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Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

Background Few studies have evaluated the health-related quality of life (HRQoL) of patients with meningiomas. Here, we report the largest prospective, longitudinal cross-sectional cohort study of HRQoL in meningiomas to date, in order to identify possible actionable determinants of global HRQoL. Methods Adults who had undergone resection of a grade I intracranial meningioma and were in routine follow-up at a single large tertiary center underwent HRQoL assessment using the QLQ-C30 questionnaire administered opportunistically at follow-up visits. Averaged transformed QLQ-C30 scores at 12-month intervals were compared with scores from a normative reference population, with reference to known minimal clinically meaningful difference (CMD) in scores. To evaluate for possible determinants of changes in global HRQoL, global HRQoL scores were correlated (Spearman's Rho) with subdomain and symptom scores and with interval time from surgical resection. Results A total of 291 postoperative patients with histologically confirmed and surgically treated grade I meningiomas consented to participation and a total of 455 questionnaires were included for analysis. Patients with meningiomas reported reduced global HRQoL at nearly every 12-month interval with clinically and statistically significant impairments at 12, 48, 108, and 120 months postoperative compared with the normative population (P < 0.05). Meningioma patients at the 12-month interval also reported a reduction of each subdomain of HRQoL assessment (P < 0.05); however, a CMD was only seen in cognitive functioning. Physical, emotional, cognitive, and social subdomains, as well as fatigue and sleep/insomnia, were significantly associated with global HRQoL at the first 12-month interval. Overall, there was no significant correlation between time from surgery and global HRQoL or the subdomain functional or symptom sections of the QLQ-C30. Conclusions Meningioma patients report considerable limitations in HRQoL for more than 120 months after surgery, particularly in cognitive, emotional, and social function, as well as suffering significant fatigue and sleep impairment compared with a normative reference population. The majority of these reported functional impairments and symptoms are strongly associated with global HRQoL and thus can be considered determinants of global HRQoL that if treated, have the potential to improve HRQoL for our meningioma patients. This hypothesis requires future study of targeted interventions to determine their efficacy.

Background Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma. Methods DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts. Results The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03–0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8–7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22–0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3–11.1, P < 0.001) with clinical implications. Conclusions The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.

Matthew E Eagles,1 Farshad Nassiri,2,3 Jetan H Badhiwala,2 Suganth Suppiah,2 Saleh A Almenawer,4 Gelareh Zadeh,3,5 Kenneth D Aldape3,6 1Section of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; 2Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada; 3MacFeeters-Hamilton Neuro-Oncology Program, University Health Network, Toronto, ON, Canada; 4Division of Neurosurgery, Department of Surgery, McMaster University, Hamilton, ON, Canada; 5Division of Neurosurgery, University Health Network, Toronto, ON, Canada; 6Division of Pathology, University Health Network, Toronto, ON, Canada Abstract: Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To date, various promising chemotherapeutic regimens have been trialed for use in GBM; however, temozolomide (TMZ) therapy remains the only US Food and Drug Administration-approved first-line chemotherapeutic option for newly diagnosed GBM. Despite maximal therapy with surgery and combined concurrent chemoradiation and adjuvant TMZ therapy, the median overall survival remains approximately 14 months. Given the failure of conventional chemotherapeutic strategies in GBM, there has been renewed interest in the role of immunotherapy in GBM. Dendritic cells are immune antigen-presenting cells that play a role in both the innate and adaptive immune system, thereby making them prime vehicles for immunotherapy via dendritic cell vaccinations (DCVs) in various cancers. There is great enthusiasm surrounding the use of DCVs for GBM with multiple ongoing trials. In this review, we comprehensively summarize the safety, efficacy, and quality of life results from 33 trials reporting on DCV for high-grade gliomas. Keywords: glioma, vaccine, dendritic cells, glioblastoma

Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas.

The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.

BACKGROUND: Long term success of dental implants directly depends on marginal bone resorption. The aim of this study was to determine the annual average bone loss on the mesial and distal aspects of implants following the first year of implantation. METHODS: This was a descriptive analytical study of patients treated with ITI (International Team of Implantology) implants at the Dental School of Isfahan University of Medical Sciences from 1998-2002 (1377-81). A total of 15 patients with 41 implants were selected by convenience sampling method. The height of the alveolar bone was measured using panoramic radiography before and after loading with calipers to determine the average bone loss. Other information such as pocket depth, bleeding index, plaque index, gingival recession, was obtained by clinical examinations. The mean bone loss on the mesial & distal sides was analyzed by ANOVA at 0.05 level of significance. RESULTS: The average bone loss on the proximal sides of ITI implants obtained annually after the first year of loading was 0.084 ± 0.035 mm with slight difference on the mesial (0.092 ± 0.035) and distal (0.072 ± 0.033) sides. There was negligible difference between male and female patients. The average survival rate for thirty three months was 95.1%. CONCLUSION: The average bone loss on the mesial and distal sides of ITI implants compared with other studies was satisfactory. Survival and success rates were acceptable. KEYWORDS: Dental implants, bone resorption, survival rate, dental plaque index.

Psoriasis is a chronic relapsing disorder that involves the skin, nails and joints. With regard to the role of the immune system in psoriasis, the current study compared serum IgE concentration in patients with psoriasis with control group. Current case-control study was conducted in Dermatology clinic of Razi hospital, Tehran University of medical sciences, Tehran, Iran in 2012. Fifty-eight patients with psoriasis e referred to the clinic were assigned as patient group and 58 healthy subjects with matched age and sex as a control group. Patient's history, family history and demographic characteristics such as age and sex, duration and severity of disease using PASI, were collected and entered into a form. Consent form was obtained from participants. Serum IgE concentrations of both study groups were measured by electrochemiluminescence assay in the laboratory A total number of 58 patients with psoriasis, mean age of 44.15 (19-76 years) and 58 controls with matched age and sex were studied. Mean average of serum IgE concentration in the control group was 115.13 versus 200/06 concentration in patients group (P=0.16). Serum IgE concentration in 22.4% of patients versus 17.2% in controls was greater than normal concentration (P=0.48). No significant correlation was between serum IgE concentration and disease severity using PASI (P=0.11, r=0.21), neither a significant correlation with disease duration, age and gender. According to the present study, serum IgE concentrations are not greater in patients with psoriasis. IgE concentration is also not associated with the severity of psoriasis based on the PASI score, therefore, the role of IgE in psoriasis can be considered insignificant as some previous studies indicate.