How to treat gliomas with second-line therapies

With the knowledge of the grim prognosis of gliomas, how do you manage a patient with a suspected or definitive high-grade astrocytoma (grade III or IV)?

If the patient presents with significant neurological deficits, or if magnetic resonance imaging (MRI) discloses significant brain edema, mass effect, or a midline shift, start the patient on 4–6 mg of dexamethasone every 6 hours. This often will help manage presenting deficits. It also will help with severe headaches.

Also, initiate anticonvulsants for patients with glioma. Currently, 500–1 000 mg of oral levetiracetam twice a day is a popular treatment regimen. However, phenytoin, administered orally 3 times a day at 100 mg, has been a gold standard for decades.

Refer patients to a neurosurgeon

Patients who have been diagnosed with glioma should be referred to a neurosurgeon. If the patient is exhibiting profound lethargy, nausea and vomiting, or severe headaches, admit them to a hospital. These are signs of increased intracranial pressure and can suggest impending and abrupt deterioration.

If the patient develops these symptoms acutely, order an emergent non-contrast computed tomography (CT) scan of the head. High-grade astrocytomas are prone to hemorrhages, which can precipitate a sudden decline.

Follow up after neurosurgery

When following up with the patient after surgery, keep in mind that they will be shell-shocked, confused, and terrified. Often, these patients will not have fully digested all that was discussed with them in the hospital.

Help guide the patient to appropriate radiation medicine and oncology follow-up appointments. Be willing to discuss their disease with them at length. Be straightforward and honest with them but try not to overwhelm them with the grim prospects of the disease.

Offer a notion of hope. Acknowledge that the prognosis is poor, but that individual responses to the disease and treatments can vary tremendously, and some high-grade astrocytoma patients survive for many years. At the same time, acknowledge that it is important to prepare for a more challenging course (e.g., to get their affairs in order), and try to involve family members in all discussions and educational efforts whenever possible.

Be very alert for depression in patients with glioma. If this is at all a concern, start a selective serotonin reuptake inhibitor (SSRI) and refer the patient for counseling. As well, investigate if there are brain tumor support groups in your area. Keep in mind, family members will also be affected and may need help as well.

After surgery, patients often come to you still on corticosteroids (such as dexamethasone). This is generally maintained throughout radiation treatments.

Follow up after radiation treatment

After radiation, seek to minimize the patient’s steroid dosage as much as possible. Total elimination may prove impossible if the patient becomes symptomatic with increasing neurological deficits, cognitive difficulties, or severe headaches during tapering protocols.

Try to taper down the steroid dosage over two or more weeks. Be aware that the patient will be adrenal suppressed from the long-term steroid treatment and may require stress level doses if they become ill or require medical procedures.

Suspect hypo-adrenal crisis if the patient presents with diminished sensorium (reduced level of consciousness) and fever. Seek endocrinology support if there is any doubt about the steroid management. Some patients can be maintained on fairly high doses of corticosteroids. Don’t be surprised if you see typical morphological changes of hypercortisolism such as moon face, buffalo hump, stria, and increased abdominal fat. As well, watch for hyperglycemia.

Continue anticonvulsants indefinitely, as the patient has an intrinsic brain tumor that will act as a constant irritant. If the patient presents with breakthrough seizures, obtain serum anticonvulsant levels (if available), and consider increasing the dose of the current medication, changing medications, or adding another anticonvulsant.

Patients will often be on levetiracetam to manage seizures. There are no serum drug levels to test for this anticonvulsant. Make sure that the patient is compliant with taking the medication since compliance is a frequent problem. If they are compliant but are experiencing breakthrough seizures, the dose can often be increased.

Dilantin, sodium valproate, and carbamazepine are anticonvulsants that are frequently used, and serum drug levels can be checked for all three anticonvulsants. Consult the patient’s neurosurgeon or a neurologist if seizure control proves to be problematic.

Encourage the patient to remain active and involved. Poor neuropsychological status correlates with less optimal survival. Encourage healthy eating, exercise, and mental activity.

Monitoring for glioma recurrence

Obtain surveillance MRI of the brain every 3–4 months after surgery to look for recurrence. Recurrent tumors usually occur at the borders of the previous resection and feature an irregular region of decreased signal, a surrounding region of irregular and heterogeneous enhancement, and significant surrounding edema.

Sometimes the question is raised as to whether these findings represent radiation necrosis rather than tumor recurrence. Don’t be fooled; the grand majority of the time there is a recurrent tumor whether there is radiation necrosis or not.

Generally, a patient will do well for many months with no evidence of tumor recurrence. Then, seemingly out of the blue, they may rapidly develop new or recurrent neurological signs and symptoms, or a surveillance MRI will demonstrate a definitive tumor recurrence.

Note that some patients will go a year or more with no signs of recurrence, but you can be fairly certain that the tumor will come back. Other patients will shock you with the rapidity of their tumor recurrence. It is possible to see patients return 6 weeks after gross total resection of their tumors with recurrent lesions twice the size of the original.

Redo surgery for glioma recurrence

Generally, upon tumor recurrence, disease progression is rapid no matter the intervention. Nonetheless, the patient should be re-evaluated by neurosurgeons, radiation oncologists, and medical oncologists for potential treatment.

A repeat craniotomy and tumor resection (also referred to as redo surgery) is often performed to debulk the recurrent tumor. Sometimes, implanted chemotherapy or radiation seeds can be inserted at the time of redo surgery. Redo surgery has a higher complication rate, and even when combined with further adjunctive therapy, rarely extends the patient’s life by more than a few months.

Additional therapies for glioma recurrence

Minimally invasive interstitial laser ablation therapy has sometimes been employed for recurrent tumors, but the effectiveness of this treatment is still in question. Whole-brain radiation cannot be repeated for recurrent tumors since the patient has already received near-lethal doses to the surrounding brain.

Sometimes, stereotactic radiation is focused on the recurrent tumor. However, results have not been overly promising. Further runs of chemotherapy or protocoled drug trials can be employed but have also shown limited results.

Further recurrence is rarely treated aggressively, and patients are more often treated symptomatically. Most patients have resigned themselves to their fate and simply want to stay functional for as long as they can.

With recurrent tumors, reinitiate dexamethasone at the lowest possible levels to assist with symptoms. Over time, many signs and symptoms can be held at bay with increasing doses of dexamethasone.

However, the patient will eventually deteriorate. Imaging at this time will often demonstrate a markedly expanded tumor, spreading out well into critical regions of the brain. Withdrawal of steroids at this time generally results in a rapid and painless decline into coma and death.

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