than 90%, RT + ACNU, and RT + TMZ, respectively. RESULTS: Mean resection rates (RR) of grade-II, -III, and -IV were 87.7%, 89.5%, and 93.7%, respectively (P = 0.0004). Five-year and 10-year- survival rates of grade-II patients were 91.7% and 78.3%, those of grade-III patients were 76.9% and 71.9%, and 5-year survival of grade-IV patients were 19% (P = 0.042). RR of all-grade patients underwent awake craniotomy with functional mapping (AC: n = 174) and general anesthesia without functional mapping (GA: n = 351) were 86% and 93% (P 0.05). RR of patients with iMRI and without iMRI were significantly different in grade IV (94% vs. 78%: P 0.05)). Overall survival of Grade-IV patients with iMRI and without MRI were 21 months and 11 months (P = 0.037). CONCLUSIONS: Information-guided management of gliomas using functional mapping and low-field-strength iMRI provides a good opportunity for maximal possible tumor resection, and may result in survival advantage. SECONDARY CATEGORY: Imaging.

Le diagnostic et le suivi thérapeutique des tumeurs cérébrales intra-parenchymateuses par l’imagerie par résonance magnétique multimodale

The multimodal magnetic resonance imaging (MMRI) has an important role in cancer care. This non-invasive and non-ionizing technique provides vital information for the diagnosis and answers to various questions of clinicians before, during and after treatment. The MMRI can specify the localization expanding process; it allows establishing the differential diagnosis of a brain tumor and a circumscribed lesion of another type, to approach the diagnosis of the tumor lesion nature as well as establishing the histological grade of glial tumor in view of lesion monitoring after treatment. The multimodal magnetic resonance imaging has a major contribution to the management progress of the brain tumors. Thus, this paper reviews the value of these MRI modalities in the diagnosis, management and therapy of brain tumors.

Critical role of imaging in the neurosurgical and radiotherapeutic management of brain tumors.

Critical role of imaging in the neurosurgical and radiotherapeutic management of brain tumors.

Novel treatment strategies for brain tumors and metastases.

This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application.

The surgical management of pediatric brain tumors causing epilepsy: consideration of the epileptogenic zone.

Children suffering from epilepsy with suspected low-grade tumors may benefit from a surgical approach that considers the epileptogenic zone, which can be more extensive than the tumor region. This study aimed to determine the prevalence of epilepsy in children undergoing supratentorial tumor resection and the factors predictive of postoperative seizure freedom in children with low-grade tumors. Subjects 3 months to 21 years undergoing supratentorial brain tumor resection between 2007 and 2011 were included in this retrospective study. Children with supratentorial, cortically based tumors and a preoperative diagnosis of epilepsy were considered epilepsy surgery candidates. Pre- and postoperative MRI were reviewed and scored for extent of resection, adjacent dysplasia, and remaining abnormal cortex postoperatively. The prevalence of seizures in all cases of supratentorial tumors was 46/87 (53 %). Eighteen were epilepsy surgery candidates. Eight of 18 (44 %) were seizure-free postoperatively with a mean follow-up of 39 months. Children who were seizure free postoperatively had tried fewer anticonvulsants than those with continued seizures (1.7 v. 2.9, p = 0.01). Presurgical evaluation was nonstandardized, and a more extensive workup and resection were performed in children who continued to have seizures postoperatively. All epilepsy surgery candidates had low-grade tumors on histological evaluation, indicating that a surgical approach that takes into consideration the epileptogenic zone is reasonable in this population. Gross total resection should be the goal, with additional attention to resection of the epileptogenic zone when located in the noneloquent cortex.

Texture Descriptors to distinguish Radiation Necrosis from Recurrent Brain Tumors on multi-parametric MRI.

Differentiating radiation necrosis (a radiation induced treatment effect) from recurrent brain tumors (rBT) is currently one of the most clinically challenging problems in care and management of brain tumor (BT) patients. Both radiation necrosis (RN), and rBT exhibit similar morphological appearance on standard MRI making non-invasive diagnosis extremely challenging for clinicians, with surgical intervention being the only course for obtaining definitive "ground truth". Recent studies have reported that the underlying biological pathways defining RN and rBT are fundamentally different. This strongly suggests that there might be phenotypic differences and hence cues on multi-parametric MRI, that can distinguish between the two pathologies. One challenge is that these differences, if they exist, might be too subtle to distinguish by the human observer. In this work, we explore the utility of computer extracted texture descriptors on multi-parametric MRI (MP-MRI) to provide alternate representations of MRI that may be capable of accentuating subtle micro-architectural differences between RN and rBT for primary and metastatic (MET) BT patients. We further explore the utility of texture descriptors in identifying the MRI protocol (from amongst T1-w, T2-w and FLAIR) that best distinguishes RN and rBT across two independent cohorts of primary and MET patients. A set of 119 texture descriptors (co-occurrence matrix homogeneity, neighboring gray-level dependence matrix, multi-scale Gaussian derivatives, Law features, and histogram of gradient orientations (HoG)) for modeling different macro and micro-scale morphologic changes within the treated lesion area for each MRI protocol were extracted. Principal component analysis based variable importance projection (PCA-VIP), a feature selection method previously developed in our group, was employed to identify the importance of every texture descriptor in distinguishing RN and rBT on MP-MRI. PCA-VIP employs regression analysis to provide an importance score to each feature based on their ability to distinguish the two classes (RN/rBT). The top performing features identified via PCA-VIP were employed within a random-forest classifier to differentiate RN from rBT across two cohorts of 20 primary and 22 MET patients. Our results revealed that, (a) HoG features at different orientations were the most important image features for both cohorts, suggesting inherent orientation differences between RN, and rBT, (b) inverse difference moment (capturing local intensity homogeneity), and Laws features (capturing local edges and gradients) were identified as important for both cohorts, and (c) Gd-C T1-w MRI was identified, across the two cohorts, as the best MRI protocol in distinguishing RN/rBT.

Neuronavigation for Intraoperative Localization of Cerebral Aneurysms (Case Report and Review of Literature)

Introduction: Localization and delineation of the extent of lesions are critical for safe management of brain tumors and vascular abnormalities. Neuronavigation systems have been developed for image-guided neurosurgery to aid accurate localization and better visualization of these lesions. Navigation has been mainly used in brain biopsy and tumor resection. There have been a few reports on its use in vascular surgery and they suggest that neuronvigation could be helpful. Case Presentation: A 53-year-old man developed a severe sudden headache 2 days before admission. He did not have any specific medical problems. On inspection of neurological status, he was alert and his motor power was normal in all extremities. CT scan on admission showed diffuse blood in sylvian fissures and basal cisterns. Angiography revealed an aneurysmal dilatation where the posterior communicating artery arises from the right internal carotid artery (ICA). MRI scan with appropriate protocol for neuronavigation was performed and demonstrated, on Gadolinium (Gd) enhanced images, a small round hyperintense lesion in parasellar region on the right side. We prepared the navigation based on CT scan and MRI for surgery of the aneurysm. Right frontotemporal craniotomy was performed, brain retracted and arachnoid membranes were opened under the guidance of navigation-MRI. The neck was dissected and a clip was applied to the aneurysm. Neurological status of the patient was unchanged postoperatively and control CT scan was unremarkable. Discussion: According to the reports and our case we suggest that MRI based neuronavigation results in accurate localization of the aneurysm, increases visualization of the lesion, decreases normal parenchymal and vascular injury and is useful for the treatment of ruptured intracranial aneurysms in special cases.

Prognostic Factors and Treatment Outcome in Glial Brain Tumors; Data from the Third Neuro-oncology Scientific Club’s Input Forum, 2013, Mashhad, Iran

ABSTRACT Management of the central nervous system malignancies are among the evolving areasof research and clinical practice requiring a well-coordinated interdisciplinary approach.The neuro-oncology scientific club (NOSC) has tried to cross the links between variousdisciplines’ experts involved in brain tumor care in Iran since 2011. The NOSC’sstructured collaborative brain tumor registry (BTCR) and the support received from itssteering committee and provincial boards have been the key elements for its successand growth so far. This scientific community not only has helped to optimize brain tumorcare but provided interdisciplinary research opportunities to its members across Iran.Mashhad’s NOSC has been the pioneer in the above. During the 3 rd Mashhad’s NOSCmeeting held in November 21 st 2013, the interim results from some important localneuro-oncology studies were presented. Some potential opportunities to improve thecoordinated interdisciplinary brain tumor care within the province were discussed byneurosurgery, neuroradiology and radiation oncology faculty at this provincial NOSCmeeting. Clinical outcome, survival data and prognostic factors in adult and pediatricgliomas over the past several years in Mashhad, the association between methylguanine methyl transferase (MGMT) methylation status (determined by MSQP ormethylation specific quantitative polymerase chain reaction) where among the mainstudies outlined during this event. We realize that optimized brain tumor managementand productive research in neuro-oncology can only be achieved through an integratedapproach and strong team work. This is what the NOSC pursues.Keywords: Neuro-oncology; consensus development; brain tumor management;interdisciplinary; Mashhad; Iran.

THE APPLICATION OF NANOMATERIALS IN DIAGNOSIS AND TREATMENT FOR MALIGNANT PRIMARY BRAIN TUMORS

Malignant primary brain tumors have a very high morbidity and mortality. Even though enormous advances have been made in primary brain tumor management, in the case of malignant primary brain tumors, current diagnostic strategies cannot identify exact infiltrating margins, surgery alone cannot achieve total mass resection, and adjuvant therapies cannot improve survivals. Therefore, there is an urgent need to explore novel strategies to diagnose and treat such infiltrating brain tumors. Nanomaterials, particularly zero-dimensional and one-dimensional platforms, can carry various compounds such as contrast agents, anticancer drugs and genes into brain tumor cells specifically. Thus, contrast agent-based nanomaterials can selectively present infiltrating tumor outlines, while anticancer agent-based nanomaterials can specifically kill malignant tumor cells. In addition, dual-targeting nanomaterials, multifunctional nanocarriers, theranostic nanovehicles as well as convection-enhanced delivery technology hold promise to increase drug accumulation in tumor tissues, which could largely improve anticancer efficacy. In this review, we will mainly focus on the application of nanomaterials in preoperative diagnosis, intraoperative diagnosis and adjuvant treatment for malignant primary brain tumors.

Managing children with raised intracranial pressure: part one (introduction and meningitis)

Intracranial pathologies in children need urgent identification and management. This article is presented in two parts, with part one describing intracranial pressure and outlining the features and management of meningitis. Part two, to be published in February 2014, outlines the features and management of brain tumours and intracranial bleeds. Each condition is accompanied by an illustrative case study to give an idea of what nurses might encounter in a child presenting with raised intracranial pressure.

INVITED REVIEW—NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.