Low Grade Gliomas

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 10222

Special Issue Editors


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Guest Editor
Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois & Université de Lausanne, 1011 Lausanne, Switzerland
Interests: brain tumors; clinical management; low grade gliomas; targeted therapies; neurological complications of cancer
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Guest Editor
Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
Interests: brain tumors; clinical management; glioblastoma; low grade tumors; patient outcome

Special Issue Information

Dear Colleagues,

The management of low-grade gliomas remains one of the most challenging and controversial aspects of neuro-oncology. Moreover, in 2021, the new WHO classification of brain tumors radically changed the definition of both high- and low-grade tumors and identified a number of new entities for which the clinical characteristics, outcome, and management remain to be defined. Moreover, specific mutations, such as NTRK fusion genes and BRAF mutations, have been identified in a subset of low-grade gliomas, for which targeted therapies are available and are changing treatment options.

This Special Issue of Cancers aims to provide a platform to highlight significant new findings in the field of neuropathology, diagnosis, clinical findings, management, and outcome of low-grade gliomas, including pediatric and rare entities of low-grade gliomas, such as pediatric MYB- or MYBL1-altered diffuse astrocytoma, angiocentric glioma, diffuse MAPK pathway altered low-grade glioma, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, MN1 altered astroblastoma, and glioneuronal and neuronal tumors.

Dr. Andreas F. Hottinger
Dr. Nimish A. Mohile
Guest Editors

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Keywords

  • low-grade gliomas
  • astrocytoma
  • oligodendroglioma
  • ependymoma
  • rare low-grade gliomas
  • pediatric low-grade gliomas
  • neuropathology and classification
  • molecular pathways
  • outcome
  • treatment strategies
  • surgery
  • radiation therapy
  • targeted therapies
  • immune therapies

Published Papers (7 papers)

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Research

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16 pages, 1402 KiB  
Article
Oncological Outcomes, Long-Term Toxicities, Quality of Life and Sexual Health after Pencil-Beam Scanning Proton Therapy in Patients with Low-Grade Glioma
by Jonas Willmann, Dominic Leiser and Damien Charles Weber
Cancers 2023, 15(21), 5287; https://doi.org/10.3390/cancers15215287 - 4 Nov 2023
Cited by 2 | Viewed by 1000
Abstract
Purpose: To assess oncological outcomes, toxicities, quality of life (QoL) and sexual health (SH) of low-grade glioma (LGG) patients treated with pencil-beam scanning proton therapy (PBS-PT). Material and methods: We retrospectively analyzed 89 patients with LGG (Neurofibromatosis type 1; n = 4 (4.5%) [...] Read more.
Purpose: To assess oncological outcomes, toxicities, quality of life (QoL) and sexual health (SH) of low-grade glioma (LGG) patients treated with pencil-beam scanning proton therapy (PBS-PT). Material and methods: We retrospectively analyzed 89 patients with LGG (Neurofibromatosis type 1; n = 4 (4.5%) patients) treated with PBS-PT (median dose 54 Gy (RBE)) from 1999 to 2022 at our institution. QoL was prospectively assessed during PBS-PT and yearly during follow-up from 2015 to 2023, while a cross-sectional exploration of SH was conducted in 2023. Results: Most LGGs (n = 58; 65.2%) were CNS WHO grade 2 and approximately half (n = 43; 48.3%) were located in the vicinity of the visual apparatus/thalamus. After a median follow-up of 50.2 months, 24 (27%) patients presented with treatment failures and most of these (n = 17/24; 70.8%) were salvaged. The 4-year overall survival was 89.1%. Only 2 (2.2%) and 1 (1.1%) patients presented with CTCAE grade 4 and 3 late radiation-induced toxicity, respectively. No grade 5 late adverse event was observed. The global health as a domain of QoL remained stable and comparable to the reference values during PBS-PT and for six years thereafter. Sexual satisfaction was comparable to the normative population. Conclusions: LGG patients treated with PBS-PT achieved excellent long-term survival and tumor control, with exceptionally low rates of high-grade late toxicity, and favorable QoL and SH. Full article
(This article belongs to the Special Issue Low Grade Gliomas)
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14 pages, 9354 KiB  
Article
Longitudinal Evaluation of Brain Plasticity in Low-Grade Gliomas: fMRI and Graph-Theory Provide Insights on Language Reorganization
by Luca Pasquini, Kyung K. Peck, Alice Tao, Gino Del Ferraro, Denise D. Correa, Mehrnaz Jenabi, Erik Kobylarz, Zhigang Zhang, Cameron Brennan, Viviane Tabar, Hernán Makse and Andrei I. Holodny
Cancers 2023, 15(3), 836; https://doi.org/10.3390/cancers15030836 - 29 Jan 2023
Cited by 3 | Viewed by 1993
Abstract
Language reorganization may represent an adaptive phenomenon to compensate tumor invasion of the dominant hemisphere. However, the functional changes over time underlying language plasticity remain unknown. We evaluated language function in patients with low-grade glioma (LGG), using task-based functional MRI (tb-fMRI), graph-theory and [...] Read more.
Language reorganization may represent an adaptive phenomenon to compensate tumor invasion of the dominant hemisphere. However, the functional changes over time underlying language plasticity remain unknown. We evaluated language function in patients with low-grade glioma (LGG), using task-based functional MRI (tb-fMRI), graph-theory and standardized language assessment. We hypothesized that functional networks obtained from tb-fMRI would show connectivity changes over time, with increased right-hemispheric participation. We recruited five right-handed patients (4M, mean age 47.6Y) with left-hemispheric LGG. Tb-fMRI and language assessment were conducted pre-operatively (pre-op), and post-operatively: post-op1 (4–8 months), post-op2 (10–14 months) and post-op3 (16–23 months). We computed the individual functional networks applying optimal percolation thresholding. Language dominance and hemispheric connectivity were quantified by laterality indices (LI) on fMRI maps and connectivity matrices. A fixed linear mixed model was used to assess the intra-patient correlation trend of LI values over time and their correlation with language performance. Individual networks showed increased inter-hemispheric and right-sided connectivity involving language areas homologues. Two patterns of language reorganization emerged: Three/five patients demonstrated a left-to-codominant shift from pre-op to post-op3 (type 1). Two/five patients started as atypical dominant at pre-op, and remained unchanged at post-op3 (type 2). LI obtained from tb-fMRI showed a significant left-to-right trend in all patients across timepoints. There were no significant changes in language performance over time. Type 1 language reorganization may be related to the treatment, while type 2 may be tumor-induced, since it was already present at pre-op. Increased inter-hemispheric and right-side connectivity may represent the initial step to develop functional plasticity. Full article
(This article belongs to the Special Issue Low Grade Gliomas)
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Review

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0 pages, 747 KiB  
Review
Immunotherapy Approaches in Isocitrate-Dehydrogenase-Mutant Low-Grade Glioma
by Marco Gallus, Darwin Kwok, Senthilnath Lakshmanachetty, Akane Yamamichi and Hideho Okada
Cancers 2023, 15(14), 3726; https://doi.org/10.3390/cancers15143726 - 22 Jul 2023
Cited by 4 | Viewed by 1863 | Correction
Abstract
Low-grade gliomas (LGGs) are slow-growing tumors in the central nervous system (CNS). Patients characteristically show the onset of seizures or neurological deficits due to the predominant LGG location in high-functional brain areas. As a molecular hallmark, LGGs display mutations in the isocitrate dehydrogenase [...] Read more.
Low-grade gliomas (LGGs) are slow-growing tumors in the central nervous system (CNS). Patients characteristically show the onset of seizures or neurological deficits due to the predominant LGG location in high-functional brain areas. As a molecular hallmark, LGGs display mutations in the isocitrate dehydrogenase (IDH) enzymes, resulting in an altered cellular energy metabolism and the production of the oncometabolite D-2-hydroxyglutarate. Despite the remarkable progress in improving the extent of resection and adjuvant radiotherapy and chemotherapy, LGG remains incurable, and secondary malignant transformation is often observed. Therefore, novel therapeutic approaches are urgently needed. In recent years, immunotherapeutic strategies have led to tremendous success in various cancer types, but the effect of immunotherapy against glioma has been limited due to several challenges, such as tumor heterogeneity and the immunologically “cold” tumor microenvironment. Nevertheless, recent preclinical and clinical findings from immunotherapy trials are encouraging and offer a glimmer of hope for treating IDH-mutant LGG patients. Here, we aim to review the lessons learned from trials involving vaccines, T-cell therapies, and IDH-mutant inhibitors and discuss future approaches to enhance the efficacy of immunotherapies in IDH-mutant LGG. Full article
(This article belongs to the Special Issue Low Grade Gliomas)
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17 pages, 2838 KiB  
Review
Brain Plasticity Profiling as a Key Support to Therapeutic Decision-Making in Low-Grade Glioma Oncological Strategies
by Sam Ng and Hugues Duffau
Cancers 2023, 15(14), 3698; https://doi.org/10.3390/cancers15143698 - 20 Jul 2023
Cited by 4 | Viewed by 1720
Abstract
The ability of neural circuits to compensate for damage to the central nervous system is called postlesional plasticity. In diffuse low-grade gliomas (LGGs), a crosstalk between the brain and the tumor activates modulations of plasticity, as well as tumor proliferation and migration, by [...] Read more.
The ability of neural circuits to compensate for damage to the central nervous system is called postlesional plasticity. In diffuse low-grade gliomas (LGGs), a crosstalk between the brain and the tumor activates modulations of plasticity, as well as tumor proliferation and migration, by means of paracrine and electrical intercommunications. Such adaptative mechanisms have a major impact on the benefits and risks of oncological treatments but are still disregarded by current neuro-oncological guidelines. In this review, the authors first aimed to highlight clinical, radiological, and oncological markers that robustly reflect the plasticity potentials and limitations in LGG patients, including the location of the tumor and the degree of critical white matter tract infiltration, the velocity of tumor expansion, and the reactional changes of neuropsychological performances over time. Second, the interactions between the potential/limitations of cerebral plasticity and the efficacy/tolerance of treatment options (i.e., surgery, chemotherapy, and radiotherapy) are reviewed. Finally, a longitudinal and multimodal treatment approach accounting for the evolutive profiles of brain plasticity is proposed. Such an approach integrates personalized predictive models of plasticity potentials with a step-by-step therapeutic decision making and supports onco-functional balanced strategies in patients with LGG, with the ultimate aim of optimizing overall survival and quality of life. Full article
(This article belongs to the Special Issue Low Grade Gliomas)
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Other

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3 pages, 145 KiB  
Correction
Correction: Gallus et al. Immunotherapy Approaches in Isocitrate-Dehydrogenase-Mutant Low-Grade Glioma. Cancers 2023, 15, 3726
by Marco Gallus, Darwin Kwok, Senthilnath Lakshmanachetty, Akane Yamamichi and Hideho Okada
Cancers 2024, 16(1), 119; https://doi.org/10.3390/cancers16010119 - 26 Dec 2023
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Abstract
It has come to our attention that the previously published manuscript contained an outdated iteration of Table 1 [...] Full article
(This article belongs to the Special Issue Low Grade Gliomas)
17 pages, 1694 KiB  
Systematic Review
How Reliable Is Fluorescence-Guided Surgery in Low-Grade Gliomas? A Systematic Review Concerning Different Fluorophores
by Andrea Bianconi, Marta Bonada, Pietro Zeppa, Stefano Colonna, Fulvio Tartara, Antonio Melcarne, Diego Garbossa and Fabio Cofano
Cancers 2023, 15(16), 4130; https://doi.org/10.3390/cancers15164130 - 16 Aug 2023
Cited by 3 | Viewed by 960
Abstract
Background: Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade gliomas, while its role is less definitely assessed in low-grade gliomas. Methods: A systematic review was conducted. 5-aminolevulinic acid, [...] Read more.
Background: Fluorescence-guided surgery has been increasingly used to support glioma surgery with the purpose of obtaining a maximal safe resection, in particular in high-grade gliomas, while its role is less definitely assessed in low-grade gliomas. Methods: A systematic review was conducted. 5-aminolevulinic acid, sodium fluorescein, indocyanine green and tozuleristide were taken into account. The main considered outcome was the fluorescence rate, defined as the number of patients in whom positive fluorescence was detected out of the total number of patients. Only low-grade gliomas were considered, and data were grouped according to single fluorophores. Results: 16 papers about 5-aminolevulinic acid, 4 about sodium fluorescein, 2 about indocyanine green and 1 about tozuleristide were included in the systematic review. Regarding 5-aminolevulinic acid, a total of 467 low-grade glioma patients were included, and fluorescence positivity was detected in 34 out of 451 Grade II tumors (7.3%); while in Grade I tumors, fluorescence positivity was detected in 9 out of 16 cases. In 16 sodium fluorescein patients, seven positive fluorescent cases were detected. As far as indocyanine is concerned, two studies accounting for six patients (three positive) were included, while for tozuleristide, a single clinical trial with eight patients (two positive) was retrieved. Conclusions: The current evidence does not support the routine use of 5-aminolevulinic acid or sodium fluorescein with a standard operating microscope because of the low fluorescence rates. New molecules, including tozuleristide, and new techniques for fluorescence detection have shown promising results; however, their use still needs to be clinically validated on a large scale. Full article
(This article belongs to the Special Issue Low Grade Gliomas)
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13 pages, 616 KiB  
Systematic Review
Supratotal Surgical Resection for Low-Grade Glioma: A Systematic Review
by Daniel Kreatsoulas, Mark Damante, Maxwell Gruber, Olivia Duru and James Bradley Elder
Cancers 2023, 15(9), 2493; https://doi.org/10.3390/cancers15092493 - 26 Apr 2023
Cited by 7 | Viewed by 1567
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Low Grade Gliomas)
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