Supratotal Resection Research Articles

Supratotal Resection Versus Gross Total Resection for Isocitrate Dehydrogenase-Wildtype Glioblastoma and Grade 4 Isocitrate Dehydrogenase-Mutant Astrocytoma: Meta-Analysis of Individual Patient Data

BACKGROUND AND OBJECTIVES: IDH-wildtype glioblastoma multiforme (GBM) and grade 4 IDH-mutant astrocytoma are challenging to manage in oncology. This study explores the contrast between gross total resection (GTR) and supratotal resection (SupTR) for IDH-wildtype GBM and grade 4 IDH-mutant astrocytoma, aiming to summarize their influence on crucial clinical outcomes. METHODS: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. PubMed, Web of Science, Embase, Scopus, and Cochrane were searched for articles until December 2023. RESULTS: Ten studies were included, involving 1043 patients with IDH-wildtype GBM and grade 4 IDH-mutant astrocytoma who underwent GTR or SupTR. SupTR demonstrated a favorable impact on long-term overall survival (OS) and progression-free survival (PFS) compared with GTR. The hazard ratio for OS was 0.655 (95% CI: 0.5703-0.7522, P < .0001), and for PFS, it was 0.732 (95% CI: 0.6279-0.8540, P = .0001) in the long-term analysis. Short-term analysis (18 months) reinforced the superiority of SupTR, with a hazard ratio for OS of 0.544 (95% CI: 0.450-0.659, P < .0001), and for PFS, it was 0.697 (95% CI: 0.586-0.830, P < .0001) in this timespan. CONCLUSION: SupTR appears to be a promising alternative to GTR for treating IDH-wildtype GBM and grade 4 IDH-mutant astrocytoma, showing improved OS and PFS outcomes. More robust studies that are less susceptible to bias are needed to strengthen this conclusion.

SURG-10. SUPRATOTAL RESECTION: AN EMERGING CONCEPT OF GLIOBLASTOMA MULTIFORME SURGERY—SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract The severe neurologic tumor known as glioblastoma (GBM), also referred to as a grade IV astrocytoma, is rapidly progressive and debilitating. Supratotal resection (SpTR) is an emerging concept within glioma surgery, which aims to achieve a more extensive resection of the tumor than is possible with conventional techniques. We performed a language-independent search of PubMed, Scopus, and Cochrane CENTRAL to identify all available literature up to August 2022 of patients undergoing SpTR assessing survival outcomes in comparison to other surgical modalities. After screening for exclusion, a total of 13 studies, all retrospective in design, were identified and included in our meta-analysis. SpTR was associated with significantly increased overall survival (hazard ratio 0.77, 95% CI 0.71–0.84; P < 0.01, I2 = 96%) and progression-free survival (hazard ratio 0.2, 95% CI 0.07–0.56; P = 0.002, I2 = 88%). SpTR is associated with greater overall survival and PFS when compared with other glioblastoma surgeries like GTR or SubTR.

NCMP-20. FACTORS RELATED TO PERMANENT AND TEMPORARY MOTOR DEFICITS IN PATIENTS UNDERGOING GLIOMA RESECTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Standard of care treatment for virtually all glioma subtypes starts with maximal safe resection. However, resections that result in motor deficits can negate any survival benefit from surgery and diminish quality of life. Because current evidence on functional outcomes following glioma resection often conflicts and is limited to a small number of case series, retrospective analyses, and reviews, here we performed the first PRISMA-compliant systematic review and meta-analysis of currently published data to identify factors related to permanent and temporary motor deficits after surgery. We searched Ovid Medline, Scopus, Web of Science, CINAHL/EBSCO, PsychInfo, Cochrane and Wiley for studies reporting motor outcomes following surgical resection of glioma. Outcomes were stratified by patient/tumor characteristics, pre-operative condition, and intra-operative factors for both permanent (≥3 months postop) and temporary (<3 months postop) motor deficits. Generalized estimating equations were used to generate odds ratios and 95% confidence intervals. A total of 1,162 titles and abstracts were reviewed for eligibility resulting in the evaluation of 211 full-text articles. Data were extracted from 55 studies including 1,801 patients with 223 (12%) permanent postoperative motor deficits, 428 (24%) temporary motor deficits, and the remaining 1,150 (64%) without motor deficit. Pre-operative deficit was the strongest predictor of permanent post-operative motor deficit (OR 10.56, CI 5.20-21.45, p=7.2E-11), while high pre-operative Karnofsky Performance Scale (KPS) (OR 0.98, CI 0.97-0.99, p=0.036) and subcortical tumor location (OR 0.15, CI 0.025-0.90, p=0.038) were associated with no permanent deficit. Supratotal resection was significantly associated with temporary motor deficits (OR 3.54E+12, CI 3.53+E13-3.56E+17, p<2E-16), and asleep craniotomies were associated with no deficit (OR 1.68E-01, CI 4.93E-02–5.71E-01, p=0.0043). Ultimately, this study represents the largest analysis of motor outcome data in glioma surgery to date.

EXTH-74. COOLING GLIOBLASTOMA WITH A NEURAL IMPLANT

Abstract Survival rates for glioblastoma (GBM) patients are low due to the difficulty in eradicating all tumor cells, leading to frequent recurrence. This recurrence is frequently within 2-cm from the original site. Studies indicate that supra-total resection improves survival, and non-destructive local therapies show promise in preventing GBM recurrence. Our research demonstrates that non-freezing, ‘cytostatic’ hypothermia is effective against GBM in rats and can be scaled to pig models. This method, unlike ablative cryogenic hypothermia, safely inhibits GBM growth without damaging healthy tissue. Using in vitro culture models and in vivo rat models via a Peltier device, we tested cytostatic hypothermia. This was followed by finite-element modeling (FEM) to simulate bioheat transfer in human and pig brains. The system consists of a neural implant with a multiprobe array, a Peltier chip, a water block, and an artificial internal circulation system with a piezoelectric pump. In vitro tests identified a cytostatic window of 20–25°C. Miniature Peltier devices were fabricated to achieve this in rats to inhibit GBM growth and extend survival. Rats whose tumors received cytostatic levels of hypothermia survived their full study period. FEM simulations confirmed that multiprobe arrays could cool brain tissue to 25°C without significantly raising skin temperature. Portable systems were successfully fabricated and tested in pigs, achieving safe target temperatures with minimal EEG and OCTA changes. Our findings suggest that cytostatic hypothermia can be scaled to larger animals and made implantable and portable, offering a promising non-destructive approach to halting GBM growth and prolonging survival, moving closer to becoming a viable treatment option for patients with GBM.

Electrocorticography and navigated transcranial magnetic stimulation-tailored supratotal resection for epileptogenic low-grade gliomas.

Epilepsy is commonly associated with low-grade gliomas (LGGs), impacting patients' well-being. While resection is the primary treatment, seizures can persist postoperatively in 27%-55% of cases. The authors aimed to evaluate an electrocorticography (ECoG) and navigated transcranial magnetic stimulation (nTMS)-tailored supratotal resection (ETT-SpTR) for LGG in controlling seizures, preserving neurological function, and enhancing treatment effectiveness. The authors retrospectively analyzed a prospectively enrolled cohort of patients with LGG presenting with epileptic seizures with ictal/interictal activity on electroencephalography (EEG) who underwent resective surgery. The authors performed preoperative nTMS to identify functional cortical areas. ECoG was used to guide the removal of the high-risk epilepsy cortical areas (HREAs). Patients were divided into two groups: group I, the control group, underwent gross-total resection alone, whereas group II patients underwent removal of HREAs identified by ECoG (ETT-SpTR). Resection avoided functionally eloquent areas as identified on nTMS, checked with cortical mapping. Postoperative seizure outcome was assessed using the Engel classification. Fifteen patients who underwent LGG resection between January and July 2023 were included. Among 24 identified nTMS-positive points, none were included in the resection. Overall, 73.3% of patients (11/15) showed positive intraoperative ECoG, with better outcomes in group II (85.7% Engel class IA) than in group I (25% Engel class IA) at the follow-up (p = 0.02, OR 0.5 [95% CI 0.035-7.10], RR 0.19 [95% CI 0.03-1.2]). Seizure control was significantly better in group II, with no notable differences in postoperative transient neurological deficits between the two groups (p = 0.45). No permanent neurological deficits were observed during follow-up. Statistical analysis revealed significant differences between the two groups (p < 0.05). This preliminary study affirms the predictive value of TMS for postoperative neurological status and safety in epileptic patients. Intraoperative ECoG effectively identified peritumoral HREAs. ETT-SpTR significantly improved epileptic outcomes, preserving functions without permanent neurological worsening. Additional resection targets the HREAs in the temporal, frontal, and parietal lobes.

Gliomagenesis, Epileptogenesis, and Remodeling of Neural Circuits: Relevance for Novel Treatment Strategies in Low- and High-Grade Gliomas.

Gliomas present a complex challenge in neuro-oncology, often accompanied by the debilitating complication of epilepsy. Understanding the biological interaction and common pathways between gliomagenesis and epileptogenesis is crucial for improving the current understanding of tumorigenesis and also for developing effective management strategies. Shared genetic and molecular mechanisms, such as IDH mutations and dysregulated glutamate signaling, contribute to both tumor progression and seizure development. Targeting these pathways, such as through direct inhibition of mutant IDH enzymes or modulation of glutamate receptors, holds promise for improving patient outcomes. Additionally, advancements in surgical techniques, like supratotal resection guided by connectomics, offer opportunities for maximally safe tumor resection and enhanced seizure control. Advanced imaging modalities further aid in identifying epileptogenic foci and tailoring treatment approaches based on the tumor's metabolic characteristics. This review aims to explore the complex interplay between gliomagenesis, epileptogenesis, and neural circuit remodeling, offering insights into shared molecular pathways and innovative treatment strategies to improve outcomes for patients with gliomas and associated epilepsy.

Multivariate mapping of low-resilient neurocognitive systems within and around low-grade gliomas.

Accumulating evidence suggests that the brain exhibits a remarkable capacity for functional compensation in response to neurological damage, a resilience potential that is deeply rooted in the malleable features of its underlying anatomofunctional architecture. This propensity is particularly exemplified by diffuse low-grade glioma, a subtype of primary brain tumour. However, functional plasticity is not boundless, and surgical resections directed at structures with limited neuroplasticity can lead to incapacitating impairments. Yet, maximizing diffuse low-grade glioma resections offers substantial oncological benefits, especially when the resection extends beyond the tumour margins (i.e. supra-tumour or supratotal resection). In this context, the primary objective of this study was to identify which cerebral structures were associated with less favourable cognitive outcomes after surgery, while accounting for intra-tumour and supra-tumour features of the surgical resections. To achieve this objective, we leveraged a unique cohort of 400 patients with diffuse low-grade glioma who underwent surgery with awake cognitive mapping. Patients benefitted from a neuropsychological assessment consisting of 18 subtests administered before and 3 months after surgery. We analysed changes in performance and applied topography-focused and disconnection-focused multivariate lesion-symptom mapping using support vector regressions, in an attempt to capture resected cortico-subcortical structures less amenable to full cognitive compensation. The observed changes in performance were of a limited magnitude, suggesting an overall recovery (13 of 18 tasks recovered fully despite a mean resection extent of 92.4%). Nevertheless, lesion-symptom mapping analyses revealed that a lack of recovery in picture naming was linked to damage in the left inferior temporal gyrus and inferior longitudinal fasciculus. Likewise, for semantic fluency abilities, an association was established with damage to the left precuneus/posterior cingulate. For phonological fluency abilities, the left dorsomedial frontal cortex and the frontal aslant tract were implicated. Moreover, difficulties in spatial exploration were associated with injury to the right dorsomedial prefrontal cortex and its underlying connectivity. An exploratory analysis suggested that supra-tumour resections were associated with a less pronounced recovery following specific resection patterns, such as supra-tumour resections of the left uncinate fasciculus (picture naming), the left corticostriatal tract and the anterior corpus callosum (phonological fluency), the hippocampus and parahippocampus (episodic memory) and the right frontal-mesial areas (visuospatial exploration). Collectively, these patterns of results shed new light on both low-resilient neural systems and the prediction of cognitive recovery following glioma surgery. Furthermore, they indicate that supra-tumour resections were only occasionally less well tolerated from a cognitive viewpoint. In doing so, they have deep implications for surgical planning and rehabilitation strategies.

"Non-Eloquent" brain regions predict neuropsychological outcome in tumor patients undergoing awake craniotomy.

Supratotal resection of primary brain tumors is being advocated especially when involving "non-eloquent" tissue. However, there is extensive neuropsychological data implicating functions critical to higher cognition in areas considered "non-eloquent" by most surgeons. The goal of the study was to determine pre-surgical brain regions that would be predictive of cognitive outcome at 4-6 months post-surgery. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer-v6.0 image analysis suite. Linear regression models were used to regress cortical volumes from both hemispheres, against the total cognitive z-score to determine the relationship between brain structure and broad cognitive functioning while controlling for age, sex, and total segmented brain volume. We identified 62 consecutive patients who underwent planned awake resections of primary (n = 55, 88%) and metastatic at the University of New Mexico Hospital between 2015 and 2019. Of those, 42 (23 males, 25 left hemispheric lesions) had complete pre and post-op neuropsychological data available and were included in this study. Overall, total neuropsychological functioning was somewhat worse (p = 0.09) at post-operative neuropsychological outcome (Mean = -.20) than at baseline (Mean = .00). Patients with radiation following resection (n = 32) performed marginally worse (p = .036). We found that several discrete brain volumes obtained pre-surgery predicted neuropsychological outcome post-resection. For the total sample, these volumes included: left fusiform, right lateral orbital frontal, right post central, and right paracentral regions. Regardless of lesion lateralization, volumes within the right frontal lobe, and specifically right orbitofrontal cortex, predicted neuropsychological difference scores. The current study highlights the gaps in our current understanding of brain eloquence. We hypothesize that the volume of tissue within the right lateral orbital frontal lobe represents important cognitive reserve capacity in patients undergoing tumor surgery. Our data also cautions the neurosurgeon when considering supratotal resections of tumors that do not extend into areas considered "non-eloquent" by current standards.

Clinical characteristics and surgical outcomes of low-grade epilepsy-associated brain tumors

Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis. Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs. Design: A retrospective study. Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators. Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma ( n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection ( p &lt; 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups ( p &lt; 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876–1.000), 0.892 (95% CI, 0.656–0.934), and 0.786 (95% CI, 0.491–0.937) at 1-, 2-, and 5-year follow-up, respectively. Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.

EXTH-04. CYTOSTATIC HYPOTHERMIA AGAINST GLIOBLASTOMA AND THE DEVELOPMENT OF A NEURAL IMPLANT FOR RODENTS AND SWINE

Abstract Survival rates for patients with glioblastoma (GBM) remain discouraging due to the near-impossibility of eradicating all tumor cells, resulting in frequent recurrence. However, studies have shown that recurrence is predominantly localized (80% of cases) and that survival outcomes are improved with supra-total resection. Consequently, non-destructive local therapies hold promise for preventing GBM recurrence. We have demonstrated that non-freezing, 'cytostatic' hypothermia is a unique and effective approach against GBM. Unlike ablative cryogenic hypothermia, which kills both neoplastic and healthy infiltrated tissue, this method safely and effectively inhibits GBM growth. Through extensive investigations, we have previously identified a cytostatic window of 20–25°C and examined its impact on multiple pathways. By implementing hypothermia, we successfully inhibited GBM growth, doubling median survival in two rodent models. Notably, all rats subjected to cytostatic hypothermia survived the study period. To further advance towards translation, we conducted computer simulations to demonstrate the feasibility of a scaled and implantable system. Subsequently, we designed and fabricated a multiprobe array capable of uniformly extracting heat from a small volume of brain tissue in swine. This heat would then be transferred to the dorsal flank through an innovative artificial internal circulation system (AICS). The system underwent iterative testing in vitro and validation in vivo using live, anesthetized swine. Unlike targeted therapeutics that often show promise in preclinical models but fail in clinical trials, cytostatic hypothermia capitalizes on fundamental physics that broadly influence biology. It has the potential to reduce brain tumor recurrence, limit tumor evolution, and simultaneously offer time to patients as other cytotoxic therapies are developed.

Supratotal Resection: An Emerging Concept of Glioblastoma Multiforme Surgery—Systematic Review And Meta-Analysis

The severe neurologic tumor known as glioblastoma (GBM), also referred to as a grade IV astrocytoma, is rapidly progressive and debilitating. Supratotal resection (SpTR) is an emerging concept within glioma surgery, which aims to achieve a more extensive resection of the tumor than is possible with conventional techniques. We performed a language-independent search of PubMed, Scopus, and Cochrane CENTRAL to identify all available literature up to August 2022 of patients undergoing SpTR assessing survival outcomes in comparison to other surgical modalities. After screening for exclusion, a total of 13 studies, all retrospective in design, were identified and included in our meta-analysis. SpTR was associated with significantly increased overall survival (hazard ratio 0.77, 95% CI 0.71-0.84; P < 0.01, I2= 96%) and progression-free survival (hazard ratio 0.2, 95% CI 0.07-0.56; P= 0.002, I2= 88%). SpTR is associated with greater overall survival and PFS when compared with other glioblastoma surgeries like GTR or SubTR.

Supratotal Surgical Resection for Low-Grade Glioma: A Systematic Review.

Low-grade gliomas (LGGs) are optimally treated with up-front maximal safe surgical resection, typically defined as maximizing the extent of tumor resection while minimizing neurologic risks of surgery. Supratotal resection of LGG may improve outcomes beyond gross total resection by removing tumor cells invading beyond the tumor border as defined on MRI. However, the evidence regarding supratotal resection of LGG, in terms of impact on clinical outcomes, such as overall survival and neurologic morbidities, remains unclear. Authors independently searched the PubMed, Medline, Ovid, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases for studies evaluating overall survival, time to progression, seizure outcomes, and postoperative neurologic and medical complications of supratotal resection/FLAIRectomy of WHO-defined LGGs. Papers in languages other than English, lacking full-text availability, evaluating supratotal resection of WHO-defined high-grade gliomas only, and nonhuman studies were excluded. After literature search, reference screening, and initial exclusions, 65 studies were screened for relevancy, of which 23 were evaluated via full-text review, and 10 were ultimately included in the final evidence review. Studies were evaluated for quality using the MINORS criteria. After data extraction, a total of 1301 LGG patients were included in the analysis, with 377 (29.0%) undergoing supratotal resection. The main measured outcomes were extent of resection, pre- and postoperative neurological deficits, seizure control, adjuvant treatment, neuropsychological outcomes, ability to return to work, progression-free survival, and overall survival. Overall, low- to moderate-quality evidence was supportive of aggressive, functional boundary-based resection of LGGs due to improvements in progression-free survival and seizure control. The published literature provides a moderate amount of low-quality evidence supporting supratotal surgical resection along functional boundaries for low-grade glioma. Among patients included in this analysis, the occurrence of postoperative neurological deficits was low, and nearly all patients recovered within 3 to 6 months after surgery. Notably, the surgical centers represented in this analysis have significant experience in glioma surgery in general, and supratotal resection specifically. In this setting, supratotal surgical resection along functional boundaries appears to be appropriate for both symptomatic and asymptomatic low-grade glioma patients. Larger clinical studies are needed to better define the role of supratotal resection in LGG.

A Preoperative Scoring System to Predict Function-Based Resection Limitation Due to Insufficient Participation During Awake Surgery.

Failure in achieving a function-based resection related to the insufficient patient's participation is a drawback of awake surgery. To assess preoperative parameters predicting the risk of patient insufficient intraoperative cooperation leading to the arrest of the awake resection. Observational, retrospective, multicentric cohort analysis enrolling 384 (experimental dataset) and 100 (external validation dataset) awake surgeries. In the experimental data set, an insufficient intraoperative cooperation occurred in 20/384 patients (5.2%), leading to awake surgery failure in 3/384 patients (ie, no resection, 0.8%), and precluded the achievement of the function-based resection in 17/384 patients (ie, resection limitation, 4.4%). The insufficient intraoperative cooperation significantly reduced the resection rates (55.0% vs 94.0%, P < .001) and precluded a supratotal resection (0% vs 11.3%, P = .017). Seventy years or older, uncontrolled epileptic seizures, previous oncological treatment, hyperperfusion on MRI, and mass effect on midline were independent predictors of insufficient cooperation during awake surgery ( P < .05). An Awake Surgery Insufficient Cooperation score was then assessed: 96.9% of patients (n = 343/354) with a score ≤2 presented a good intraoperative cooperation, while only 70.0% of patients (n = 21/30) with a score >2 presented a good intraoperative cooperation. In the experimental data set, similar date were found: 98.9% of patients (n = 98/99) with a score ≤2 presented a good cooperation, while 0% of patients (n = 0/1) with a score >2 presented a good cooperation. Function-based resection under awake conditions can be safely performed with a low rate of insufficient patient intraoperative cooperation. The risk can be assessed preoperatively by a careful patient selection.

Metabolic delineation of IDH1 wild-type glioblastoma surgical anatomy: how to plan the tumor extent of resection.

Magnetic resonance imaging (MRI) is the current standard for preoperative planning of glioblastoma (GBM) surgery. However, recent data on the use of 11C-methionine positron emission tomography (11[C]-MET PET) suggest its role in providing additional information beyond MRI. The purpose of this study is to establish if there is a correlation between anatomical and metabolic data. We retrieved all GBM cases treated from 2014 to January 2021. Preoperative MRI (Enhancing Nodule -EN-, FLAIR and Total Tumor Volume -TTV-), PET volumes and histological samples obtained from the different tumor regions were evaluated to analyze potential correlations between anatomical, metabolic and pathological data. 150 patients underwent surgery for GBM and 49 of these were also studied preoperatively with 11[C]-MET PET; PET volume was evaluated in 47 patients. In 33 patients (70.21%) preoperative 11[C]-MET PET volume > preoperative EN volume and in 11 (23.4%) preoperative 11[C]-MET PET volume > preoperative TTV. We found a significant correlation between preoperative TTVs and PET volumes (p = 0.016) as well as between preoperative EN volumes and PET volumes (p = < 0.001). Histologically, 109 samples were evaluated. ENs samples exhibited the conventional GBM morphology while samples from the FLAIR regions showed white matter tissue, with focal to diffuse tumor cells infiltration and areas of reactive astrogliosis. We submit that 11[C]-MET PET volume generally overcome EN. The presence of neoplastic cells confirm these metabolic data. It should be considered in the surgical planning to achieve a Supra Total Resection (SupTR).

874 Direct Visualization of Planned Resection Volumes with Microbubble-Enhanced MR-Guided Focused Ultrasound Blood-Brain Barrier Opening and Sodium Fluorescein in Infiltrating Gliomas

INTRODUCTION: Surgical resection of infiltrating gliomas (IG,Grade II-IV) can be challenging, as many do not consistently enhance on gadolinium-enhanced MRI. Evidence of survival benefit of supratotal resection is mounting. No method exists to preoperatively demarcate a planned surgical resection volume. Such physical demarcation could significantly improve the resection of IGs. METHODS: Four patients were treated (3M:1F), with a mean age of 32.5 (29-36). All were suspected of having or were previously diagnosed with a supratentorial IG. Patients underwent awake transcranial MB-FUS BBBO of the lesion bed and perilesional areas planned for resection at the discretion of the operating neurosurgeon (GFW). Subsequently, patients were transported directly to the operating room. For each patient, sodium fluorescein was administered, and then tumors were resected with standard craniotomies under general anesthesia, using neuronavigation and fluorescent microscopy. RESULTS: Patients tolerated the procedure well without adverse events with a median follow-up of 15.7 months. The mean tumor volume was 18.2 cm3 (6.8-32.9). The demarcated planned resection volume was visualized with fluorescent microscopy. Fluorescing tissue was completely resected. Gross-total or supratotal resection was achieved in all patients. Pathologies included diffuse astrocytoma, oligodendroglioma, and anaplastic oligodendroglioma. CONCLUSIONS: MB-FUS BBBO and sodium fluorescein present a safe and novel method of demarcating a preoperatively planned surgical resection volume with resultant intraoperative visualization in IGs. This method is resilient to brain shift, and is an addition to the current repertoire for visualizing non-contrast-enhancing gliomas. The same method can be investigated for use in epilepsy surgery.

H3 G34-mutant high-grade gliomas: integrated clinical, imaging and pathological characterisation of a single-centre case series.

Diffuse hemispheric glioma, H3 G34-mutant, is a novel paediatric tumour type in the fifth edition of the WHO classification of CNS tumours associated with an invariably poor outcome. We present a comprehensive clinical, imaging and pathological review of this entity. Patients with confirmed H3 G34R-mutant high-grade glioma were included in a single-centre retrospective cohort study and examined for clinical, radiological and histo-molecular data. Twelve patients were enrolled in the study - 7 males/5 females; the mean age was 17.5years (10-57years). Most patients presented with signs of raised intracranial pressure (8/12). The frontal lobe (60%) was the prevalent location, with a mixed cystic-nodular appearance (10/12) and presence of vascular flow voids coursing through/being encased by the mass (8/12), and all tumours showed cortical invasion. Nine patients had subtotal resection limited by functional margins, two patients underwent supra-total resection, and one patient had biopsy only. 5-ALA was administered to 6 patients, all of whom showed positive fluorescence. Histologically, the tumours showed a marked heterogeneity and aggressive spread along pre-existing brain structures and leptomeninges. In addition to the diagnostic H3 G34R/V mutation, pathogenic variants in TP53 and ATRX genes were found in most cases. Potential targetable mutations in PDGFRA and PIK3CA genes were detected in five cases. The MGMT promoter was highly methylated in half of the samples. Methylation profiling was a useful diagnostic tool and highlighted recurrent structural chromosome abnormalities, such as PDGFRA amplification, CDKN2A/B deletion, PTEN loss and various copy number changes in the cyclin D-CDK4/Rb pathway. Radiochemotherapy was the most common adjuvant treatment (9/12), and the average survival was 19.3months. H3 G34R-mutant hemispheric glioma is a distinct entity with characteristic imaging and pathological features. Genomic landscaping of individual tumours can offer an opportunity to adapt individual therapies and improve patient management.

Evaluation of the Efficiency of Neuronavigation in Patients with Glioblastoma

Objective: To investigate the effect of neuronavigation use on mortality in patients with glioblastoma. Methods: For each of the 26 patients that underwent neuronavigation-assisted supratotal resection for glioblastoma between 2018 and 2020, one patient that underwent supratotal resection without navigation was selected. Results: Radiographic radicality was observed in 35% of the cases in the neuronavigation-assisted surgery group and 29% of those in the conventional surgery group. Absolute and relative residual tumor volumes were significantly lower in the neuronavigation-assisted surgery group. Radical tumor resection was associated with a very significant increase in survival. There was no significant difference in the survival rates between the patients that underwent surgery with and without neuronavigation. This was attributed to the small number of participants and supratotal resection being performed in all statistically determined patients The low median survival period of glioblastoma may have also contributed to this finding. Conclusions: Surgery plays an important role in the treatment of glioblastoma. A combination of techniques including intraoperative magnetic resonance imaging, neuronavigation, ultrasound, and fluorescence guidance allows for safe and maximum surgical resection, leading to better outcomes in terms of survival and postoperative functional recovery. However, despite maximal surgical resection and adjuvant chemotherapy-radiotherapy, most cases develop tumor recurrence within 10 months, which is considered to be due to established cancer stem cells. Therefore, there is an urgent need to develop more effective treatment strategies for glioblastoma.

Supratotal Resection of Glioblastoma: Better Survival Outcome than Gross Total Resection

Supratotal resection (SupTR) of glioblastoma allows for a superior long-term disease control and increases overall survival. On the other hand, aggressive conventional approaches, including gross total resections (GTR), are limited by the impairment risk of adjacent eloquent areas, which may cause severe postoperative functional morbidity. This study aimed to analyze institutional cases with respect to the potential survival benefits of additional resection, including lobectomy, as a paradigm for SupTR in patients of glioblastoma. Between 2014 and 2018, 15 patients with glioblastoma underwent SupTR (GTR and additional lobectomy) at the authors' institution. The postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS) were analyzed for the patients. Patients with SupTR showed significantly prolonged PFS and OS. The median PFS and OS values for the entire study group were 33.5 months (95% confidence intervals (CI): 18.5-57.3 months) and 49.1 months (95% CI: 24.7-86.6 months), respectively. Multivariate analysis revealed that the O6-DNA-methylguanine methyltransferase (MGMT) promoter methylation status was the only predictor for both superior PFS (p = 0.03, OR 5.7, 95% CI 1.0-49.8) and OS (p = 0.04, OR 6.5, 95% CI 1.1-40.2). There was no significant difference between the pre- and postoperative KPS scores. Our results suggest that SupTR with lobectomy allows for a superior PFS and OS without negatively affecting patient performance. However, due to the small number of patients, further studies that include more patients are needed.

The clinical and neurocognitive functional changes with awake brain mapping for gliomas invading eloquent areas: Institutional experience and the utility of The Montreal Cognitive Assessment.

Awake craniotomy with intraoperative brain functional mapping effectively reduces the potential risk of neurological deficits in patients with glioma invading the eloquent areas. However, glioma patients frequently present with impaired neurocognitive function. The present study aimed to investigate the neurocognitive and functional outcomes of glioma patients after awake brain mapping and assess the experience of a tertiary neurosurgical center in China over eight years. This retrospective study included 80 patients who underwent awake brain mapping for gliomas invading the eloquent cortex between January 2013 and December 2021. Clinical and surgical factors, such as the extent of resection (EOR), perioperative Karnofsky Performance Score (KPS), progression-free survival (PFS), and overall survival (OS), were evaluated. We also used the Montreal Cognitive Assessment (MoCA) to assess the neurocognitive status changes. The most frequently observed location of glioma was the frontal lobe (33/80, 41.25%), whereas the tumor primarily invaded the language-related cortex (36/80, 45%). Most patients had supratotal resection (11/80, 13.75%) and total resection (45/80, 56.25%). The median PFS was 43.2 months, and the median OS was 48.9 months in our cohort. The transient (less than seven days) neurological deficit rate was 17.5%, whereas the rate of persistent deficit (lasting for three months) was 15%. At three months of follow-up, most patients (72/80, 90%) had KPS scores > 80. Meanwhile, compared to the preoperative baseline tests, the changes in MoCA scores presented significant improvements at discharge and three months follow-up tests. Awake brain mapping is a feasible and safe method for treating glioma invading the eloquent cortex, with the benefit of minimizing neurological deficits, increasing EOR, and extending survival time. The results of MoCA test indicated that brain mapping plays a critical role in preserving neurocognitive function during tumor resection.

SURG-25. PATTERNS OF RECURRENCES ACCORDING TO THE EXTENT OF RESECTION IN PARIETNS WITH GLIOBLASTOMA, IDH-WILDTYPE: A RETROSPECTIVE STUDY

Abstract OBJECTIVE In glioblastoma (GBM) patients, controlling the microenvironment around the tumor using various treatment modalities, including surgical intervention, is essential in determining the outcome of treatment. This study was conducted to elucidate whether recurrence patterns differ according to the extent of resection (EOR) and whether this difference affects prognosis. METHODS This single-center study included 358 eligible patients with histologically confirmed isocitrate dehydrogenase (IDH)-wild-type GBM from November 1, 2005, to December 31, 2018. Patients were assigned to one of three separate groups according to EOR: supratotal resection (SupTR), gross-total resection (GTR), and subtotal resection (STR) groups. The patterns of recurrence were classified as local, marginal, and distant based on the range of radiation. The relationship between EOR and recurrence pattern was statistically analyzed. RESULTS Observed tumor recurrence rates for each group were as follows: SupTR group, 63.4%; GTR group, 75.3%; and STR group, 80.5% (p = 0.072). Statistically significant differences in patterns of recurrences among groups were observed with respect to local recurrence (SupTR, 57.7%; GTR, 76.0%; STR, 82.8%; p = 0.036) and distant recurrence (SupTR, 50.0%; GTR, 30.1%; STR, 23.2%; p = 0.028). Marginal recurrence showed no statistical difference between groups. Both overall survival and progression-free survival were significantly increased in the SupTR group compared with the STR and GTR groups (p &amp;lt; 0.0001). CONCLUSIONS In this study, the authors investigated the association between EOR and patterns of recurrence in patients with IDH-wild-type GBM. The findings not only show that recurrence patterns differ according to EOR but also provide clinical evidence supporting the hypothesized mechanism by which distant recurrence occurs.