I sent my friend a funny text the other day. She didn't send back a laughing emoji, but instead told me that her brother had been diagnosed with glioblastoma. No emoji for that.
Glioblastoma is uncomfortably common (17,000 new cases per year), more so in whites and men than in blacks and women. (JAMA 2013;310:1842; http://bit.ly/2D7nj6k.) If you have a family history of glioblastoma, your risk of developing one increases twofold. Oddly enough, if you have asthma, eczema, or hay fever, the risk is lower. (J Natl Cancer Inst 2007;99:1544; http://bit.ly/2PcX45N.)
The term glioblastoma multiforme, which isn't used anymore, refers to the tumor's pleomorphic cells. Glioblastoma is the most common primary malignant tumor in adults and the deadliest of four grades of malignant gliomas, with a sobering survival rate of 35 percent at one year and four percent at five years. (Cancer Epidemiol Biomarkers Prev 2014;23:1985; http://bit.ly/2D77FI1.) Ionizing radiation is associated with the development of glioblastoma (Cancer 2008;113[7 Suppl]:1953; http://bit.ly/2Pbr4yR), and there has been noise about cell phone use increasing the risk. Although the explosion of cell phone use in the past 20 years has not been accompanied by a similar increase in glioblastoma, we don't know what the lag time is for development, especially in young brains with high cell turnover.
Half of glioblastoma patients present with a nonspecific headache that might have awoken them, and they are typically unilateral with gradual onset. Other characteristics to watch for include focal symptoms, nausea and vomiting, and cognitive or behavioral symptoms that might be mistaken for dementia. Imaging should be initiated to rule out a tumor in any patient over 50 with some of these characteristics. Papilledema from intracranial hypertension may be present, but is not usually seen in the undifferentiated patient at earlier stages. Around 40 percent of patients will have a focal onset seizure; gait abnormality and incontinence are other signs.
Get an MRI—the test of choice—with and without contrast if you are suspicious. You will likely see tumors with central necrosis and surrounding edema. These findings will be radiologically indistinguishable from those of other metastatic diseases, so rule out a primary malignancy. Other diagnoses may also present as mimics, including early stroke, abscess, lymphoma, autoimmune disease (MS, sarcoidosis, Behcet's), infectious lesions, and CNS tuberculosis. The most important one to recognize before treatment is CNS lymphoma because steroids will provide symptomatic edema relief. Dexamethasone is most commonly used (12-16 mg/day in divided doses), but will quickly mask the characteristic MRI findings of CNS lymphoma. Steroids should not be started before lymphoma is ruled out, which requires biopsy.
A Rough Road
Antiepileptic medication should be started if the patient has a seizure, but prophylaxis is not beneficial. Levetiracetam is preferred because it doesn't interact with most chemotherapy regimens. Importantly, phenytoin, carbamazepine, and phenobarbital will interact with chemotherapy agents.
Glioblastoma tumors do not metastasize but are highly infiltrative, making them extremely difficult to resect. Surgical treatment is a debulking procedure to decrease symptoms from mass effect, obtain some cells for identification, and reduce the tumor burden, but it doesn't eradicate the malignancy. Chemotherapy and radiation are also first-line adjuvant treatment regimens. The most commonly used chemotherapy is temozolomide, a DNA alkylating agent. Some patients will have an increased tumor size and mass effect from chemo and radiation, which is challenging to differentiate from simple tumor progression.
Bevacizumab is another agent in trial phase. This monoclonal antibody targets angiogenesis, and it has been proven to decrease the progression of symptoms but not to improve survival. Its most common use is for salvage therapy and to decrease the amount of steroids required to keep symptoms at bay. Research is aggressively seeking a cure, but recurrence is expected after roughly seven to 10 months once a patient has gone through first-line tumor debulking, chemo, and radiation. The options are limited. The use of low-intensity, alternating electric fields is in the experimental phase (Eur J Cancer 2012;48:2192; http://bit.ly/2PeFkXH), and therapies that target molecular mechanisms are being sought. (Ann Oncol 2017;28:1457; http://bit.ly/2PdYvkg.)
We take care of patients with glioblastoma in the emergency department at every phase of their care. The most important tool for evaluation is the neurologic exam, which will gauge progression. Patients may present with seizures, altered mental status, or neurologic deterioration. A well-documented neurologic exam from the last visit will facilitate a comparative assessment and treatment. Up to 30 percent of patients with glioblastoma will have VTE. Anticoagulation is used for inpatients and considered for outpatients. Low-molecular-weight heparin agents are preferred because they are easily reversed in case of hemorrhagic lesions. We should have a low threshold to image patients for DVT or PE. The common use of steroids also leads to insulin resistance, corticosteroid-related myopathy, confusion, personality change, insomnia, and weight gain.
It's a rough and uncertain road for patients with glioblastoma. We have the privilege of taking care of them, optimizing their quality of life, and helping their families understand the disease and what to expect. One of the best things we can do is to connect the patient and family with palliative care. My friend is a strong person and her family is involved and compassionate, which will be her brother's most valuable asset going forward.