GliomasEdit

Gliomas are a diverse group of primary brain tumors that arise from glial cells, the supportive cells of the central nervous system. They range from relatively slow-growing lesions to highly aggressive cancers that progress rapidly. Among gliomas, the most aggressive and well-known form is the glioblastoma, typically categorized as a grade IV tumor. The modern classification of these tumors integrates both traditional histology and molecular features, reflecting advances in our understanding of their biology. For example, mutations in isocitrate dehydrogenase (IDH) and the co-deletion of chromosomal arms 1p and 19q play important roles in prognosis and treatment planning. See how these terms relate in the broader landscape of neuro-oncology, including Glioma biology, Glioblastoma behavior, and the molecular subtypes defined by IDH1/IDH2 status and 1p/19q codeletion.

The clinical significance of gliomas lies in Their heterogeneity. Low-grade gliomas tend to grow slowly and may be compatible with longer survival, especially when they are located in non-eloquent brain regions; however, even these tumors can transform into higher-grade disease over time. In contrast, glioblastoma commonly presents with rapidly progressive symptoms and, despite advances in surgery, radiotherapy, and chemotherapy, remains the most challenging adult brain tumor to treat effectively. Management decisions reflect a balance between maximizing tumor control and preserving neurologic function, quality of life, and independence. See Epidemiology and Neuro-oncology for broader context.

Definition and classification

Glial tumors are grouped into categories that reflect both histology and molecular features. The major histologic types include:

Astrocytomas, which arise from astrocytes and can be graded from low to high grade.
Oligodendrogliomas, associated with a characteristic 1p/19q codeletion and often a better prognosis with alkylating chemotherapy.
Ependymomas, which originate from ependymal cells lining the ventricles and spinal canal, with variable behavior.

In recent WHO classifications, molecular markers are integrated with histology. Key factors include IDH1/IDH2 mutation status, 1p/19q codeletion, and for pediatric and midline tumors, specific alterations like H3 K27M. The term glioblastoma typically refers to a highly malignant, grade IV astrocytoma, most often IDH-wildtype in adults, though IDH-mutant glioblastomas also occur with distinct biology. See WHO Classification of Tumors of the Nervous System for the overarching framework.

Epidemiology and risk factors

Gliomas occur across age groups, with different subtypes showing distinct age distributions. Low-grade gliomas are more common in younger adults, while glioblastoma predominantly affects middle-aged and older individuals. Known risk factors include prior exposure to ionizing radiation; most cases arise sporadically, with inherited susceptibility playing a relatively small role outside known familial cancer syndromes. The landscape of risk is actively studied, with research exploring how genetic background and environmental factors influence susceptibility and tumor biology. See Epidemiology and Genetic predisposition to cancer for broader context.

Pathology and molecular biology

Histology provides essential information about tumor type and grade, but molecular markers have become equally important for prognosis and treatment decisions. Key molecular features include:

IDH mutations, which define a subset of lower-grade gliomas with a generally better prognosis and different treatment considerations. See IDH1 and IDH2.
1p/19q codeletion, classically associated with oligodendrogliomas and a more favorable response to certain chemotherapies. See 1p/19q codeletion.
MGMT promoter methylation, which predicts response to alkylating chemotherapy in some glioblastomas.
Other alterations such as EGFR amplification or TERT promoter mutations, which help define the biology of certain subtypes.

These molecular characteristics are used alongside histologic grading to stratify patients and guide management. For a broader view of tumor biology, see Genomics of brain tumors and Tumor mutational burden in the CNS context.

Clinical presentation

Patients with gliomas may present with a variety of neurologic symptoms that reflect tumor location and growth. Common presentations include new-onset seizures, headaches often worse in the morning, cognitive or personality changes, weakness or sensory loss on one side of the body, and visual or speech disturbances when tumors affect related networks. The symptom pattern can evolve as tumors progress or recur, which informs follow-up and imaging strategies. See Seizures and Neurologic examination for related topics.

Diagnosis

Diagnosis typically involves imaging and tissue sampling. Magnetic resonance imaging (MRI) with contrast is the standard noninvasive tool to characterize lesion size, location, and radiographic features suggestive of glioma. Definitive diagnosis requires histopathologic examination of a specimen obtained by biopsy or surgical resection, with concurrent molecular testing for factors such as IDH status, 1p/19q codeletion, MGMT methylation, and other relevant alterations. Multidisciplinary teams interpret imaging and pathology together to establish the diagnosis and plan treatment. See MRI and Neurosurgical biopsy for related topics.

Treatment

Therapeutic approaches depend on tumor type, grade, molecular features, patient age, and neurological status. Broad principles include maximal safe surgical resection when feasible, followed by adjuvant therapy to control residual disease.

Surgery: Aim is maximal safe resection to reduce tumor burden while preserving function. In eloquent cortex, surgeons use awake mapping and advanced techniques to minimize deficits.
Radiotherapy: Conventional fractionated radiotherapy is a standard component for many glial tumors, particularly after surgical resection or for unresectable disease.
Chemotherapy: The alkylating agent temozolomide is central to many regimens, especially in glioblastoma when combined with radiotherapy (the Stupp protocol). For oligodendrogliomas with 1p/19q codeletion, PCV chemotherapy plus radiotherapy is a commonly used approach that improves outcomes relative to radiotherapy alone.
Tumor treating fields (TTFields): A device delivering alternating electric fields has shown benefit in certain settings for glioblastoma, often in combination with chemotherapy, though access and cost considerations are discussed in practice.
Recurrent disease and trials: Bevacizumab is used for some recurrent cases to improve symptoms and progression-free survival but has not consistently demonstrated a clear overall survival benefit in all settings. Enrollment in clinical trials and consideration of re-resection, reirradiation, targeted therapies, or immunotherapies may be appropriate in selected patients. See Temozolomide, Bevacizumab, and Tumor treating fields for more.

Clinical guidelines and practice vary by region and over time as new evidence emerges. See Stupp protocol for the classic glioblastoma regimen and PCV chemotherapy for details on that strategy.

Prognosis

Prognosis varies widely by tumor type, molecular characteristics, and patient factors. Glioblastoma generally carries a poorer prognosis, with median survival on the order of roughly 12–18 months under standard therapy, though outcomes have improved for some patients with aggressive, multimodal management and favorable biology (such as certain IDH-mutant and 1p/19q codeleted tumors). Lower-grade gliomas can have substantially longer disease courses, particularly when they harbor favorable molecular features. Prognostic stratification now heavily weighs molecular markers in addition to histology. See Prognosis (cancer) and Glioblastoma for related discussions.

Controversies and debates

In the clinical realm, several ongoing debates influence care paths and research priorities. These include:

-Extent of resection in eloquent brain regions: balancing tumor debulking against the risk of lasting neurologic deficits. Centers vary in approaches to achieve durable control without compromising quality of life. See Surgical oncology and Neurosurgical mapping. - Use of TTFields: while evidence supports progression-free and sometimes overall survival benefits in glioblastoma, discussions continue about patient selection, cost-effectiveness, and long-term outcomes. See Tumor treating fields. - Bevacizumab for newly diagnosed glioblastoma: some guidelines restrict its use to progression, given mixed data on overall survival benefit versus symptom relief and cost considerations. See Bevacizumab in brain tumors. - Treatment of elderly patients: determining when aggressive therapy is warranted versus palliative approaches remains nuanced, with emphasis on functional status and patient preferences. See Geriatric oncology. - Access and equity: high-cost therapies and advanced imaging/genomic testing may create disparities in who benefits from modern care. See Health economics and Health disparities for broader context.