Metastatic Brain Tumors

Chapter 35 Metastatic Brain Tumors



Juanita M. Celix, Daniel L. Silbergeld



Clinical Pearls




• A metastatic brain tumor means that the patient has stage IV cancer, with median survival of under 1 year.


• When a patient presents with a new brain metastasis, without a known primary site, the chance of finding the primary tumor during the patient’s lifetime is approximately 50%.


• As long as brain metastases undergo some form of treatment, the vast majority of patients will succumb to progression of systemic disease as opposed to brain metastases.


• Therapies for brain metastases are roughly equivalent, with local recurrence rate of 40% to 50% at 1 year. Therefore, the choice of therapy must be tailored to the individual patient, taking into account Karnofsky performance scale (KPS) score, medical comorbid conditions, systemic disease status, number of metastases, size and location of metastases, and symptoms.


• It is essential that treatment decisions for this lethal disease be made as a multidisciplinary team of oncologists, radiation oncologists, and neurosurgeons, as well as the patient and the patient’s family.


Greater than half of all clinically diagnosed brain tumors in adults are cerebral metastases. Past estimates of the incidence of cerebral metastases were based on large population studies. Recent clinical series and autopsy studies demonstrate an increasing incidence of cerebral metastases, but the true incidence of cerebral metastases is difficult to ascertain. Estimates of the annual incidence of cerebral metastases in the United States range from 100,000 to 200,000 new cases, compared to fewer than 20,000 new cases of primary brain tumors. The apparent increase in the incidence of cerebral metastases may be due to a variety of factors. Improvements in systemic cancer treatments have increased the length of survival of many cancer patients, and advancements in cerebral imaging technology have augmented the ability to diagnose cerebral metastases. During the course of their lifetime 20% to 40% of patients with systemic cancer are diagnosed with cerebral metastases. Cerebral metastases are the presenting symptom of an undiagnosed primary cancer in at least 30% of patients and despite complete medical evaluation in 15% of patients a primary cancer will not be diagnosed. The use of magnetic resonance imaging (MRI) in the diagnosis of cerebral metastases has shown that greater than 60% of cancer patients with cerebral metastases have more than one metastatic brain lesion.


The histology and epidemiology of the primary cancer are the principal determinants of the frequency of cerebral metastases. Although the most common cancers diagnosed in adults in the United States are colorectal, prostate, breast, and lung, the two of these with the greatest proclivity to spread to the brain are lung and breast. In decreasing order of relative frequency, the majority of cerebral metastases are due to lung, breast, melanoma, renal, and colon cancers. Primary lung cancer accounts for 30% to 60% of all cerebral metastases. Lung cancer is more frequently diagnosed in males, and as a result, primary lung cancer is the most common cause of cerebral metastases in males. Brain metastases from lung cancer are often synchronous at diagnosis. Breast cancer accounts for 10% to 30% of all cerebral metastases and is the most common cause of cerebral metastases in females. Unlike brain metastases from lung cancer, breast metastases to the brain are more often metachronous. Melanoma accounts for 5% to 20% of all cerebral metastases, while renal and colon cancer each account for 5% to 10% of cerebral metastatic disease. The tendency of a primary cancer to metastasize to the brain has a distinct order of relative frequency. The frequency of cerebral metastases for melanoma is greater than 50%, but the low incidence of melanoma relative to other cancers accounts for its lower overall relative frequency of all cerebral metastases. Lung cancer has the second highest overall tendency to metastasize to the brain. The frequency of cerebral metastases for lung cancer is 20% to 60%, but there is variability in the frequency of cerebral metastases based on lung tumor type. Small cell lung cancer and lung adenocarcinoma tend to metastasize to the brain more frequently than other types of lung cancer. Breast cancer has the third highest overall tendency to metastasize to the brain, with a frequency of 20% to 30%.


Metastatic brain tumors in children with a primary cancer are rare. The most common sources of cerebral metastases in the pediatric population are neuroblastoma, rhabdomyosarcoma, and Wilms’ tumor.



Clinical Presentation and Diagnostic Studies


Brain metastases are most commonly parenchymal, but can also involve the ventricles, dura (most often with breast cancer), or leptomeninges. The major route of spread of metastatic brain tumors is hematogenous, and brain metastases often arise at the gray-white matter junction within the cerebral hemispheres, though brain metastases can occur in any part of the brain. The highest incidence of parenchymal brain metastases occurs in the distribution of the middle cerebral artery at the temporo-parieto-occipital junction, often near the eloquent cortex. Supratentorial metastases (80%) are more common than infratentorial metastases (15%). Within the posterior fossa in adults, metastatic brain tumors are the most common tumors. Therefore, a single cerebellar lesion in an adult is a metastasis until proved otherwise. Within the cerebellum, metastases can be located deep or hemispheric. Hematogenous spread of metastatic disease to the cerebellum can occur via the spinal epidural venous plexus or the vertebral arteries.


Similar to most primary brain tumors, metastatic brain tumors frequently present with slowly progressive signs and symptoms. Even with a history of treated cancer, there are no clinical findings that are specific for metastatic disease. Headache is the most common presenting symptom, occurring in 50% of patients. Nausea and vomiting may occur due to elevated intracranial pressure (ICP) from mass effect of the tumor or blockage of normal cerebrospinal fluid (CSF) drainage pathways. Focal neurological deficits, such as weakness, language difficulties, or cognitive impairment, will occur in up to two thirds of patients. This can be due to compression of brain parenchyma by the tumor mass or peritumoral edema, or compression of cranial nerves. Seizures occur in 15% to 20% of patients. Patients may present with symptoms of a transient ischemia attack (TIA) or stroke due to vascular compression or occlusion by the tumor or hemorrhage into the tumor. Intratumoral hemorrhage occurs in 5% to 15% of patients and is seen most frequently with metastatic choriocarcinoma (60-100%), melanoma (40%), and renal cell carcinoma. Mental status changes such as confusion, lethargy, apathy, and depression are not uncommon.


A complete history and physical examination is essential in the workup of a patient with a suspected metastatic brain tumor, because up to 30% of patients with no history of cancer will present with a cerebral metastasis. It is important to ask about constitutional symptoms, such as unintended weight loss, night sweats, loss of appetite, and so on. A family history of breast cancer and colorectal cancer may prove important. Any past history of cancer should be detailed, including stage at diagnosis and treatment, regardless of how remote the diagnosis, as approximately 90% of patients with newly diagnosed brain lesions and a known systemic cancer will prove to have metastases from the known cancer. Exposure to tobacco smoke and other toxins should be ascertained. Any abnormalities on routine screening evaluations, such as a Papanicolaou test, mammogram, or colonoscopy, should be investigated. Screening of the most common primary sites—lung, breast, skin, kidneys, and colon—should include a chest radiograph, mammogram, skin survey, urinalysis, stool guaic test, complete blood count, and extended metabolic panel. An oral and intravenous contrast-enhanced computed tomography (CT) scan of the chest, abdomen, and pelvis is a routine diagnostic tool in many institutions. Radionuclide bone scan and positron emission tomography/CT (PET/CT) scan can be useful in detecting small malignancies or alternative biopsy sites. However, many cancers lack PET avidity, so the PET scan alone (rather than PET/CT) should be interpreted with caution.


CT is the most common initial imaging study to assess for an intracranial lesion. On a nonenhanced CT, cerebral metastases typically appear as isodense or hypodense mass(es) at the gray-white matter junction. Significant white matter edema is characteristic, but peritumoral edema can be variable. Intratumoral hemorrhage or hemorrhage into the surrounding parenchyma may be present and appears hyperdense. On a contrast-enhanced CT, cerebral metastases characteristically appear as round, well-circumscribed masses with peripheral enhancement. From 50% to 65% of cerebral metastases are solitary on CT. Gadolinium-enhanced MRI of the brain is much more sensitive than contrast-enhanced CT imaging in detecting cerebral metastases, particularly in the posterior fossa and brainstem. In 20% of patients with a single metastasis detected on CT, MRI, with the ability to detect lesions as small as 1 to 2 mm, will detect multiple metastases.


The best imaging tool for cerebral metastases is contrast-enhanced MRI (Figs. 35.1 and 35.2). On nonenhanced T1-weighted sequences, cerebral metastases generally appear isointense or hypointense. Certain metastases with intrinsically short T1, such as melanoma (due to the ferromagnetic melanin within the tumor), can appear hyperintense. Hemorrhage within the tumor will appear disorganized, with atypical evolution, and is best evaluated on T2-weighted gradient echo (GRE) sequences. On nonenhanced T2-weighted sequences, cerebral metastases generally appear hyperintense, but can be variable. Similarly, on FLAIR (fluid-attenuated inversion recovery) sequences the appearance of cerebral metastases can be variable, but is generally hyperintense. Both FLAIR and T2-weighted images usually demonstrate marked vasogenic edema. Tumor cysts and surrounding edema appear markedly hyperintense. The vast majority of cerebral metastases will enhance. On contrast-enhanced T1-weighted sequences cerebral metastases show strong enhancement in variable patterns. Cerebral metastases usually do not show restriction on diffusion-weighted imaging (DWI) sequences and exhibit elevated apparent diffusion coefficient (ADC) values. The differential diagnosis of cerebral lesions with imaging characteristics similar to cerebral metastases includes abscess, encephalitis, malignant glioma, radiation necrosis, thromboembolic stroke, demyelinating disease, and resolving hematoma. Multiplicity of lesions or location in the posterior fossa may increase the likelihood that the lesions are metastatic, rather than primary.


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FIGURE 35.1 A, Axial contrast-enhanced T1-weighted magnetic resonance imaging (MRI) scan showing multiple non–small cell lung cancer metastases (right occipital and left temporal). Lesions are typically ring-enhancing and often multiple. B, Sagittal view of the left temporal lesion seen in A.

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Jul 16, 2016 | Posted by in NEUROSURGERY | Comments Off on Metastatic Brain Tumors

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