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.

Protocol digest of a phase III randomized trial of gross total resection versus possible resection of fluid-attenuated inversion recovery-hyperintense lesion on MRI for newly diagnosed supratentorial glioblastoma: JCOG2209 (FLAMINGO).

The goal of surgery for patients with newly diagnosed glioblastoma (GBM) is maximum safe resection of the contrast-enhancing (CE) lesion on magnetic resonance imaging. However, there is no consensus on the efficacy of FLAIRectomy, which is defined as the possible resection of fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions surrounding the CE lesion. Although retrospective analyses suggested the potential benefits of FLAIRectomy, such outcomes have not been confirmed by prospective studies. Therefore, we planned a multicenter, open-label, randomized controlled phase III trial to evaluate the efficacy of FLAIRectomy compared with gross total resection of CE lesions in patients with newly diagnosed GBM. The primary endpoint is overall survival. In total, 130 patients will be enrolled from 47 institutions over 5 years. This trial has been registered at the Japan Registry of Clinical Trials (study number jRCT1031230245).

A consensus definition of supratotal resection for anatomically distinct primary glioblastoma: an AANS/CNS Section on Tumors survey of neurosurgical oncologists.

INTRODUCTION: Supratotal resection (SpTR) of glioblastoma may be associated with improved survival, but published results have varied in part from lack of consensus on the definition and appropriate use of SpTR. A previous small survey of neurosurgical oncologists with expertise performing SpTR found resection 1-2 cm beyond contrast enhancement was an acceptable definition and glioblastoma involving the right frontal and bilateral anterior temporal lobes were considered most amenable to SpTR. The general neurosurgical oncology community has not yet confirmed the practicality of this definition. METHODS: Seventy-six neurosurgical oncology members of the AANS/CNS Tumor Section were surveyed, representing 34.0% of the 223 members who were administered the survey. Participants were presented with 11 definitions of SpTR and rated each definition's appropriateness. Participants additionally reviewed magnetic resonance imaging for 10 anatomically distinct glioblastomas and assessed the tumor location's eloquence, perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans. RESULTS: Most neurosurgeons surveyed agree that gross total plus resection of some non-contrast enhancement (n = 57, 80.3%) or resection 1-2 cm beyond contrast enhancement (n = 52, 73.2%) are appropriate definitions for SpTR. Cases were divided into three anatomically distinct groups by perceived equipoise between gross total and SpTR. The best clinical trial candidates were thought to be right anterior temporal (n = 58, 76.3%) and right frontal (n = 55, 73.3%) glioblastomas. CONCLUSION: Support exists among neurosurgical oncologists with varying familiarity performing SpTR to adopt the proposed consensus definition of SpTR of glioblastoma and to potentially investigate the utility of SpTR to treat right anterior temporal and right frontal glioblastomas in a clinical trial. A smaller proportion of general neurosurgical oncologists than SpTR experts would personally treat a left anterior temporal glioblastoma with SpTR.

Anatomical distribution of cancer stem cells between enhancing nodule and FLAIR hyperintensity in supratentorial glioblastoma: time to recalibrate the surgical target?

It is ge nerally accepted that glioblastoma (GBM) arise from cancer stem cells (CSC); however, there is little evidence on their anatomical distribution. We investigated the expression and distribution of SOX-2-positive and CD133-positive CSCs both in the enhancing nodule (EN) of GBM and in the FLAIR hyperintensity zones on a surgical, histopathological series of 33 GBMs. The inclusion criterion was the intraoperative sampling of different tumor regions individualized, thanks to neuronavigation and positivity to intraoperative fluorescence with the use of 5-aminolevulinic acid (5-ALA). Thirty-three patients (20 males and 13 females with a mean age at diagnosis of 56 years) met the inclusion criterion. A total of 109 histological samples were evaluated, 52 for ENs and 57 for FLAIR hyperintensity zone. Considering the quantitative distribution of levels of intensity of staining (IS), ES (extent score), and immunoreactivity score (IRS), no difference was found between ENs and FLAIR regions for both the SOX-2 biomarker (respectively, IS p = 0.851, ES p = 0.561, IRS p = 1.000) and the CD133 biomarker (IS p = 0.653, ES p = 0.409, IRS p = 0.881). This evidence suggests to recalibrate the target of surgery for FLAIRECTOMY and 5-ALA could improve the possibility to achieve this goal.

Neuropsychological outcomes following supratotal resection for high-grade glioma: a review.

PURPOSE: Supratotal resection (SpTR) of high-grade glioma (HGG), in which surgical removal of the tumor is extended outside the margins of the preoperative radiographic abnormality, has been suggested to improve overall survival (OS) and progression free survival (PFS) in patients harboring tumors of non-eloquent cortex when compared to gross total resection (GTR). While current literature demonstrates these findings without an increase in post-operative complications or neurological deficits, there remains a paucity of data examining the neuropsychological outcomes of SpTR for HGG. As quality of life dramatically influences survival rates in these patients, it is crucial for neurosurgeons, neuro-oncologists, and neuropsychiatrists to understand the behavioral and cognitive outcomes following SpTR, such that optimal treatment strategies can be tailored for each patient. METHODS: We performed a comprehensive review of the available literature regarding survival, neuropsychological, and quality of life (QOL) outcomes following SpTR for HGG. We also review neuropsychological and QOL outcomes following GTR for HGG to serve as a framework for better understanding potential implications of SpTR. RESULTS: While results are limited following SpTR for HGG, available data suggests similar outcomes to those seen in patients undergoing GTR of HGG, as well as low-grade glioma. These include a short-term decline in neuropsychological functioning post-surgically with a return to baseline across most neurocognitive domains occurring within several months. Memory and attention remain relatively diminished at long term follow-up. CONCLUSIONS: Limited data exist examining postoperative cognitive and behavioral outcomes following SpTR for HGG. While the available data suggests a return to baseline for many neurocognitive domains, attention and memory deficits may persist. However, sample sizes are relatively small and have not been examined in the context of QOL and OS/PFS. More rigorous pre- and post-surgical neuropsychological assessment will help shed light on the long-term cognitive and behavioral effects of SpTR in the setting of HGG and inform clinical care and counseling when SpTR is considered.

Impact of the extent of resection on the survival of patients with grade II and III gliomas using awake brain mapping.

PURPOSE: The aim of this study was to assess the effect of the extent of resection (EOR) of tumors on survival in a series of patients with grade II and III gliomas (GII/III-gliomas) who underwent awake brain mapping. METHODS: We retrospectively analyzed 126 patients with GII/III-gliomas in the dominant and non-dominant hemisphere who underwent awake brain surgery at the same institution between December 2012 and May 2020. RESULTS: EOR cut-off values for improved progression-free survival (PFS) were determined by a receiver operator characteristic (ROC) analysis of 5-year PFS. The ROC for EOR showed a cut-off value of ≥ 85.3%. The median PFS rate of patients with GII/III-gliomas in the group with an EOR ≥ 100%, including supratotal resection (n = 47; median survival [MS], not reached), was significantly higher than that in the group with an EOR < 90% (n = 52; MS, 43.1 months; 95% CI 37.7-48.5 months; p = 0.03). In patients with diffuse astrocytomas and anaplastic astrocytomas, the group with EOR ≥ 100%, including supratotal resection (n = 25; MS, not reached), demonstrated a significantly better PFS rate than did the group with an EOR < 100% (n = 45; MS, 35.8 months; 95% CI 19.9-51.6 months; p = 0.03). Supratotal or gross total resection was correlated with better PFS in IDH-mutant type of diffuse astrocytomas and anaplastic astrocytomas (n = 19; MS, not reached vs. n = 35; MS, 40.6 months; 95% CI 22.3-59.0 months; p = 0.02). By contrast, supratotal or gross total resection was not associated with longer PFS rates in patients with IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas. CONCLUSIONS: The present study demonstrates a significant association between tumor EOR and survival in patients with GII/III gliomas. The EOR cut-off value for 5-year PFS was ≥ 85.3%. It is noteworthy that supratotal or gross total resection significantly correlated with better PFS in IDH-mutant type of WHO grade II and III astrocytic tumors. In light of our finding that EOR did not correlate with PFS in patients with aggressive IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas, we suggest treatments that are more intensive will be needed for the control of these tumors.

Distinct topographic-anatomical patterns in primary and secondary brain tumors and their therapeutic potential.

PURPOSE: Understanding the topographic-anatomical patterns of brain tumors has the potential to improve our pathophysiological understanding and may allow for anatomical tailoring of surgery and radiotherapy. This study analyzed topographic-anatomical patterns underlying neuroepithelial tumors, primary CNS lymphoma and metastases. METHODS: Any histologically confirmed supra- or infratentorial parenchymal neoplasia of one institution over a 4-year period was included. Using high-resolution magnetic resonance imaging data, a detailed analysis of the topographic-anatomical tumor features was performed. Differences between neuroepithelial tumors, primary central nervous system lymphoma (PCNSL) and metastases were assessed using pairwise comparisons adjusted for multiple testing, upon significance of the omnibus test. RESULTS: Based on image analysis of 648 patients-419 (65%) neuroepithelial tumors, 28 (5%) PCNSL and 201 (31%) metastases-entity-specific topographic-anatomical patterns were identified. Neuroepithelial tumors showed a radial ventriculo-cortical orientation, inconsistent with the current belief of a growth along white matter tracts, whereas the pattern in PCNSL corresponded to a growth along such. Metastases preferentially affected the cortex and subcortical white matter of large arteries' terminal supply areas. This study provides a comprehensive anatomical description of the topography of NT, PCNSL and metastases intended to serve as a topographic reference for clinicians and neuroscientists. CONCLUSIONS: The identified distinct anatomical patterns provide evidence for a specific interaction between tumor and anatomical structures, following a pathoclitic concept. Understanding differences in their anatomical behavior has the potential to improve our pathophysiological understanding and to tailor therapy of brain tumors.

A systematic review and meta-analysis of supratotal versus gross total resection for glioblastoma.

PURPOSE: Due to the infiltrative nature of glioblastoma (GBM) outside of the contrast-enhancing region on MRI, there is interest in exploring supratotal resections (SpTR) that extend beyond the contrast-enhancing portion of the tumor. However, there is currently no consensus on the potential survival benefit of SpTR in GBM compared to gross total resection (GTR). In this study, we compare the impact of SpTR versus GTR on overall survival (OS) of GBM patients. METHODS: We performed a systematic review and meta-analysis of literature published on PubMed, Embase, The Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov, from inception to August 16, 2018, to identify articles comparing OS after SpTR versus GTR. RESULTS: We identified 8902 unique citations, of which 11 articles met study inclusion criteria. 810 patients underwent SpTR out of a total of 2056 patients. 9 of 11 studies demonstrated improved outcomes with SpTR compared to GTR (median improvement in OS of 10.5 months), with no significant difference in postoperative complication rate. Overall study quality was variable, with ten studies presenting level IV evidence and one study presenting level IIIb evidence. Subgroup meta-analysis based on SpTR definition demonstrated a statistically significant 35% lower risk of mortality in patients who underwent anatomical SpTR compared to patients who underwent GTR (Hazard ratio = 0.65, 95% CI 0.47- 0.91, p = 0.003). CONCLUSION: Our systematic review indicates SpTR may be associated with improved OS compared to GTR for GBM, especially with anatomical SpTR. However, this is limited by variable study design and significant clinical and methodological heterogeneity among studies. There is need for prospective clinical data to further guide parameters regarding the use of SpTR in GBM.

Incorporating genomic signatures into surgical and medical decision-making for elderly glioblastoma patients.

Glioblastoma (GBM) is the most common type of malignant primary brain tumor in adults. It is a uniformly fatal disease (median overall survival 16 months) even with aggressive resection and an adjuvant temozolomide-based chemoradiation regimen. Age remains an independent risk factor for a poor prognosis. Several factors contribute to the dismal outcomes in the elderly population with GBM, including poor baseline health status, differences in underlying genomic alterations, and variability in the surgical and medical management of this subpopulation. The latter arises from a lack of adequate representation of elderly patients in clinical trials, resulting in limited data on the response of this subpopulation to standard treatment. Results from retrospective and some prospective studies have indicated that resection of only contrast-enhancing lesions and administration of hypofractionated radiotherapy in combination with temozolomide are effective strategies for optimizing survival while maintaining baseline quality of life in elderly GBM patients; however, survival remains dismal relative to that in a younger cohort. Here, the authors present historical context for the current strategies used for the multimodal management (surgical and medical) of elderly patients with GBM. Furthermore, they provide insights into elderly GBM patient-specific genomic signatures such as isocitrate dehydrogenase 1/2 (IDH1/2) wildtype status, telomerase reverse transcriptase promoter (TERTp) mutations, and somatic copy number alterations including CDK4/MDM2 coamplification, which are becoming better understood and could be utilized in a clinical trial design and patient stratification to guide the development of more effective adjuvant therapies specifically for elderly GBM patients.

Extending the resection beyond the contrast-enhancement for glioblastoma: feasibility, efficacy, and outcomes.

OBJECT: It is becoming well-established that increasing extent of resection with decreasing residual volume is associated with delayed recurrence and prolonged survival for patients with glioblastoma (GBM). These prior studies are based on evaluating the contrast-enhancing (CE) tumour and not the surrounding fluid attenuated inversion recovery (FLAIR) volume. It therefore remains unclear if the resection beyond the CE portion of the tumour if it translates into improved outcomes for patients with GBM. METHODS: Adult patients who underwent resection of a primary glioblastoma at a tertiary care institution between January 1, 2007 and December 31, 2012 and underwent radiation and temozolomide chemotherapy were retrospectively reviewed. Pre and postoperative MRI images were measured for CE tumour and FLAIR volumes. Multivariate proportional hazards were used to assess associations with both time to recurrence and death. Values with p < 0.05 were considered statistically significant. RESULTS: 245 patients met the inclusion criteria. The median [IQR] preoperative CE and FLAIR tumour volumes were 31.9 [13.9-56.1] cm3 and 78.3 [44.7-115.6] cm3, respectively. Following surgery, the median [IQR] postoperative CE and FLAIR tumour volumes were 1.9 [0-7.1] cm3 and 59.7 [29.7-94.2] cm3, respectively. In multivariate analyses, the postoperative FLAIR volume was not associated with recurrence and/or survival (p > 0.05). However, the postoperative CE tumour volume was significantly associated with both recurrence [HR (95%CI); 1.026 (1.005-1.048), p = 0.01] and survival [HR (95%CI); 1.027 (1.007-1.032), p = 0.001]. The postoperative FLAIR volume was also not associated with recurrence and/or survival among patients who underwent gross total resection of the CE portion of the tumour as well as those who underwent supratotal resection. CONCLUSIONS: In this study, the volume of CE tumour remaining after resection is more important than FLAIR volume in regards to recurrence and survival for patients with GBM.

Long-term outcomes after supratotal resection of diffuse low-grade gliomas: a consecutive series with 11-year follow-up.

BACKGROUND: Total or subtotal surgical resection of WHO grade II glioma (diffuse low-grade glioma, DLGG) can significantly increase survival. Moreover, a supratotal resection, i.e., an extended resection with a margin beyond MR imaging abnormalities, could decrease the risk of malignant transformation. Here, the goal is to analyze the long-term functional and oncological outcomes following supratotal resection for DLGG. METHODS: Sixteen consecutive patients who underwent supratotal resection for a DLGG with a minimum follow-up of 8 years after surgery were included. The resection was continued up to functional cortical and subcortical structures defined by intrasurgical electrical mapping. The extent of resection was evaluated on postoperative FLAIR-weighted MR imaging. Data regarding clinicoradiological features, therapeutic management, and outcomes were analyzed. RESULTS: Seven men and nine women (mean age, 41.3 years, range, 26-63 years) were included (seizure in 15 cases, one incidental discovery). All patients resumed a normal life after surgery (no neurological deficits, no epilepsy). The volume of postoperative cavity was larger than the preoperative tumor volume in the 16 patients. Neuropathological examination confirmed the diagnosis of WHO grade II glioma in all cases. No adjuvant treatment was administrated after resection. The mean duration of postoperative follow-up was 132 months (range, 97-198 months). There was no relapse in eight cases. Eight patients experienced tumor recurrence, with an average time to relapse of 70.3 months (range, 32-105 months), but without malignant transformation. Five of them have been re-treated, with a reoperation (two cases), chemotherapy (three cases) and radiotherapy (two cases). All patients continue to enjoy a normal life. CONCLUSIONS: This is the first series demonstrating the prolonged impact of supratotal resection on malignant transformation of DLGG. These original data may suggest to remove a margin around the FLAIR-weighted MR imaging abnormalities in a more systematic manner for DLGG not involving eloquent structures.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: SpTR is associated with greater overall survival and PFS when compared with other glioblastoma surgeries like GTR or SubTR.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 surgical management of diffuse gliomas: Current state of neurosurgical management and future directions.

After recent updates to the World Health Organization pathological criteria for diagnosing and grading diffuse gliomas, all major North American and European neuro-oncology societies recommend a maximal safe resection as the initial management of a diffuse glioma. For neurosurgeons to achieve this goal, the surgical plan for both low- and high-grade gliomas should be to perform a supramaximal resection when feasible based on preoperative imaging and the patient's performance status, utilizing every intraoperative adjunct to minimize postoperative neurological deficits. While the surgical approach and technique can vary, every effort must be taken to identify and preserve functional cortical and subcortical regions. In this summary statement on the current state of the field, we describe the tools and technologies that facilitate the safe removal of diffuse gliomas and highlight intraoperative and postoperative management strategies to minimize complications for these patients. Moreover, we discuss how surgical resections can go beyond cytoreduction by facilitating biological discoveries and improving the local delivery of adjuvant chemo- and radiotherapies.

IDH-wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model.

OBJECTIVE: Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH-wild-type glioblastoma (GBM) to further improve patients' overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D). The aim of this study was to investigate OS of patients with IDH-wild-type GBM who underwent SMR based on a mathematical model of cell distribution and infiltration profile (tumor invasiveness profile). METHODS: Volumetric measurements were obtained from the selected regions of interest from pre- and postoperative MRI studies of included patients. The tumor invasiveness profile (proliferation/diffusion [ρ/D] ratio) was calculated using the following formula: ρ/D ratio = (4π/3)2/3 × (6.106/[VT21/1 - VT11/1])2, where VT2 and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were split into subgroups based on their tumor invasiveness profiles. In this analysis, tumors were classified as nodular, moderately diffuse, or highly diffuse. RESULTS: A total of 101 patients were included. Tumors were classified as nodular (n = 34), moderately diffuse (n = 34), and highly diffuse (n = 33). On multivariate analysis, increasing SMR had a significant positive correlation with OS for moderately and highly diffuse tumors (HR 0.99, 95% CI 0.98-0.99; p = 0.02; and HR 0.98, 95% CI 0.96-0.99; p = 0.04, respectively). On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10% to 59%, and 30% to 90%, for nodular, moderately diffuse, and highly diffuse, respectively. CONCLUSIONS: The impact of SMR on OS for patients with IDH-wild-type GBM is influenced by the degree of tumor invasiveness. The authors' results show that increasing SMR is associated with increased OS in patients with moderate and highly diffuse IDH-wild-type GBMs. When grouping SMR into 10% intervals, this benefit was seen for all tumor subgroups, although for nodular tumors, the maximum beneficial SMR percentage was considerably lower than in moderate and highly diffuse tumors.

Supratotal Resection of Gliomas With Awake Brain Mapping: Maximal Tumor Resection Preserving Motor, Language, and Neurocognitive Functions.

Gliomas are a category of infiltrating glial neoplasms that are often located within or near the eloquent areas involved in motor, language, and neurocognitive functions. Surgical resection being the first-line treatment for gliomas, plays a crucial role in patient outcome. The role of the extent of resection (EOR) was evaluated, and we reported significant correlations between a higher EOR and better clinical prognosis of gliomas. However, recurrence is inevitable, even after aggressive tumor removal. Thus, efforts have been made to achieve extended tumor resection beyond contrast-enhanced mass lesions in magnetic resonance imaging (MRI)-defined areas, a process known as supratotal resection. Since it has been reported that tumor cells invade beyond regions visible as abnormal areas on MRI, imaging underestimates the true spatial extent of tumors. Furthermore, tumor cells have the potential to spread 10-20 mm away from the MRI-verified tumor boundary. The primary goal of supratotal resection is to maximize EOR and prolong the progression-free and overall survival of patients with gliomas. The available data, as well as our own work, clearly show that supratotal resection of gliomas is a feasible technique that has improved with the aid of awake functional mapping using intraoperative direct electrical stimulation. Awake brain mapping has enabled neurosurgeons achieve supratotal resection with favorable motor, language, and neurocognitive outcomes, ensuring a better quality of life in patients with gliomas.

A Crowdsourced Consensus on Supratotal Resection Versus Gross Total Resection for Anatomically Distinct Primary Glioblastoma.

BACKGROUND: Gross total resection (GTR) of contrast-enhancing tumor is associated with increased survival in primary glioblastoma. Recently, there has been increasing interest in performing supratotal resections (SpTRs) for glioblastoma. OBJECTIVE: To address the published results, which have varied in part due to lack of consensus on the definition and appropriate use of SpTR. METHODS: A crowdsourcing approach was used to survey 21 neurosurgical oncologists representing 14 health systems nationwide. Participants were presented with 11 definitions of SpTR and asked to rate the appropriateness of each definition. Participants reviewed T1-weighed postcontrast and fluid-attenuated inversion-recovery magnetic resonance imaging for 22 anatomically distinct glioblastomas. Participants were asked to assess the tumor location's eloquence, the perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans. RESULTS: Most neurosurgeons surveyed (n = 18, 85.7%) agree that GTR plus resection of some noncontrast enhancement is an appropriate definition for SpTR. Overall, moderate inter-rater agreement existed regarding eloquence, equipoise, and personal treatment plans. The 4 neurosurgeons who had performed >10 SpTRs for glioblastomas in the past year were more likely to recommend it as their treatment plan (P < .005). Cases were divided into 3 anatomically distinct groups based upon perceived eloquence. Anterior temporal and right frontal glioblastomas were considered the best randomization candidates. CONCLUSION: We established a consensus definition for SpTR of glioblastoma and identified anatomically distinct locations deemed most amenable to SpTR. These results may be used to plan prospective trials investigating the potential clinical utility of SpTR for glioblastoma.

Survival Benefit of Supratotal Resection in a Long-term Survivor of IDH-wildtype Glioblastoma: A Case Report and Literature Review.

Glioblastoma multiforme (GBM) is an aggressive cancer type, with fewer than 3-5% of patients surviving for more than 3 years. We describe a 48-year-old right-handed man who presented with generalized seizure attacks. Magnetic resonance imaging (MRI) revealed a heterogeneous gadolinium-enhancing lesion in the left inferior parietal lobule. The patient underwent awake surgery, and tumor resection included abnormalities on T2-weighted MRI, with subcortical mapping used to identify the deep functional boundaries. After supratotal resection, the tumor was diagnosed as GBM without isocitrate dehydrogenase (IDH) 1 and 2 mutations. At a follow-up evaluation, 9 years and 2 months after the surgery, the patient appeared healthy, and no relapse or recurrence was observed. We present the case of a long-term survivor of IDH-wildtype GBM. This case suggests that supratotal resection with intraoperative awake brain mapping can improve survival without impairing the patient's neurological functions.

Role of Resection in Glioblastoma Management.

Whenever possible, maximal safe resection is the first intervention for management of glioblastoma. Resection offers tissue for diagnosis, decompression of the brain, cytoreduction, and has been associated with prolonged survival in numerous retrospective studies. In this review, we provide a critical overview of the literature associating glioblastoma resection with survival. We discuss techniques that enhance extent of resection, and the role of clinical and surgeon-variables. At last, we analyze the covariates and confounders that might influence the relationship between extent of resection and survival for glioblastoma, as these might ultimately also influence outcomes and other therapeutic interventions tested in trials.

Patterns of recurrence according to the extent of resection in patients with IDH-wild-type glioblastoma: a retrospective study.

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 < 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.