Table of Contents
Overview
Definition and Classification
Gliomas are a type of tumor that originates from glial cells, which are non-neuronal cells that provide support and protection for neurons in the brain and spinal cord. They represent the most common type of primary brain tumor, accounting for approximately 30% to 40% of all intracranial tumors, with glioblastomas being the most prevalent subtype among adults, constituting about half of all gliomas.[3.1] The classification of gliomas has evolved significantly, particularly with the introduction of molecular genetic profiling. Historically, gliomas were classified primarily based on histopathological criteria; however, the World Health Organization (WHO) updated its classification system in 2016 to incorporate molecular biomarkers, such as IDH mutations and 1p/19q codeletion, which are crucial for accurate diagnosis and prognosis.[37.1] This shift towards molecular classification allows for a more nuanced understanding of glioma subtypes, which can be categorized into low-grade, atypical/anaplastic, or high-grade tumors based on cell morphology, mitotic activity, and specific molecular markers.[4.1] Furthermore, advancements in genome-wide molecular profiling have revealed characteristic genetic alterations and epigenetic profiles associated with different glioma types. These molecular characteristics not only refine glioma classification but also enhance the prediction of patient outcomes and guide individualized treatment strategies.[40.1] As research continues, it is anticipated that the classification of gliomas will further evolve, leading to the identification of additional subtypes and a deeper understanding of the genetic heterogeneity present within these tumors.[38.1]Types of Gliomas
Gliomas are a diverse group of brain tumors that originate from glial cells, which include astrocytes, oligodendrocytes, and ependymal cells. Among the various types of gliomas, astrocytomas are the most prevalent, arising from astrocytes that clean the brain's environment and support neuronal function. Astrocytomas can be classified into different subtypes and grades, with Grade IV astrocytoma, commonly known as glioblastoma, being the most invasive and aggressive form.[8.1] Genetic markers play a crucial role in categorizing gliomas and influencing their behavior and treatment responses. For instance, the presence of an isocitrate dehydrogenase (IDH) mutation is associated with a less aggressive tumor phenotype and improved patient survival rates. This mutation is identified in over 80% of World Health Organization (WHO) grade II and III gliomas, and it is also frequently found in secondary glioblastomas.[19.1] Additionally, the co-deletion of chromosomal arms 1p and 19q is another genetic alteration that indicates a more favorable response to chemotherapy.[18.1] The classification of gliomas is essential for determining appropriate treatment strategies and prognostic outcomes, highlighting the importance of understanding the specific genetic and histological characteristics of these tumors.History
Early Discoveries
The first recorded observations of gliomas date back to the early 19th century, with significant contributions from researchers such as Berns in 1800 and Abernety in 1804. The comprehensive histomorphological description of gliomas was later provided by Rudolf Virchow in 1865, marking a pivotal moment in the understanding of these tumors.[48.1] In the 1920s, Percival Bailey and Harvey Cushing made substantial advancements in glioma classification. Their seminal study published in 1925 analyzed over 400 gliomas and established a four-tiered grading system that correlated histological and anatomical properties of gliomas with patient outcomes. This classification laid the groundwork for modern diagnostic criteria and treatment approaches.[52.1] The insights gained from their work were prescient, as they drew parallels between the histological appearances of glial tumors and the developmental stages of glia, which significantly influenced the understanding of glioma subtypes.[51.1] The World Health Organization (WHO) later adopted and refined these classifications in 2016, describing gliomas as tumors arising from glia, the supportive cells of the central nervous system. This evolution in classification reflects the ongoing advancements in histopathology and the need for precise diagnostic criteria in the management of gliomas.[49.1] Overall, the early discoveries and classifications have been foundational in shaping contemporary glioma research and treatment strategies.[47.1]Evolution of Treatment Approaches
Advancements in the treatment of gliomas have evolved significantly over the years, particularly with the integration of advanced imaging technologies and a deeper understanding of the molecular biology of these tumors. Historically, the outcomes for glioblastoma patients improved incrementally from the time of Harvey Cushing, primarily due to advancements in localization, imaging, anesthesia, surgical techniques, and the management of cerebral edema. However, a pivotal moment occurred in the 1990s with the introduction of magnetic resonance imaging (MRI), which enabled better degrees of tumor resection and significantly influenced surgical approaches to glioma treatment.[53.1] Modern MRI techniques, including diffusion-weighted imaging and functional MRI, have become essential in diagnosing and managing gliomas, the most prevalent primary brain tumors.[54.1] These advanced imaging modalities not only enhance the visualization of tumor characteristics but also allow for a more precise assessment of intra- and intertumoral heterogeneity, which is crucial for tailoring treatment strategies.[55.1] The necessity for greater standardization and collaborative research in utilizing MRI's full potential has been emphasized, advocating for a more profound understanding of glioma biology to improve personalized therapy.[56.1] Intraoperative imaging technologies, such as intraoperative MRI (iMRI), functional MRI (fMRI), and diffusion tensor imaging (DTI), have also emerged as game-changers in glioma surgery. These modalities help mitigate the effects of brain shift during surgery, thereby maximizing safe resection margins and improving postoperative outcomes.[57.1] Additionally, intraoperative ultrasound (iUS) is variably used to delineate neuroanatomical structures, enhancing the precision of glioma resections.[58.1] The evolution of treatment approaches has also been significantly influenced by advancements in understanding the genetic mutations associated with gliomas. The introduction of molecular profiling in glioma classification by the World Health Organization in 2016 has allowed for a more nuanced approach to treatment, integrating molecular characteristics with histopathological criteria.[62.1] This shift has led to the identification of oncogenic gene fusions and mutations, such as IDH and BRAF, which serve as potential therapeutic targets and prognostic indicators.[60.1] Targeted therapies, including IDH inhibitors and BRAF/MEK inhibitors, are currently under investigation and represent a promising avenue for personalized treatment options.[67.1] Furthermore, recent advancements in molecularly targeted therapies and immunotherapies have transformed the care of patients with malignant gliomas. These strategies aim to address the challenges posed by the aggressive nature of gliomas by targeting specific genetic alterations and enhancing therapeutic efficacy.[66.1] The ongoing research into the molecular biology of gliomas, including insights gained from single-cell RNA sequencing, continues to uncover new aspects of tumor behavior and communication, further informing treatment strategies.[69.1]In this section:
Symptoms And Diagnosis
Common Symptoms
The symptoms of glioma can vary significantly depending on the tumor's type, location, and growth rate. Commonly reported symptoms include headaches, which are experienced by approximately half of glioma patients, particularly those with glioblastoma, who may suffer from severe headaches that are often worse in the morning.[106.1] Seizures are another prevalent symptom, especially in cases of astrocytoma, and can manifest as an early sign of the condition.[108.1] Other frequent symptoms include nausea and vomiting, which may occur alongside cognitive changes such as confusion or memory loss.[105.1] Patients may also experience difficulties with speech, weakness or numbness in the limbs, and alterations in mood or personality.[93.1] Vision changes, including loss of vision, can also be indicative of glioma, as the tumor may exert pressure on surrounding brain structures.[108.1] The specific symptoms experienced by an individual can be influenced by the glioma's location within the brain or spinal cord, as well as its size and growth dynamics.[105.1] For instance, tumors located in areas responsible for motor function may lead to weakness in specific limbs, while those affecting cognitive areas may result in significant changes in mental function.[91.1] Overall, the diverse range of symptoms underscores the complexity of gliomas and the necessity for thorough diagnostic evaluations, including neurological examinations and imaging studies, to accurately identify and manage the condition.[96.1]Diagnostic Methods
Advanced neuroimaging techniques play a crucial role in the diagnosis and management of gliomas, the most prevalent primary brain tumors. Among these techniques, magnetic resonance imaging (MRI) has established itself as the gold standard for identifying gliomas and assessing their extent. Detailed imaging provided by MRI is essential for pinpointing tumor borders, which informs surgical approaches and techniques.[116.1] However, conventional MRI often lacks the physiological detail necessary for effective clinical decision-making, highlighting the need for more advanced imaging modalities.[118.1] Recent advancements in MRI, including diffusion-weighted imaging and perfusion MRI, have significantly enhanced the ability to predict glioma malignancy and understand tumor behavior.[119.1] These modern MRI techniques are pivotal in diagnosing gliomas, as they can noninvasively assess the genetic profile of tumors, which influences their metabolic pathways and cell behavior.[100.1] Furthermore, the integration of artificial intelligence (AI) with multimodal MRI data is anticipated to usher in a new era of precision in glioma diagnosis and therapy, leading to increasingly personalized treatment strategies.[101.1] Diffusion-tensor imaging (DTI), a functional imaging technology based on diffusion-weighted imaging, allows for a comprehensive evaluation of the diffusion movement of water molecules. This technique provides insights into the degree of compression, infiltration, and destruction of surrounding white matter fiber bundles, which is critical for understanding the tumor's impact on adjacent brain structures.[102.1] Additionally, resting state fMRI (rs-fMRI) is increasingly utilized to analyze spontaneous fluctuations in blood-oxygenated-level-dependent (BOLD) signals, further enhancing the diagnostic capabilities for gliomas.[103.1] Despite these advancements, the diagnostic accuracy of imaging techniques to delineate gliomas has not been systematically addressed. A meta-analysis has sought to estimate and compare the diagnostic accuracies of conventional imaging techniques and advanced MRI and PET imaging for newly diagnosed diffuse gliomas.[115.1] The findings suggest that while conventional imaging provides useful structural information, it is often insufficient for reliable differentiation between low-grade and high-grade gliomas, underscoring the importance of integrating advanced imaging techniques into clinical practice.[118.1]In this section:
Treatment Options
Surgical Interventions
Surgical interventions for glioma treatment have evolved significantly, focusing on maximizing tumor removal while minimizing surgical morbidity and postoperative neurological deficits. The primary objectives of low-grade glioma (LGG) surgery are to achieve maximal tumor resection and to reduce the risks associated with the procedure.[137.1] Recent advancements in surgical tools and techniques, such as intra-operative imaging, fluorescent agents, and functional imaging sequences, have enhanced the ability to identify tumor borders and critical brain areas, thereby improving the rates of complete resections.[136.1] The decision-making process regarding the extent of tumor resection is influenced by several factors, including the resectability of the tumor, which is determined by its characteristics and location.[154.1] Surgeons must assess whether a gross total resection (GTR) is feasible, or if a partial resection or biopsy is more appropriate. The aim of resection is not only to alleviate mass effect but also to obtain brain tissue for pathological analysis, which is crucial for determining the appropriate treatment plan.[155.1] Intraoperative techniques, such as neuronavigation and intraoperative MRI, have been shown to improve the extent of resection and subsequently enhance patient outcomes. A systematic review indicated that the use of intraoperative MRI correlates with improved quality of life and survival rates in glioma patients.[155.1] Furthermore, studies have demonstrated that achieving at least 90% extent of resection (EOR) is associated with significantly better overall survival rates, with patients reaching a 5-year overall survival (OS) of 97% compared to 76% for those with less than 90% EOR.[139.1] Despite these advancements, the risks associated with surgical interventions remain a concern. Treatment-associated morbidity can be moderate, and factors such as patient age and performance status are critical predictors of survival outcomes.[156.1] As the field progresses, the balance between the benefits of aggressive tumor resection and the potential risks continues to be a subject of ongoing research and evaluation.[156.1]Adjuvant Therapies (Radiation and Chemotherapy)
Adjuvant therapies for glioma, particularly radiation and chemotherapy, play a crucial role in the management of this type of brain tumor. Following initial treatment, which often includes surgery, adjuvant therapies are employed to target residual tumor cells and reduce the risk of recurrence. Radiation therapy is commonly recommended after surgery, especially for high-grade gliomas, to eliminate remaining cancer cells and improve overall survival rates. The standard approach typically involves conventionally fractionated radiation therapy, delivering a total dose of approximately 60 Gy in 2-Gy fractions.[158.1] Recent advancements in radiation techniques, such as hypofractionated proton beam therapy, have shown promise in improving outcomes for patients, particularly those over the age of 65 with newly diagnosed glioblastoma.[146.1] Additionally, innovative methods like proton-minibeam radiation therapy (pMBRT) are being explored, which may enhance dose distribution and minimize damage to surrounding healthy tissue.[148.1] Chemotherapy is another critical component of adjuvant treatment for gliomas. The choice of chemotherapy agents often depends on the molecular characteristics of the tumor, including specific genetic mutations. For instance, targeted therapies such as IDH inhibitors and BRAF/MEK inhibitors have emerged as effective options for gliomas with corresponding mutations, potentially offering more personalized treatment strategies.[150.1] The integration of molecular testing into treatment planning allows for a tailored approach, enhancing the therapeutic ratio of conventional and experimental therapies.[151.1]Recent Advancements
Molecular Characterization and Targeted Therapies
Recent advancements in molecular characterization have significantly influenced the development of targeted therapies for gliomas. The integration of high-throughput Next Generation Sequencing (NGS) has enhanced the understanding of the molecular pathogenesis of high-grade gliomas, allowing for the identification of genetic alterations that can direct personalized cancer treatments for patients with these tumors.[192.1] This progress has been pivotal in informing diagnostic classifications and targeted treatment strategies, thereby facilitating personalized medicine approaches in neuro-oncology.[193.1] Moreover, the role of molecular profiling has become integral to the 2021 WHO classification of gliomas, underscoring its importance in the treatment landscape.[194.1] Despite the challenges posed by the blood-brain barrier and tumor heterogeneity, advancements in molecular profiling have opened new avenues for investigating glioma mechanisms and therapies.[195.1] These developments are crucial for the validation of biomarkers that can aid in treatment decisions, ultimately allowing for more tailored therapeutic strategies.[193.1] In addition to molecular profiling, the emergence of molecular targeted therapies and immunotherapies has marked a significant breakthrough in glioma treatment. These therapies are a result of advances in tumor molecular biology and molecular immunology, which have paved the way for precision treatment approaches.[173.1] Promising agents such as Zotiraciclib and Lerapolturev are currently being explored within the context of immunotherapy, highlighting the potential for these strategies to improve patient outcomes.[174.1] The future of glioma treatment is increasingly leaning towards personalized medicine, which aims to tailor therapeutics to individual patients based on their unique genomic profiles.[203.1] This approach not only maximizes therapeutic efficacy but also addresses the evolving molecular targets present in malignant glioblastoma cells.[203.1] As research continues to progress, the combination of molecular characterization and targeted therapies holds great promise for enhancing treatment efficacy and improving survival rates for glioma patients.In this section:
Epidemiology And Risk Factors
Incidence and Demographics
Gliomas represent the most common type of primary intracranial tumors, with diffuse gliomas being the predominant malignant brain tumors in adults. The epidemiology of gliomas, including their incidence and mortality rates, has been the subject of extensive research, revealing significant trends over time. Notably, the incidence of gliomas did not change significantly from 1975 to 2018, with an average annual percentage change (APC) of 0.0% during this period; however, a significant increase in incidence was observed from 1975 to 1987.[221.1] Demographic studies have highlighted variations in glioma incidence by subtype and age. For instance, research conducted in the United States from 1992 to 2007 indicated that different glioma subtypes, such as astrocytomas and oligodendrogliomas, exhibited distinct demographic trends.[223.1] Furthermore, a significant decline in glioma incidence and mortality rates was noted from 1987 to 2018, particularly in non-glioblastoma astrocytomas, which contributed most to the overall trends.[224.1] The analysis of glioma incidence data from the SEER-9 incidence database, which encompasses cases from nine high-quality registries covering approximately 9.4% of the U.S. population, provides a comprehensive overview of these trends.[227.1] This data indicates that while the overall incidence remained stable, specific demographic factors, including age and calendar period, may influence the incidence rates of different glioma subtypes.[226.1]Environmental and Genetic Risk Factors
Gliomas are influenced by a combination of environmental and genetic risk factors. Among the environmental factors, exposure to ionizing radiation is the only well-established risk factor for glioma development. This association is particularly evident in patients who have received high-dose radiotherapy for other cancers during childhood, as well as in those exposed to low-dose cranial and cervical irradiation for conditions such as tinea capitis.[245.1] Despite the established link with ionizing radiation, the overall incidence of gliomas remains low, and the role of other environmental exposures has been less thoroughly investigated.[248.1] In addition to ionizing radiation, certain lifestyle and occupational exposures may also contribute to glioma risk. Analytic epidemiologic studies have sought to identify potential risk factors by comparing individuals with and without glioblastoma, focusing on various characteristics, including environmental and occupational exposures.[247.1] However, the evidence regarding these additional environmental factors remains inconclusive, necessitating further research to clarify their roles in glioma etiology.[248.1] Genetic factors also play a significant role in glioma risk. Approximately 25% of the variance in glioma incidence can be attributed to genetic factors, with only a portion of this explained by currently identified genetic variants.[220.1] While most gliomas develop without a family history, certain inherited genetic variations have been linked to increased susceptibility. For instance, rare genetic syndromes such as Li-Fraumeni syndrome, associated with TP53 mutations, and neurofibromatosis types 1 and 2 are known to contribute to glioma risk.[239.1] Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) that are associated with glioma, with some variants significantly increasing the relative risk of developing specific types of gliomas.[240.1]In this section:
Prognostic Factors
Clinical Characteristics
The clinical characteristics of gliomas are critical in determining prognosis and guiding treatment decisions. Histopathological analysis remains a cornerstone in the diagnosis and classification of gliomas, with the World Health Organization (WHO) tumor grade being the most established prognostic factor. This grading system assesses tumor aggressiveness and its resemblance to normal brain tissue, which is essential for predicting patient outcomes and tailoring treatment strategies.[273.1] Molecular factors have increasingly been recognized as significant prognostic indicators. Key molecular markers include isocitrate dehydrogenase (IDH) status and 1p/19q co-deletion, which have been shown to influence survival outcomes in glioma patients. IDH mutations are particularly important, as they correlate with better prognoses in glioma patients, especially when combined with extensive surgical resection.[276.1] Additionally, the presence of CDKN2A deletions has been associated with shorter progression-free survival (PFS) and overall survival (OS) in both lower-grade and high-grade gliomas.[264.1] Age is another critical factor influencing prognosis. Younger patients generally have better outcomes, while older patients (aged 60 years and above) are at a higher risk for poor prognosis.[270.1] The relationship between age and prognosis is complex and non-linear, suggesting that treatment decisions should be individualized based on precise age considerations.[267.1] Furthermore, clinical parameters such as the Karnofsky Performance Status (KPS) and the extent of surgical resection also play vital roles in prognostication. Low preoperative KPS scores and partial tumor resection are associated with worse survival outcomes.[271.1]Molecular Markers
Molecular markers have become increasingly significant in the prognostication and treatment of gliomas, particularly following the 2016 update to the World Health Organization (WHO) classification system, which integrated molecular profiles into glioma classification. This shift has prompted extensive research into the utility of molecular signatures for predicting prognosis and therapeutic responses in glioma patients.[279.1] Among the most notable molecular prognostic factors are mutations in the IDH1 and IDH2 genes, as well as the methylation status of the MGMT promoter. These factors have been identified as promising biomarkers that can significantly influence survival outcomes in patients with glioblastoma (GBM).[280.1] The presence of IDH mutations, particularly IDH1, is associated with a better prognosis and has been shown to affect the tumor's biological behavior, including its response to chemotherapy.[297.1] Specifically, IDH1 mutations lead to cell cycle arrest and increased sensitivity to chemotherapy, which may explain the improved survival rates observed in patients with these mutations compared to those with wild-type IDH1.[297.1] Furthermore, the classification of gliomas now relies heavily on the identification of these mutations and the presence of 1p/19q co-deletions, which are essential for accurate diagnosis and treatment planning.[296.1] In addition to IDH mutations, the methylation status of the MGMT promoter is another critical factor that influences treatment decisions. Methylation of the MGMT promoter is associated with a favorable response to alkylating agents, making it a vital consideration in the development of personalized treatment plans for glioma patients.[280.1] The integration of these molecular markers into clinical practice aims to enhance the personalization of treatment strategies, allowing for more tailored therapeutic approaches based on individual tumor characteristics.[282.1] Despite the promising potential of molecular biomarkers, several challenges remain in their integration into routine clinical practice. One significant obstacle is the high degree of intratumoral heterogeneity, which can result in varying genetic and molecular profiles within the same tumor.[283.1] This complexity complicates the application of molecular markers in clinical settings and highlights the need for ongoing research to refine prognostic models and improve treatment outcomes for glioma patients.[281.1]Challenges In Treatment
Treatment Resistance
Glioblastoma (GBM), classified as a Grade 4 glioma by the World Health Organization (WHO), presents significant treatment resistance due to its aggressive and invasive nature, rapid growth, and inherent resistance to conventional therapies such as chemotherapy and radiation.[304.1] Approximately 80%-85% of malignant brain tumors in adults are gliomas, with GBM being the most prevalent and lethal form.[305.1] The diffuse invasion characteristic of GBM allows the tumor to evade complete surgical resection and diminishes the efficacy of chemoradiation therapy.[306.1] The resistance mechanisms in GBM are multifaceted. One major factor is the unique biology of GBM cells, which can evade the effects of standard treatments through increased resistance to cell death and the presence of genetically unstable and heterogeneous cell populations.[327.1] Additionally, GBM tumors often exhibit amplified expression of the epithelial growth factor receptor (EGFR), which enhances cell proliferation via the receptor tyrosine kinase/Ras/PI3K/AKT signaling pathway, further complicating treatment efforts.[307.1] Moreover, the complex microenvironment of GBM contributes to therapeutic resistance, characterized by immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood-brain barrier (BBB).[309.1] This environment not only protects the tumor from immune responses but also hinders the effectiveness of systemic therapies.[313.1] Recent advancements in nanotechnology have introduced innovative strategies aimed at overcoming these challenges. Engineered nanomaterials (ENMs) are being explored for their potential to enhance drug delivery specifically to glioma cells, thereby improving treatment outcomes.[320.1] However, the integration of these novel approaches into clinical practice remains challenging due to the need for effective targeting and the complexities of the tumor microenvironment.[315.1]In this section:
Future Directions
Emerging Research Areas
Emerging research areas in glioma treatment are increasingly focusing on the integration of novel therapeutic strategies and advanced technologies. One significant area of exploration is the use of immunotherapy, which includes approaches such as immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy. These strategies have shown promise in improving outcomes for glioblastoma (GBM) patients, with ongoing studies investigating combinatorial therapies aimed at enhancing antitumor immune responses while minimizing adverse side effects.[349.1] Additionally, the complex microenvironment of GBM presents substantial challenges to effective therapy, primarily due to factors such as immune evasion and limited drug penetration across the blood-brain barrier (BBB).[350.1] To address these challenges, recent advancements in nanocarrier-based drug delivery systems are being emphasized. These include innovative drug delivery methods utilizing liposomes, nanoparticles, and dendrimers, which are currently under investigation in clinical trials.[350.1] Another promising area of research involves the application of CRISPR/Cas9 gene-editing technology. This tool is being utilized to enhance our understanding of glioma biology, facilitate the establishment of tumor models, and screen for targeted therapies. Specifically, CRISPR/Cas9 has been employed to knock out genes associated with glioma cell survival and resistance to treatments such as temozolomide (TMZ), thereby providing insights into potential therapeutic targets.[380.1] The technology is also being explored for its role in immunotherapy, with studies indicating its potential to advance gene research and engineering strategies in glioma therapy.[378.1]Potential Innovations in Therapy
Integration of genome-wide data from various technologies has significantly advanced the identification of potential protein targets in glioma, enhancing the reliability and biological interpretability of results. This integration includes multi-omics data, such as genomics, transcriptomics, proteomics, and pathomics, which, when combined with radiomics, improves the understanding of the biological significance of radiomic features and enhances the prediction of genetic mutations, prognosis, and treatment response in glioma patients.[352.1] Furthermore, the identification of oncogenic gene fusions in diffuse gliomas has emerged as a potential therapeutic target and prognostic indicator, representing a novel strategy for personalized medicine in glioma treatment.[353.1] Despite these advancements, challenges remain in implementing personalized medicine based on genetic markers due to the heterogeneous genetic background of tumor cells, which is further complicated by epigenetic changes. These factors create obstacles for the detection, characterization, and treatment of glioblastomas, yet they also present opportunities for developing advanced diagnostic modalities and individualized therapies.[354.1] In terms of therapeutic innovations, nanoparticle technology has shown promise in targeting glioma cells more effectively than traditional treatment methods. Various classes of nanoparticles have been developed for glioma treatment, offering advantages such as multifunctionality, effective drug transport, and regulated drug cargo release.[358.1] Notably, nanoparticles can exploit biological pathways to achieve specific delivery to cellular and intracellular targets, including the ability to cross the blood-brain barrier, which many anticancer drugs cannot.[359.1] Recent studies have demonstrated the efficacy of bioadhesive nanoparticles that adhere to tumor sites and release therapeutic agents slowly, enhancing treatment outcomes for glioblastoma.[357.1] Moreover, a combinatorial, personalized approach to therapy is gaining traction, integrating standard care methods such as surgery, radiation, and chemotherapy with active immunotherapy and multiagent targeting of immunosuppressive checkpoints.[360.1] Immunotherapy strategies, including immune checkpoint inhibitors, adoptive T-cell therapies, tumor vaccines, and oncolytic viral therapies, are being explored to improve treatment outcomes in glioblastoma.[364.1] Trials involving dendritic cell vaccines targeting specific antigens have shown promising results, indicating a potential shift towards more effective immunotherapeutic strategies in glioma treatment.[363.1]References
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[93] Glioma: Types, Symptoms & Treatment Options Explained — The symptoms of glioma vary from person to person. The most common symptoms include: Headaches. Seizures. Nausea or vomiting. Difficulty with speech. Changes in vision or hearing. Weakness or numbness in limbs. Trouble thinking. Dizziness or lightheadedness. Changes in mood or personality
[96] Glioma | Brain Tumor Center | Stanford Medicine — Key Takeaways Diffuse gliomas are tumors that arise within the central nervous system. Headache and seizure are common presenting symptoms. Most gliomas occur in people without risk factors. Neurological examination, imaging, and tissue biopsy are the mainstays of glioma diagnosis. Surgical resection, radiation therapy, and chemotherapy are the primary treatment options.
[100] Beyond conventional imaging: Advancements in MRI for glioma malignancy ... — This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent primary brain tumors. Since the genetic profile of a tumor influences its metabolic pathways and can result in specific changes in cell behavior, advanced magnetic resonance imaging (MRI) techniques hold great promise as a noninvasive means to predict the type and behavior of gliomas. This article discusses glioma imaging diagnostics, focusing on modern MRI techniques to predict malignancy grade and genetic alterations, which play a pivotal role in shaping personalized treatment approaches. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas
[101] Multimodal MRI and artificial intelligence: Shaping the future of glioma — Multimodal MRI and artificial intelligence: Shaping the future of glioma - ScienceDirect Multimodal MRI and artificial intelligence: Shaping the future of glioma Magnetic resonance imaging (MRI) has not only remained at the forefront of glioma management but has also evolved significantly with the advent of multimodal MRI. Looking ahead, the integration of artificial intelligence (AI) with MRI data heralds a new era of unparalleled precision in glioma diagnosis and therapy. In summary, with the continuous advancement of multimodal MRI techniques and future deep integrations with artificial intelligence, glioma care is poised to evolve toward increasingly personalized, precise, and efficacious strategies. For all open access content, the relevant licensing terms apply.
[102] Study on the Relationship Between MRI Functional Imaging and Multiple ... — Diffusion-tensor imaging (DTI) is an in vivo functional imaging technology developed on the basis of diffusion-weighted imaging (DWI). It can comprehensively evaluate the diffusion movement of water molecules, the degree of compression, infiltration, and destruction of surrounding white matter fiber bundles from the microscopic perspective.
[103] Optimal Approaches to Analyzing Functional MRI Data in Glioma Patients — 1. Introduction. Functional magnetic resonance imaging (fMRI) is increasingly used to study patients with gliomas (Lv et al., 2022; Sighinolfi et al., 2022).Analysis of resting state fMRI (rs-fMRI) data involves evaluation of statistical features of spontaneous fluctuations in blood-oxygenated-level-dependent (BOLD) signals observed in the task-free state.
[105] Glioma - Symptoms and causes - Mayo Clinic — Symptoms. Glioma symptoms depend on the location of the glioma. Symptoms also may depend on the type of glioma, its size and how quickly it's growing. Common signs and symptoms of gliomas include: Headache, particularly one that hurts the most in the morning. Nausea and vomiting.
[106] Glioma Signs and Symptoms - Memorial Sloan Kettering Cancer Center — Headaches are a common symptom in people who have a glioma. About half of people with a glioma experience this symptom. For people with a glioblastoma, the headaches can be severe and are typically worse in the morning. Seizures. People with a glioma, especially an astrocytoma, often have seizures as an early sign of the condition. Nausea and
[108] Gliomas - Johns Hopkins Medicine — What are the symptoms of glioma? Gliomas cause symptoms by pressing on the brain or spinal cord. The most common, including glioblastoma symptoms are: Headaches Seizures Personality changes Weakness in the arms, face or legs Numbness Problems with speech Other symptoms include: Nausea and vomiting Vision loss Dizziness Glioblastoma symptoms and other symptoms of glioma appear slowly and may be
[115] Diagnostic Accuracy of Neuroimaging to Delineate Diffuse Gliomas within ... — The diagnostic accuracy of imaging techniques to delineate gliomas has not been systematically addressed, to our knowledge. In this meta-analysis, we estimate and compare the diagnostic accuracies of conventional imaging techniques and advanced MR imaging and PET to delineate newly diagnosed diffuse gliomas within brain tissue in adults.
[116] Advancements in Glioma MRI Techniques Explained — Diagnostic Accuracy: MRI is the gold standard for identifying gliomas and assessing their extent. Detailed imaging helps in pinpointing tumor borders, which informs surgical approaches and techniques.
[118] Clinical Imaging for Diagnostic Challenges in the Management of Gliomas ... — Neuroimaging plays a critical role in the management of patients with gliomas. While conventional magnetic resonance imaging (MRI) remains the standard imaging modality, it is frequently insufficient to inform clinical decision-making. There is a need for noninvasive strategies for reliably distinguishing low-grade from high-grade gliomas, identifying important molecular features of glioma
[119] Beyond conventional imaging: Advancements in MRI for glioma ... - PubMed — Beyond conventional imaging: Advancements in MRI for glioma malignancy prediction and molecular profiling - PubMed Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Your saved search Name of saved search: Beyond conventional imaging: Advancements in MRI for glioma malignancy prediction and molecular profiling Beyond conventional imaging: Advancements in MRI for glioma malignancy prediction and molecular profiling This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent primary brain tumors. The paper underscores the importance of integrating modern MRI modalities, such as diffusion-weighted imaging and perfusion MRI, which are essential for assessing glioma malignancy and predicting tumor behavior.
[136] Advances in Glioblastoma Operative Techniques - ScienceDirect — Advances in surgical tools and techniques such as intra-operative imaging, fluorescent agents, and functional imaging sequences are allowing for better identification of tumor borders and vital eloquent cortex in order to safely achieve higher rates of complete resections. ... Volumetric assessment of glioma removal by intraoperative high-field
[137] Advances in the Surgical Management of Low-Grade Glioma — Advanced Surgical Techniques Understanding the role of advanced surgical techniques. The objective of LGG surgery is twofold: 1) maximize tumor removal, and 2) minimize surgical morbidity and post-operative neurologic deficits. Modern surgical techniques have emerged in an attempt to better navigate these two operative obstacles.
[139] Surgical Management and Advances in the Treatment of Glioma — The role of surgical intervention and whether resection affects the progression toward malignancy for these lesions has been similarly debated and no conclusive, randomized controlled trial evidence exists owing to their rarity and propensity to affect younger patients.17 However, a study in 2012 of 212 patients with hemispheric LGG provided strong evidence that greater EOR was associated with improved outcomes and survival.18 Patients with at least 90% EOR achieved a 5-year OS of 97% compared with 76% for those with less than 90% EOR, and the significance of EOR on OS persisted after multivariate adjustment (p < 0.001). | Yong et al112 | 2014 | Prospective cohort | 97 | 97 (100%) | Survival benefit of maximal safe tumor resection in series of patients undergoing reoperation | Total postoperative survival: 12.4 mo (95% [CI]: 9.0–15.6 mo)
[146] Breakthrough in treatment approach showing promise in the fight against ... — Breakthrough in treatment approach showing promise in the fight against glioblastoma - Mayo Clinic Comprehensive Cancer Center Blog Sujay Vora, M.D., radiation oncologist with the Mayo Clinic Comprehensive Cancer Center, led a team of researchers investigating the use of short-course hypofractionated proton beam therapy incorporating advanced imaging techniques in patients over the age of 65 with newly diagnosed World Health Organization (WHO) grade 4, malignant glioblastoma. While El-Afandi's results are encouraging, William Breen, M.D., a radiation oncologist with the Mayo Clinic Comprehensive Cancer Center and principal investigator of the current study says it is too early to draw any conclusions about the safety and efficacy of the treatment until the study is complete. Brain Cancer Dr. Sujay Vora Featured glioblastoma glioma proton beam therapy Research and Clinical Trials
[148] From pre-clinical studies to human treatment with proton-minibeam ... — The implementation and spread of new radiation therapy (RT) techniques are often rushed through before or without high-quality proof of a clinical benefit. ... proton-minibeam radiation therapy (pMBRT) is considered an innovation in RT . This new technique of ... Dose distributions of proton-minibeam radiation therapy for a glioma case and
[150] New Hope for Glioma Patients: Explaining Advancing Treatments ... — Glioma Treatment Advances: New Therapies Explained_Dr. Howard Colman_Huntsman Cancer Institute Targeted Therapies: Newer treatments, such as IDH inhibitors (vorasidenib) and BRAF/MEK inhibitors, target specific genetic mutations in gliomas, potentially offering more personalized and effective treatment options. Dr. Howard Colman, a neuro-oncologist at the Huntsman Cancer Institute at the University of Utah in Salt Lake City, tells us that while medical advancements have significantly deepened our understanding of this disease and its treatment, there is still much research to be done to provide much needed hope in the treatment of gliomas. IDH Inhibitors: For gliomas with IDH1 or IDH2 mutations, these treatments work by targeting the cancer’s growth process, helping to slow down tumor development and help your body fight the disease.
[151] Recent advancements in multimodality treatment of gliomas — Identifying the best treatment for each grade and molecular subtype of gliomas will help guide physicians in providing more effective therapies for patients. The current trends in cancer research aim to identify novel molecular targets for each glioma grade, and thereby enhance the therapeutic ratio of conventional and experimental therapeutics.
[154] Implications of use of different intraoperative ultrasound modalities ... — The resectability of the tumor likely influences the surgeon's goal, dictating whether a GTR would be achievable or not, whether debulking (partial resection or subtotal resection) would be indicated or whether a patient should undergo a biopsy only .Due to the complex nature of these tumors , the resectability of the tumor is assessed from tumor characteristics derived from
[155] Chapter 12 Surgical Management of Glioblastoma - National Center for ... — The purpose of resection is to remove as much tumor as possible to alleviate mass effect and to obtain brain tissue for pathological analysis (class I evidence) (30).Tumor recurrence occurs within a 2-cm margin of the primary site in 90% of the cases (31–33). A systematic review of existing data on the use of intraoperative MRI for glioma surgery revealed 12 high-quality studies providing level II evidence for the use of intraoperative MRI to improve the extent of resection, quality of life, and survival in glioma patients (46). A key element to reduce surgical complications is the correct position of the patient, as it will provide a good surgical corridor minimizing brain tissue retraction.
[156] Risks and Benefits of Glioblastoma Resection in Older Adults: A ... — Nonetheless, the observed treatment-associated morbidity and treatment burden were moderate in the patients, and patient age and performance status remained the strongest predictors for survival. The risks and benefits of tumor resection in the age of biomarker-adjusted treatment concepts require further prospective evaluation.
[158] Radiation therapy for glioblastoma: Executive summary of an American ... — Purpose: To present evidence-based guidelines for radiation therapy in treating glioblastoma not arising from the brainstem. ... Results: Following biopsy or resection, glioblastoma patients with reasonable performance status up to 70 years of age should receive conventionally fractionated radiation therapy (eg, 60 Gy in 2-Gy fractions) with
[173] Advancements in targeted and immunotherapy strategies for glioma ... — Frontiers | Advancements in Targeted and Immunotherapy Strategies for Glioma: Toward Precision Treatment Frontiers in Immunology More from Frontiers Frontiers in Immunology More from Frontiers Frontiers in Immunology Frontiers in Immunology This article is part of the Research Topic Harnessing Molecular Insights for Enhanced Drug Sensitivity and Immunotherapy in Cancer View all 10 articles You have multiple emails registered with Frontiers: In recent years, significant breakthroughs have been made in cancer therapy, particularly with the development of molecular targeted therapies and immunotherapies, owing to advances in tumor molecular biology and molecular immunology. Keywords: high-grade glioma, Immunotherapy, targeted therapy, Molecular Biology, Treatment Copyright: © 2024 Guangyuan, Jiang, Zhou and Su. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
[174] Innv-18. Focus on Current and Emerging Treatment Options for Glioma: a ... — With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev.
[192] Impact of next generation sequencing in high grade glioma management ... — Background: Recent advances in genomic profiling have improved our understanding of the molecular pathogenesis of high grade gliomas. Increased availability of high-throughput Next Generation Sequencing (NGS) allows the identification of genetic alterations which could direct personalized cancer treatments for HGG patients.
[193] Molecular Profiling in Neuro-Oncology: Where We Are, Where We're ... — Advances in molecular profiling have led to improved understanding of glioma heterogeneity. Results have been used to inform diagnostic classification and targeted treatment strategies. Validation of these tests is necessary in the development of biomarkers that can aid in treatment decision, allowing for personalized medicine in neuro
[194] Molecular Profiling and Targeted Therapies in Gliomas — Molecular profiling is an integral part of the 2021 WHO classification of gliomas. Progress in the development of targeted therapies remains limited due to many factors including the presence of the blood-brain barrier and issues of tumor heterogeneity. Nonetheless, advances have been made with the …
[195] Machine learning unravels the mysteries of glioma typing and ... - PubMed — Gliomas, which are complex primary malignant brain tumors known for their heterogeneous and invasive nature, present substantial challenges for both treatment and prognosis. Recent advancements in whole-genome studies have opened new avenues for investigating glioma mechanisms and therapies. Through …
[203] Personalised therapeutic approaches to glioblastoma: A systematic ... — (A) Glioblastoma presents as a space occupying tumour within the central nervous system, most commonly occurring within the supratentorial region.(B) Personalised medicine aims to tailor therapeutics to individual patients to maximise efficacy: numerous genomic variants have been identified as potential targets in glioblastoma.(C) Molecular targets in malignant glioblastoma cells evolve over
[220] Risk factors for childhood and adult primary brain tumors — The proportion in incidence variance of glioma estimated as being attributable to genetic factors is 25%, and ~30% of this is explained by currently identified variants, with 70% of the genetic risk unexplained. 13,21 Many of these factors have stronger associations with specific grades and histologies of glioma, though some confer increased
[221] Trends in Intracranial Glioma Incidence and Mortality in the United ... — According to demographic and glioma characteristics, trends in glioma incidence was showed in Figure 1 and Table 2. Joinpoint program divided the trends into a minimum of 1 to a maximum of 5. During the entire study period, glioma incidence did not change significantly (APC=0.0), but its incidence increased significantly from 1975 to 1987
[223] Demographic variation in incidence of adult glioma by subtype, United ... — Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007. Robert Dubrow 1 and ... We also tested the hypothesis that calendar period trends in adult glioma incidence varied by subtype. The three main categories of adult glioma according to traditional pathological classification are astrocytoma, oligodendroglioma
[224] Trends in Intracranial Glioma Incidence and Mortality in the United ... — Significant decline in glioma incidence (1987-2018) and mortality (1995-2018) were observed. Epidemiological changes in non-glioblastoma astrocytoma contributed the most to overall trends in glioma incidence and mortality. These findings can improve understanding of risk factors and guide the focus …
[226] (PDF) Trends in Intracranial Glioma Incidence and Mortality in the ... — | Trends in Annual Glioma Incidence Rates. (A) represents glioma incidence (1975-2018), overall and by histologic type. (B) represents glioblastoma incidence (1975-2018) by age group.
[227] Trends in Intracranial Glioma Incidence and Mortality in the United ... — Information on glioma incidence was extracted from the SEER-9 incidence database , containing cases from nine high-quality registries (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta), which covers approximately 9.4% of the U.S. population. Though the SEER database contains cases diagnosed starting with
[239] Genetics in glioma- lessons learned from genome wide association ... — Rare genetic syndromes with germline mutations are well known to be causal for gliomas, such as the Li-Fraumeni syndrome caused by TP53 mutations, neurofibromatosis type 1 and 2. ... EGFR and CDKN2A/B are frequently mutated in gliomas and SNPs within or near these genes are associated with the development of gliomas. SNPs in 8q24 and 11q23.3
[240] Genes linked to familial brain cancer identified in Stanford Medicine ... — All told, the researchers identified 54 mutations in 28 genes or non-coding regions that were associated with familial glioma in 50 out of 304 families in the Gliogene study. Many of the genes are involved in cell division, blood vessel development and immune regulation - all factors that can contribute to tumor growth.
[245] Environmental risk factors of primary brain tumors: A review — The role of ionizing radiation as a risk factor for brain tumors, and especially glioma, meningioma and nerve sheath tumors, is well established, especially in patients who underwent brain high-dose radiotherapy for cancer treatment in childhood , .Moreover, among 10,834 patients receiving low-dose cranial and cervical irradiation for tinea capitis (mean dose to neural tissue: 1.5 Gy
[247] Potential risk factors for incident glioblastoma multiforme: the ... — Analytic epidemiologic studies of glioblastoma compare the risk of developing GBM in persons with and without certain characteristics (cohort studies) or compare the histories of persons with and without GBM (case–control studies) to identify possible risk factors including lifestyle habits, environmental and occupational exposures to toxic agents, genetic factors and infections. The incidence rate for GBM in this study of 6.2 per 100,000 person–years is lower than that reported for US men and women in the 65–74 year age group (12.47 per 100,000 person–years) . Although this study has a relatively small number of incident GBM cases and resultant statistical power is low, results indicate that at least two variables are worthy of further investigation, intensity of carbon tetrachloride exposure and dietary levels of glucose.
[248] Impacts of Environmental Pollution on Brain Tumorigenesis — Environmental components often combine with other risk factors, such as the individual genetic component, which increases the chance of developing cancer. The objective of this review is to discuss the impact of environmental carcinogens on modulating the risk of brain tumorigenesis, focusing our attention on certain categories of pollutants
[264] Prognostic and Predictive Biomarkers in Gliomas - PMC — Negative Prognostic Factor . Many studies have reported that CDKN2A deletion is associated with significantly shorter PFS and OS in both lower-grade glioma (LGG) and HGG (see Table 1) . The CDKN2A homozygous deletion is a significant prognostic factor in IDH-mutant glioma patients across multiple histologic WHO grades .
[267] Effect of age on treatment decisions in low-grade glioma — The age of the patients should therefore be considered when decisions on the treatment of supratentorial, non-pilocytic, low-grade gliomas. For patients under 35 years of age who have either epilepsy or a surgically inaccessible tumour, it is advisable to defer treatment. The tumour should be largely excised, if possible.
[270] Analysis of the Factors Affecting the Prognosis of Glioma Patients — Univariate analysis showed that age, tumor grade, preoperative KPS, surgical method, postoperative radiotherapy and chemotherapy, and postoperative TMZ treatment were the factors affecting prognosis (Table 1). Multivariate analysis indicated that elderly (age ≥ 60 years), high-grade, partial resection, low preoperative KPS (< 70), no postoperative radiotherapy and chemotherapy, and shorter course of postoperative TMZ (< 4 courses) were independent risk factors for prognosis of glioma patients (Table 2). Multivariate regression analysis showed that elderly (age < 60 years) patients, advanced tumors, partial resection, low preoperative KPS (< 70), no radiotherapy, no chemotherapy, and short TMZ course (< 4) are independent risk factors for the prognosis of glioma patients.
[271] Prognostic factors of patients with Gliomas - an analysis on 335 ... — In this study, we investigated clinical manifestations and prognostic factors of patients with gliomas through a retrospective analysis of clinical characteristics and follow-up data of 335 patients. The data included patient’s demographic data, tumor characteristics (i.e. lesion sites, pathological classification, grade, etc.), treatment approaches (i.e. surgical resection, radiotherapy, and chemotherapy), tumor markers expression (i.e. Ki-67, GFAP, p53, etc.), and survival time after treatment. Significant association of clinical parameters with the overall survival of glioma patients as examined by Kaplan-Meier analysis Our analysis clearly suggested that old age, high tumor grade, multiple lesions, and low KPS are associated with the poor survival of the patients. Our analysis suggested that low KPS is an independent risk factor for mortality within the first year after treatment and in long-term survival of glioma patients.
[273] Glioblastoma Histology - Key Insights - Acibadem Health Point ... — Tumor Grading in Glioblastoma When it comes to glioblastoma histology, tumor grading plays a pivotal role in determining the prognosis and guiding treatment decisions. Histopathological analysis allows pathologists to assess the characteristics of the tumor and assign a grade based on its aggressiveness and resemblance to normal brain tissue.
[276] Isocitrate dehydrogenase (IDH) status prediction in histopathology ... — As IDH is a very important prognostic, diagnostic and therapeutic biomarker for glioma, it is of paramount importance to determine its mutational status. The haematoxylin and eosin (H&E) staining is a valuable tool in precision oncology as it guides histopathology-based diagnosis and proceeding patient's treatment.
[279] Molecular Markers of Gliomas to Predict Treatment and Prognosis ... — Gliomas used to be classified mainly based on histopathological criteria. In 2016, the Word Health Organization introduced a new classification system incorporating the molecular profile of gliomas. This has prompted research on the utility of molecular signature of gliomas to predict prognosis and response to therapy. While experimental data appear to be promising, the clinical use of
[280] Molecular prognostic factors in glioblastoma: state of the art and ... — Classic prognostic factors such as patient's age and performance status, together with tumor characteristics, including grade and molecular features, predict survival in GBM patients. The methylation status of the MGMT gene promoter and mutation in IDH1 and IDH2 genes are among the most promising prognostic biomarkers in GBM.
[281] Molecular mechanisms and therapeutic targets in glioblastoma multiforme ... — The prognostic model enabled risk stratification among patients with gliomas. Validation of the prognostic model across multiple datasets and the correlation of the risk score with OS indicated
[282] Role of molecular biomarkers in glioma resection: a systematic review — Molecular biomarkers detected in diffuse gliomas are not only potential targets for radiotherapy, chemotherapy, and immunotherapy, but are also able to guide surgical treatment. Previous studies have suggested that the optimal extent of resection of diffuse gliomas varies according to the expression of specific molecular biomarkers.
[283] Predictive and Prognostic Significance of Molecular Biomarkers in ... — Using biomarkers in GBM treatment and prognosis faces several significant obstacles and limitations, which complicate their integration into routine clinical practice. One primary challenge is the high degree of intratumoral heterogeneity, where distinct regions within the same tumor display different genetic and molecular profiles.
[296] Next-Generation Sequencing Panel for 1p/19q Codeletion and IDH1-IDH2 ... — IDH mutations and 1p/19q codeletions are essential for proper classification of diffuse gliomas (oligodendroglioma, astrocytoma, and glioblastoma). 5 As previously shown for IDH1/IDH2 status, an appropriate technique for detecting molecular alterations in glioma is crucial to make the correct molecular diagnosis. 15 With this cytogenetic assay
[297] IDH1 overexpression induced chemotherapy resistance and IDH1 mutation ... — The IDH1 mutation caused cell cycle arrest in G1 stage and a reduction of proliferation and invasion ability, while raising sensitivity to chemotherapy. This may provide an explanation for the better prognosis of IDH1 mutated glioma patients and the relative worse prognosis of their wild-type IDH1 counterparts.
[304] Standard of Care Treatment for Glioblastoma Multiforme (GBM) — Glioblastoma (GBM) is the most aggressive and lethal form of primary brain tumor. Classified as a Grade 4 glioma by the World Health Organization (WHO), glioblastoma presents significant challenges for treatment due to its highly invasive nature, rapid growth, and resistance to most conventional therapies.
[305] Current challenges in the treatment of gliomas: The molecular era — Gliomas originate from glial cells in the central nervous system. Approximately 80%-85% of malignant brain tumors in adults are gliomas. The most common central nervous system tumor in children is low-grade pediatric glioma. Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological
[306] Glioblastoma — treatment and obstacles - PMC — The main obstacle for treatment efficacy is the diffuse invasion of the glioblastoma, which enables the tumor to evade complete resection and chemoradiation therapy .
[307] Current Challenges and Opportunities in Treating Glioblastoma — Additionally, epithelial growth factor receptor (EGFR) expression is amplified in some GBM tumors, leading to increased cell proliferation through the receptor tyrosine kinase/Ras/PI3K/AKT signaling pathway (Huang et al., 2009). Large-scale proteomic research has shown that GBM tumors have increased expression of membrane proteins involved in cellular function and maintenance (P = 2.03 × 10−8), protein synthesis (P = 7.74 × 10−11), cell-to-cell signaling and interaction (P = 1.82 × 10−10), cellular movement (P = 1.34 × 10−8), and antigen presentation (P = 2.24 × 10−7) compared with normal brain tissue (Fig. 4) (Polisetty et al., 2012). Annexin A2 is a calcium-binding cytoskeletal protein expressed in cancer cells and is strongly correlated with tumor aggression, metastasis, and glioma patient survival (Maule et al., 2016).
[309] Contemporary strategies in glioblastoma therapy: Recent developments ... — Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood–brain barrier (BBB). In this review, a comprehensive overview of recent advancements in nanocarrier-based drug delivery systems for GBM therapy is emphasized. Emphasis is placed on novel drug delivery systems, including liposomes, nanoparticles, and dendrimers, and the challenges they present in GBM treatment. Table 3 highlight the current status of clinical trials investigating drug delivery systems for GBM, highlighting ongoing research efforts, promising approaches, and their potential impact on improving treatment outcomes. Brain-targeted, drug-loaded solid lipid nanoparticles against glioblastoma cells in culture
[313] Nanotechnology as a new strategy for the diagnosis and treatment of gliomas — The current challenges in glioma treatment include difficulty in complete surgical resection, poor blood‒brain barrier (BBB) drug permeability, therapeutic resistance, and difficulty in tumor-specific targeting. In recent years, the rapid development of nanotechnology has provided new directions for diagnosing and treating gliomas.
[315] A Systematic Review of Nanomedicine in Glioblastoma Treatment: Clinical ... — Encasing anticancer medications into carbohydrate polymer NPs and directing them toward the tumor cells is one method of employing these NPs for the treatment of gliomas . It has been demonstrated that GBM is a non-T cell-inflamed cancer characterized by an immunosuppressive microenvironment and high immune escaping ability [ 66 ].
[320] Glioma diagnosis and therapy: Current challenges and ... - PubMed — Glioma diagnosis and therapy: Current challenges and nanomaterial-based solutions - PubMed 2 Interdisciplinary Center of High Magnetic Field Physics of Shenzhen University, College of Physics and Optoelectronic Engineering; Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen 518060, China; Shenzhen International Institute for Biomedical Research, 3/F, Building 1-B, Silver Star Hi-tech Industrial Park, Longhua District, Shenzhen 518110, China. 2 Interdisciplinary Center of High Magnetic Field Physics of Shenzhen University, College of Physics and Optoelectronic Engineering; Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen 518060, China; Shenzhen International Institute for Biomedical Research, 3/F, Building 1-B, Silver Star Hi-tech Industrial Park, Longhua District, Shenzhen 518110, China. Although glioma treatment remains a significant challenge for researchers and clinicians, the rapid development of nanomedicine provides tremendous opportunities for long-term glioma therapy.
[327] Glioblastoma Multiforme Therapy and Mechanisms of Resistance — 1. Introduction. Glioblastoma multiforme (GBM) is a grade IV brain tumor characterized by a heterogeneous population of cells that are genetically unstable, highly infiltrative, angiogenic, and resistant to chemotherapy [].GBM tumors harbor a series of mutations that provide cells with selective growth advantages that promote survival and proliferation in a hostile and hypoxic environment [].
[349] Emerging therapies for glioblastoma: current state and future directions — Following these encouraging findings, immunotherapy including immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have offered new hope for improving GBM outcomes; ongoing studies are using combinatorial therapies with the aim of minimizing adverse side-effects and augmenting antitumor immune responses. With these encouraging findings, immunotherapy including immune checkpoint blockade, chimeric antigen receptor T (CAR-T) cell therapy, oncolytic virotherapy and vaccine therapy have been actively tested in clinical trials for GBM . Recently, in an open-label, randomized, phase III trial (NCT01149109), combined lomustine-TMZ chemotherapy prolonged overall OS survival compared with standard adjuvant therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter , providing new evidence that dual agent treatment may be superior to TMZ alone for GBM .
[350] Contemporary strategies in glioblastoma therapy: Recent developments ... — Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood–brain barrier (BBB). In this review, a comprehensive overview of recent advancements in nanocarrier-based drug delivery systems for GBM therapy is emphasized. Emphasis is placed on novel drug delivery systems, including liposomes, nanoparticles, and dendrimers, and the challenges they present in GBM treatment. Table 3 highlight the current status of clinical trials investigating drug delivery systems for GBM, highlighting ongoing research efforts, promising approaches, and their potential impact on improving treatment outcomes. Brain-targeted, drug-loaded solid lipid nanoparticles against glioblastoma cells in culture
[352] Radiomics in glioma: emerging trends and challenges - PMC — Integrating multi‐omics data, such as genomics, transcriptomics, proteomics, and pathomics, with radiomics, aids the understanding of the biological significance of the underlying radiomics features and improves the prediction of genetic mutations, prognosis, and treatment response in patients with glioma.
[353] Identification of the clinical and genetic characteristics of gliomas ... — The identification of oncogenic gene fusions in diffuse gliomas may serve as potential therapeutic targets and prognostic indicators, representing a novel strategy for treating gliomas consistent with the principles of personalized medicine. This study identified detectable oncogene fusions in glioma patients through an integrated analysis of genomic and transcriptomic data, which encompassed
[354] Personalized medicine for glioblastoma: current challenges and future ... — In addition, epigenetic changes provide another means of modifying the existing heterogeneous genetic background of tumor cells. These cumulative changes create challenges for the detection, characterization and treatment of glioblastomas, but new opportunities allow the development of advanced diagnostic modalities and individualized therapies.
[357] New treatment merges two technologies to fight brain cancer — A team of researchers from Yale and the University of Connecticut (UC onn) has developed a nanoparticle-based treatment that targets multiple culprits in glioblastoma, a particularly aggressive and deadly form of brain cancer. The results are published Feb. 8 in Science Advances. The new treatment uses bioadhesive nanoparticles that adhere to the site of the tumor and then slowly release the
[358] Multimodal targeting of glioma with functionalized nanoparticles — The different classes of nanoparticles used for the treatment of glioma including their advantages and disadvantages are summarized in (Fig. 1). Nanomedicine has several advantages over traditional cancer therapies, including multifunctionality, effective drug transport, and regulated drug cargo release .
[359] Application of Nanoparticles on Diagnosis and Therapy in Gliomas — Nanoparticles can exploit some biological pathways to achieve specific delivery to cellular and intracellular targets, including transport across the blood-brain barrier, which many anticancer drugs cannot bypass. This review addresses the advancements of nanoparticles in drug delivery, imaging, diagnosis, and therapy in gliomas.
[360] Overview of current immunotherapeutic strategies for glioma — An emerging therapeutic strategy is represented by a combinatorial, personalized approach, including the standard of care: surgery, radiation, chemotherapy with added active immunotherapy and multiagent targeting of immunosuppressive checkpoints. ... (GBM [WHO grade IV]) is the deadliest and most common form of glioma (0.59-3.69 new cases in
[363] Advancements in targeted and immunotherapy strategies for glioma ... — Batich et al.’s phase I trial using a dendritic cell vaccine targeting CMV pp65 showed promising results, with median PFS and OS of 25.3 and 41.1 months, respectively, and some patients progression-free for over 7 years (53). Yao et al.’s phase II trial using dendritic cell vaccines loaded with GBM stem cell-like antigens demonstrated improved survival, with B7-H4-low expressing patients showing significantly better OS, indicating B7-H4 as a new target for glioma immunotherapy (54). Platten et al.’s phase I trial with an IDH1-targeting vaccine (IDH1-vac) led to a 3-year PFS of 63% and OS of 84%, marking a significant improvement in patient outcomes (56). doi: 10.1016/j.heliyon.2024.e37060 [DOI] [PMC free article] [PubMed] [Google Scholar] doi: 10.1016/j.cell.2013.09.034 [DOI] [PMC free article] [PubMed] [Google Scholar]
[364] Immunotherapy for glioblastoma: current state, challenges, and future ... — In this section, we discuss the current immunotherapeutic strategies designed for GBM, which include immune checkpoint inhibitors (ICIs), adoptive T-cell therapies, tumor vaccines, and oncolytic viral (OV) therapies (Fig. 1 and Tables 1, 2). Four main immunotherapeutic strategies (immune checkpoint inhibitors, adoptive T-cell therapies, cancer vaccines, and oncolytic viral therapies) have been developed for GBM. TIM-3 is a coinhibitory molecule expressed on immune cells, and TIM-3-targeted therapies are currently under investigation in various cancer types, including GBM . Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines, anti-PD-1 and poly I:C. Combination anti-CXCR4 and anti-PD-1 immunotherapy provides survival benefit in glioblastoma through immune cell modulation of tumor microenvironment.
[378] CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review — Current research is honing in on the promising potential of CRISPR/Cas9 as a cutting-edge gene-editing technology in the realm of immunotherapy for GBM. This innovation is gaining traction in various studies and holds the promise of evolving into a pivotal tool for advancing gene research and engineering strategies in glioma therapy [ 47 , 48 ].
[380] Progresses, Challenges, and Prospects of CRISPR/Cas9 Gene-Editing in ... — knocked out Ninjurin2 shRNA (via CRISPR/Cas9 gene-editing) in established primary human glioma cells, which effectively inhibited cell survival, growth, proliferation, migration, and invasion while inducing the activation of apoptosis . Some research also studied immunotherapy targeting glioma stem cells by knock-out B7-H6 with CRISPR/Cas9 gene-editing . introduced the CRISPR/Cas9 whole-genome lentivirus screening library into the human glioblastoma cell line to knock out or activate genes in order to identify the genes regulating the resistance of glioma cells to TMZ. The potential pathogenesis of glioma can also be studied with CRISPR/Cas9 gene-editing technology by mediating the directed mutation of glioma cells. 102.Kleinstiver B.P., Pattanayak V., Prew M.S., Tsai S.Q., Nguyen N.T., Zheng Z., Joung J.K. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects.