Astrocytoma Treatment & Management

Updated: Dec 07, 2017
  • Author: Benjamin Kennedy, MD; Chief Editor: Herbert H Engelhard, III, MD, PhD, FACS  more...
  • Print
Treatment

Approach Considerations

Treatment options in astrocytomas include operative intervention and the use of chemotherapy and radiation therapy. Treatment decisions are generally best made by a team approach, including input from the involved neurosurgeon, radiation oncologist, and medical oncologist or neurologist. Generally, care is primarily directed by a neurologist or specialist in neurooncology.

A study by Ishkanian et al found that adjuvant radiotherapy for pilocytic astrocytoma significantly prolonged progression-free survival (PFS) at both 5 years and 10 years compared with observation alone. However, the overall survival was equivalent. [22]

There is no accepted standard of treatment for low-grade or anaplastic astrocytoma. Typically, anaplastic astrocytomas are treated with surgery, radiotherapy, and adjuvant temozolomide. Some practitioners add concomitant temozolomide, though no data from controlled trials exist to support concomitant temozolomide. [2, 3]  

In a retrospective study of 165 adult patients with anaplastic astrocytoma who were receiving adjuvant radiation, concurrent treatment with temozolomide were associated with improved survival, as was isocitrate dehydrogenase (IDH) mutation. On univariable analysis, improved 5-year survival was independently associated with concurrent temozolomide  (46.2 vs. 29.3%, P = 0.02) and IDH mutation (78.9 vs. 22.0%, P <0.001). [23]

Anaplastic astrocytomas are usually more responsive to chemotherapy than glioblastomas. [24, 25] For recurrent anaplastic astrocytomas previously treated with nitrosoureas, temozolomide showed a 35% response rate, and compared to therapies with lower response rates, temozolomide provided an increased 6-month survival rate (46% vs 31%). [26, 27] Some smaller survival benefit has been shown with adjuvant carmustine. [4]

Treatment of low-grade astrocytomas remains more controversial. The role of maximal surgical resection, timing of radiotherapy, and the role, timing, and appropriate agents of chemotherapy are not clear. The controversy due to a lack of strong data is compounded by the relatively young age of the patients, the relatively indolent natural history of low-grade astrocytomas, and the morbidity associated with these interventions. [28, 29]

Patients with an astrocytoma and a history of seizures should receive anticonvulsant therapy with monitoring of the drug concentration in the blood. The use of anticonvulsants prophylactically in astrocytoma patients with no prior history of seizures has been reported but remains controversial.

The use of corticosteroids, such as dexamethasone, yields rapid improvement in most patients secondary to a reduction of tumor mass effect. Concurrent prophylaxis for gastrointestinal ulcers should be prescribed with corticosteroid administration.

See Brain Cancer Treatment Protocols for summarized information.

Brainstem gliomas

Brainstem tumors account for 10-20% [30] of all central nervous system (CNS) tumors in the pediatric population, and are typically diagnosed in children 7-9 years old. [31, 32] Though many classification schemes exist, treatment and prognosis for brainstem gliomas typically depend on whether the tumor is diffuse or focal.

Diffuse brainstem gliomas

Diffuse brainstem gliomas make up 58-75% [33] of all brainstem tumors, typically arise in the pons, and are noncircumscribed on MRI. They are often malignant fibrillary astrocytomas (WHO grade III or IV) that infiltrate along white-matter tracts into the midbrain and thalamus and have a rapidly progressive and fatal course.

Clinical presentation of these tumors often involves ataxia, cerebellar signs, and long tract signs. [34] When clinical and radiographic evidence suggests diffuse brainstem glioma, biopsy is of limited use as tumor histology does not often alter treatment. [33, 35, 36, 37, 38, 39, 40, 41]

No treatment has been shown to cure or prolong survival in these patients, and radiation necrosis and chemotherapy side effects can be significant. No benefit of surgical resection has been shown, largely due to the eloquence of the region and diffuse and aggressive nature of the tumor. [34, 42] Corticosteroids may provide temporary benefit by reducing edema.

Irradiation has been shown to provide temporary clinical improvement and is sometimes employed, but a large phase III trial showed no benefit. [43] Even with radiation therapy, 1-year survival has been shown to be 35-46%, and 3-year survival 11-17%. [44, 45]

Chemotherapy is also sometimes used. [46] Convection-enhanced delivery of chemotherapy offers one potential avenue for improving the prognosis of these patients, and studies are ongoing.

Focal brainstem gliomas

Focal brainstem gliomas are usually WHO grade I or II, well-circumscribed on MRI with variable contrast enhancement, are more often found in the medulla and midbrain and have a much better prognosis than diffuse brainstem gliomas. Surgery is often the primary treatment for focal brainstem gliomas as well as dorsal exophytic brainstem gliomas, though the decision to operate, surgical approach, and extent of resection depend on location, patient factors, and the surgeon's judgment.

Obstructive hydrocephalus is common. It is usually treated by a separate procedure, either endoscopic third ventriculostomy or shunt placement. [5]

In a study of 39 children (median age, 10 years) with low-grade glioma, treatment with intensity-modulated radiotherapy (IMRT) after incomplete resection or disease progression was found to provide local control rates comparable to those provided by 2-dimensional and 3-dimensional radiotherapy. The 8-year progression-free and overall survival rates with IMRT were 78.2% and 93.7%, respectively. [47, 48]

The researchers used three approaches to identify the target area for IMRT: The first method (n=19) was to delineate the gross tumor volume (GTV) and add a 1-cm margin to create the clinical target volume. In the second method (n=6), a 0.5-cm margin was added around the GTV to create the clinical target volume. For both methods, the prescribed GTV dose was the same as the clinical treatment volume: a median dose of 50.4 Gy.

Method 3 (n=14) was dose painting: the GTV was delineated and a second target volume was created by adding 1 cm to the GTV. The second target volume was treated with a lower radiation dose than the GTV (median, 41.4 Gy versus 50.4 Gy). Multivariate analysis showed no difference in progression according to the method of target delineation, suggesting that a 1-cm margin may not be necessary. [47, 48]

For a complete discussion of this topic, see Brainstem Gliomas.

Next:

Surgical Care

The roles of surgery in the patient with astrocytoma are (1) to remove or debulk the tumor and (2) to provide tissue for histological diagnosis, permitting tailoring of adjuvant therapy and assessment of prognosis. [49] A stereotactic biopsy is a safe and simple method for establishing a tissue diagnosis. The use of stereotactic biopsy can be limited by sampling error and the risk of biopsy-induced intracerebral hemorrhage. Diversion of CSF by external ventricular drain (EVD) or ventriculoperitoneal shunt (VPS) may be required to decrease ICP as part of nonoperative management or prior to definitive surgical therapy if hydrocephalus is present.

Total resection of astrocytoma is often impossible because the tumors often invade into adjacent regions of the brain and exhibit tumor infiltration that is detectable only on a microscopic scale. Therefore, surgical resection provides for improved survival advantage and histological diagnosis of the tumor rather than offering a cure. However, craniotomy for tumor resection can be performed safely and is generally undertaken with the intent to cause the least possible neurological injury to the patient.

Complete resection (>98% based on volumetric MRI) has been shown to improve median survival compared with subtotal resection (13 vs 8.8 mo). [50] For low-grade gliomas, some data support supratotal resection (ie, removal of tissue beyond the MRI-defined abnormalities), suggesting an increase in overall survival with this strategy. [51]

Previous
Next:

Consultations

A neurologist should be consulted to document a patient's detailed neurological examination. This establishes a baseline and partly assesses the possibility of occult disease. Employing multiple modalities, the neurologist must correlate the patient's symptoms with the findings on anatomic and functional imaging. This physician also may manage antiepileptic medication for patients who are having seizures.

A neurosurgeon should be consulted to assess the risks and benefits of surgical resection, stereotactic biopsy, stereotactic radiosurgery, and cerebrospinal fluid diversion.

A neurooncologist may be consulted to help coordinate a comprehensive therapeutic plan. Once a histological diagnosis is determined, the neurooncologist should be consulted to provide comprehensive adjunctive therapy, including the use of chemotherapy and radiation.

Previous
Next:

Activity

No broad restrictions on activity are prescribed, other than those dictated by the nature and the extent of neurological symptoms and disability. Seizures, if uncontrolled, may preclude driving. Physical and occupational therapy may be required for recovery of full or partial function.

Previous