Astrocytoma Treatment & Management

Treatment options in astrocytomas include operative intervention, chemotherapy and radiotherapy. Treatment decisions are generally best made through a team approach, including input from the involved neurosurgeon, radiation oncologist, and medical oncologist or neurologist, as well as the patient and/or their family.

The multimodal treatment guidelines for IDH-mutated astrocytomas from the American Society of Clinical Oncology (ASCO) and Society of Neuro-Oncology (SNO) are summarized in the flow chart below.

IDH-mutant astrocytoma treatment guidelines.

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Surgical resection is the mainstay of operative treatment for astrocytomas. The goals of surgery are to debulk the tumor and collect sufficient tissue for diagnosis, while avoiding or limiting complications such as further neurologic injury. ^[28] Alternatively, stereotactic biopsy can be used for establishing a tissue diagnosis, but while it is safe and simple, it can be limited by the quantity of tissue obtained. The decision whether to perform surgical resection for astrocytoma necessitates a patient-specific discussion of risks and benefits and should be a shared decision between the neurosurgeon and the patient and/or family.

Surgical resection is often used for high-grade lesions, and in low-grade lesions if the neurosurgeon believes it can be done in a safe manner. Retrospective studies have reported that in patients with low-grade glioma, early surgical resection provides longer survival compared with watchful waiting. ^[32] In addition, in patients with IDH-mutant low-grade gliomas, larger extent of resection is associated with improved survival. ^[33]

Complete resection of astrocytoma is impossible, as the tumors often invade into adjacent regions of the brain, with diffuse microscopic tumor infiltration. Gross total resection (> 98% based on volumetric MRI) has been shown to improve median survival compared with subtotal resection (13 vs 8.8 mo). ^[34] For low-grade gliomas, retrospective data suggest that supratotal resection (ie, removal of tissue beyond the MRI-defined abnormalities) may increase overall survival. ^[35]

The boundaries of infiltrating tumors extend far beyond what can be seen on imaging studies. New methods of tumor imaging are being developed to specifically fluorescently tag or label tumor cells so they may be visualized in the operating room, to guide surgical resection. Such methods used for astrocytomas include preoperative infusion of fluorescein and Gleolan (5-ALA/PPIX). ^[3]

Several methods can be used preoperatively and intraoperatively to map functional areas of the brain, such as those that control speech, language, and motor and sensory functions, if the tumor abuts these regions, to ensure the safe resection of the lesion while avoiding eloquent brain structures. Preoperative imaging studies that can assist in mapping critical motor and language areas include functional MRI (fMRI) and diffusion tensor imaging (DTI) tractography. ^[27] Mapping of these eloquent structures can also be done intraoperatively using direct cortical and subcortical stimulation, often with the patient awake and under local anesthesia, to test whether a suspected brain region corresponds to a critical motor or language area, ^[27] in a fashion similar to what is done in epilepsy surgery.

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.

If surgery is anticipated, patients should be transferred to institutions with an appropriately equipped and adequately staffed neurosurgical intensive care unit for postoperative monitoring. Patients may require extensive or focused postoperative rehabilitation that may necessitate transfer to specialized institutions dedicated to physical and occupational therapy. A postoperative MRI scan is often performed, to assess the extent of resection and potentially guide future oncologic management.

Radiotherapy and chemotherapy

In addition to surgical resection, external beam radiation therapy and adjuvant chemotherapy can be considered for patients with IDH-mutated astrocytomas, depending on extent of surgical resection and WHO grade. See Guidelines section for a summary of the recommendations by the American Society of Clinical Oncology (ASCO) and Society of Neuro-Oncology (SNO).

Management of low-grade astrocytomas can be controversial, as tumors may be radiographically stable and clinically quiescent for long periods after the initial presentation. ^{[36, 37]} For adult patients with low-grade astrocytoma, radiation therapy plus adjuvant chemotherapy has been found superior to radiation therapy alone. A phase II study of temozolomide-based chemoradiation therapy in 132 patients with high-risk low-grade astrocytomas reported median overall survival of 8.2 years. Long-term overall survival rates—73.5% at 3 years, 60.9% at 5 years, and 34.6% at 10 years—confirmed efficacy and exceeded historical survival rates of patients receiving radiation only. ^[38]  

In a phase III trial that included patients with low-grade astrocytoma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone tumor biopsy or resection, treatment with procarbazine, lomustine (CCNU), and vincristine (PCV) after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival at 10 years—51%, versus 21% with radiation therapy only—and overall survival at 10 years of 60% versus 40%, respectively.{ref31. It is important to note that these studies were performed on patients whose disease was classified using prior WHO grading, and thus the findings are not limited to IDH-mutated astrocytomas. ^[39]

Typically, higher-grade astrocytomas are treated with surgery, radiotherapy, and adjuvant temozolomide. Furthermore, some practitioners add temozolomide concurrently with adjuvant radiation, which has been associated with improved survival in higher-grade astrocytomas. ^[40]

Postoperative and symptomatic care

After undergoing surgical resection, most patients require initial admission to a neurologic or surgical intensive care unit for close monitoring of neurologic status, as well as management of any potential surgical complications. A postoperative MRI scan of the brain is often performed in the days to weeks following resection.

Patients with an astrocytoma and a history of seizures should receive anticonvulsant therapy, with monitoring of the drug concentration in the blood. For seizures, the patient is usually started on levetiracetam, phenytoin, or carbamazepine. Levetiracetam is often used because it lacks the effects on the P450 system seen with phenytoin and carbamazepine, which can interfere with antineoplastic therapy. The use of anticonvulsants prophylactically in astrocytoma patients with no history of seizures has been reported but remains controversial.

The use of corticosteroids, such as dexamethasone, can yield rapid improvement in many patients secondary to a reduction of tumor-associated vasogenic edema. Concurrent prophylaxis for gastrointestinal ulcers should be prescribed with corticosteroid administration.

Investigational therapy

Prognosis is still poor for many types of astrocytomas and other brain tumors. Thousands of patients with astrocytomas enroll in clinical trials each year. Investigational treatments are wide ranging, and fall into the following categories:

• Novel methods of radiotherapy, such as proton beam therapy and photodynamic therapy. ^{[41, 42]}
• New intracranial drug delivery strategies, such as convection-enhanced delivery and focused ultrasound. ^{[43, 44]}
• Therapies directed at key molecular alterations, such as drugs that target the IDH mutation. ^[45]
• Therapies targeted to engage the patient's own immune system to fight the tumor, such as cellular vaccines (eg, autologous tumor lysate–loaded dendritic cell vaccine), oncolytic viruses, chimeric antigen receptor (CAR) T-cell therapy, and immune checkpoint blockade. ^{[46, 47]}

Consultations for patients with astrocytoma include the following:

• A neurologist should be consulted to document a patient's detailed neurologic examination. This establishes a baseline and partly assesses the possibility of occult disease. 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 neuro-oncologist may be consulted to help coordinate a comprehensive therapeutic plan. Once a histologic diagnosis is determined, the neuro-oncologist should be consulted to provide comprehensive adjunctive therapy, including the use of chemotherapy and radiation.
• A radiation oncologist may be consulted for expertise on radiation therapy, including dosing and timing, and potential options for targeted radiation therapy.
• A neuroradiologist should be consulted to interpret cranial imaging, such as CT and MRI, to help narrow down a differential diagnosis and report any relevant anatomic considerations for surgical planning.

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

Neurologic injury (potentially devastating) and death are possible sequelae of operative intervention, neurosurgery for astrocytomas is intended to debulk tumor and to obtain tissue for diagnosis while minimizing neurologic injury. Several pre-operative and intraoperative studies can be used to map functional areas, such as those that control speech, language, motor and sensory functions, if the tumor abuts these regions, to ensure the safe resection of the lesion while avoiding eloquent brain structures.

Patients with astrocytomas often have significant vasogenic edema surrounding the tumor, which can cause mass effect and neurologic deficits. Corticosteroids, such as dexamethasone, can reduce tumor-associated vasogenic edema and produce rapid improvement in many patients. Steroids are often given first in a loading dose and subsequently tapered. ^[48]

Patients with astrocytomas often have glioma-associated epilepsy and seizures, and therefore should be monitored with electroencephalography and treated with anti-epileptic drugs, if necessary. See Treatment/Medical Care

Outpatient management includes the following:

• Patients should follow up with a neuro-oncologist to observe for progression of neurologic signs and symptoms, obtain serial MRI scans, and manage chemotherapy, radiotherapy, and steroid and anticonvulsant regimens.

• Patients may follow with a radiation oncologist if they are undergoing radiotherapy.

• Outpatient neurosurgery observation is necessary for tumor monitoring and management of hydrocephalus if a shunt has been placed.

• The frequency of postoperative MRIs is determined by both the neurosurgeon and other physicians involved in the ongoing care of the patient, including the neuro-oncologist and radiation oncologist.