Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
ABTA A national nonprofit organisation founded in 1973 to advance the understanding and treatment of brain tumors with the goals of improving, extending and, ultimately, saving the lives of those impacted by a brain tumor diagnosis.
A national, not-for-profit organization, founded in 1982 to provide support to people affected by brain tumors. The Web site has both English and French language pages which provide details of the organisation, its services, events, collaborations.
PubMed Central search for free-access publications about Brain and CNS Tumours MeSH term: Central Nervous System Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
Springer Journal of the Japan Society of Brain Tumor Pathology. This international journal documents the latest research and topical debate in all clinical and experimental fields relating to brain tumors, especially brain tumor pathology.
EANO EANO is an organisation for Neurooncologists in Europe formed in 1994. This site includes a background to the organisation, membership details, reports from scientific meetings, clinical trial details, a calendar of events, and links to related sites.
This list of publications is regularly updated (Source: PubMed).
Zhang L, Zhao D Applications of nanoparticles for brain cancer imaging and therapy. J Biomed Nanotechnol. 2014; 10(9):1713-31 [PubMed] Related Publications
The most common types of malignant brain tumors in adults are brain metastasis and primary glioblastoma multiforme (GBM), both of which are highly lethal, with a median survival of less than a year. A critical challenge in treating brain tumors is the delivery of drugs to the central nervous system (CNS). The blood brain barrier (BBB), which has been shown to be partially disruptive even in the late stage of these brain tumors, prevents the access of therapeutic concentrations of systemic drugs to the tumor in brain parenchyma. Nanoparticle systems can represent optimal carriers for delivery of therapeutic agents. We will summarize various strategies used to improve nano-delivery of imaging contrast or therapeutic agents across BBB to brain tumors. Recent advances in molecular and cellular identifications of neurooncological biomarkers promise the advent of nanotechnology-based brain tumor-targeted detection and therapy. In this review, we will further discuss the current understanding of brain tumor biology and tumor type-specific genetic and epigenetic alterations, and advances in development of the novel nanoparticles for brain tumor imaging and therapy.
Ba JL, Jandial R, Nesbit A, et al. Current and emerging treatments for brain metastases. Oncology (Williston Park). 2015; 29(4):250-7 [PubMed] Related Publications
Brain metastasis in patients with cancer can be indicative of multisystem spread or lead to neurological demise if not locally controlled, and is associated with poor survival and high morbidity. Compared with metastasis to other areas of the body, brain metastasis possesses a unique biology that confers high resistance to systemic therapies. This phenomenon has been historically attributed to the inability of chemotherapeutic agents to pass through the blood-brain barrier. Recent studies challenge this premise, revealing other potentially targetable mechanism(s). Therapies that exploit recent advances in the understanding of brain metastasis are still in early stages of development. Encouragingly, and discovered by happenstance, some molecularly targeted drugs already appear to have efficacy against certain tumors and accompanying cerebral edema. In the meantime, conventional treatment modalities such as surgery and radiation have iteratively reached new levels of refinement. However, these achievements are somewhat muted by the emergence of magnetic resonance (MR)-guided laser interstitial thermal therapy, a minimally invasive neuroablative technique. On the horizon, MR-guided focused ultrasound surgery is similarly intriguing. Even in the absence of further advances, local control is frequently achieved with state-of-the-art therapies. Dramatic improvements will likely require sophisticated approaches that account for the particular effects of the microenvironment of the central nervous system on metastasis.
Doron O, Carmon E An incidental suprasellar mass in a military flying cadet: implications for aircrew. Aerosp Med Hum Perform. 2015; 86(5):477-80 [PubMed] Related Publications
BACKGROUND: Incidental findings pose a dilemma in aviation medicine, where every finding must be carefully considered in order to ensure the well-being of the aircrew for flight and mission safety. Since suprasellar masses are not uncommon, their possible effects should be addressed. CASE REPORT: We present an incidental finding of 11.5 mm × 14.4 mm, hyper-intense on T2 and iso-intense on T1-weighted images, of a suprasellar mass in a 19-yr-old man. This finding led to the re-evaluation of his position as a military flight cadet, followed by his later disqualification. DISCUSSION: No medical waiver regarding asymptomatic suprasellar mass exists. We have carefully examined the differential diagnosis and generated a profile for each possible diagnosis consisting of risks for sudden incapacitation, progression likelihood, and the effect of an aerial environment on a brain lesion. We were able to draw up a medical waiver for some of the possible diagnoses (namely, Rathke's cyst or craniopharyngioma) for nonhigh performance aircraft.
Netravathi M, Kumari R, Kapoor S, et al. Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation. BMC Med Genet. 2015; 16:5 [PubMed] Free Access to Full ArticleRelated Publications
BACKGROUND: Coats plus syndrome is an autosomal recessive, pleiotropic, multisystem disorder characterized by retinal telangiectasia and exudates, intracranial calcification with leukoencephalopathy and brain cysts, osteopenia with predisposition to fractures, bone marrow suppression, gastrointestinal bleeding and portal hypertension. It is caused by compound heterozygous mutations in the CTC1 gene. CASE PRESENTATION: We encountered a case of an eight-year old boy from an Indian family with manifestations of Coats plus syndrome along with an unusual occurrence of dextrocardia and situs inversus. Targeted resequencing of the CTC1 gene as well as whole exome sequencing (WES) were conducted in this family to identify the causal variations. The identified candidate variations were screened in ethnicity matched healthy controls. The effect of CTC1 variation on telomere length was assessed using Southern blot. A novel homozygous missense mutation c.1451A > C (p.H484P) in exon 9 of the CTC1 gene and a rare 3'UTR known dbSNP variation (c.*556 T > C) in HES7 were identified as the plausible candidates associated with this complex phenotype of Coats plus and dextrocardia. This CTC1 variation was absent in the controls and we also observed a reduced telomere length in the affected individual's DNA, suggesting its likely pathogenic nature. The reported p.H484P mutation is located in the N-terminal 700 amino acid regionthat is important for the binding of CTC1 to ssDNA through its two OB domains. WES data also showed a rare homozygous missense variation in the TEK gene in the affected individual. Both HES7 and TEK are targets of the Notch signaling pathway. CONCLUSIONS: This is the first report of a genetically confirmed case of Coats plus syndrome from India. By means of WES, the genetic variations in this family with unique and rare complex phenotype could be traced effectively. We speculate the important role of Notch signaling in this complex phenotypic presentation of Coats plus syndrome and dextrocardia. The present finding will be useful for genetic diagnosis and carrier detection in the family and for other patients with similar disease manifestations.
Wang Y, Fan X, Li H, et al. Tumor border sharpness correlates with HLA-G expression in low-grade gliomas. J Neuroimmunol. 2015; 282:1-6 [PubMed] Related Publications
Human leukocyte antigen-G (HLA-G) is a tumor microenvironment molecule that is involved in the escape of cancerous tumors from host immune recognition and destruction. This study investigated the potential relationship between HLA-G expression levels and the sharpness of low-grade glioma tumor borders in magnetic resonance images. Preoperative T2-weighted images from 72 patients were retrospectively examined by manually segmenting the hyperintensive tumor areas and subsequently registering them to a standard brain template. Then, the intensity of the voxels inside the tumor border (tumor voxels) was compared with that of the voxels outside the tumor border (paratumor voxels). The radiologic sharpness of a tumor was defined as the mean ratio of the intensity of the tumor voxels to the intensity of the paratumor voxels. Tumors with high HLA-G expression were associated with larger tumors and lower mean hyperintensive contrast. These findings suggest that tumors with blurred boundaries may be those prone to diffuse invasion. Additionally, patients with tumors having high HLA-G expression were less likely to have undergone complete resections. Thus, this study is the first to identify an association between HLA-G expression and the radiologic morphology of the tumor border, and may further our understanding of the role of the HLA gene in immune escape in patients with low-grade gliomas.
Rotim K, Sajko T, Škoro I, et al. Complete neurological recovery after surgery for mesencephalic cavernoma: case report. Acta Clin Croat. 2014; 53(4):494-8 [PubMed] Related Publications
Cavernous malformations are classified as a group of vascular malformations of the central nervous system. Conservative treatment of brainstem cavernomas is accompanied with poor outcome. Surgery ofbrainstem cavernomas still poses a challenge due to the high risk of neurological damage and respectable morbidity. We report a case of complete neurological recovery in a 24-year-old female patient with mesencephalic cavernoma treated surgically. This case highlights that careful microsurgical treatment with the goal of complete cavernoma excision remains the treatment of choice in cases with de novo or recurrent hemorrhage. Intraoperative neurophysiologic monitoring should be used as the gold standard during brainstem cavernoma operations in order to avoid nuclear and long tract damages.
Morina A, Kelmendi F, Morina Q, Morina D Cerebellar dermoid cyst with contrast enhancement mural nodule: case report. Acta Clin Croat. 2014; 53(4):479-82 [PubMed] Related Publications
Typical dermoid cysts are well-circumscribed fat-density masses with no associated contrast enhancement; rarely, they may appear hyperattenuating on CT scan. CT hyperattenuating dermoid cyst (CHADC) is very uncommon, with only nine case reports in the literature update, which occurs exclusively in the posterior fossa. CHADC with mural nodule is extremely rare and, to the best of our knowledge, only two cases have been documented previously in the literature. A 49-year-old farmer had a 2-month history of occipital headaches, which were not suggestive of raised intracranial pressure. During the last month, he experienced loss of balance, frequent falls, anorexia and loss of weight. Magnetic resonance imaging (MRI) showed a huge mass from the tentorium to the foramen occipitale magnum with obliteration of the fourth ventricle; the lesion was well circumscribed. We completely removed the tumor and postoperative MRI showed no residual tumor. Epidermoid tumors with enhancing mural nodule on MRI and with hyperattenuating lesion on CT are extremely rare. Dermoid cysts are never associated with edema and extremely rarely cause obstructive hydrocephalus. MRI investigations are mandatory to diagnose these cases. The best curative treatment is total removal of the lesion.
Lin T, Wang M, Liang HS, Liu EZ The expression of p53, mgmt and egfr in brain glioma and clinical significance. J Biol Regul Homeost Agents. 2015 Jan-Mar; 29(1):143-9 [PubMed] Related Publications
In order to discuss the expression of P53, MGMT (O6-methylguanine-DNA methyltransferase) and EGFR (epidermal growth factor receptor) in brain glioma and their clinical significance, this paper collected clinical features of 40 patients. We observed the expression of P53, MGMT and EGFR in samples using immuohisto-chemistry assay and analyzed their interaction, as well as their relationship to brain glioma. It was found that among 40 cases of brain glioma samples, cases with positive P53 expression accounted for 47.5%, and its expression in high-grade brain glioma was higher than in low-grade brain glioma (P less than 0.05); cases with positive MGMT expression accounted for 37.5%;, and its expression in high-grade glioma and low-grade brain glioma had no statistical significance (P>0.05); cases with positive EGFR expression accounted for 55%, and its expression in high-grade brain glioma was higher than in low-grade brain glioma (P less than 0.05); the expression of P53, MGMT and EGFT were not correlated to age, gender or size of tumor; P53 expression was negatively correlated to MGMT expression (P < 0.05) but positively correlated to EGFR expression (P < 0.05) demonstration that P53, EGFR and MGMT play important roles in the occurrence and development of brain glioma.
Nadi MM, Nadi AM, Zabara MY, Ahmad TM Management of infiltrating spinal epidural angiolipoma. Neurosciences (Riyadh). 2015; 20(2):159-63 [PubMed] Related Publications
Angiolipomas of the spine are rare benign tumors commonly presenting with compressive myelopathy. The present report describes a case of spinal angiolipoma with thoracic mediastinal extension in a 50-year-old woman. She presented with a long-standing history of mid-back pain with progressive lower extremities weakness. An MRI showed a heterogeneously enhancing mass located in the posterior epidural space of the thoracic spine with mediastinal extension. Histopathological examination demonstrated features consistent with spinal angiolipoma. This report emphasizes the diagnosis and therapeutic management options of infiltrating spinal angiolipomas.
Sabbagh AJ, Alaqeel AM Focal brainstem gliomas. Advances in intra-operative management. Neurosciences (Riyadh). 2015; 20(2):98-106 [PubMed] Related Publications
Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals.
Pedeutour-Braccini Z, Burel-Vandenbos F, Gozé C, et al. Microfoci of malignant progression in diffuse low-grade gliomas: towards the creation of an intermediate grade in glioma classification? Virchows Arch. 2015; 466(4):433-44 [PubMed] Related Publications
Low-grade gliomas (GII) inescapably progress to high-grade gliomas (GIII). The duration of this transition is highly variable between patients and reliable predictive markers do not exist. We noticed in a subset of cases of GII, obtained by awake neurosurgery, the presence of microfoci with high cellular density, high vascular density, or minimal endothelial proliferation, which we called GII+. Our aim was to investigate whether these foci display immunohistochemical and molecular characteristics similar to GIII and whether their presence is correlated to poor prognosis. We analyzed cell proliferation, hypoxia, vascularization, and alterations of tumorigenic pathways by immunohistochemistry (Ki-67, CD31, HIF-1-alpha, EGFR, P-AKT, P53, MDM2) and fluorescence in situ hybridization (EGFR, MDM2, PDGFRA) in the hypercellular foci of 16 GII+ cases. We compared overall survival between GII, GII+, and GIII. Ki-67, and CD31 expression was higher in the foci than in the tumor background in all cases. Aberrant expression of protein markers and genomic aberrations were also observed in some foci, distinct from the tumor background. Survival was shorter in GII+ than in GII cases. Our results suggest that these foci are the early histological hallmark of anaplastic transformation, which is supported by molecular aberrations. Our study is the first to demonstrate intratumoral morphological, immunohistochemical, and molecular heterogeneity in resection specimens of GII, the presence of which is correlated to shorter survival. Our findings question the discriminative capacity of the current glioma classification and provide arguments in favor of the creation of a grade intermediate between GII and GIII, to optimize the treatment strategy of GII.
Furnari FB, Cloughesy TF, Cavenee WK, Mischel PS Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma. Nat Rev Cancer. 2015; 15(5):302-10 [PubMed] Related Publications
As tumours evolve, the daughter cells of the initiating cell often become molecularly heterogeneous and develop different functional properties and therapeutic vulnerabilities. In glioblastoma (GBM), a lethal form of brain cancer, the heterogeneous expression of the epidermal growth factor receptor (EGFR) poses a substantial challenge for the effective use of EGFR-targeted therapies. Understanding the mechanisms that cause EGFR heterogeneity in GBM should provide better insights into how they, and possibly other amplified receptor tyrosine kinases, affect cellular signalling, metabolism and drug resistance.
Reis GF, Pekmezci M, Hansen HM, et al. CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas. J Neuropathol Exp Neurol. 2015; 74(5):442-52 [PubMed] Article available free on PMC after 01/05/2016 Related Publications
Lower-grade (World Health Organization Grades II and III) gliomas vary widely in clinical behavior and are classified as astrocytic, oligodendroglial, or mixed. Anaplasia depends greatly on mitotic activity, with CDKN2A loss considered as the most common mechanism for cell cycle dysregulation. We investigated whether loss of the CDKN2A gene is associated with overall survival across pathologically and genetically defined glioma subtypes. After adjustment for IDH mutation, sex, and age, CDKN2A deletion was strongly associated with poorer overall survival in astrocytomas but not in oligodendrogliomas or oligoastrocytomas. Molecular classification of astrocytomas by IDH mutation, TP53 mutation, and /or ATRX loss of expression revealed that CDKN2A loss in IDH/TP53 mutated tumors was strongly associated with worse overall survival. CDKN2A loss in IDH mutated tumors with ATRX loss was only weakly associated with worse overall survival. These findings suggest that CDKN2A testing may provide further clinical aid in lower-grade glioma substratification beyond IDH mutation and 1p19q codeletion status, particularly in IDH/TP53 mutated astrocytomas.
Gielen PR, Schulte BM, Kers-Rebel ED, et al. Increase in both CD14-positive and CD15-positive myeloid-derived suppressor cell subpopulations in the blood of patients with glioma but predominance of CD15-positive myeloid-derived suppressor cells in glioma tissue. J Neuropathol Exp Neurol. 2015; 74(5):390-400 [PubMed] Related Publications
Myeloid-derived suppressor cells (MDSCs), defined as CD33-positive major histocompatibility complex class II-negative cells, are increased in a variety of human tumors and are associated with immunosuppression. Myeloid-derived suppressor cells can be further subdivided into CD14-positive monocytic MDSC and CD15-positive granulocytic MDSC (polymorphonuclear MDSC) subpopulations. Here we analyzed MDSC subsets in the blood and tumor tissue of patients with glioma, including the most malignant variant, glioblastoma multiforme (GBM). CD33-positive major histocompatibility complex class II-negative MDSCs in blood from 21 patients with glioma and 12 healthy individuals were phenotyped and quantified by flow cytometry. Myeloid populations of the monocytic MDSC and polymorphonuclear MDSC phenotypes were both significantly increased in the blood of patients with GBM versus healthy controls. The myeloid activation markers CD80 and PD-L1 could not be detected on either of these MDSC subsets; CD124, CD86, and CD40 were detected at similar levels on MDSCs in patients with glioma and healthy donors. By contrast, in tumor cell suspensions, the MDSC population consisted almost exclusively of CD15-positive cells. Immunohistochemistry confirmed infiltration of CD15-positive major histocompatibility complex class II-negative cells in glioma tissue samples. These data support a role for cells with an MDSC phenotype in the blood and tumor microenvironment of patients with GBM.
Mallawaaratchy DM, Buckland ME, McDonald KL, et al. Membrane proteome analysis of glioblastoma cell invasion. J Neuropathol Exp Neurol. 2015; 74(5):425-41 [PubMed] Related Publications
Glioblastoma multiforme (GBM) tumor invasion is facilitated by cell migration and degradation of the extracellular matrix. Invadopodia are actin-rich structures that protrude from the plasma membrane in direct contact with the extracellular matrix and are proposed to participate in epithelial-mesenchymal transition. We characterized the invasiveness of 9 established GBM cell lines using an invadopodia assay and performed quantitative mass spectrometry-based proteomic analyses on enriched membrane fractions. All GBM cells produced invadopodia, with a 65% difference between the most invasive cell line (U87MG) and the least invasive cell line (LN229) (p = 0.0001). Overall, 1,141 proteins were identified in the GBM membrane proteome; the levels of 49 proteins correlated with cell invasiveness. Ingenuity Pathway Analysis predicted activation "cell movement" (z-score = 2.608, p = 3.94E(-04)) in more invasive cells and generated a network of invasion-associated proteins with direct links to key regulators of invadopodia formation. Gene expression data relating to the invasion-associated proteins ITGA5 (integrin α5), CD97, and ANXA1 (annexin A1) showed prognostic significance in independent GBM cohorts. Fluorescence microscopy demonstrated ITGA5, CD97, and ANXA1 localization in invadopodia assays, and small interfering RNA knockdown of ITGA5 reduced invadopodia formation in U87MG cells. Thus, invasion-associated proteins, including ITGA5, may prove to be useful anti-invasive targets; volociximab, a therapeutic antibody against integrin α5β1, may be useful for treatment of patients with GBM.
Suzuki H, Aoki K, Chiba K, et al. Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet. 2015; 47(5):458-68 [PubMed] Related Publications
Grade II and III gliomas are generally slowly progressing brain cancers, many of which eventually transform into more aggressive tumors. Despite recent findings of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis is still incomplete. Here, combining two large sets of high-throughput sequencing data, we delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes. Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors. Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection. Extensive serial and multi-regional sampling analyses further supported this finding and also identified a high degree of temporal and spatial heterogeneity generated during tumor expansion and relapse, which is likely shaped by the complex but ordered processes of multiple clonal selection and evolutionary events.
Mari AR, Shah I, Imran M, Ashraf J Role of intraoperative ultrasound in achieving complete resection of intra-axial solid brain tumours. J Pak Med Assoc. 2014; 64(12):1343-7 [PubMed] Related Publications
OBJECTIVES: To determine the frequency of completeness of resection for intra-axial solid brain tumours with the help of intra-operative ultrasound to detect residual brain tumour. METHODS: The cross-sectional study was conducted at the Department of Neurosurgery, Dow University of Health Sciences and Civil Hospital Karachi, from September 2009 to June 2010 and comprised patients with intra-axial solid brain lesion. During operation following standard craniotomy, multi-plane sonographic examination was performed using intra-operative ultrasound for tumour localisation and calculation of dimension, followed by tumour resection in the standard fashion. At the end of tumour resection ultrasound was again used for the detection of any residual tumour. Results of intra-operative ultrasound were compared with post-operative contrast magnetic resonance imaging. RESULTS: Of the 39 cases in which intra-operative ultrasound was performed, 32(82.1%) were males and 7(17.9%) were females, with an overall mean age of 42.6±19.7 years. Intra-operative ultrasonography was able to localise and delineate the tumour in all 39 (100%) cases. It showed no residual tumour in 36 (92.3%) cases, but in 3(7.7%) cases residual tumour was detected. Post-operative contrast enhancing magnetic resonance imaging showed no residual tumour in 35(89.7%) cases and in 4(10.3%) cases residual tumour was detected. The frequency of completely resected intra-axial solid brain tumour was 35(89.7%), while in 4(10.3%) cases incomplete resection was observed. CONCLUSION: The study concluded that intra-operative ultrasonography has an important role in achieving increased frequency of completely resected intra-axial solid brain tumours.
Chiarelli M, De Simone M, Gerosa M, et al. An incidental pulmonary meningioma revealing an intracranial meningioma: primary or secondary lesion? Ann Thorac Surg. 2015; 99(4):e83-4 [PubMed] Related Publications
A 68-year-old man underwent a resection of the right middle lobe for a solitary lesion detected at computed tomography. The histologic result was suggestive for a pulmonary meningioma. Although the result of a preoperative brain computed tomography scan was negative, magnetic resonance imaging showed a skull-base meningioma. On the basis of the absence of symptoms, we decided to observe the intracranial meningioma. At 3 years of follow-up, the patient was free of recurrence and the cerebral lesion was stable. Primary pulmonary meningioma and benign meningioma metastasis share identical microscopic findings, and only a central nervous system radiologic study allows their distinction. The pulmonary lesion in our patient was classified as a meningioma metastasis.
Brachman DG, Pugh SL, Ashby LS, et al. Phase 1/2 trials of Temozolomide, Motexafin Gadolinium, and 60-Gy fractionated radiation for newly diagnosed supratentorial glioblastoma multiforme: final results of RTOG 0513. Int J Radiat Oncol Biol Phys. 2015; 91(5):961-7 [PubMed] Related Publications
PURPOSE: The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical controls. METHODS AND MATERIALS: Dose escalation in phase 1 progressed through 3 cohorts until 2 of 6 patients experienced dose-limiting toxicity or a dose of 5 mg/kg was reached. Once MTD was established, a 1-sided 1-sample log-rank test at significance level of .1 had 85% power to detect a median survival difference (13.69 vs 18.48 months) with 60 deaths over a 12-month accrual period and an additional 18 months of follow-up. OS and PFS were estimated using the Kaplan-Meier method. RESULTS: In phase 1, 24 patients were enrolled. The MTD established was 5 mg/kg, given intravenously 5 days a week for the first 10 RT fractions, then 3 times a week for the duration of RT. The 7 patients enrolled in the third dose level and the 94 enrolled in phase 2 received this dose. Of these 101 patients, 87 were eligible and evaluable. Median survival time was 15.6 months (95% confidence interval [CI]: 12.9-17.6 months), not significantly different from that of the historical control (P=.36). Median PFS was 7.6 months (95% CI: 5.7-9.6 months). One patient (1%) experienced a grade 5 adverse event possibly related to therapy during the concurrent phase, and none experience toxicity during adjuvant TMZ therapy. CONCLUSIONS: Treatment was well tolerated, but median OS did not reach improvement specified by protocol compared to historical control, indicating that the combination of standard RT with TMZ and MGd did not achieve a significant survival advantage.
Alam MS, Ahsan H, Sajjad Z, et al. Magnetic resonance spectroscopy of enhancing cerebral lesions: analysis of 78 histopathology proven cases. J Pak Med Assoc. 2014; 64(10):1141-5 [PubMed] Related Publications
OBJECTIVES: To investigate the efficacy of magnetic resonance spectroscopy in differentiating various types of neoplastic and non-neoplastic enhancing cerebral lesions. METHODS: The prospective study was conducted from January 2007 to December 2009 at the Department of Radiology, Aga Khan University Hospital, Karachi. All patients with enhancing brain lesions on magnetic resonance imaging who underwent magnetic resonance spectroscopy and a biopsy with histopathological analysis were included in study. The lesions were categorised into neoplastic and non-neoplastic lesions on the basis of spectroscopy findings. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of magnetic resonance spectroscopy were calculated. Predicted probabilities were computed and comparison of median values of metabolites and their ratios was analysed using non-parametric Mann Whitney U test to differentiate between neoplastic and non-neoplastic lesions. RESULTS: Of the 102 patients enrolled, 78 (76.5%) comprised the final study sample. There were 53 (68%) male and 25 (32%) female patients with an overall mean age of 40.21 ± 17.69 years (range: 4-76 years). The mean overall size of the lesion was 4.01 ± 1.79 cm, and 61(78%) lesions were neoplastic and 17 (22%) were non-neoplastic. The sensitivity, specificity, positive predictive value and negative predictive value and diagnostic accuracy of magnetic resonance spectroscopy in differentiating neoplastic and non-neoplastic lesions were 90.16%, 64.70%, 90.16%, 64.70% and 78.20% respectively. A cut-off value of 2.55 of Choline/N-Acetyl Aspartate ratio depicted sensitivity of 70% in differentiating the lesions. CONCLUSION: Magnetic resonance spectroscopy is a highly sensitive technique in addition to conventional magnetic resonance imaging in characterising and differentiating between neoplastic and non-neoplastic cerebral lesions.
Deutsch MB, Mendez MF Neurocognitive features distinguishing primary central nervous system lymphoma from other possible causes of rapidly progressive dementia. Cogn Behav Neurol. 2015; 28(1):1-10 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
OBJECTIVE: Define the neurocognitive features of primary central nervous system lymphoma (PCNSL) presenting with dementia, and compare with other causes of rapidly progressive dementia (RPD). BACKGROUND: PCNSL can present as an RPD. Differentiating PCNSL from other RPDs is critical because lymphomatous dementia may be reversible, and untreated PCNSL is fatal. METHODS: We performed a meta-analysis of case reports of dementia from PCNSL (between 1950 and 2013); 20 patients (14 with lymphomatosis cerebri) met our criteria. We compared these patients to a case series of patients with RPD from Creutzfeldt-Jakob disease and other non-PCNSL etiologies (Sala et al, 2012. Alzheimer Dis Assoc Disord. 26:267-271). RESULTS: Median age was 66 years (range 41 to 81); 70% were men. Time from symptom onset to evaluation was <6 months in 65%. No patients had seizures; 5% had headaches; 45% had non-aphasic speech difficulty. There was significantly more memory impairment in patients with PCNSL than other RPDs and significantly less myoclonus and parkinsonism. Behavioral changes and cerebellar signs were not significantly different. Significantly more patients with PCNSL than other RPDs had white matter changes; significantly fewer had atrophy. Elevated CSF protein and pleocytosis were more frequent in PCNSL; patients with other RPDs tended to have normal CSF±14-3-3 protein. CONCLUSIONS: Unlike patients with RPD from other causes, those with PCNSL commonly present with impaired memory, apathy, and abnormal speech and gait, without headache, seizure, or myoclonus. White matter changes and CSF abnormalities predominate. Improved clinical awareness of PCNSL can prompt earlier diagnosis and treatment.
Lee KM, Hwang JM, Woo SJ Optic disc drusen associated with optic nerve tumors. Optom Vis Sci. 2015; 92(4 Suppl 1):S67-75 [PubMed] Related Publications
PURPOSE: To propose a theory based on clinical observation, namely, whether axonal distress induced by optic nerve tumors could be a triggering factor for optic disc drusen (ODD) formation. CASE REPORTS: A 28-year-old woman with ODD and optic disc melanocytoma, a 53-year-old woman with ODD and optic nerve meningioma, and a 29-year-old woman with ODD and optic nerve glioma underwent comprehensive ophthalmologic examinations including spectral-domain optical coherence tomography, swept-source optical coherence tomography, visual field tests, color vision tests, and complete neurologic examinations including brain magnetic resonance imaging. In two cases, unilateral ODD existed on the same side of optic nerve tumors. In the bilateral case, the nerve that contained the tumor had ODD that were located more deeply and on both nasal and temporal sides of the optic nerve compared with the contralateral eye. In two cases, optic disc edema (ODE) was also present, and ODD persisted after ODE resolved. CONCLUSIONS: Optic nerve tumors can trigger the formation of ODD, which suggests that ODD pathogenesis involves axonal flow distress in the optic nerve. The presence of asymmetric ODD and ODE may indicate the presence of an optic nerve tumor.
Child CJ, Conroy D, Zimmermann AG, et al. Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study. Eur J Endocrinol. 2015; 172(6):779-90 [PubMed] Related Publications
OBJECTIVE: Speculation remains that GH treatment is associated with increased neoplasia risk. Studies in GH-treated childhood cancer survivors suggested higher rates of second neoplasms, while cancer risk data for GH-treated and untreated hypopituitary adults have been variable. We present primary cancer risk data from the Hypopituitary Control and Complications Study (HypoCCS) with a focus on specific cancers, and assessment of recurrence rates for pituitary adenomas (PA) and craniopharyngiomas (CP). DESIGN: Incident neoplasms during HypoCCS were evaluated in 8418 GH-treated vs 1268 untreated patients for primary malignancies, 3668 GH-treated vs 720 untreated patients with PA history, and 956 GH-treated vs 102 untreated patients with CP history. METHODS: Using population cancer rates, standardised incidence ratios (SIRs) were calculated for all primary cancers, breast, prostate, and colorectal cancers. Neoplasm rates in GH-treated vs untreated patients were analysed after propensity score adjustment of baseline treatment group imbalances. RESULTS: During mean follow-up of 4.8 years, 225 primary cancers were identified in GH-treated patients, with SIR of 0.82 (95% CI 0.71-0.93). SIRs (95% CI) for GH-treated patients were 0.59 (0.36-0.90) for breast, 0.80 (0.57-1.10) for prostate, and 0.62 (0.38-0.96) for colorectal cancers. Cancer risk was not statistically different between GH-treated and untreated patients (relative risk (RR)=1.00 (95% CI 0.70-1.41), P=0.98). Adjusted RR for recurrence was 0.91 (0.68-1.22), P=0.53 for PA and 1.32 (0.53-3.31), P=0.55 for CP. CONCLUSIONS: There was no increased risk for all-site cancers: breast, prostate or colorectal primary cancers in GH-treated patients during HypoCCS. GH treatment did not increase the risk of PA and CP recurrences.
Mandong BM, Emmanuel I, Vandi KB, et al. Secondary brain choriocarcinoma: a case report. Niger J Med. 2015 Jan-Mar; 24(1):81-3 [PubMed] Related Publications
Choriocarcinoma metastasizes widely. One in every ten choriocarcinoma that leaves its primary site, metastasizes to the brain. This 27 years old patient presented with symptoms of space occupying lesion that was confirmed by CT-SCAN. There was no history of vaginal bleeding and amenorrhoea was concealed by unmarried patient. Chest X-ray was normal. Tumor was excised after craniotomy. Histology of tumor was that of secondary choriocarcinoma. Patient responded excellently to chemotherapy and was well one year after. We strongly recommend a high index of suspicion of choriocarcinoma in management of brain tumors. β-HCG assay should be included in investigation of all patients with intracranial tumors irrespective of sex.
Molitch ME Endocrinology in pregnancy: management of the pregnant patient with a prolactinoma. Eur J Endocrinol. 2015; 172(5):R205-13 [PubMed] Related Publications
A woman with a prolactinoma is usually infertile. Dopamine agonists usually restore ovulation and fertility and such treatment generally is preferred over transsphenoidal surgery because of higher efficacy and safety. Cabergoline is usually preferred over bromocriptine because of its better efficacy with fewer adverse effects. Either drug increases the rates of spontaneous abortions, preterm deliveries, multiple births, or congenital malformations over what may be expected. However, the number of pregnancies reporting such experience is about sevenfold greater for bromocriptine. Tumor growth causing significant symptoms and requiring intervention has been reported to occur in 2.4% of those with microadenomas, 21% in those with macroadenomas without prior surgery or irradiation, and 4.7% of those with macroadenomas with prior surgery or irradiation. Visual fields should be assessed periodically during gestation in women with macroadenomas. If significant tumor growth occurs, most patients respond well to reinstitution of the dopamine agonist. Delivery of the baby and placenta can also be considered if the pregnancy is sufficiently advanced. Transsphenoidal debulking of the tumor is rarely necessary.
Rabade N, Goel N, Goel A Clival dedifferentiated chordoma: a case report. Anal Quant Cytopathol Histpathol. 2014; 36(6):330-4 [PubMed] Related Publications
BACKGROUND: Chordoma is a rare, slowly growing tumor arising from notochordal rests and occurring in several anatomical locations with different clinical patterns of presentation. Dedifferentiation or sarcomatous transformation in a chordoma is a known but rarely recorded event. CASE: We report the case of a 58-year-old man diagnosed with chordoma of the clivus who, over the course of 5 years, showed histological and immunohistochemical evidence of progressive dedifferentiation in the tumor. CONCLUSION: Sarcomatous transformation in chordomas is seen less frequently in the clival region. A high degree of suspicion and extensive sampling are essential for diagnosis, especially in recurrent tumors.
Consonni D, Pierobon M, Gail MH, et al. Lung cancer prognosis before and after recurrence in a population-based setting. J Natl Cancer Inst. 2015; 107(6):djv059 [PubMed] Related Publications
BACKGROUND: Population-based estimates of absolute risk of lung cancer recurrence, and of mortality rates after recurrence, can inform clinical management. METHODS: We evaluated prognostic factors for recurrences and survival in 2098 lung cancer case patients from the general population of Lombardy, Italy, from 2002 to 2005. We conducted survival analyses and estimated absolute risks separately for stage IA to IIIA surgically treated and stage IIIB to IV non-surgically treated patients. RESULTS: Absolute risk of metastases exceeded that of local recurrence in every stage and cell type, highlighting the systemic threat of lung cancer. In stage I, the probability of dying within the first year after diagnosis was 2.7%, but it was 48.3% within first year after recurrence; in stage IV, the probabilities were 57.3% and 80.6%, respectively. Over half the patients died within one year of first metastasis. Although in stages IA to IB about one-third of patients had a recurrence, stage IIA patients had a recurrence risk (61.2%) similar to stage IIB (57.9%) and IIIA (62.8%) patients. Risk of brain metastases in stage IA to IIIA surgically treated non-small cell lung cancer patients increased with increasing tumor grade. Absolute risk of recurrence was virtually identical in adenocarcinoma and squamous cell carcinoma patients. CONCLUSIONS: This population-based study provides clinically useful estimates of risks of lung cancer recurrence and mortality that are applicable to the general population. These data highlight the need for more effective adjuvant treatments overall and within specific subgroups. The estimated risks of various endpoints are useful for designing clinical trials, whose power depends on absolute numbers of events.
Tanaka K, Sasayama T, Irino Y, et al. Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment. J Clin Invest. 2015; 125(4):1591-602 [PubMed] Article available free on PMC after 01/03/2016 Related Publications
The mechanistic target of rapamycin (mTOR) is hyperactivated in many types of cancer, rendering it a compelling drug target; however, the impact of mTOR inhibition on metabolic reprogramming in cancer is incompletely understood. Here, by integrating metabolic and functional studies in glioblastoma multiforme (GBM) cell lines, preclinical models, and clinical samples, we demonstrate that the compensatory upregulation of glutamine metabolism promotes resistance to mTOR kinase inhibitors. Metabolomic studies in GBM cells revealed that glutaminase (GLS) and glutamate levels are elevated following mTOR kinase inhibitor treatment. Moreover, these mTOR inhibitor-dependent metabolic alterations were confirmed in a GBM xenograft model. Expression of GLS following mTOR inhibitor treatment promoted GBM survival in an α-ketoglutarate-dependent (αKG-dependent) manner. Combined genetic and/or pharmacological inhibition of mTOR kinase and GLS resulted in massive synergistic tumor cell death and growth inhibition in tumor-bearing mice. These results highlight a critical role for compensatory glutamine metabolism in promoting mTOR inhibitor resistance and suggest that rational combination therapy has the potential to suppress resistance.
Paw I, Carpenter RC, Watabe K, et al. Mechanisms regulating glioma invasion. Cancer Lett. 2015; 362(1):1-7 [PubMed] Article available free on PMC after 28/06/2016 Related Publications
Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments for the disease. For example, GBM cells have the propensity to aggressively infiltrate/invade into the normal brain tissues and along the vascular tracks, which prevents complete resection of all malignant cells and limits the effect of localized radiotherapy while sparing normal tissue. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the signaling pathways that have been shown to positively and negatively regulate GBM invasion, including, the PI3K/Akt, Wnt, sonic hedgehog-GLI1, and microRNAs. The review will also discuss several approaches to cancer therapies potentially altering GBM invasiveness.
Huan C, Cui G, Lu C, et al. Role of Ki-67 in acromegalic patients with hyperprolactinemia: retrospective analysis in 61 Chinese Patients. Pak J Pharm Sci. 2015; 28(2 Suppl):719-23 [PubMed] Related Publications
To evaluate the specific characteristics in acromegalic patients with hyperprolactinemia by analyzing the differences between patients with different Ki-67 values. Between 2002 and 2010, a set of data on 61 patients undergoing transsphenoidal surgery was available at the Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University. Patients were divided into Ki-67 >3% group and <3% group. A retrospective analysis of clinical, hormonal, immunohistochemical, and imaging was observed in all patients. There were no significant differences in age, gender, tumor size and apoplexy between the two groups. Time interval in Ki-67 ≥3% group was longer than <3% group (P=0.037). Patients in Ki-67 >3% group had a higher rate of invasiveness (P=0.048), higher incidences of diabetes mellitus (P=0.036), coarse facial features (P=0.048), large hands and feet (P=0.003), higher GH levels (P<0.05), higher diabetes insipidus rate (P<0.001), and more frequent recurrence (P=0.011) than Ki-67 <3% group. Patients with higher Ki-67 value harbored longer time interval, more aggressive tumors, more acromegaly manifestations, higher GH level, and higher recurrence than patients with lower Ki-67 value.