Many gliomas infiltrate brain tissue diffusely and irregularly.
Astrocytomas are the most common gliomas. They are classified histologically and, in some cases, based on the presence of specific genetic markers, according to the WHO classification (1).
In ascending order of malignancy, astrocytomas are classified as
Pilocytic, low-grade, or anaplastic astrocytomas tend to develop in younger patients and can later evolve into glioblastomas (called secondary glioblastomas). Glioblastomas can also develop de novo (called primary glioblastomas), usually in middle-aged or elderly people. Glioblastomas contain chromosomally heterogeneous cells. Both primary and secondary glioblastomas have distinct genetic characteristics, which can change as the tumors evolve. Secondary glioblastomas typically have the IDH1 mutation.
Some astrocytomas contain oligodendroglioma cells; patients with these tumors (called oligoastrocytomas) usually have a better prognosis than those with pure astrocytomas.
Oligodendrogliomas (WHO grade II) are among the most slow-growing gliomas. They are most common in the forebrain, particularly the frontal lobes. Oligodendrogliomas are typically characterized by deletion of the p arm of chromosome 1 (1p deletion), deletion of the q arm of chromosome 19 (19q deletion), or both. These deletions are diagnostic for oligodendroglial tumors, predict longer survival, and predict a better response to radiation therapy and chemotherapy. Like astrocytomas, oligodendrogliomas can evolve into more aggressive forms, such as anaplastic oligodendrogliomas (WHO grade III), which are managed accordingly.
Diffuse midline gliomas are high-grade (WHO grade III to IV) astrocytic tumors that primarily affect children. These tumors include diffuse intrinsic pontine gliomas, which are aggressive and typically lethal tumors that infiltrate the brain stem with rostral extension into the hypothalamus and thalamus and that infiltrate the medulla and spinal cord inferiorly. Children with neurofibromatosis type 1 are at an increased risk of developing these tumors.
Ependymomas are uncommon in adults. They are classified as
All ependymomas typically arise from the ventricular wall and hence may arise in the brain, brain stem, or spinal cord. Ependymomas of the 4th ventricle in particular can manifest with obstructive hydrocephalus.
Symptoms and signs of gliomas vary by location (see Table: Common Localizing Manifestations of Primary Brain Tumors ). Diagnosis is the same as that of other brain tumors: MRI followed by biopsy.
1. Louis DN, Perry A, Reifenberger G, et al: The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 131 (6):803–820, 2016. doi: 10.1007/s00401-016-1545-1.
Treatment involves surgery, radiation therapy, and chemotherapy to reduce tumor mass. Excising as much tumor as possible is safe, prolongs survival, and improves neurologic function.
After surgery, patients receive a full tumor dose of radiation therapy (60 Gy over 6 wk); ideally, conformal radiation therapy, which targets the tumor and spares normal brain tissue, is used.
For glioblastomas, chemotherapy with temozolomide is now routinely given with radiation therapy. The dose is
During treatment with temozolomide, trimethoprim/sulfamethoxazole 800 mg/160 mg is given 3 times/wk to prevent Pneumocystis jirovecii pneumonia.
Patients receiving chemotherapy require a CBC at varying intervals.
Implantation of chemotherapy wafers during surgical resection may be appropriate for some patients.
Use of tumor-treating fields plus adjuvant temozolomide may be appropriate for some patients. Tumor-treating fields interfere with glioblastoma mitosis and organelle assembly by delivering alternating electric fields to the scalp. In one randomized clinical trial, tumor-treating fields appeared to improve survival in patients with glioblastoma (1).
Investigational therapies (eg, stereotactic radiosurgery, new chemotherapeutic drugs, gene or immune therapy, radiation therapy plus temozolomide) should also be considered.
After conventional multimodal treatment, the survival rate for patients with glioblastomas is about 50% at 1 yr, 25% at 2 yr, and 10 to 15% at 5 yr. Prognosis is better in the following cases:
Patients are < 45 yr.
Histology is that of anaplastic astrocytoma or a lower-grade tumor (rather than glioblastoma).
Initial excision improves neurologic function and leaves minimal or no residual tumor.
Tumors have the IDH1 mutation.
MGMT (methylguanine-methyltransferase) promoter methylation is present.
With standard treatment, the median survival time is about 30 mo for patients with anaplastic astrocytoma and about 15 mo for patients with glioblastomas.
Maximal safe surgical resection is indicated for low-grade astrocytomas and oligodendrogliomas. After complete resection in patients < 40, observation may be considered. For other patients, radiation therapy plus adjuvant chemotherapy prolongs survival (2).
Median survival ranges from 1 to 2 yr in high-risk patients (without the IDH1 mutation, with incomplete resection) to > 10 yr in those with favorable prognostic factors. In high-risk patients, malignancy is likely to progress further.
CSF sampling and craniospinal imaging should be used to stage ependymomas and to assess spread in the CNS.
Treatment of ependymomas includes maximal safe surgical resection for unifocal disease or symptomatic tumors. For higher-grade tumors, radiation therapy can be directed locally or include the entire craniospinal axis depending on how far the tumor has spread. The role of chemotherapy is not well-defined.
With treatment, overall 5-yr survival rate is about 50%; however, for patients with no residual tumor, the 5-yr survival rate is > 70%.
1. Stupp R, Taillibert S, Kanner A, et al: Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: A randomized clinical trial. JAMA 318 (23):2306–2316, 2017. doi: 10.1001/jama.2017.18718.
2. Buckner JC, Shaw EG, Pugh SL, et al: Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 374 (14):1344-1355, 2016. doi: 10.1056/NEJMoa1500925
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|No US brand name|