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Background: Neurosurgical 3D visualizers and simulators are innovative devices capable of defining a surgical strategy in advance and possibly making neurosurgery safer by rehearsing the phases of the operation beforehand. The aim of this study is to evaluate Surgical Theater™ (Surgical Theater LLC, Mayfield, OH, USA), a new 3D neurosurgical planning, simulation, and navigation system, and qualitatively assess its use in the operating room., Methods: Clinical data were collected from 30 patients harboring various types of brain tumors; Surgical Theater™ was used for the preoperative planning and intraoperative 3D navigation. Preoperative and postoperative questionnaires were completed by first and second operators to get qualitative feedback on the system's functionality. Furthermore, we measured and compared the impact of this technology on surgery duration., Results: Neurosurgeons were overall satisfied when using this rehearsal and navigation tool and found it efficient and easy to use; interestingly, residents considered this device more useful as compared to their more senior colleagues (with significantly higher scores, P<0.05), possibly because of their limited anatomical experience and spatial/surgical rehearsal ability. The length of the surgical procedure was not affected by this technology (P>0.05)., Conclusions: Surgical Theater™ system was found to be clinically useful in improving anatomical understanding, surgical planning, and intraoperative navigation, especially for younger and less experienced neurosurgeons.

Long-term risks and survival times of ventriculoperitoneal (VP) shunts implanted due to hydrocephalus (HC) after craniotomy for brain tumors are largely unknown. The aim of this study was to establish the overall VP shunt survival rates during a decade after shunt insertion and to determine risks of shunt failure after brain tumor surgery in the long-term period. In this population-based cohort from a well-defined geographical region, all adult patients (> 18 years) from 2004 to 2013 who underwent craniotomies for intracranial tumors leading to VP shunt dependency were included. Our brain tumor database was cross-linked to procedure codes for shunt surgery (codes AAF) to extract brain tumor patients who became VP shunt dependent after craniotomy. The VP shunt survival time, i.e. the shunt longevity, was calculated from the day of shunt insertion after brain tumor surgery until the day of its failure. A total of 4174 patients underwent craniotomies, of whom 85 became VP shunt dependent (2%) afterwards. Twenty-eight patients (33%) had one or more shunt failures during their long-term follow-up, yielding 1-, 5-, and 10-year shunt success rates of 77%, 71%, and 67%, respectively. Patient age, sex, tumor location, primary/repeat craniotomy, placement of external ventricular drainage (EVD), ventricular entry, post-craniotomy hemorrhage, post-shunting meningitis/infection, and multiple shunt revisions were not statistically significant risk factors for shunt failure. Median shunt longevity was 457.5 days and 21.5 days for those with and without pre-craniotomy HC, respectively (p < 0.01). This study can serve as benchmark for future studies., (© 2021. The Author(s).)

Risks and survival times of ventriculoperitoneal (VP) shunts implanted due to hydrocephalus after craniotomies for brain tumors are largely unknown. The purpose of this study was to determine the overall timing of VP shunting and its failure after craniotomy for brain tumors in adults. The authors also wished to explore risk factors for early VP shunt failure (within 90 days). A population-based consecutive patient cohort of all craniotomies for intracranial tumors leading to VP shunt dependency in adults (> 18 years) from 2004 to 2013 was studied. Patients with pre-existing VP shunts prior to craniotomy were excluded. The survival time of VP shunts, i.e., the shunt longevity, was calculated from the day of shunt insertion post-craniotomy for a brain tumor until the day of shunt revision requiring replacement or removal of the shunt system. Out of 4774 craniotomies, 85 patients became VP shunt-dependent (1.8% of craniotomies). Median time from craniotomy to VP shunting was 1.9 months. Patients with hydrocephalus prior to tumor resection (N = 39) had significantly shorter time to shunt insertion than those without (N = 46) (p < 0.001), but there was no significant difference with respect to early shunt failure. Median time from shunt insertion to shunt failure was 20 days (range 1-35). At 90 days, 17 patients (20%) had confirmed shunt failure. Patient age, sex, tumor location, primary/secondary craniotomy, extra-axial/intra-axial tumor, ventricular entry, post-craniotomy bleeding, and infection did not show statistical significance. The risk of early shunt failure (within 90 days) of shunts after craniotomies for brain tumors was 20%. This study can serve as benchmark for future studies., (© 2021. The Author(s).)

Background: Malignant melanomas frequently metastasize to the brain, but metastases in the cerebellum are underrepresented compared with metastases in the cerebrum., Methods: We established animal models by injecting intracardially in athymic nude fox1 nu mice two human melanoma cell lines, originating from a cerebral metastasis (HM19) and a cerebellar metastasis (HM86)., Results: Using magnetic resonance imaging (MRI), metastases were first detected after a mean of 34.5 days. Mean survival time was 59.6 days for the mice in the HM86 group and significantly shorter (43.7 days) for HM19-injected animals (p < 0.001). In the HM86 group, the first detectable metastasis was located in the cerebellum in 15/55 (29%) mice compared with none in the HM19 group (p < 0.001). At sacrifice, cerebellar metastases were found in 34/55 (63%) HM86-injected mice compared with 1/53 (2%) in the HM19-injected (p < 0.001) mice. At that time, all mice in both groups had detectable metastases in the cerebrum. Comparing macroscopic and histologic appearances of the brain metastases with their clinical counterparts, the cell line-based tumors had kept their original morphologic characteristics., Conclusions: The present work demonstrates that human brain-metastatic melanoma cells injected intracardially in mice had retained inherent characteristics also in reproducing interaction with subtle microenvironmental brain tissue compartment-specific features. The models offer new possibilities for investigating tumor- and host-associated factors involved in determining tissue specificity of brain metastasis., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation status on overall survival (OS) in patients with glioblastoma., Methods: A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships between MGMT and perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored by MGMT methylation in terms of OS., Results: rCBV distributions did not differ significantly (p > 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73), MGMT methylation was a positive predictive factor for OS (HR = 2.73, p = 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect of MGMT methylation (HR = 1.72, p = 0.10, AUC = 0.56)., Conclusions: Our results indicate the existence of complementary prognostic information provided by MGMT methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from MGMT methylation. Not considering this information may lead to bias in the interpretation of clinical studies., Key Points: • MRI perfusion provides complementary prognostic information to MGMT methylation. • MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile. • Failure to consider these relations may lead to bias in the interpretation of clinical studies.

Purpose: Relative cerebral blood volume (rCBV) from dynamic susceptibility contrast (DSC)-MRI is a valuable biomarker in patients with glioblastoma for assessing treatment response and predicting overall survival. DSC-MRI based on echo planar images (EPI) may possess severe geometric distortions from magnetic field inhomogeneities up to the order of centimeters. The aim of this study is to assess how much two readily available EPI-based geometric distortion correction methods, FSL TOPUP and EPIC, affect rCBV values from DSC-MRI in patients with confirmed glioblastoma., Method: We used a combined single-shot 2D gradient-echo (T2*), spin-echo (T2) EPI sequence to estimate both T2* and T2-weighted rCBV from the same contrast agent injection. Effects of distortion correction on the positive phase-encoded T2- and T2*-images were assessed in healthy anatomical brain regions in terms of Wilcoxon signed rank tests on median rCBV change and on Dice coefficients, as well as in tumor lesions in terms of Wilcoxon signed rank tests on median rCBV change., Results: Our results show that following distortion correction, both gradient-echo and spin-echo rCBV increased in cortical areas of the frontal, temporal and occipital lobe, including the posterior orbital gyri in the frontal lobe and middle frontal gyri (p < 0.0008). Similar, improved Dice coefficients were observed for gradient-echo EPI in temporal, occipital and frontal lobe. Only spin-echo rCBV in enhancing lesion increased with correction (p = 0.0002)., Conclusion: Our study sheds light on the importance of performing geometric distortion correction on EPI-based MRI data before assessing functional information such as rCBV values. Our findings may indicate that uncorrected rCBV values can be underestimated from positive phase-encoding EPI and that geometric distortion correction is warranted when comparing EPI-based data to conventional MRI., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE)., Purpose: To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols., Study Type: Multicenter retrospective study., Population: In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study., Field Strength/sequence: 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium-based contrast agent-enhanced T 1 -weighted MRI, T 2 - and FLAIR T 2 -weighted, and dynamic susceptibility contrast (DSC) T 2 * perfusion., Assessment: We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBV max ) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed., Statistical Tests: Uniparametric Cox regression; Kaplan-Meier test; Mann-Whitney test., Results: The rCBV max derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate-" and "high-vascular" groups (P < 0.05). The Mann-Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02-0.685; LAT: P = 0.010-0.769; IPE: P = 0.093-0.939; VPE: P = 0.016-1.000)., Data Conclusion: The rCBV max calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability., Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1478-1486., (© 2019 International Society for Magnetic Resonance in Medicine.)

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in-house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Background: The aim of this study was to investigate changes in structural magnetic resonance imaging (MRI) according to the RANO criteria and perfusion- and permeability related metrics derived from dynamic contrast-enhanced MRI (DCE) and dynamic susceptibility contrast MRI (DSC) during radiochemotherapy for prediction of progression and survival in glioblastoma., Methods: Twenty-three glioblastoma patients underwent biweekly structural and perfusion MRI before, during, and two weeks after a six weeks course of radiochemotherapy. Temporal trends of tumor volume and the perfusion-derived parameters cerebral blood volume (CBV) and blood flow (CBF) from DSC and DCE, in addition to contrast agent capillary transfer constant (K trans ) from DCE, were assessed. The patients were separated in two groups by median survival and differences between the two groups explored. Clinical- and MRI metrics were investigated using univariate and multivariate survival analysis and a predictive survival index was generated., Results: Median survival was 19.2 months. A significant decrease in contrast-enhancing tumor size and CBV and CBF in both DCE- and DSC-derived parameters was seen during and two weeks past radiochemotherapy (p < 0.05). A 10%/30% increase in K trans /CBF two weeks after finishing radiochemotherapy resulted in significant shorter survival (13.9/16.8 vs. 31.5/33.1 months; p < 0.05). Multivariate analysis revealed an index using change in K trans and relative CBV from DSC significantly corresponding with survival time in months (r 2  = 0.843; p < 0.001)., Conclusions: Significant temporal changes are evident during radiochemotherapy in tumor size (after two weeks) and perfusion-weighted MRI-derived parameters (after four weeks) in glioblastoma patients. While DCE-based metrics showed most promise for early survival prediction, a multiparametric combination of both DCE- and DSC-derived metrics gave additional information., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The efficacy of tumor removal via craniotomies on preoperative hydrocephalus (HC) in adult patients with intracranial tumors is largely unknown. Therefore, we sought to evaluate the effect of tumor resection in patients with preoperative HC and identify the incidence and risk factors for postoperative VP shunt dependency. All craniotomies for intracranial tumors at Oslo University Hospital in patients ≥ 18 years old during a 10-year period (2004-2013) were reviewed. Patients with radiologically confirmed HC requiring surgery and subsequent development of shunt dependency were identified by cross-linking our prospectively collected tumor database to surgical procedure codes for hydrocephalus treatment (AAF). Patients with preexisting ventriculoperitoneal (VP) shunts (N = 41) were excluded. From 4774 craniotomies performed on 4204 patients, a total of 373 patients (7.8%) with HC preoperatively were identified. Median age was 54.4 years (range 18.1-83.9 years). None were lost to follow-up. Of these, 10.5% (39/373) required permanent CSF shunting due to persisting postoperative HC. The risk of becoming VP shunt dependent in patients with preexisting HC was 7.0% (26/373) within 30 days and 8.9% (33/373) within 90 days. Only secondary (repeat) surgery was a significant risk factor for VP shunt dependency. In this large, contemporary, single-institution consecutive series, 10.5% of intracranial tumor patients with preoperative HC became shunt-dependent post-craniotomy, yielding a surgical cure rate for HC of 89.5%. To the best of our knowledge, this is the first and largest study regarding postoperative shunt dependency after craniotomies for intracranial tumors, and can serve as benchmark for future studies.

Background: Craniotomies carry inherent risks of postoperative complications that may have a negative impact on patients' status. Recognizing and preventing surgical complications is of paramount importance, especially in meningioma surgery, where most of these tumors are benign and current management protocols are effective in terms of disease control and maintenance of higher quality of life. The objective of this study was to describe the early complications after surgery and their predictive factors in patients undergoing resection of intracranial meningiomas., Methods: A partly retrospective, partly prospective review was conducted in a Norwegian population-based cohort of 1469 consecutive cases of meningioma surgery treated at the university hospitals of Oslo, totaling 11,414 patient-years of follow-up., Results: 2.6% of patients had a postoperative hematoma, 2.7% a postoperative infection, 3.9% a postoperative worsening of neurologic status; 5.4% of patients died during a 30-day period after surgery. Predictive factors of increased risk of postoperative complications were patient's age for the hematoma, a non-skull base meningioma for infection, and postoperative hematoma for the risk of neurologic worsening or 30-day mortality., Conclusions: Early postoperative complications in meningioma surgery have a negative impact on patient survival and postoperative neurologic status, in a disease where survival is usually not limited by the meningioma itself. In this study, we identified risk factors for early postoperative complications, the identification of at-risk populations may help to prevent the occurrence of these risk factors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To compare the Nordic and the Memorial Sloan-Kettering Cancer Center (MSKCC) chemotherapy protocols for Overall Survival (OS) and Progression-Free Survival (PFS) for intracranial primary CNS lymphoma (PCNSL)., Methods: A prospective database at Oslo University Hospital of PCNSL was reviewed over a 12-year period (2003-2014)., Results: Overall, 79 patients with PCNSL were identified, of whom 57 received chemotherapy. MSKCC with Rituximab (RTX) was used in 18 patients (32%) who had median OS of 46.3 months [9.8-131.9] and median PFS of 34.6 months [6.4-131.9]. The Nordic protocol was used in 14 patients (25%) who had median OS of 30.9 months [2.7-106.3] and PFS of 14.3 months [0.0-106.3]. The MSKCC was used without RTX in 25 patients (44%) who had OS of 15.2 months [0.7-136.5] and PFS of 12.0 months [0.0-117.0]. MSKCC with RTX had a significantly longer median OS (p < 0.05) compared to the other regimens in univariate analysis. In multivariate analysis, the only prognostic factor for OS and PFS of significance was deep brain involvement (p < 0.005)., Conclusions: In univariate analysis, the MSKCC with RTX achieved significantly longer median OS compared to the Nordic protocol. However, in multivariate analysis, the only prognostic factor for survival of statistical significance was deep brain involvement., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This aimed to evaluate the effect of surgery for overall survival (OS) and progression-free survival (PFS) in intracranial primary CNS lymphoma (PCNSL) of all patients diagnosed at a single center. A prospective database at Oslo University Hospital of PCNSL was reviewed over a 12-year period (2003-2014). Seventy-nine patients with intracranial PCNSL were identified. Deep brain involvement was shown in 63 patients. Thirty-two patients underwent craniotomy with resection, while all other patients had a biopsy. Fifty-seven patients were given chemotherapy: 18 were treated with the MSKCC (Memorial Sloan-Kettering Cancer Center) with rituximab, 21 with the MSKCC without rituximab, and 14 within a Nordic prospective phase II protocol. Forty-four patients achieved complete response (CR) and had OS of 46.3 months. Patients who underwent resection had a median OS of 28.6 versus 11.7 months for those who had a biopsy performed. Resection showed an insignificant prolongation of OS. Multivariate analysis confirmed statistical significance of deep brain involvement only (p < 0.005). Neither chemotherapy regimen, Karnofsky Performance Status (KPS), type of surgery, nor patient age was significant factors for OS or PFS. Resective surgery played no role in significantly improving either OS or PFS and therefore it is not recommended as treatment for PCNSL.

Objective: According to the new World Health Organization 2016 classification for tumors of the central nervous system, 1p/19q codeletion defines the genetic hallmark that differentiates oligodendrogliomas from diffuse astrocytomas. The aim of our study was to evaluate whether relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) histogram analysis can stratify survival in adult patients with genetic defined diffuse glioma grades II and III., Methods: Sixty-seven patients with untreated diffuse gliomas World Health Organization grades II and III and known 1p/19q codeletion status were included retrospectively and analyzed using ADC and rCBV maps based on whole-tumor volume histograms. Overall survival and progression-free survival (PFS) were analyzed by using Kaplan-Meier and Cox survival analyses adjusted for known survival predictors., Results: Significant longer PFS was associated with homogeneous rCBV distribution-higher rCBVpeak (median, 37 vs 26 months; hazard ratio [HR], 3.2; P = 0.02) in patients with astrocytomas, and heterogeneous rCBV distribution-lower rCBVpeak (median, 46 vs 37 months; HR, 5.3; P < 0.001) and higher rCBVmean (median, 44 vs 39 months; HR, 7.9; P = 0.003) in patients with oligodendrogliomas. Apparent diffusion coefficient parameters (ADCpeak, ADCmean) did not stratify PFS and overall survival., Conclusions: Tumors with heterogeneous perfusion signatures and high average values were associated with longer PFS in patients with oligodendrogliomas. On the contrary, heterogeneous perfusion distribution was associated with poor outcome in patients with diffuse astrocytomas.

The risk of developing a de novo shunt-dependent hydrocephalus (HC) after undergoing a craniotomy for brain tumor in adult patients is largely unknown. All craniotomies for intracranial tumors at Oslo University Hospital in adult patients ≥18 years of age during a 10-year period (2004-2013) were included. None were lost to follow-up. Patients who developed a shunt-dependent HC were identified by cross-linking our prospectively collected tumor database to patients with a NCSP surgical procedure code of hydrocephalus (AAF). Patients with pre-existing HC or ventriculoperitoneal (VP) shunts were excluded from the study. A total of 4401 craniotomies were performed. Of these, 46 patients (1.0%) developed de novo postoperative HC requiring a VP shunt after a median of 93 days (mean 115 days, range 6-442). Median age was 62.0 years (mean 58.9 years, range 27.3-80.9) at time of VP shunt surgery. Patients without pre-existing HC had a 0.2% (n = 8/4401) risk of becoming VP shunt dependent within 30 days and 0.5% (n = 22/4401) within 90 days. Age, sex, tumor location, primary/secondary surgery, and radiotherapy were not associated with VP shunt dependency. Choroid plexus tumors and craniopharyngiomas had increased risk of VP shunt dependency. In this large, contemporary, single-institution consecutive series, the risk of postoperative shunt-dependency after craniotomies for brain tumors without pre-existing HC was very low. This is the largest study with regards to de novo postoperative shunt-dependency after craniotomies for patients with intracranial tumors and can serve as a benchmark for future studies.

We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

OBJECTIVE The impact of pregnancy on survival in female patients with low-grade glioma (LGG) is unknown and controversial. The authors designed a retrospective cohort study on prospectively collected registry data to assess the influence of pregnancy and child delivery on the survival of female patients with LGG. METHODS In Norway, the reporting of all births and cancer diagnoses to the Medical Birth Registry of Norway (MBRN) and the Cancer Registry of Norway (CRN), respectively, is compulsory by law. Furthermore, every individual has a unique 11-digit identification number. The CRN was searched to identify all female patients with a histologically confirmed diagnosis of World Health Organization (WHO) Grade II astrocytoma, oligoastrocytoma, oligodendroglioma, or pilocytic astrocytoma who were 16-40 years of age at the time of diagnosis during the period from January 1, 1970, to December 31, 2008. Obstetrical information was obtained from the MBRN for each patient. The effect of pregnancy on survival was evaluated using a Cox model with parity as a time-dependent variable. RESULTS The authors identified 65 patients who gave birth to 95 children after an LGG diagnosis. They also identified 281 patients who did not give birth after an LGG diagnosis. The median survival was 14.3 years (95% CI 11.7-20.6 years) for the entire study population. The effect of pregnancy was insignificant in the multivariate model (HR 0.71, 95% CI 0.35-1.42). CONCLUSIONS Pregnancy does not seem to have an impact on the survival of female patients with LGG.

Background: We have previously characterized 19 ependymal tumors using Giemsa banding and high-resolution comparative genomic hybridization. The aim of this study was to analyze these tumors searching for fusion genes., Methods: RNA sequencing was performed in 12 samples. Potential fusion transcripts were assessed by seed count and structural chromosomal aberrations. Transcripts of interest were validated using fluorescence in situ hybridization and PCR followed by direct sequencing., Results: RNA sequencing identified rearrangements of the anaplastic lymphoma kinase gene (ALK) in 2 samples. Both tumors harbored structural aberrations involving the ALK locus 2p23. Tumor 1 had an unbalanced t(2;14)(p23;q22) translocation which led to the fusion gene KTN1-ALK. Tumor 2 had an interstitial del(2)(p16p23) deletion causing the fusion of CCDC88A and ALK. In both samples, the breakpoint of ALK was located between exons 19 and 20. Both patients were infants and both tumors were supratentorial. The tumors were well demarcated from surrounding tissue and had both ependymal and astrocytic features but were diagnosed and treated as ependymomas., Conclusions: By combining karyotyping and RNA sequencing, we identified the 2 first ever reported ALK rearrangements in CNS tumors. Such rearrangements may represent the hallmark of a new entity of pediatric glioma characterized by both ependymal and astrocytic features. Our findings are of particular importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients with lung cancer harboring ALK rearrangements. Thus, ALK emerges as an interesting therapeutic target in patients with ependymal tumors carrying ALK fusions., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To develop a generic support vector machine (SVM) model by using magnetic resonance (MR) imaging-based blood volume distribution data for preoperative glioma survival associations and to prospectively evaluate the diagnostic effectiveness of this model in autonomous patient data., Materials and Methods: Institutional and regional medical ethics committees approved the study, and all patients signed a consent form. Two hundred thirty-five preoperative adult patients from two institutions with a subsequent histologically confirmed diagnosis of glioma after surgery were included retrospectively. An SVM learning technique was applied to MR imaging-based whole-tumor relative cerebral blood volume (rCBV) histograms. SVM models with the highest diagnostic accuracy for 6-month and 1-, 2-, and 3-year survival associations were trained on 101 patients from the first institution. With Cox survival analysis, the diagnostic effectiveness of the SVM models was tested on independent data from 134 patients at the second institution., Results: were adjusted for known survival predictors, including patient age, tumor size, neurologic status, and postsurgery treatment, and were compared with survival associations from an expert reader., Results: Compared with total qualitative assessment by an expert reader, the whole-tumor rCBV-based SVM model was the strongest parameter associated with 6-month and 1-, 2-, and 3-year survival in the independent patient data (area under the receiver operating characteristic curve, 0.794-0.851; hazard ratio, 5.4-21.2)., Discussion: Machine learning by means of SVM in combination with whole-tumor rCBV histogram analysis can be used to identify early patient survival in aggressive gliomas. The SVM model returned higher diagnostic accuracy values than an expert reader, and the model appears to be insensitive to patient, observer, and institutional variations., (© RSNA, 2014 Online supplemental material is available for this article.)

Object: The aim of this study was to investigate the incidence of CSF disturbances before and after intracranial surgery for pediatric brain tumors in a large, contemporary, single-institution consecutive series., Methods: All pediatric patients (those < 18 years old), from a well-defined population of 3.0 million inhabitants, who underwent craniotomies for intracranial tumors at Oslo University Hospital in Rikshospitalet between 2000 and 2010 were included. The patients were identified from the authors' prospectively collected database. A thorough review of all medical charts was performed to validate all the database data., Results: Included in the study were 381 consecutive craniotomies, performed on 302 patients (50.1% male, 49.9% female). The mean age of the patients in the study was 8.63 years (range 0-17.98 years). The follow-up rate was 100%. Primary craniotomies were performed in 282 cases (74%), while 99 cases (26%) were secondary craniotomies. Tumors were located supratentorially in 249 cases (65.3%), in the posterior fossa in 105 (27.6%), and in the brainstem/diencephalon in 27 (7.1%). The surgical approach was supratentorial in 260 cases (68.2%) and infratentorial in 121 (31.8%). Preoperative hydrocephalus was found in 124 cases (32.5%), and 71 (86.6%) of 82 achieved complete cure with tumor resection only. New-onset postoperative hydrocephalus was observed in 9 (3.5%) of 257 cases. The rate of postoperative CSF leaks was 6.3%., Conclusions: Preoperative hydrocephalus was found in 32.5% of pediatric patients with brain tumors treated using craniotomies. Tumor resection alone cured preoperative hydrocephalus in 86.6% of cases and the incidence of new-onset hydrocephalus after craniotomy was only 3.5%.

Ependymomas are rare tumors of the central nervous system (CNS). They are classified based on tumor histology and grade, but the prognostic value of the WHO grading system remains controversial. Treatment is mainly surgical and by radiation. An improved knowledge of ependymoma biology is important to elucidate the pathogenesis, to improve classification schemes, and to identify novel potential treatment targets. Only 113 ependymoma karyotypes with chromosome aberrations are registered in the Mitelman database. We present the first study of ependymoma genomes combining karyotyping and high resolution comparative genomic hybridization (HR-CGH). Nineteen tumor samples were collected from three pediatric and 15 adult patients treated at Oslo University Hospital between 2005 and 2012. Histological diagnoses included subependymoma and myxopapillary ependymoma (WHO grade I), ependymoma (WHO grade II) and anaplastic ependymoma (WHO grade III). Four tumors were intraspinal and 15 were intracranial. Seventeen samples were successfully karyotyped, HR-CGH analysis was undertaken on 17 samples, and 15 of 19 tumors were analyzed using both methods. Twelve tumors had karyotypic abnormalities, mostly gains or losses of whole chromosomes. Structural rearrangements were found in four tumors, in two of which 2p23 was identified as a breakpoint region. Twelve tumors displayed genomic imbalances by HR-CGH analysis with loss of material at 6q as the most common. 6q loss, which was detected by one or both methods in seven of 12 (58%) abnormal tumors, and 5p gain (observed in five tumors; 42%) were the most common genomic aberrations in this series.

Purpose: To retrospectively evaluate the performance of an automatic support vector machine (SVM) routine in combination with perfusion-based dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for preoperative survival associations in patients with gliomas and compare our results to traditional MRI., Materials and Methods: The study was approved by the Ethics Committee and informed consent was signed. Structural, diffusion- and perfusion-weighted MRI was performed at 1.5-T preoperatively in 94 adult patients (49 males, 45 females, 23-82 years; mean 51 years) later diagnosed with a primary glioma. Patients were randomly assigned in training and test datasets and the resulting DSC-based survival associations by SVM were compared to traditional MRI features including contrast-agent enhancement, perfusion- and diffusion-weighted imaging, tumor size, and location. The results were adjusted for age, neurological status, and postoperative factors associated with survival, including surgery and adjuvant therapy., Results: For 1- (26/33 alive, 11/14 deceased), 2- (15/21, 21/26), 3- (12/16, 27/31) and 4- (12/15, 28/32) year survival associations in the test dataset (47 patients), the SVM routine was the only biomarker to consistently associate with survival (Cox; P < 0.001)., Conclusion: The automatic machine learning routine presented in our study may provide the operator with a reliable instrument for assessing survival in patients with glioma., (© 2013 Wiley Periodicals, Inc.)

Background: Several studies acknowledge a higher risk of morbidity and mortality following intracranial meningioma surgery in the elderly, yet there is no consensus with regards to risk factors. Four prognostic scoring systems have been proposed. To evaluate their usefulness, we assess the very old meningioma patients in our neuro-oncological database according to the four methods, and correlate the findings with mortality and morbidity., Methods: We retrospectively calculated scores according to the Clinical-Radiological Grading System (CRGS), the Sex, Karnofsky Performance Scale, American Society of Anesthesiology Class, Location of Tumor, and Peritumoral Edema grading system (SKALE), the Geriatric Scoring System (GSS) and the Charlson Comorbidity Index (CCI) from all patients aged 80-90 years who had primary surgery for intracranial meningiomas 2003-2013 (n = 51), and related our findings to morbidity and mortality., Results: The mortality rates were 3.9 %, 5.9 % and 15.7 % at 30-days, 3-months and 1-year post-surgery. The rate of complications requiring surgery was 13.7 %, 5.9 % had evacuation of intracerebral hematomas and two patients (3.9 %) had surgery for intracranial infection/osteitis. 15.7 % of the patients were neurologically worsened on discharge. The patients with SKALE scores ≤ 8 had significantly increased mortality rates. The GSS, the CRGS and the CCI were not found to correlate with mortality., Conclusions: Retrospectively evaluating four proposed scoring systems, we find that the SKALE score reflects the mortality at 1 month and 1 year following primary surgery for intracranial meningiomas in our very old patients. It may represent a helpful adjunct to their preoperative assessment.

The effect of temozolomide (TMZ) and radiotherapy (RT) in the treatment of glioblastoma multiforme (GBM) has been well documented in randomized controlled trials. Here we present our findings on the effect of TMZ added to RT at a population level. The Cancer Registry of Norway was searched for patients with a GBM diagnosis from January 1, 2000 to December 31, 2007. Subsequently, the prescriptions registered to these patients were obtained from the Norwegian Prescription Database. The data were analyzed according to era (pre-TMZ introduction or post-TMZ introduction) and according to treatment received. Furthermore, a matching procedure was utilized to reduce the bias between the RT + TMZ and RT alone treatments so that the effect of TMZ could be better scrutinized. We identified 1157 GBM patients. The median overall survival (OS), in months, was 8.3 (95% confidence interval: 7.6-9.0) and 10.1 (95% confidence interval: 9.1-11.0) in the pre-TMZ and TMZ eras, respectively (P < .001). By treatment, we found median OS for the control, RT alone, and RT + TMZ groups to be 2.5, 9.0, and 16.2 months, respectively (P < .001). Two-year survival was 0%, 4%, and 25%, respectively. The effect of age on TMZ effect was insignificant. In the matched group analysis, TMZ provided a 7.6-month OS benefit. Our population data reproduce the beneficial effect of TMZ from randomized controlled trials with a median OS of 16.2 months and 25% 2-year survival.

Background: In order to weigh the risks of surgery against the presumed advantages, it is important to have specific knowledge about complication rates. Contemporary reports on complications following craniotomy for tumor resection in pediatric patients are scarce., Objective: To study the surgical mortality and rate of hematomas, infections, meningitis, infarctions, and cerebrospinal fluid (CSF) leaks, as well as neurological morbidity, after craniotomy for pediatric brain tumors in a large, contemporary, single-institution consecutive series., Methods: All pediatric patients (< 18 years) from a well-defined population of 3.0 million inhabitants who underwent craniotomies for intracranial tumors at Oslo University Hospital, Rikshospitalet, during 2003 to 2009 were included. The patients were identified from our prospectively collected database, and all charts were reviewed to validate the database entries., Results: Included in the study were 273 craniotomies, performed on 211 patients. Mean age was 8.5 years (range, 0-18). Follow-up was 100%. One hundred ninety-nine cases (72.9%) were primary craniotomies, while 74 cases (27.1%) were secondary craniotomies. Surgical approach was supratentorial in 194 (71.1%) and infratentorial in 79 (28.9%). Surgical mortality within 30 days was 0.4% (n = 1). Complication rates were intracerebral hemorrhage 0.4%, chronic subdural hematoma 1.1%, meningitis 1.8%, cerebral infarctions 1.5%, and postoperative CSF leak 7.3%. Neurological deficit rates were no change or improvement 87.2%, minor or moderate new deficits 9.5%, and severe new neurological deficits 2.9%., Conclusion: Overall, the complication rates are low and compare favorably with similar data from adult series. The authors' data could be used as a baseline for future studies.

Giant cell ependymoma, a rare ependymoma subtype, was recently recognized as a separate diagnostic entity with variations both in malignant potential and course of disease. We analyzed the first supratentorial giant cell ependymoma using G-band karyotyping, DNA ploidy analysis, and array comparative genomic hybridization. The tumor was hypodiploid, and the karyotype showed multiple monosomies. This novel cytogenetic pattern seems specific for giant cell ependymoma as the only previous cytogenetic analysis of a giant cell ependymoma found similar monosomies. We were also able to analyze cytogenetically the subsequent recurrent tumor, phenotypically an anaplastic ependymoma, allowing a first insight into the genetic events involved in disease progression., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: In order to weigh the risks of surgery against the presumed advantages, it is important to have specific knowledge about complication rates., Objective: To study the surgical mortality and rate of reoperations for hematomas and infections after intracranial surgery for brain tumors in a large, contemporary, single-institution consecutive series., Methods: All adult patients from a well-defined population of 2.7 million inhabitants who underwent craniotomies for intracranial tumors at Oslo University Hospital from 2003 to 2008 were included (n = 2630). The patients were identified from our prospectively collected database and their charts studied retrospectively. Follow-up was 100%., Results: The overall surgical mortality, defined as death within 30 days of surgery, was 2.3% (n = 60). The mortality rates for high- and low-grade gliomas, meningiomas, and metastases were 2.9%, 1.0%, 0.9%, and 4.5%, respectively. Age >60 (odds ratio 1.84, P < 0.05) and biopsy compared with resection (odds ratio 4.67, P < 0.01) were significantly positively associated with increased surgical mortality. Hematomas accounted for 35% of the surgical mortality. Postoperative hematomas needing evacuation occurred in 2.1% (n = 54). Age >60 was significantly correlated to increased risk of postoperative hematomas (odds ratio 2.43, P < 0.001). A total of 39 patients (1.5%) were reoperated for postoperative infection. Meningiomas had an increased risk of infections compared with high-grade gliomas (odds ratio 4.61, P < 0.001)., Conclusion: The surgical mortality within 30 days of surgery was 2.3%, with age >60 and biopsy vs resection being the 2 factors significantly associated with increased mortality. Postoperative hematomas caused about one third of the surgical mortality.

Background and Methods: Brain metastases are far more common than primary central nervous system tumours. Based on our own clinical experiences and relevant literature published over the last decade (Medline), we present an overview of diagnosis and treatment., Results: Brain metastases are caused by haematogenous spread from extracranial tumours, most frequently from cancers in the lung, breast, melanoma, renal carcinomas and colorectal carcinomas. Three out of four patients present with multiple brain metastases. Cerebral MR is the most sensitive investigation. The most important prognostic factors for survival are Karnofsky score, age < 65, well controlled primary cancer and absence of systemic cancer disease., Interpretation: Some patients are offered neurosurgical treatment (surgery or gamma knife), depending on their clinical status, the number and location of brain metastases, and the histology and degree of systemic involvement of the primary tumour. The gamma knife is the treatment of choice with multiple and solitary tumours smaller than 3 cm that lie deep within the brain or within eloquent areas, whereas surgery is the treatment of choice with solitary metastases larger than 3-3.5 cm that are surgically accessible and cause significant mass effects. Solitary lesions without significant mass effect can be treated with either technique, as their documented efficacies are similar. However, the gamma knife is often preferred since this method is rapid, less invasive, has low morbidity and shortens the hospital stay.

Our capacity to flexibly shift between internally and externally directed attention is crucial for successful performance of activities in our daily lives. Neuroimaging studies have implicated the lateral prefrontal cortex (LPFC) in both internally directed processes, including autobiographical memory retrieval and future planning, and externally directed processes, including cognitive control and selective attention. However, the causal involvement of the LPFC in regulating internally directed attention states is unknown. The current study recorded scalp EEG from patients with LPFC lesions and healthy controls as they performed an attention task that instructed them to direct their attention either to the external environment or their internal milieu. We compared frontocentral midline theta and posterior alpha between externally and internally directed attention states. While healthy controls showed increased theta power during externally directed attention and increased alpha power during internally directed attention, LPFC patients revealed no differences between the two attention states in either electrophysiological measure in the analyzed time windows. These findings provide evidence that damage to the LPFC leads to dysregulation of both types of attention, establishing the important role of LPFC in supporting sustained periods of internally and externally directed attention.