Abstract
AIMS
Objective: a CT chest, abdomen and pelvis (CT CAP) is probably unnecessary if a glioblastoma multiforme (GBM) is detected on initial CT brain (CTB) prior to definitive MRI. We audited ...its frequency to develop a management pathway
METHOD
Methods: 12-month retrospective case series from 2018 of patients having an initial CTB suspicious for GBM. We dichotomised patients into two groups a) tissue proven and b) non-tissue proven, due to these representing distinct patient profiles. We quantified frequencies of plain and contrast CTBs, CT CAPs and extra-cranial malignancy.
RESULTS
Results: Group 1 (total n=84 mean age 59 years): 64% had a CT CAP. Plain CTB occurred in 24% and contrast CTB in 76%. Extra-cranial malignancy was 8% and 12%. Group 2 (total n=47 mean age 73 years): 85% had a CT CAP. Plain CTB occurred in 22% and contrast CTB in 78%. Extra-cranial malignancy was 33% and 23%. Negative CT CAPs in ~88% of CTBs in Group 1 and ~75% of CTBs in Group 2.
CONCLUSION
Conclusions: patients having a contrast CTB as their initial imaging modality, being suggestive of GBM, prior to definitive MRI, and managed surgically, having no history of extra-cranial malignancy, do not need a CT CAP unless MRI is non-diagnostic.
Abstract
AIMS
The aim of this study was to test if a correlation exists between the median voxel DTI-Q and overall survival in patients with GBM.
METHOD
The median voxel anisotropic (DTI-Q) values, ...calculated for the whole brain, the contrast-enhancing hemisphere and the contralateral hemisphere, were calculated using FSL (FMRIB Software Library, Oxford) for 33 patients with a primary diagnosis of GBM. Overall survival was calculated by subtracting the date of initial resection surgery from the date of death, for each included patient. Using R statistical software, the Pearson’s correlation coefficient was computed to establish the significance of the relationship between overall survival and whole brain median DTI-Q values, contrast-enhancing hemisphere median DTI-Q values and non-contrast-enhancing hemisphere median DTI-Q values.
RESULTS
There is a significant correlation between the median voxel DTI-Q of the whole brain and overall survival (t = -2.5362, df = 31, p-value = 0.01646), median voxel DTI-Q of the contrast-enhancing hemisphere and overall survival (t = -2.1235, df = 31, p-value = 0.0418) and the median voxel DTI-Q of the contralateral (non-contrast-enhancing) hemisphere and overall survival (t = -2.5212, df = 31, p-value = 0.01705).
CONCLUSION
The median anisotropic component of the diffusion tensor, calculated for the whole brain, contrast-enhancing and non-contrast-enhancing hemisphere, is significantly related to overall survival. This demonstrates the potential utility of DTI metrics as prognostic biomarkers that can readily be calculated in routine practice.
Abstract
AIMS
This study aimed to describe our institutional use of a commercially available mixed reality viewer within a multi-disciplinary planning workflow for awake craniotomy surgery and to ...report an assessment of its usability.
METHOD
Three Tesla MRI scans, including 32-direction diffusion tensor sequences, were reconstructed with BrainLab Elements auto-segmentation software. Magic Leap mixed reality viewer headsets were registered to a shared virtual viewing space to display image reconstructions. System Usability Scale was used to assess the usability of the mixed reality system.
RESULTS
The awake craniotomy planning workflow utilises the mixed reality viewer to facilitate a stepwise discussion through four progressive anatomical layers; skin, cerebral cortex, subcortical white matter tracts and tumour with surrounding vasculature. At each stage relevant members of the multi-disciplinary team reviewed key operative considerations, including patient positioning, cortical and subcortical speech mapping protocols and surgical approaches to the tumour. The mixed reality system was used in 10 consecutive awake craniotomy procedures over a 5-month period. Ten participants (2 Anaesthetists, 5 Neurosurgical trainees, 2 Speech therapists, 1 Neuropsychologist) completed System Usability Scale assessments, reporting a mean score of 71.5. Feedback highlighted the benefit of being able to rehearse important steps in the procedure, including patient positioning and anaesthetic access and visualising the testing protocol for cortical and subcortical speech mapping.
CONCLUSION
This study supports the use of mixed reality for multi-disciplinary planning for awake craniotomy surgery, with an acceptable degree of interface usability. We highlight the need to consider the requirements of non-technical, non-neurosurgical team members when involving mixed reality activities.
Abstract
AIMS
Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)’s sensitivity to predict morbidity after brain tumour ...resection. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and following awake surgery; (2) evaluate the use of early post-operative DT to predict recovery from post-surgical deficits.
METHOD
We performed a retrospective review our first 100 awake neurosurgery procedures using DTneuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations.
RESULTS
Between 2014 and 2019 a total of 91 adult brain tumour patients (mean age 49.2 years) underwent 100 awake surgeries with subcortical stimulation. The sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (39%), but were prolonged (>3 months) in only 4 patients (4%). Post-operative DT was available in 51 patients and confirmed surgical preservation of tracts. Post-operative DT anticipated complete recovery in a patient with supplementary motor area syndrome, and indicated infarct-related damage to corticospinal fibers associated with delayed, partial recovery in a second patient.
CONCLUSION
Pre-operative DT provided very accurate predictions of the spatial location of tracts in relation to a tumour. As expected, however, the presence of a tract did not provide information on its functional status, resulting in variable DT specificity among individual tracts. While prolonged deficits were rare in our series, DT in the immediate post-operative period offered additional information to monitor neurological deficits and anticipate recovery potential.
Abstract
AIMS
Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study aimed to ...evaluate survival prognosticators in elderly glioblastoma patients to more accurately guide their treatment.
METHOD
The records of 169 elderly (≥70 years) patients with a new diagnosis of glioblastoma who had undergone neurosurgical intervention were retrospectively examined for patient sex, age, performance status, comorbidities, MGMT promoter methylation, surgical intervention and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate patient survival at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS).
RESULTS
The median overall survival (mOS) of the cohort was 28.8 weeks. Gross-total and subtotal resection were associated with improved survival compared to biopsy alone (respective mOS 65.3 and 28.1 vs 15.7 weeks, p<0.001). Hypofractionated radiotherapy (40Gy in 15 fractions) with Temozolomide was non-inferior to the Stupp protocol, p=0.72. Exploratory subgroup analysis revealed a significant benefit of Temozolomide-based approaches in MGMT-methylated patients as well as a trend towards improved survival in MGMT-unmethylated patients. Our EGSS and EGOS scores successfully estimated survival in this retrospective cohort with 65% and 73% accuracy.
CONCLUSION
Where appropriate and safe, elderly glioblastoma patients may benefit from surgical resection and combined chemoradiotherapy with Temozolomide. The proposed EGSS and EGOS scores take into account important prognostic factors to help guide which patients should receive such treatment.
Abstract
AIMS
Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite aggressive treatment, a resistant tumour recurs in practically all patients. We therefore aimed ...to better understand the mechanisms driving this treatment resistance through investigating changes in gene expression across pairs of primary and recurrent GBM tumours.
METHOD
We generated or acquired bulk tumour RNA sequencing data for primary and first recurrent tumours from 107 patients who received standard treatment. Differential expression analysis between primary and recurrent samples found that the most dysregulated genes were involved in neurodevelopment and neurodifferentiation. We therefore used a publicly available ChIP-seq database to identify DNA binding factors for which binding sites are enriched in the promotors of genes with the largest expression changes from primary to recurrent.
RESULTS
Jumonji and AT-Rich Interacting Domain 2 (JARID2) was the most strongly enriched for binding to promotors of dysregulated genes. 65 patients showed an up-regulation and 42 showed a down-regulation of genes bound by this protein. The same set of JARID2 bound genes were found to be dysregulated in each direction, and correlated with the largest source of variation between samples in their response to treatment. Further enrichment analyses indicated that ‘Up’ responders may resist treatment through reduced proliferation and increased interaction with the tumour microenvironment, whereas ‘Down’ responders instead rely on a shift to mesenchymal cell states.
CONCLUSION
These results indicate that GBM tumours can be split into two subtypes that transcriptionally reprogramme in different directions through treatment and may benefit from different treatment approaches.
Abstract
AIMS
An Awake Craniotomy is a neuro-surgical procedure where the patient remains awake for all or part of their surgery to allow a lesion to be maximally resected without damaging healthy ...brain functioning. An annual audit of our Patient Satisfaction Survey demonstrated that ‘Receiving Written Information’ was scoring below standard. A new leaflet was designed to address this and it was developed into a ‘Video Leaflet’ comprising a 10 minute audio-visual production, accessed by QR code.
METHOD
The team created a scripted description of the patient Awake Craniotomy experience. The script was coded into: audio narration, written information or video content. The areas covered were: consultations with the team; pre and intra-operative testing; fMRI scanning; hospital environments; and follow-up. The script was filmed with written consent from all involved and then collated by the Communications Department. There were several revisions made based on feedback from all involved resulting in the final product.
RESULTS
The Video Leaflet is ready to be demonstrated to and evaluated by patients using a structured questionnaire. The annual audit of Satisfaction Surveys will be compared prior to and post the introduction of the Video Leaflet to determine whether ratings for ‘Receiving Written Information’ have improved. Questionnaire results which are available by the conference date will be presented as preliminary findings.
CONCLUSION
It is anticipated that the Video Leaflet will further optimise patient preparation, facilitate informed consent and contribute to maximising coping and engagement from a patient perspective to improve patient experience for a complex and daunting procedure.
Abstract
AIMS
In the UK, brain, other CNS and intracranial tumours incidence rates are increasing with over 12,200 new cases diagnosed each year. The overall survival rate over 5 years in these ...tumours is approximately 12%. There is a need for predictive biomarkers to detect the presence of gliomas to improve prognosis for such patients. A novel modified Mendelian randomization (MR)-based technique has been proposed to discover predictive biomarkers for diagnostic applications. The aim of this project is to identify circulating blood biomarkers that are genetically liable to all gliomas, glioblastoma (GB), or non-GBs.
METHOD
We generated polygenic scores for genetic liability to glioma and a separate GWAS of plasma protein levels from the INTERVAL study. We used sensitivity analyses methods to further assess our findings. The results were then validated by the plasma pQTL GWAS data from the Fenland cohort.
RESULTS
We identified a potential blood biomarker called erythroblast membrane associated protein (ERMAP) which showed consistent results across all sensitivity analyses in our discovery cohort β: -0.0778, P-value: 2.1E-04. We identified that decreased levels of ERMAP β: -0.078 SD of ERMAP abundance per SD increase in glioma risk, 95% confidence interval (CI) 0.037 to 0.119, P-value: 2.1E-04 in the blood are associated with increased risk of glioma.
CONCLUSION
ERMAP protein is found to have a potential genetic liability for all gliomas. Predictive biomarkers are novel to glioma research and could be important for diagnostic applications and population screening in early detection. However, further clinical research is required to validate these findings.
Abstract
AIMS
Arterial spin labelling (ASL) is a non-invasive perfusion technique that uses endogenous contrast and is proving to be of value in paediatric neuro-oncology. ASL derived rCBV has been ...shown to correlate with Dynamic Susceptibility Contrast (DSC) -derived CBV and could be an alternative perfusion technique when DSC is not possible. The aim of the study was to investigate whether early post-treatment tumour ASL can stratify patient survival at 12 months.
METHOD
180 consecutive patients diagnosed with glioblastoma and undergoing treatment between 2017-2021 were imaged with an extended MRI protocol that included pseudo-continuous ASL (pCASL). Patients that were imaged with pCASL within 1-3 months of completing radiotherapy were identified retrospectively. Scanner generated Perfusion weighted images were inspected and regions of interest encompassing the tumour were generated and compared with a control region in the contra-lateral grey matter. Overall survival data was collated and a comparison of tumour ASL was assessed with t-test statistics between patients surviving < and >12 months.
RESULTS
43 patients were identified (23 male, median age 58 years, diagnoses: IDHwt-GBM 17, IDHmut-Astrocytoma 13, IDHmut 1p19q co-deleted Oligodendroglioma 13). Tumour ASL was 3.22 (± 2.1) in patients that survived less than 12 months compared to 1.64 (± 1.9) in patients that survived greater than 12 months, p=0.02).
CONCLUSION
Early post-treatment ASL can stratify patient survival at 12 months and show promise as an alternative to DSC perfusion in the prognostication of patients being treated for glioma.
Abstract
AIMS
Rapid, detailed feedback is needed to understand the individualized biological impacts of novel glioma therapies. We are performing glioma biomarker discovery by serial cerebrospinal ...fluid (CSF) sampling from Ommaya reservoirs to determine how the CSF proteome can reveal early longitudinal intelligence regarding glioma status, biology, and therapeutic response.
METHOD
Global proteomic analysis of CSF was performed on the Somalogic platform – an aptamer-based technology for highly sensitive and specific analysis of over 7,000 proteins. Discovery analysis comprised of the top-500 ranked proteins in CSF from seven patients with high-grade gliomas (HGG) versus non-glioma controls. The top-500 HGG proteins were then preliminarily filtered to include only proteins that met two additional criteria of decrease with resection and increase with recurrence in individual paired patient samples.
RESULTS
Proteomic enrichment analysis revealed a conserved HGG CSF proteomic signature defined by 79 proteins, including ones known to be over-expressed in solid tumor malignancies, such as retinoblastoma binding protein 4, heat shock protein 90, and sorcin. The HGG proteomic signature was consistently enriched in an independent validation cohort consisting of 13 gliomas diverse in primary versus recurrent status, subtype, and grade, when compared to control CSF samples. Encouragingly, proteins in the HGG signature decreased in the two patients for whom CSF was collected prior to and after resection (both at POD16 and POD18) with decreased tumor burden.
CONCLUSION
Our data demonstrate the ability to gain detailed, individualized insights regarding glioma biology, tumor burden, and evolution through global CSF proteomics acquired from longitudinal access to gliomas via Ommaya reservoirs.
