The outcomes measured and reported in observational studies of incidental and untreated intracranial meningioma: A systematic review.

Background: The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies. Methods: A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative. Results: Thirty-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective n = 27 and prospective n = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas. Conclusions: Outcome measurement across observational studies of incidental and untreated intracranial meningioma is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set for use in future observational studies.

The outcomes measured and reported in intracranial meningioma clinical trials: A systematic review.

Background: Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials. Methods: Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative. Results: Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 n = 33, phase 3 n = 14. Common interventions included: Surgery n = 13, radiotherapy n = 8, and pharmacotherapy n = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas. Conclusions: Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials.

IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.

BACKGROUND: Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur. RESULTS: Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation. CONCLUSIONS: We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.

Tectal Plate Glioma: A Clinical and Radiologic Analysis of Progression and Management in Adults.

BACKGROUND: Tectal plate gliomas (TPGs) are a heterogeneous group of uncommon brain tumors. TPGs are considered indolent and are usually managed conservatively but they have the potential to transform into higher-grade tumors. The aims of this study were to investigate the natural history of adult TPG, treatment outcomes, and overall survival. METHODS: A retrospective cohort analysis was performed of adult patients with TPG between 1993 and 2021. Baseline clinical, radiologic, and management characteristics were collected. The primary outcome was tumor progression, defined as increasing size on radiologic assessment or new gadolinium contrast enhancement. Secondary outcomes included management and mortality. RESULTS: Thirty-nine patients were included, of whom 23 (52.2%) were men. Median age at diagnosis was 35 years (interquartile range, 27-53). Radiologic tumor progression was observed in 8 patients (20.5%). The 10-year progression-free survival was 72.6% (95% confidence interval [CI], 0.58-0.91). The 10-year overall survival was 86.5% (95% confidence interval, 0.75-1.0). Cerebrospinal fluid diversion procedures were used in 62% of the cohort (n = 24). Seventeen patients (43.6%) underwent at least 1 endoscopic third ventriculostomy, whereas only 6 patients (15.4%) underwent at least 1 ventriculoperitoneal shunt. CONCLUSIONS: TPG has an overall favorable clinical prognosis, although progression occurs in 1 in 5 patients. Showing accurate factors by which patients with TPG may be risk stratified should be a key area of further research. A follow-up duration of 10 years would be a reasonable window based on the radiologic progression rates in this study; however, larger cohort studies are needed to answer both questions definitively.

Health-related quality of life following cranioplasty - a systematic review.

Cranioplasty is a neurosurgical procedure that repairs a defect in the skull Coupled with the underlying pathology cranioplasty associated morbidity can have a large impact on patient quality of life, which is often poorly explored. The objective of this systematic review was to identify patient-reported outcomes evaluating health-related quality of life following cranioplasty. The review protocol was registered on PROSPERO (CRD42021251543) and a systematic review was conducted in accordance with the PRISMA statement. PubMed, Embase, CINAHL Plus, and the Cochrane databases were searched from inception to 1 May 2022. All studies reporting HRQoL following cranioplasty were included. Reporting was assessed using the ISOQOL checklist and risk of bias was assessed using the Newcastle-Ottawa Scale or the Johanna-Briggs Institute Scale, as appropriate. A total of 25 studies were included of which 20 were cross-sectional and 2 longitudinal. Most studies utilized study specific questionnaires and Likert scales to assess HRQoL. The studies found a significant improvement in physical functioning, social functioning, cosmetic outcome, and overall HRQoL following cranioplasty. Further longitudinal studies utilising validated measurement tools are required to better understand the effect of cranioplasty at a patient level.

Cranial meningioma with bone involvement: surgical strategies and clinical considerations.

BACKGROUND: Intracranial meningioma with bone involvement and primary intraosseous meningioma is uncommon. There is currently no consensus for optimal management. This study aimed to describe the management strategy and outcomes for a 10-year illustrative cohort, and propose an algorithm to aid clinicians in selecting cranioplasty material in such patients. METHODS: A single-centre, retrospective cohort study (January 2010-August 2021). All adult patients requiring cranial reconstruction due to meningioma with bone involvement or primary intraosseous meningioma were included. Baseline patient and meningioma characteristics, surgical strategy, and surgical morbidity were examined. Descriptive statistics were performed using SPSS v24.0. Data visualisation was performed using R v4.1.0. RESULTS: Thirty-three patients were identified (mean age 56 years; SD 15) There were 19 females. Twenty-nine patients had secondary bone involvement (88%). Four had primary intraosseous meningioma (12%). Nineteen had gross total resection (GTR; 58%). Thirty had primary 'on-table' cranioplasty (91%). Cranioplasty materials included pre-fabricated polymethyl methacrylate (pPMMA) (n = 12; 36%), titanium mesh (n = 10; 30%), hand-moulded polymethyl methacrylate cement (hPMMA) (n = 4; 12%), pre-fabricated titanium plate (n = 4; 12%), hydroxyapatite (n = 2; 6%), and a single case combining titanium mesh with hPMMA cement (n = 1; 3%). Five patients required reoperation for a postoperative complication (15%). CONCLUSION: Meningioma with bone involvement and primary intraosseous meningioma often requires cranial reconstruction, but this may not be evident prior to surgical resection. Our experience demonstrates that a wide variety of materials have been used successfully, but that pre-fabricated materials may be associated with fewer postoperative complications. Further research within this population is warranted to identify the most appropriate operative strategy.

Tranexamic acid use in meningioma surgery - A systematic review and meta-analysis.

Tranexamic Acid (TXA) has been used in medical and surgical practice to reduce haemorrhage. The aim of this review was to evaluate the effect of TXA use on intraoperative and postoperative outcomes of meningioma surgery. A systematic review and meta-analysis was conducted in accordance with the PRISMA statement and registered in PROSPERO (CRD42021292157). Six databases were searched up to November 2021 for phase 2-4 control trials or cohort studies, in the English language, examining TXA use during meningioma surgery. Studies ran outside of dedicated neurosurgical departments or centres were excluded. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random effects meta-analysis were performed to delineate differences in operative and postoperative outcomes. Four studies (281 patients) were included. TXA use significantly reduced intraoperative blood loss (mean difference 315.7 mls [95% confidence interval [CI] -532.8, -98.5]). Factors not affected by TXA use were transfusion requirement (odds ratio = 0.52; 95% CI 0.27, 0.98), operation time (mean difference = -0.2 h; 95% CI -0.8, 0.4), postoperative seizures (Odds Ratio [OR] = 0.88; 95% CI 0.31, 2.53), hospital stay (mean difference = -1.2; 95% CI -3.4, 0.9) and disability after surgery (OR = 0.50; 95% CI 0.23, 1.06). The key limitations of this review were the small sample size, limited data for secondary outcomes and a lack of standardised method for measuring blood loss. TXA use reduces blood loss in meningioma surgery, but not transfusion requirement or postoperative complications. Larger trials are required to investigate the impact of TXA on patient-reported postoperative outcomes.

Volumetric Growth and Growth Curve Analysis of Residual Intracranial Meningioma.

BACKGROUND: After meningioma surgery, approximately 1 in 3 patients will have residual tumor that requires ongoing imaging surveillance. The precise volumetric growth rates of these tumors are unknown. OBJECTIVE: To identify the volumetric growth rates of residual meningioma, growth trajectory, and factors associated with progression. METHODS: Patients with residual meningioma identified at a tertiary neurosurgery center between 2004 and 2020 were retrospectively reviewed. Tumor volume was measured using manual segmentation, after surgery and at every follow-up MRI scan. Growth rates were ascertained using a linear mixed-effects model and nonlinear regression analysis of growth trajectories. Progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria (40% volume increase). RESULTS: There were 236 patients with residual meningioma. One hundred and thirty-two patients (56.0%) progressed according to the RANO criteria, with 86 patients being conservatively managed (65.2%) after progression. Thirteen patients (5.5%) developed clinical progression. Over a median follow-up of 5.3 years (interquartile range, 3.5-8.6 years), the absolute growth rate was 0.11 cm 3 per year and the relative growth rate 4.3% per year. Factors associated with residual meningioma progression in multivariable Cox regression analysis were skull base location (hazard ratio [HR] 1.60, 95% CI 1.02-2.50) and increasing Ki-67 index (HR 3.43, 95% CI 1.19-9.90). Most meningioma exhibited exponential and logistic growth patterns (median R 2 value 0.84, 95% CI 0.60-0.90). CONCLUSION: Absolute and relative growth rates of residual meningioma are low, but most meet the RANO criteria for progression. Location and Ki-67 index can be used to stratify adjuvant treatment and surveillance paradigms.

Sporadic multiple intracranial meningioma does not infer worse patient outcomes: results from a case control study.

BACKGROUND: Sporadic multiple meningioma are uncommon. Population-based data suggests that these patients have a reduced overall survival when compared to patients with solitary meningioma. The aim of this study was to investigate the clinical outcomes in multiple and solitary meningioma. METHODS: A single-center matched cohort study (2008-2018) was performed. Patients with synchronous multiple meningioma at presentation, with no history of prior intracranial radiation, concurrent hormone replacement therapy or features of NF2-schwannomatosis were included. Eligible patients were matched 1:1 to patients with solitary meningioma. Outcomes of interest were occurrence of an intervention, recurrence, new meningioma development and mortality. RESULTS: Thirty-four patients harboring 76 meningioma at presentation were included. Mean age was 59.3 years (SD = 13.5). Thirty-one (91.2%) were female. The median number of meningioma per patient was 2 (range 2-6). Eighteen patients (52.9%) were symptomatic at presentation. Median overall follow-up was 80.6 months (IQR 44.1-99.6). Compared to patients with a sporadic meningioma, there was no difference in intervention rates (67.6% vs 70.6%, P = 0.792). Eight patients (34.8%) with a multiple meningioma had a WHO grade 2 meningioma compared to 7 (29.2%) with a solitary meningioma (P = 0.679). Median recurrence-free survival was 89 months (95% CI 76-104) with no difference between the two groups (P = 0.209). Mean overall survival was 132 months (95% CI 127-138) with no difference between the two groups (P = 0.860). One patient with multiple meningioma developed two further new meningioma 36 months following diagnosis. CONCLUSION: Sporadic multiple meningioma may not have worse clinical outcomes. Management of patients with sporadic multiple meningioma should be tailored towards the symptomatic meningioma or high-risk asymptomatic meningioma.

Quality of life outcomes in incidental and operated meningiomas (QUALMS): a cross-sectional cohort study.

INTRODUCTION: Few studies have evaluated meningioma patients' longer-term health-related quality of life (HRQoL) following diagnosis and treatment, particularly in those with incidental, actively monitored tumours. METHODS: A single-center, cross-sectional study was completed. Adult patients with surgically managed or actively monitored meningioma with more than five years of follow-up were included. The patient-reported outcome measures RAND SF-36, EORTC QLQ-C30 and QLQ-BN20 were used to evaluate HRQoL. HRQoL scores were compared to normative population data. Outcome determinants were evaluated using multivariate linear regression analysis. RESULTS: 243 patient responses were analyzed, and the mean time from diagnosis was 9.8 years (range 5.0-40.3 years). Clinically relevant, statistically significant HRQoL impairments were identified across several SF-36 and QLQ-C30 domains. Increasing education level (ß = 2.9, 95% CI 0.9 to 4.9), P = .004), employment (ß = 7.7, 95% CI 2.2 to 13.1, P = .006) and absence of postoperative complications (ß=-6.7, 95% CI -13.2 to (-)0.3, P = .041) were associated with a better QLQ-C30 summary score. Other tumour and treatment variables were not. CONCLUSION: This study highlights the longer-term disease burden of patients with meningioma nearly one decade after diagnosis or surgery. Patients with actively monitored meningioma have similar HRQoL to operated meningioma patients. Healthcare professionals should be mindful of HRQoL impairments and direct patients to sources of support as needed.

When is a staging scan required for newly diagnosed brain lesions on CT? A multivariate logistic regression analysis.

PURPOSE: For patients with a new lesion on CT head (CTH) suspected to be a brain tumor, a staging chest, abdomen, and pelvis CT (CTCAP) is only warranted if a metastatic lesion is suspected. Unnecessary CTCAPs are often performed too early in a patient's journey due to poor patient selection. We sought to create a protocol to guide the selection of patients for CTCAPs based on their CTH findings. METHODS: Patients with suspected new brain tumors discussed at the neuro-oncology MDT at a tertiary neurosurgical center were reviewed. Patient demographics and CTH features were collected. For protocol creation, data was collected from July to December 2020, and predictor variables were identified using multivariate logistic regression. Candidate protocols were assessed in a protocol testing stage using similar data collected from January to June 2021. Sensitivity, specificity, and area under the curve (AUC) were computed for each protocol. RESULTS: Variables from the protocol creation stage (222 patients) were assessed in the protocol testing stage (216 patients). The most sensitive variables predicting metastatic disease were a previous history of cancer, multiple lesions, lesion < 4 cm, and infratentorial location. A protocol recommending a CTCAP based on the presence of one of these features has a sensitivity of 99.1% (AUC 0.704). CONCLUSIONS: Unnecessary CTCAPs are reduced if performed only if a patient has one of the four identified predictor variables.

Assessment of patients with a Chiari malformation type I.

Introduction: The prevalence of Chiari malformation type I (CM-I) has been estimated as up to 1% of the general population. The majority of patients are asymptomatic and usually do not need treatment. Symptomatic patients, and some asymptomatic patients with associated conditions, may benefit from further assessment and treatment. Research question: The aim of this review was to describe the clinical and radiological assessment of patients presenting with a CM-I. Material and methods: A literature search was performed using the PubMed and Embase databases focused on clinical assessment and imaging techniques used to diagnose CM-I. Results: Following a complete clinical evaluation in patients with symptomatic CM-I and/or radiologically significant CM-I (tonsillar impaction, resulting tonsillar asymmetry and loss of CSF spaces), MRI of the brain and whole spine enables an assessment of the CM-I and potential associated or causative conditions. These include hydrocephalus, syringomyelia, spinal dysraphism, and tethered cord. Flow and Cine MRI can provide information on CSF dynamics at the craniocervical junction, and help in surgical decision-making. Hypermobility or instability at the upper cervical and craniocervical junction is less common and can be measured with CT imaging and flexion/extension or upright MRI. Discussion and conclusion: The majority of CM-I detected are incidental findings on MRI imaging of brain or spine, and do not require intervention. Once a radiological diagnosis and concern has been raised, clinical assessment by an appropriate specialist is required. A MRI brain and cervical spine is indicated in all radiologically labelled CM-I. In symptomatic patients or cases of radiologically significant CM-I, MRI of the brain and entire spine is indicated. Further investigations should be tailored to individuals' needs.

Chronic CSF leak from lumbar-peritoneal shunt tract: A case report.

Background: We describe a case of long-standing intracranial hypotension caused by an iatrogenic arachnoid diverticulum. This case illustrates two learning points. First, excessive CSF absorption may occur through an acquired arachnoid-epidural venous plexus at a dural defect. Second, a long-standing CSF leak may benefit from definitive surgical repair in the first instance. Case Description: A 55-year-old female, with known idiopathic intracranial hypertension, presented with disabling chronic low-pressure symptoms after having a lumboperitoneal shunt removed 5 years previously. MRI scan revealed a Chiari I malformation (CMI) and a small dural interruption at the L3/4 space. CT myelography confirmed the abnormality. Intraoperatively, a dural defect and arachnoid bleb with an overlying attachment of adipose tissue and a vessel were found. Postoperatively, the patient has marked resolution of her headaches and dizziness and is mobilizing independently. Conclusion: Excessive CSF absorption appears to have occurred through an acquired arachnoid-epidural venous plexus. A high index of suspicion for intracranial hypotension is required in patients with low pressure symptoms and a CMI.

Cranioplasty with hydroxyapatite or acrylic is associated with a reduced risk of all-cause and infection-associated explantation.

OBJECTIVE: Cranioplasty remains an essential procedure following craniectomy but is associated with high morbidity. We investigated factors associated with outcomes following first alloplastic cranioplasty. METHODS: A single-centre, retrospective cohort study of patients undergoing first alloplastic cranioplasty at a tertiary neuroscience centre (01 March 2010-01 September 2021). Patient demographics and craniectomy/cranioplasty details were extracted. Primary outcome was all-cause explantation. Secondary outcomes were explantation secondary to infection, surgical morbidity and mortality. Multivariable analysis was performed using Cox proportional hazards regression or binary logistic regression. RESULTS: Included were 287 patients with a mean age of 42.9 years [SD = 15.4] at time of cranioplasty. The most common indication for craniectomy was traumatic brain injury (32.1%, n = 92). Cranioplasty materials included titanium plate (23.3%, n = 67), hydroxyapatite (22.3%, n = 64), acrylic (20.6%, n = 59), titanium mesh (19.2%, n = 55), hand-moulded PMMA cement (9.1%, n = 26) and PEEK (5.6%, n = 16). Median follow-up time after cranioplasty was 86.5 months (IQR 44.6-111.3). All-cause explantation was 12.2% (n = 35). Eighty-three patients (28.9%) had surgical morbidity. In multivariable analysis, the risk of all-cause explantation and explantation due to infection was reduced with the use of both hydroxyapatite (HR 0.22 [95% CI 0.07-0.71], p = .011, HR 0.22 [95% CI 0.05-0.93], p = .040) and acrylic (HR 0.20 [95% CI 0.06-0.73], p = .015, HR 0.24 [95% CI 0.06-0.97], p = .045), respectively. In addition, risk of explantation due to infection was increased when time to cranioplasty was between three and six months (HR 6.38 [95% CI 1.35-30.19], p = .020). Mean age at cranioplasty (HR 1.47 [95% CI 1.03-2.11], p = .034), titanium mesh (HR 5.36 [95% CI 1.88-15.24], p = .002), and use of a drain (HR 3.37 [95% CI 1.51-7.51], p = .003) increased risk of mortality. CONCLUSIONS: Morbidity is high following cranioplasty, with over a tenth requiring explantation. Hydroxyapatite and acrylic were associated with reduced risk of all-cause explantation and explantation due to infection. Cranioplasty insertion at three to six months was associated with increased risk of explantation due to infection.

Development of 'Core Outcome Sets' for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings.

INTRODUCTION: Meningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma. METHODS AND ANALYSIS: Two systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups. ETHICS AND DISSEMINATION: Institutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available. TRIAL REGISTRATION NUMBER: COMET study ID 1508.

Opportunities and challenges for the development of "core outcome sets" in neuro-oncology.

Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors.

Tumour treating fields in glioblastoma: is the treatment tolerable, effective, and practical in UK patients?

BACKGROUND: Tumour Treating Fields (TTF) in combination with standard therapy, prolongs survival in patients with glioblastoma (GBM). The aim of the current study was to assess the feasibility of integrating TTF into a standard UK neuro-oncology service with a focus on patient tolerability, compliance, and treatment delivery. METHODS: A prospective study was performed of UK patients with IDH 1 Wild Type, MGMT Unmethylated GBM treated with TTF, in conjunction with conventional therapy. Patient compliance data, device-specific tolerability questions, and an evaluation of disease progression and survival were collected. Monthly quality of life (QoL) questionnaires (EORTC QLQ-C30 with BN-20) examined the trend of global health, psychosocial function, and symptom progression. RESULTS: Nine patients were enrolled with a median age of 47 (seven males; two females). Overall, compliance with TTF was 89% (range 16-97%). Only one patient failed to comply with treatment. Patients tolerated the device with minimal side effects. Eight patients described mild to moderate skin irritation, whilst all patients were keen to recommend the device to other patients (100%). Most patients found the weight and size of the device to be its biggest drawback (72%). Progression-free survival was 5.5 months and median overall survival was 14.9 months. CONCLUSIONS: TTF was well-tolerated amongst a small cohort of UK patients, who were able to comply with treatment without any significant complication. QoL questionnaires showed no sustained deterioration in global health, physical and emotional function until the final months of life when the disease burden was greatest.

Genome-wide methylation analyses identifies Non-coding RNA genes dysregulated in breast tumours that metastasise to the brain.

Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient's serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers.