High-grade Glial Tumors Research Articles

Frameless Stereotactic Functional Neuronavigation Combined with Intraoperative Magnetic Resonance Imaging as a Strategy in Highly Eloquent Located Tumors Causing Epilepsy

Background: Intractable epilepsy due to tumors located in highly eloquent brain regions is often considered surgically inaccessible because of a high risk of postoperative neurological deterioration. Intraoperative MRI and functional navigation contribute to overcome this problem. Objectives: To retrospectively investigate the long-term results and impact of functional neuronavigation and 1.5-tesla intraoperative MRI on patients who underwent surgery of tumors associated with epilepsy located close to or within eloquent brain areas. Methods: Nineteen patients (9 female, 10 male, mean age 41.4 ± 13.4 years, 11 low-grade and 8 high-grade glial tumors) were evaluated preoperatively using BOLD imaging, diffusion-tensor imaging tractography and magnetoencephalography. Functional data were implemented into neuronavigation in this multimodal approach. Results: In 14 of 19 patients (74%), complete resection was achieved, and in 5 patients significant tumor volume reduction was accomplished. Eight of 14 (57%) complete resections were achieved only by performing an intraoperative image update. Neurological deterioration was found permanently in 2 patients. After a mean follow-up of 43.8 ± 23.8 months, 15 patients (79%) became seizure free (Engel class Ia). Conclusions: Despite the highly eloquent location of tumors causing intractable epilepsy, our multimodal approach led to complete resection in more than two-thirds of patients with an acceptable neurological morbidity and excellent long-term seizure control.

Gamma Knife Radiosurgery for High Grade Glial Neoplasms: A Canadian Experience

To review our institutional experience with Gamma Knife (GK) stereotactic radiosurgery in treating focally recurrent high grade glial neoplasms of World Health Organization (WHO) grade III or IV. We conducted a retrospective cohort review of all patients treated with GK for focally recurrent high grade gliomas at our institution between November 2003 and April 2013. Data on age, sex, tumor volume, location and maximal diameter, presenting clinical status, complications and clinical outcome was recorded. A total of 33 patients were identified. Four were lost to follow-up. Average post-GK and overall survival was 20.4 months (range: 3–72) and 63.3 months (range: 10–214) respectively. For WHO grade IV gliomas, the average post-GK and overall survival was 15.8 months (range: 3–77) and 40.1 months (range: 13–148) respectively. Similarily, for WHO grade III gliomas, the average post-GK and overall survival was 34.9 months (range: 6–72) and 136.4 months (range: 22–214) respectively. Twenty-two patients (75.9%) had post-GK edema, with 14 requiring dexamethasone and eight being asymptomatic. Four patients (13.8%) had imaging defined radiation necrosis. Gamma Knife SRS affords an extension of local tumor control, acceptable morbidity, and potentially prolonged survival, for highly selected patients with focally recurrent high grade glial neoplasms.

Can Behenic Acid (C22:0) Levels be a Prognostic Factor in Glial Tumors?

Inhibition of fatty acid synthase leads to apoptosis in cancers, which leads to high levels of fatty acid synthesis. This indicates that cancer cells depend on fatty acid in order to survive. In this study, we investigated whether or not there was a relationship between the glial tumor grade and free fatty acid level of tumor tissue. Twenty patients who had high grade glial tumors and 20 patients who had low grade glial tumors, were included in the study. Tumors samples were obtained intraoperatively in order to measure the fatty acid levels. The fatty acids were studied in three groups: saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. They were analyzed with gas chromatography. The oleic acid, linoleic acid, eicosadienoic acid, arachidonic acid, and docosadienoic acid levels were high in the tumor tissue of low grade tumors. The myristic acid, palmitic acid, stearic acid, alpha linoleic acid, eicosenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, and ceramide levels were high in the tumor tissue of high grade glial tumors. However, none of these high values were statistically significant. The high values of behenic acid, a saturated fatty acid, in low grade glial tumors were statistically significant. High levels of behenic acid in patients with low grade glial tumor is important as it indicates persistence of the tissue integrity and tissue resistance. behenic acid levels can be a prognostic factor in glial tumors.

Tumor progression and transformation of low-grade glial tumors associated with pregnancy

Brain tumor growth or progression has been shown to occur in low-grade glial tumors and meningiomas. While progression has been documented in this population, transformation to a more aggressive high-grade glial tumor that can lead to increased morbidity and mortality has not been identified. In this case series, we document transformation from low-grade gliomas to high-grade gliomas (WHO grade III and IV) in young women during pregnancy. We further discuss the possible etiologies of this phenomenon.

Case Report: Glioblastoma Multiforme Complicating Familial Cavernous Malformations

Cerebral cavernous malformations (CCMs) are vascular lesions characterized by enlarged capillary cavities without intervening brain parenchyma, and may be sporadic or familial [2]. Their prevalence is close to 0.5 % in the general population [22]. Familial CCMs are increasingly diagnosed, and newer susceptibility-weighted imaging (sWI) sequences are more sensitive to detection than conventional T2-weighted gradient echo (T2*-Gre) [5]. These lesions have an autosomal dominant inheritance with associated genes mapped to the long and short arms of chromosomes 7, and to the long arm of chromosome 3 [4, 7]. Familial CCMs are multiple, with a 2000 retrospective study in 40 patients from 29 unrelated French families finding that the risk of acute hemorrhage was at least twice as high as that observed in sporadic cases, 13–17 % per patient-year or 2–2.5 % per lesion-year [14]. Usually, CCMs can be differentiated from hemorrhagic malignant lesions of the brain such as metastases and glioma. CCMs generally lack mass effect or surrounding vasogenic edema, but these features may be observed in the settings of acute hemorrhage. occasionally, follow-up is performed for CCMs demonstrating surrounding edema on T2-weighted Mr sequences. While numerous “collision” tumors have been reported in the literature, glial neoplasms occurring in an existing CCM are extremely rare. An ependymoma, anaplastic oligo-astrocytoma, and oligo-dendroglioma have all been observed [3, 8, 25]. The exact etiological relationship between CCMs and these lesions is unclear. We report a case of high-grade glial neoplasm complicating familial cavernomatosis, which has not been described until very recently [19]. The described case highlights features of presumed cavernous malformations that should be viewed with suspicion.

Aquaporin-4 in glioma and metastatic tissues harboring 5-aminolevulinic acid-induced porphyrin fluorescence

IntroductionAquaporin channels (AQPs) are a group of integral membrane proteins that regulate the transport of water through cell membranes. Previous studies have shown that up-regulation of AQP1 and AQP4, two of the predominant AQPs in the human brain, in high grade glial tumors contribute to cerebral edema. Others link AQPs to the regulation of human glioma cell migration and invasion. The aim of this study was to determine AQPs expression in tumor tissue harboring 5-aminolevulinic acid (ALA)-induced porphyrin fluorescence with flow cytometry and compare it to the expression in normal brain tissue. MethodsTissue samples were obtained from fluorescing brain tumors of 26 patients treated with ALA prior to surgery (20mg/kg b.w.). Expression levels of aquaporin channels were measured in primary tissue cultures using a FACS CANTO I flow cytometer. A control group consisted of four non-fluorescing tissue samples, the C6 and the U87 cell line. ResultsNineteen gliomas (14 high grade, 5 low grade) and 7 metastases were analyzed. On the 4th post-operative day, expression levels of AQP4 channels, but not of AQP1 channels, were significantly increased in samples from fluorescing tissue compared to non-fluorescing tissue. In addition we could see how ALA induces fluorescence in metastases. ConclusionFlow cytometry appears to be an auspicious method for the analysis of porphyrins and AQPs in primary brain cell tumor cultures. ALA fluorescing tissue showed higher AQP4 expression compared to normal brain tissue. The demonstrated expression in a context with ALA could open a targeted therapeutic spectrum, for example to selectively target AQP4.

Second primary brain tumors following cranial irradiation for pediatric solid brain tumors

We describe our institution's experience with seven patients who developed second brain tumors following cranial irradiation. The median age at first irradiation was 8 years (range, 3-20 years). Initial diagnoses were two cases of germinoma, one non-germinomatous germ cell tumor (NGGCT), three cases of medulloblastoma, and one pineal gland tumor (pathology undetermined). All patients received craniospinal irradiation followed by local boost and the median dose to the initial tumor area was 54.0 Gy (range, 49.8-60.6 Gy). Four patients (two medulloblastomas, one germinoma, and one NGGCT) received chemotherapy. Second brain tumors were diagnosed a median of 114 months (range, 64-203) after initial radiation. Pathologic diagnoses were one glioblastoma, two cases of anaplastic astrocytoma, one medulloblastoma, one low-grade glioma, one high-grade glial tumor, and one atypical meningioma. Five patients underwent surgical resection with subsequent radiotherapy. One anaplastic astrocytoma patient received chemotherapy only following stereotactic biopsy. The meningioma patient was alive 32 months after total resection and radiosurgery for subsequent recurrences. Six patients died within 18 months and most deaths were due to disease progression. Most patients diagnosed with second brain tumors had received high-dose, large-volume radiotherapy with chemotherapy at a young age. Further studies are required to determine the relationship between radiotherapy/chemotherapy and the development of secondary brain tumors.

Exomic Sequencing of Four Rare Central Nervous System Tumor Types

A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C:G>T:A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.

Multicentric glioblastoma arising in two unusual sites: cerebellum and thalamus

Multicentric glioblastomas (MGBM) arising in infra/supratentorial regions are uncommon lesions. The authors report a case of MGBM in a 61 year-old female patient, who presented a sudden onset of left hemiplegia. The magnetic resonance imaging (MRI) showed two expansive large lesions affecting cerebellum and thalamus, with strong contrast enhancement. The patient underwent resection of the cerebellar lesion. Microscopy revealed a high grade glial neoplasm exhibiting high mitotic index, areas of necrosis and microvascular proliferation. The neoplastic cells showed positive immunoexpression for glial fibrillary acidic protein (GFAP). The morphological findings were consistent with glioblastoma (GBM). The patient was referred to radiotherapy, with discrete signs of tumor regression after a 60-day clinical follow-up.

Spontaneous high‐grade glial intramedullary tumor of the spine in a rhesus macaque (Macaca mulatta)

A 4-year-old rhesus macaque presented with acute, progressive paresis of the extremities. A complete blood count, serum biochemical analysis, neurologic exam and necropsy were performed. The clinical, histopathological, and immunohistochemical findings confirmed a high-grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma. We describe a case of a naturally occurring spontaneous spinal cord neoplasia in a non-human primate.

Multimodal MR imaging findings of a congenital glioblastoma multiforme

Dear Editor: We wish to report a case of congenital glioblastoma multiforme which is a rare high-grade glial tumor, with diffusionweighted magnetic resonance images and MR spectroscopy. Published reports are mostly based on clinical, genetical, and pathological behavior of the tumor; reports of radiological appearance are relatively uncommon. The imaging in those reports most commonly involved antenatal diagnoses by ultrasound; we did not recognize any report of MRI with diffusion and spectroscopy so far. An 8-month-old female infant from North Iraq presenting with an enlarging head was admitted to our hospital. The parents stated that they were told that the head circumference was larger than normal limits at birth. No further investigation was made at that time. On her routine follow-up onthe second month,aheadCTwasperformedbecauseoftheenlargedhead which revealeda supratentorialmass.The parents didnot seek any treatment at that time. Six months later, the baby was seen at our hospital, with the complaint of increasing enlargement of the head circumference. On physical examination, the patient was fine, with normal reflexes and normal responses to the stimuli, except for the macrocephaly. An MRI of the brain revealed a huge mass in the right frontal and parietal lobes which contained multiple small and large cystic areas and solid components that were isointense to gray matter on both T1-weighted- (Fig. 1a) and T2-weighted images. The

Prognostic importance of markers for inflammation, angiogenesis and apoptosis in high grade glial tumors during temozolomide and radiotherapy

IntroductionAngiogenesis, inflammation and apoptosis have an important place in the carcinogenesis of high-grade gliomas (HGG). We evaluated the postoperative levels and the prognostic importance of tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6), endoglin (CD105), vascular endothelial growth factor (VEGF), M65 and M30 as markers of inflammation, angiogenesis and apoptosis in patients with HGG. Methods and resultsPostoperative pretreatment sera were collected from 44 newly diagnosed patients with HGG. The control group was also consisted of 44 healthy people. The median age of all patients with HGG was 59 (range: 30–80). Temozolomide concurrent with radiotherapy was given to 37 patients. Thereafter 24 patients received consolidation temozolomide monotherapy. Mean chemotherapy cycle was 4.2. Progression free survival and overall survival were 6 (95% CI; 5.16–6.83) and 16months (95% CI; 13.07–18.93) respectively in patients treated with concurrent chemoradiotherapy and consolidation chemotherapy. Relative to the control cohort endoglin (p=0.000) and TNFα (p=0.000) levels were significantly lower; however VEGF (p=0.030) levels were higher in the patient group. In contrast, there were no significant change in IL-6 levels and the plasma apoptotic markers M65 (p=0.085) and M30 (p=0.292). In separate log rank tests, these biological markers did not correlate with survival. Discussion and conclusionIn HGG, a significant decrease in endoglin and TNFα levels was observed, while VEGF levels were significantly increased postoperatively. However, with the power from this patient population, no correlation with survival was observed.

Abstract 2360: Complex DNA damage cooperates with Ink4a/Ink4b/Arf loss to generate high grade gliomas in transgenic mouse models

Abstract Glioblastoma multiforme (GBM) are highly lethal brain tumors for which exposure to ionizing radiation is the only known risk factor. GBMs are characterized by alterations in three core signaling pathways: 1) RTK-PI3K-Akt, 2) ARF-MDM2-p53, and 3) Ink4a-RB1. In order to objectively evaluate the risk of developing malignant gliomas from exposure to ionizing radiation, we have developed mouse models with brain-specific deletions of Ink4a, Ink4b, Arf, or PTEN in logical combinations representing the progression of primary or secondary GBMs. Specifically, we examined whether complex, unrepairable DNA lesions, such as those induced by charged particles, are more tumorigenic compared to simple breaks that are efficiently repaired, such as those induced by gamma-rays. Using CDKN2A knockout murine astrocytes in which the tumor suppressors Ink4a and Arf have been deleted (abrogating RB1 and p53 pathways, respectively), we have previously shown that Fe ions are highly tumorigenic compared to gamma-rays. Importantly, we find that loss of a third tumor suppressor, Ink4b, is a critical event in tumorigenesis triggered by charged particles. Based on our in vitro results, we are now using transgenic mouse models with brain-specific deletions of these three key tumor suppressors (Ink4a/b, Arf) to evaluate radiation-induced gliomagenesis in vivo. Nestin-Cre; Ink4ab-/-; Arf f/f mice were irradiated with a single dose of 1 Gy Fe ions or 4 Gy gamma-rays. While gamma-induced damage is efficiently repaired by 1 day, unrepaired DNA lesions are evident up to 1 month following Fe irradiation. Most importantly, we find that combined loss of Ink4a/b and Arf cooperate with DNA damage by Fe ions resulting in a high incidence (25%) of malignant gliomas. These highly heterogeneous tumors arise with an average latency of 4.8 months and are classified as high grade (III and IV) glial tumors. Although tumors arising after gamma irradiation are also classified as high grade, they arise with a longer latency (5.6 months) and occur at a lower frequency (15%). To identify key genetic alterations involved in radiation-induced gliomagenesis, tumors are being analyzed by array CGH and microarray platforms. Strikingly, a 20- to 40-fold amplification of the MET proto-oncogene is observed in a high percentage of tumors. As MET is frequently amplified in human GBMs, it is likely that MET activation may be an important event in tumorigenesis triggered by charged particles in these mouse models. We are hopeful that a global and accurate picture of the genetic changes underlying radiation-induced gliomagenesis will emerge from this study. The data obtained will allow for comparison with changes recently identified in human gliomas by large scale genomic analyses and will allow us to understand whether radiation-induced gliomas are fundamentally similar to those occurring spontaneously, both in mouse models and in human patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2360. doi:1538-7445.AM2012-2360

Mechanisms of blood flow and hypoxia production in rat 9L-epigastric tumors.

Classical descriptions of tumor physiology suggest two origins for tumor hypoxia; steady-state (diffusion-limited) hypoxia and cycling (perfusion-modulated) hypoxia. Both origins, primarily studied and characterized in murine models, predict relatively small, isolated foci or thin shells of hypoxic tissue interspersed with contrasting oxic tissue. These foci or shells would not be expected to scale with overall tumor size since the oxygen diffusion distance (determined by oxygen permeability and tissue oxygen consumption rate) is not known to vary dramatically from tumor to tumor. We have identified much larger (macroscopic) regions of hypoxia in rat gliosarcoma tumors and in larger human tumors (notably sarcomas and high-grade glial tumors), as indicated by biochemical binding of the hypoxia marker, EF5. Thus, we considered an alternative cause of tumor hypoxia related to a phenomenon first observed in window-chamber tumor models: namely longitudinal arteriole gradients. Although longitudinal arteriole gradients, as originally described, are also microscopic in nature, it is possible for them to scale with tumor size if tumor blood flow is organized in an appropriate manner. In this organization, inflowing blood would arise from relatively well-oxygenated sources and would branch and then coalesce to poorly-oxygenated outflowing blood over distances much larger than the length of conventional arterioles (multi-millimeter scale). This novel concept differs from the common characterization of tumor blood flow as disorganized and/or chaotic. The organization of blood flow to produce extended longitudinal gradients and macroscopic regional hypoxia has many important implications for the imaging, therapy and biological properties of tumors. Herein, we report the first experimental evidence for such blood flow, using rat 9L gliosarcoma tumors grown on the epigastric artery/vein pair.

Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

BackgroundThe cancer stem cell (CSC) hypothesis posits that deregulated neural stem cells (NSCs) form the basis of brain tumors such as glioblastoma multiforme (GBM). GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall.MethodsWe described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques.ResultsThe patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice.ConclusionsThis brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer stem cells, which are likely the driving force for the rapid recurrence of the tumor in the patient.

Institutional experience of paediatric high-grade central nervous system tumours: An analysis of 74 patients and review of the literature

Aim of the studyAlthough the survival for children with certain central nervous system (CNS) tumour types has improved through current surgical and adjuvant treatment modalities, the prognosis of many high-grade tumours remains poor despite aggressive treatment. The aim of this study is to analyse patients with high-grade brain tumours in our institution to determine the histopathology, clinical characteristics, treatment modalities, and survival.Material and methodsA total of 74 patients with a diagnosis of high-grade brain tumour were analysed. There were a total of 31 patients with embryonal tumours, 27 patients with high-grade glial tumours, 12 patients with brain stem gliomas and 4 patients with other high-grade brain tumours.ResultsThere were 48 (65%) boys and 26 (35%) girls (ratio: 1.85) with a median age of 99.7 months (range = 2-204 months). The median follow-up period was 19 months (range = 1-204 months). Tumour recurrence was observed in 38 patients (51.4%). The overall survival rate and event-free survival rate of our patients were 27% and 19.5%, respectively.ConclusionsPediatric high-grade CNS tumours have a very aggressive behaviour and a significant number of children eventually succumb to disease despite multimodal treatment. There is a need of more effective therapeutic approaches for these tumours with poor prognosis. The future improvement in childhood high-grade brain tumour management depends on a better understanding of the molecular genetics and biology of brain tumours.

Diffusion Tensor Imaging Provides an Insight Into the Microstructure of Meningiomas, High-Grade Gliomas, and Peritumoral Edema

Fractional anisotropy (FA) is a measure for the degree of microstructural organization. Several studies have used FA values to assess microstructural organization of brain tumors and peritumoral edema. The purpose of our study was to validate FA and apparent diffusion constant (ADC) values in the diagnosis of meningiomas versus high-grade glial tumors, with the focus on the ability of diffusion tensor imaging (DTI) to reveal tumor ultrastructure. Our hypothesis was that FA and ADC values significantly differ between high-grade gliomas and meningiomas, and in the peritumoral edema. Diffusion tensor imaging values were obtained from 20 patients with meningiomas (21 tumors) and 15 patients with high-grade gliomas. Regions of interest were outlined in FA and ADC maps for solid-enhancing tumor tissue and peritumoral edema. Fractional anisotropy and ADC values were normalized by comparison to normal-appearing white matter (NAWM) in the contralateral hemisphere. Differences between meningiomas and high-grade gliomas were statistically analyzed. Meningiomas showed a significantly higher FA tumor/FA NAWM ratio (P = 0.0001) and lower ADC tumor/ADC NAWM ratio (P = 0.0008) compared to high-grade gliomas. On average, meningiomas also showed higher FA values in peritumoral edema than high-grade gliomas (P = 0.016). Apparent diffusion constant values of peritumoral edema for the 2 tumor groups did not differ significantly (P = 0.5). Diffusion tensor imaging can be used to reveal microstructural differences between meningiomas and high-grade gliomas and may contribute toward predicting the histopathology of intracranial tumors. We advocate that diffusion tensor imaging should be included in the standard imaging protocol for patients with intracranial tumors.

Prognostic importance of inflammation, apoptosis, and angiogenesis markers in high-grade glial tumors.

e12522 Background: High-grade glial tumors (HGGT) are aggressive tumors. We evaluate the prognostic importance of M65, M30, TNFα, CD105, VEGF, IL6, which are markers of inflammation, apoptosis, and angiogenesis, in HGGTs. Methods: Postoperative pretreatment serums were collected from 44 newly diagnosed HGGT patients. Control group (n=44) consisted of healthy people. Serum M30, M65, CD 105, VEGF, IL6 and TNFα levels were evaluated. Results: Median age of 44 patients with GBM (n=38, %86.3) and anaplastic glioma (n=6, %13.) was 59 (range: 30-80). Thirty-one patients were diagnosed with gross total excision, 10 with subtotal excision and 3 with stereotactic biopsy. Temozolomide concurrent with RT was performed in 37 patients. RT alone was performed in 6 patients. One patient did not receive RT because of poor performance status. Thereafter 24 patients received consolidation temozolomide monotherapy. In 37 patients, proggression free survival (PFS) and overall survival (OS) were 6 (%95 CI; 5.16-6.83) and 16 months (%95 CI; 13.07-18.93) respectively. CD105 (p=0.000) and TNFα (p=0.000) levels were statistically lower, however VEGF (p=0.030) levels were higher in patient group. Statistically insignificant low IL6 levels and high plasma apoptotic markers as M65 (p=0.085) ve M30 (p=0.292) levels were detected. In multiple regression analysis, biological markers did not show significance in survival (0.05<p). Conclusions: In HGGTs, low TNFα and IL6 levels with reduced proinflammatory activity and immunity, besides increased apoptotic activity and VEGF related angiogenesis were detected. Serum levels of markers. Markers N Mean Range P M30 (U/L) Patient Control 44 43 153.43 110.06 57.60-1006.27 57.60-259.05 0.292 M65(U/L) Patient Control 44 43 417.87 298.71 195.31-1590.51 191.64-600.40 0.850 IL6 (pg/mL) Patient Control 44 44 7.23 7.56 0.50-27.71 0.33-29.33 0.957 TNFα (pg/mL) Patient Control 44 44 14.01 45.57 0.60-87.24 0.95-93.05 0.000 VEGF (pg/mL) Patient Control 44 44 626.73 380.49 99.76-5200.53 72.76-1584.12 0.030 CD 105 (ng/mL) Patient Control 44 44 5.51 9.98 0.35-21.23 2.00-23.71 0.000

Carmustine-impregnated wafers and their impact in the management of high-grade glioma

Introduction: Carmustine-impregnated biodegradable wafers provide a locoregional adjunct to the treatment of patients with high-grade glial neoplasms. Their impact is that of delivering a chemotherapeutic agent directly to the tumor site at the time of neurosurgical intervention with a resulting increased local drug concentration and an ongoing therapeutic effect lasting several days to weeks.Areas covered: This manuscript reviews the preclinical and clinical studies that established carmustine-impregnated wafers as a locoregional therapy in the treatment of de novo as well as recurrent high-grade gliomas and compares it with other locoregional modalities currently under development. A pertinent English language literature search dating back to 1990 was undertaken.Expert opinion: Carmustine-impregnated wafers represent but one component of a multimodality armamentarium for the treatment of high-grade gliomas. The development of biodegradable compounds capable of incorporating additional therapeutic agents beyond carmustine is a subject of ongoing research. Integration of diverse treatment modalities into the management of complex high-grade cancers, taking advantage of predictive markers of efficacy, be they molecular or otherwise, will remain a major focus of clinical research in the second decade of this century.

Tumor vascular leakiness and blood volume estimates in oligodendrogliomas using perfusion CT: an analysis of perfusion parameters helping further characterize genetic subtypes as well as differentiate from astroglial tumors

The purpose of this study was to determine the usefulness of perfusion CT (PCT) parameters particularly blood volume and neovascular permeability estimates (permeability surface area-product, PS) in the evaluation of oligodendrogliomas (OG), correlation with genetic subtypes of OGs (with or without loss of heterozygosity/LOH on 1p/19q) as well as comparison of perfusion parameters of OGs with astroglial tumors. Pre-operative PCT done in 21 patients with OGs was retrospectively correlated with our previously published PCT data for 32 patients with astroglial neoplasms (Jain R et al., AJNR Am J Neuroradiol 29:694-700, 2008). All OGs were also analyzed for genetic subtypes of with or without LOH. PCT parameters PS and cerebral blood volume (CBV) were obtained for the entire lesion and a statistical analysis done to correlate various histopathological variants. Low grade OGs (n=13) showed slightly lower CBV (1.42 vs. 1.72ml/100g; P value 0.391) and PS (0.56 vs. 0.95ml/100g/min; P value 0.099) as compared to high grade OGs (n=8), though not statistically significant. LOH positive OGs (n=13) showed higher mean CBV (1.59 vs. 1.45; P value 0.712) and slightly lower PS (0.68 vs. 0.75; P value 0.718) as compared to LOH negative OGs (n=8), although not statistically significant. Low grade OGs (n=13) showed higher mean CBV 1.42ml/100g as compared to low grade astroglial tumors (n=8) 0.95ml/100g (P value=0.08), however no statistically significant difference was noted for PS (0.56 vs. 0.52ml/100g/min, P value 0.695). Statistically significant differences were observed in CBV and PS values of high grade OGs and high grade astroglial tumors with the high grade glial tumors showing higher mean CBV (2.79 vs. 1.72; P value 0.03) as well as higher PS (2.37 vs. 0.95; P value<0.01), however this difference was not significant if only comparing grade III OGs with grade III astroglial tumors. PCT perfusion parameters including PS values do not help grade OGs despite showing a trend for higher CBV and PS in higher grade OGs. Similarly LOH positive OGs also showed slightly higher CBV, but again failed to reach any statistically significant level. Low grade OGs showed slightly higher CBV as compared to low grade astroglial tumors, whereas higher grade OGs showed significantly lower PS values as compared to higher grade astroglial tumors despite showing high CBV.