Frontiers in Neurooncology and Neurosurgery

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuro-oncology".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 31691

Special Issue Editors

Department of Neurological Surgery, Policlinico "G. Rodolico-S. Marco" University Hospital, Catania, Italy
Interests: neurosurgery; neurooncology; neuroanatomy; skull-base surgery
N.E.S.M.O.S. Department, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Roma, Italy
Interests: neurosurgery; minimally invasive neurosurgery; cerebrovascular pathology; brain-tumor pathologies; vertebral trauma; degenerative pathology of the spine; neurovascular conflicts; excellence in neurosurgery; neurovascular surgery; miss technique for the spine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,  

Discovering a cure for high-grade gliomas (HGGs) remains one of the greatest unsolved problems in modern medicine. The crucial battles of every war are disputed in the periphery and, nowadays, the peritumoral zones (PTZ) of the HGGs, and this has received special scientific interest. Using T1w MRI, HGG was generally identified, from a radiological point of view, as an enhancing nodule (EN); however, in recent years, the FLAIR hyperintensity beyond the EN has attracted the attention of clinicians and scientists. It has been demonstrated that the cellular composition and molecular signatures of the HGG core, compared with infiltrative margins, are different. In this Special Issue, we aim to clarify the biological, pathological and therapeutical role of the peritumoral areas of HGGs that deepen the role of cross-talk between tumoral cells and the tumoral microenvironment (with particular focus on the cross-talk with the microglia) in the regulation of tumor growth, progression and invasion. Moreover, we aim to further investigate the diagnostic possibilities of studying the PTZ (advanced MRI, PET, etc.) and the new therapeutic approach on the PTZ (FLAIRectomy, supratotal resection guided by awake brain mapping, intraoperative MRI, intraoperative CT scan, and intraoperative fluorescence). For this Special Issue, we have encouraged the submission of original papers, reviews of the literature, and metanalyses.

Dr. Roberto Altieri
Prof. Dr. Antonino Raco
Guest Editors

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Keywords

  • high-grade gliomas
  • glioblastoma
  • FLAIRectomy
  • microglia
  • peritumoral zone
  • supratotal resection
  • PET, awake surgery, 5-ALA

Published Papers (16 papers)

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Editorial

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3 pages, 187 KiB  
Editorial
Editorial: Frontiers in Neuro Oncology and Neurosurgery
by Roberto Altieri
Brain Sci. 2023, 13(4), 565; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci13040565 - 28 Mar 2023
Viewed by 878
Abstract
Despite advances in our knowledge and treatments, Central Nervous System (CNS) Tumors remain the most difficult clinical challenge for the worldwide medical community [...] Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)

Research

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12 pages, 622 KiB  
Article
Hemispheric Asymmetry of the Hand Motor Representations in Patients with Highly Malignant Brain Tumors: Implications for Surgery and Clinical Practice
by Elisa Cargnelutti, Giada Pauletto, Tamara Ius, Lorenzo Verriello, Marta Maieron, Miran Skrap and Barbara Tomasino
Brain Sci. 2022, 12(10), 1274; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12101274 - 21 Sep 2022
Cited by 1 | Viewed by 1270
Abstract
We addressed both brain pre-surgical functional and neurophysiological aspects of the hand representation in 18 right-handed patients harboring a highly malignant brain tumor in the sensorimotor (SM) cortex (10 in the left hemisphere, LH, and 8 in the right hemisphere, RH) and 10 [...] Read more.
We addressed both brain pre-surgical functional and neurophysiological aspects of the hand representation in 18 right-handed patients harboring a highly malignant brain tumor in the sensorimotor (SM) cortex (10 in the left hemisphere, LH, and 8 in the right hemisphere, RH) and 10 healthy controls, who performed an fMRI hand-clenching task with both hands alternatively. We extracted the main ROI in the SM cortex and compared ROI values and volumes between hemispheres and groups, in addition to their motor neurophysiological measures. Hemispheric asymmetry in the fMRI signal was observed for healthy controls, namely higher signal for the left-hand movements, but not for either patients’ groups. ROI values, although altered in patients vs. controls, did not differ significantly between groups. ROI volumes associated with right-hand movement were lower for both patients’ groups vs. controls, and those associated with left-hand movement were lower in the RH group vs. all groups. These results are relevant to interpret potential preoperative plasticity and make inferences about postoperative plasticity and can be integrated in the surgical planning to increase surgery success and postoperative prognosis and quality of life. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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15 pages, 4643 KiB  
Article
Clinical Characterization and Prognostic Value of TPM4 and Its Correlation with Epithelial–Mesenchymal Transition in Glioma
by Jin Wang, Ying Yang and Bo Du
Brain Sci. 2022, 12(9), 1120; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12091120 - 24 Aug 2022
Cited by 4 | Viewed by 1819
Abstract
Tropomyosin 4 (TPM4) has been reported as an oncogenic gene across different malignancies. However, the role of TPM4 in glioma remains unclear. This study aimed to determine the clinical characterization and prognostic value of TPM4 in gliomas. Transcriptome expression and clinical information were [...] Read more.
Tropomyosin 4 (TPM4) has been reported as an oncogenic gene across different malignancies. However, the role of TPM4 in glioma remains unclear. This study aimed to determine the clinical characterization and prognostic value of TPM4 in gliomas. Transcriptome expression and clinical information were collected from the CGGA and TCGA datasets, which included 998 glioma patients. ScRNA-seq data were obtained from CGGA. R software was utilized for statistical analyses. There was a positive correlation between TPM4 and WHO grades. IDH-wildtype and mesenchymal subtype gliomas were accompanied by TPM4 upregulation. GO and GSEA analysis suggested that TPM4 was profoundly associated with epithelial-to-mesenchymal transition (EMT). Subsequent GSVA revealed a robust correlation between TPM4 and three signaling pathways of EMT (hypoxia, TGF-β, PI3K/AKT). Furthermore, TPM4 showed a synergistic effect with mesenchymal biomarkers, particularly with N-cadherin, Slug, Snail, TWIST1, and vimentin. ScRNA-seq analysis suggested that higher TPM4 was mainly attributed to tumor cells and macrophages and associated with tumor cell progression and macrophage polarization. Finally, high TPM4 was significantly associated with unfavorable outcomes. In conclusion, our findings indicate that TPM4 is significantly correlated with more malignant characteristics of gliomas, potentially through involvement in EMT. TPM4 could predict worse survival for patients with glioma. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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10 pages, 4695 KiB  
Article
Prediction of Higher Ki-67 Index in Pituitary Adenomas by Pre- and Intra-Operative Clinical Characteristics
by Xuanzhi Wang, Mingwu Li, Xiaofeng Jiang, Fei Wang, Shiying Ling and Chaoshi Niu
Brain Sci. 2022, 12(8), 1002; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12081002 - 28 Jul 2022
Cited by 2 | Viewed by 1448
Abstract
Objective: The Ki-67 index is an indicator of the active proliferation and aggressive behavior of pituitary adenomas (PAs). Appropriate pre- and intra-operatives of the Ki-67 index can help surgeons develop better and more personalized treatment strategies for patients with PAs. This study aimed [...] Read more.
Objective: The Ki-67 index is an indicator of the active proliferation and aggressive behavior of pituitary adenomas (PAs). Appropriate pre- and intra-operatives of the Ki-67 index can help surgeons develop better and more personalized treatment strategies for patients with PAs. This study aimed to investigate the influence factors for predicting the Ki-67 index in PAs. Methods: Data of 178 patients with PAs confirmed by pathology were retrospectively analyzed. According to the Ki-67 index, the patients were divided into the Ki-67 < 3% and Ki-67 ≥ 3% cohorts. Patient data, including age, sex, postoperative immunohistochemical pituitary hormone positive index, Knosp grade, tumor breaking through the sellar floor, rich blood supply to the tumor, tumor located inside the sella, erosion of the dorsum sellae bone, and pituitary-specific transcription factor, were collected. A univariate logistic analysis was used to evaluate the influence factors for a high Ki-67 index. Multiple regression and receiver operating characteristic (ROC) curve were used to analyze the factors with p < 0.05. The mutant status of Ki-67 index was predicted by nomogram. Results: Multivariate regression analysis showed that rich blood supply to the tumor and erosion of the dorsum sellae bone were independent risk factors for the Ki-67 proliferation index. The ROC curves demonstrated that age, rich blood supply to the tumor, and erosion of the dorsum sellae bone can predict the occurrence of a high Ki-67 index. Together, the three risk factors provide a stronger ability to predict the Ki-67 index. The nomogram was developed and validated. Conclusion: Age, rich blood supply to the tumor, and erosion of the dorsum sellae bone are influencing factors for predicting the Ki-67 index. Suitable nomogram prediction models were developed and validated, and there is potential for personalized treatment for PA patients. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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17 pages, 29322 KiB  
Article
The Surgical Risk Factors of Giant Intracranial Meningiomas: A Multi-Centric Retrospective Analysis of Large Case Serie
by Daniele Armocida, Antonia Catapano, Mauro Palmieri, Umberto Aldo Arcidiacono, Alessandro Pesce, Fabio Cofano, Veronica Picotti, Maurizio Salvati, Diego Garbossa, Giancarlo D’Andrea, Antonio Santoro and Alessandro Frati
Brain Sci. 2022, 12(7), 817; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12070817 - 22 Jun 2022
Cited by 3 | Viewed by 1941
Abstract
Giant intracranial meningiomas (GIMs) are a subgroup of meningiomas with huge dimensions with a maximum diameter of more than 5 cm. The mechanisms by which a meningioma can grow to be defined as a “giant” are unknown, and the biological, radiological profile and [...] Read more.
Giant intracranial meningiomas (GIMs) are a subgroup of meningiomas with huge dimensions with a maximum diameter of more than 5 cm. The mechanisms by which a meningioma can grow to be defined as a “giant” are unknown, and the biological, radiological profile and the different outcomes are poorly investigated. We performed a multi-centric retrospective study of a series of surgically treated patients suffering from intracranial meningioma. All the patients were assigned on the grounds of the preoperative imaging to giant and medium/large meningioma groups with a cut-off of 5 cm. We investigated whether the presence of large diameter and peritumoral brain edema (PBE) on radiological diagnosis indicates different mortality rates, grading, characteristics, and outcomes in a multi-variate analysis. We found a higher risk of developing complications for GIMs (29.9% versus 14.8%; p < 0.01). The direct proportional relationship between PBE volume and tumor volume was present only in the medium/large group (Pearson correlation with p < 0.01) and not in the GIM group (p = 0.47). In conclusion, GIMs have a higher risk of developing complications in the postoperative phase than medium/large meningioma without higher risk of mortality and recurrence. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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6 pages, 854 KiB  
Communication
Brain Tsunamis in Human High-Grade Glioma: Preliminary Observations
by Kayli Colpitts, Masoom J. Desai, Michael Kogan, C. William Shuttleworth and Andrew P. Carlson
Brain Sci. 2022, 12(6), 710; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12060710 - 30 May 2022
Cited by 2 | Viewed by 1600
Abstract
Gliomas make up nearly 40% of all central nervous system tumors, with over 50% of those being high-grade gliomas. Emerging data suggests that electrophysiologic events in the peri-tumoral region may play a role in the behavior and progression of high-grade gliomas. While seizures [...] Read more.
Gliomas make up nearly 40% of all central nervous system tumors, with over 50% of those being high-grade gliomas. Emerging data suggests that electrophysiologic events in the peri-tumoral region may play a role in the behavior and progression of high-grade gliomas. While seizures in the peri-tumoral zone are well described, much larger and slowly propagating waves of spreading depolarization (SD) may potentially have roles in both non-epileptic transient neurologic deficits and tumor progression. SD has only recently been observed in pre-clinical glioma models and it is not known whether these events occur clinically. We present a case of SD occurring in a human high-grade glioma using gold-standard subdural DC ECoG recordings. This finding could have meaningful implications for both clinical symptomatology and potentially for disease progression in these patients. Our observations and hypotheses are based on analogy with a large body of evidence in stroke and acute neurological injury that have recently established SD as cause of transient neurological deficits as well as a fundamental mechanism of ischemic expansion. Whether SD could represent a mechanistic target in this process to limit such progression is a high priority for further clinical investigations. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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20 pages, 314 KiB  
Article
Elderly Gliobastoma Patients: The Impact of Surgery and Adjuvant Treatments on Survival: A Single Institution Experience
by Francesco Bruno, Alessia Pellerino, Edoardo Pronello, Rosa Palmiero, Luca Bertero, Cristina Mantovani, Andrea Bianconi, Antonio Melcarne, Diego Garbossa and Roberta Rudà
Brain Sci. 2022, 12(5), 632; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12050632 - 11 May 2022
Cited by 9 | Viewed by 1399
Abstract
Introduction. Elderly glioblastoma (GBM) patients often show limited response to treatment and poor outcome. Here, we provide a case series of elderly GBM patients from our Institution, in whom we assessed the clinical characteristics, feasibility of surgical resection, response to adjuvant treatments, [...] Read more.
Introduction. Elderly glioblastoma (GBM) patients often show limited response to treatment and poor outcome. Here, we provide a case series of elderly GBM patients from our Institution, in whom we assessed the clinical characteristics, feasibility of surgical resection, response to adjuvant treatments, and outcome, along with the impact of comorbidities and clinical status on survival. Patients and Methods. We included patients ≥ 65-year-old. We collected information about clinical and molecular features, extent of resection, adjuvant treatments, treatment-related complications, and outcome. Results. We included 135 patients. Median age was 71 years. In total, 127 patients (94.0%) had a Karnofsky Performance Status (KPS) ≥70 and 61/135 (45.2%) a Charlson Comorbidity Score (CCI) > 3. MGMTp methylation was found in 70/135 (51.9%). Subtotal resections (STRs), gross-total resections (GTRs), and biopsies were 102 (75.6%), 10 (7.4%) and 23 (17.0%), respectively. Median progression-free survival and overall survival (mOS) were 8.0 and 10.5 months for the whole cohort. Notably, GTR and radio-chemotherapy with temozolomide in patients with MGMTp methylation were associated with significantly longer mOS (32.8 and 44.8 months, respectively). In a multivariable analysis, risk of death was affected by STR vs. GTR (HR 2.8, p = 0.002), MGMTp methylation (HR 0.55, p = 0.007), and KPS at baseline ≥70 (HR 0.43, p = 0.031). Conversely, CCI and post-surgical complications were not significant. Conclusions. Elderly GBM patients often have a dismal prognosis. However, it is possible to identify a subgroup with favourable clinical and molecular features, who benefit from GTR and radio-chemotherapy with temozolomide. A comprehensive prognostic score is needed to guide treatment modality and predict the outcome. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
10 pages, 861 KiB  
Article
Fluorescence-Guided Surgery in Glioblastoma: 5-ALA, SF or Both? Differences between Fluorescent Dyes in 99 Consecutive Cases
by Pietro Zeppa, Raffaele De Marco, Matteo Monticelli, Armando Massara, Andrea Bianconi, Giuseppe Di Perna, Stefania Greco Crasto, Fabio Cofano, Antonio Melcarne, Michele Maria Lanotte and Diego Garbossa
Brain Sci. 2022, 12(5), 555; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12050555 - 26 Apr 2022
Cited by 13 | Viewed by 2348
Abstract
Background: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor’s borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are [...] Read more.
Background: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor’s borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. Methods: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. Results: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). Conclusions: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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8 pages, 1451 KiB  
Article
Circulating Exosomal-DNA in Glioma Patients: A Quantitative Study and Histopathological Correlations—A Preliminary Study
by Amedeo Piazza, Paolo Rosa, Luca Ricciardi, Antonella Mangraviti, Luca Pacini, Antonella Calogero, Antonino Raco and Massimo Miscusi
Brain Sci. 2022, 12(4), 500; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12040500 - 14 Apr 2022
Cited by 6 | Viewed by 1644
Abstract
Glial neoplasms are a group of diseases with poor prognoses. Not all risk factors are known, and no screening tests are available. Only histology provides certain diagnosis. As already reported, DNA transported by exosomes can be an excellent source of information shared by [...] Read more.
Glial neoplasms are a group of diseases with poor prognoses. Not all risk factors are known, and no screening tests are available. Only histology provides certain diagnosis. As already reported, DNA transported by exosomes can be an excellent source of information shared by cells locally or systemically. These vesicles seem to be one of the main mechanisms of tumor remote intercellular signaling used to induce immune deregulation, apoptosis, and both phenotypic and genotypic modifications. In this study, we evaluated the exosomal DNA (exoDNA) concentration in blood samples of patients affected by cerebral glioma and correlated it with histological and radiological characteristics of tumors. From 14 patients with diagnosed primary or recurrent glioma, we obtained MRI imaging data, histological data, and preoperative blood samples that were used to extract circulating exosomal DNA, which we then quantified. Our results demonstrate a relationship between the amount of circulating exosomal DNA and tumor volume, and mitotic activity. In particular, a high concentration of exoDNA was noted in low-grade gliomas. Our results suggest a possible role of exoDNAs in the diagnosis of brain glioma. They could be particularly useful in detecting early recurrent high-grade gliomas and asymptomatic low-grade gliomas. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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14 pages, 3136 KiB  
Article
Topological Characteristics Associated with Intraoperative Stimulation Related Epilepsy of Glioma Patients: A DTI Network Study
by Jianing Yang, Chunyao Zhou, Yuchao Liang, Yinyan Wang and Lei Wang
Brain Sci. 2022, 12(1), 60; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12010060 - 31 Dec 2021
Cited by 3 | Viewed by 1569
Abstract
Background: Awake craniotomy with intraoperative stimulation has been utilized in glioma surgical resection to preserve the quality of life. Epilepsy may occur in 5–20% of cases, leading to severe consequences. This study aimed to discuss the mechanism of intraoperative stimulation-related epilepsy (ISE) [...] Read more.
Background: Awake craniotomy with intraoperative stimulation has been utilized in glioma surgical resection to preserve the quality of life. Epilepsy may occur in 5–20% of cases, leading to severe consequences. This study aimed to discuss the mechanism of intraoperative stimulation-related epilepsy (ISE) using DTI-based graph theoretical analysis. Methods: Twenty patients with motor-area glioma were enrolled and divided into two groups (Ep and nEp) according to the presence of ISE. Additionally, a group of 10 healthy participants matched by age, sex, and years of education was also included. All participants underwent T1, T2, and DTI examinations. Graph theoretical analysis was applied to reveal the topological characteristics of white matter networks. Results: Three connections were found to be significantly lower in at least one weighting in the Ep group. These connections were between A1/2/3truL and A4ulL, A1/2/3truR and A4tR, and A6mL and A6mR. Global efficiency was significantly decreased, while the shortest path length increased in the Ep group in at least one weighting. Ten nodes exhibited significant differences in nodal efficiency and degree centrality analyses. The nodes A6mL and A6mR showed a marked decrease in total four weightings in the Ep group. Conclusions: The hub nodes A6mL and A6mR are disconnected in patients with ISE, causing subsequent lower efficiency of global and regional networks. These findings provide a basis for presurgical assessment of ISE, for which caution should be taken when it involves hub nodes during intraoperative electrical stimulation. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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Review

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11 pages, 978 KiB  
Review
Supramarginal Resection for Glioblastoma: It Is Time to Set Boundaries! A Critical Review on a Hot Topic
by Francesco Guerrini, Elena Roca and Giannantonio Spena
Brain Sci. 2022, 12(5), 652; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12050652 - 16 May 2022
Cited by 12 | Viewed by 2301
Abstract
Glioblastoma are the most common primary malignant brain tumors with a highly infiltrative behavior. The extent of resection of the enhancing component has been shown to be correlated to survival. Recently, it has been proposed to move the resection beyond the contrast-enhanced portion [...] Read more.
Glioblastoma are the most common primary malignant brain tumors with a highly infiltrative behavior. The extent of resection of the enhancing component has been shown to be correlated to survival. Recently, it has been proposed to move the resection beyond the contrast-enhanced portion into the MR hyper intense tissue which typically surrounds the tumor, the so-called supra marginal resection (SMR). Though it should be associated with better overall survival (OS), a potential harmful resection must be avoided in order not to create new neurological deficits. Through this work, we aimed to perform a critical review of SMR in patients with Glioblastoma. A Medline database search and a pooled meta-analysis of HRs were conducted; 19 articles were included. Meta-analysis revealed a pooled OS HR of 0.64 (p = 0.052). SMR is generally considered as the resection of any T1w gadolinium-enhanced tumor exceeding FLAIR volume, but no consensus exists about the amount of volume that must be resected to have an OS gain. Equally, the role and the weight of several pre-operative features (tumor volume, location, eloquence, etc.), the intraoperative methods to extend resection, and the post-operative deficits, need to be considered more deeply in future studies. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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15 pages, 617 KiB  
Review
The Concept of «Peritumoral Zone» in Diffuse Low-Grade Gliomas: Oncological and Functional Implications for a Connectome-Guided Therapeutic Attitude
by Melissa Silva, Catalina Vivancos and Hugues Duffau
Brain Sci. 2022, 12(4), 504; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12040504 - 15 Apr 2022
Cited by 11 | Viewed by 2642
Abstract
Diffuse low-grade gliomas (DLGGs) are heterogeneous and poorly circumscribed neoplasms with isolated tumor cells that extend beyond the margins of the lesion depicted on MRI. Efforts to demarcate the glioma core from the surrounding healthy brain led us to define an intermediate region, [...] Read more.
Diffuse low-grade gliomas (DLGGs) are heterogeneous and poorly circumscribed neoplasms with isolated tumor cells that extend beyond the margins of the lesion depicted on MRI. Efforts to demarcate the glioma core from the surrounding healthy brain led us to define an intermediate region, the so-called peritumoral zone (PTZ). Although most studies about PTZ have been conducted on high-grade gliomas, the purpose here is to review the cellular, metabolic, and radiological characteristics of PTZ in the specific context of DLGG. A better delineation of PTZ, in which glioma cells and neural tissue strongly interact, may open new therapeutic avenues to optimize both functional and oncological results. First, a connectome-based “supratotal” surgical resection (i.e., with the removal of PTZ in addition to the tumor core) resulted in prolonged survival by limiting the risk of malignant transformation, while improving the quality of life, thanks to a better control of seizures. Second, the timing and order of (neo)adjuvant medical treatments can be modulated according to the pattern of peritumoral infiltration. Third, the development of new drugs specifically targeting the PTZ could be considered from an oncological (such as immunotherapy) and epileptological perspective. Further multimodal investigations of PTZ are needed to maximize long-term outcomes in DLGG patients. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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15 pages, 1167 KiB  
Review
Relapsing High—Grade Glioma from Peritumoral Zone: Critical Review of Radiotherapy Treatment Options
by Maria Chiara Lo Greco, Roberto Milazzotto, Rocco Luca Emanuele Liardo, Grazia Acquaviva, Madalina La Rocca, Roberto Altieri, Francesco Certo, Giuseppe Maria Barbagallo, Antonio Basile, Pietro Valerio Foti, Stefano Palmucci, Stefano Pergolizzi, Antonio Pontoriero and Corrado Spatola
Brain Sci. 2022, 12(4), 416; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12040416 - 22 Mar 2022
Cited by 5 | Viewed by 2527
Abstract
Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of about 15 months. After the prior treatment, GBM tends to relapse within the high dose radiation field, defined as the peritumoral brain zone (PTZ), needing a [...] Read more.
Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of about 15 months. After the prior treatment, GBM tends to relapse within the high dose radiation field, defined as the peritumoral brain zone (PTZ), needing a second treatment. In the present review, the primary role of ionizing radiation in recurrent GBM is discussed, and the current literature knowledge about the different radiation modalities, doses and fractionation options at our disposal is summarized. Therefore, the focus is on the necessity of tailoring the treatment approach to every single patient and using radiomics and PET/MRI imaging to have a relatively good outcome and avoid severe toxicity. The use of charged particle therapy and radiosensitizers to overcome GBM radioresistance is considered, even if further studies are necessary to evaluate the effectiveness in the setting of reirradiation. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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Other

8 pages, 4626 KiB  
Brief Report
Histologic Definition of Enhancing Core and FLAIR Hyperintensity Region of Glioblastoma, IDH-Wild Type: A Clinico-Pathologic Study on a Single-Institution Series
by Giuseppe Broggi, Roberto Altieri, Valeria Barresi, Francesco Certo, Giuseppe Maria Vincenzo Barbagallo, Magda Zanelli, Andrea Palicelli, Gaetano Magro and Rosario Caltabiano
Brain Sci. 2023, 13(2), 248; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci13020248 - 31 Jan 2023
Cited by 4 | Viewed by 1389
Abstract
The extent of resection beyond the enhancing core (EC) in glioblastoma IDH-wild type (GBM, IDHwt) is one of the most debated topics in neuro-oncology. Indeed, it has been demonstrated that local disease recurrence often arises in peritumoral areas and that radiologically-defined FLAIR hyperintensity [...] Read more.
The extent of resection beyond the enhancing core (EC) in glioblastoma IDH-wild type (GBM, IDHwt) is one of the most debated topics in neuro-oncology. Indeed, it has been demonstrated that local disease recurrence often arises in peritumoral areas and that radiologically-defined FLAIR hyperintensity areas of GBM IDHwt are often visible beyond the conventional EC. Therefore, the need to extend the surgical resection also to the FLAIR hyperintensity areas is a matter of debate. Since little is known about the histological composition of FLAIR hyperintensity regions, in this study we aimed to provide a comprehensive description of the histological features of EC and FLAIR hyperintensity regions sampled intraoperatively using neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence, in 33 patients with GBM, IDHwt. Assessing a total 109 histological samples, we found that FLAIR areas consisted in: (i) fragments of white matter focally to diffusely infiltrated by tumor cells in 76% of cases; (ii) a mixture of white matter with reactive astrogliosis and grey matter with perineuronal satellitosis in 15% and (iii) tumor tissue in 9%. A deeper knowledge of the histology of FLAIR hyperintensity areas in GBM, IDH-wt may serve to better guide neurosurgeons on the choice of the most appropriate surgical approach in patients with this neoplasm. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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35 pages, 1202 KiB  
Systematic Review
Glioma-Associated Microglia Characterization in the Glioblastoma Microenvironment through a ‘Seed-and Soil’ Approach: A Systematic Review
by Grazia Menna, Pier Paolo Mattogno, Carlo Maria Donzelli, Lucia Lisi, Alessandro Olivi and Giuseppe Maria Della Pepa
Brain Sci. 2022, 12(6), 718; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12060718 - 31 May 2022
Cited by 8 | Viewed by 2463
Abstract
Background and aim: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A “seed and soil” approach has been recently introduced to describe [...] Read more.
Background and aim: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A “seed and soil” approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile “soil” and interact with the “seed” (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). Methods: An online literature search was launched on PubMed Medline and Scopus using the following research string: “((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))”. The last search for articles pertinent to the topic was conducted in February 2022. Results: The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Conclusions: Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile ‘soil’ for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia–glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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10 pages, 675 KiB  
Perspective
FLAIRectomy: Resecting beyond the Contrast Margin for Glioblastoma
by Alexander F. Haddad, Jacob S. Young, Ramin A. Morshed and Mitchel S. Berger
Brain Sci. 2022, 12(5), 544; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12050544 - 25 Apr 2022
Cited by 20 | Viewed by 2716
Abstract
The standard of care for isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is maximal resection followed by chemotherapy and radiation. Studies investigating the resection of GBM have primarily focused on the contrast enhancing portion of the tumor on magnetic resonance imaging. Histopathological studies, however, have [...] Read more.
The standard of care for isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is maximal resection followed by chemotherapy and radiation. Studies investigating the resection of GBM have primarily focused on the contrast enhancing portion of the tumor on magnetic resonance imaging. Histopathological studies, however, have demonstrated tumor infiltration within peri-tumoral fluid-attenuated inversion recovery (FLAIR) abnormalities, which is often not resected. The histopathology of FLAIR and local recurrence patterns of GBM have prompted interest in the resection of peri-tumoral FLAIR, or FLAIRectomy. To this point, recent studies have suggested a significant survival benefit associated with safe peri-tumoral FLAIR resection. In this review, we discuss the evidence surrounding the composition of peri-tumoral FLAIR, outcomes associated with FLAIRectomy, future directions of the field, and potential implications for patients. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
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