Metastatic brain tumors

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Metastatic brain tumors are the most common intracranial neoplasm. As treatment for systemic cancers improves, their detection has become more common, particularly with widespread use of MRI. Lung, breast, and melanoma remain the most common primary sources for metastatic brain tumors. Treatment modalities include surgical resection (generally for solitary or single metastases), with whole brain radiation (although some will forgo this due to reported cognitive side effects), and stereotactic radiosurgery for oligometastatic disease.

Contents

Definition

Brain metastases are neoplasms that originate in tissues outside the central nervous system and spread secondarily to the brain. Solitary metastatic disease refers to one metastasis to the brain in the setting of no other extracranial metastatic disease. Single metastatic disease refers to one metastasis in the brain in the setting of metastatic disease elsewhere in the body. Multiple metastases refers to mutliple lesions in the brain. Metastatic disease may be diagnosed synchronously: at the same time as the primary tumor is discovered, or metachronously: either afterward or before the primary tumor is discovered.

Epidemiology

The incidence has been reported to be between 8.2-12.5 per 100,000 in the United States. This yields at a minimum 100,000 new cases a year, although some authors place this figure as high as 200,000 a year due to the fact that advances in imaging and more frequent use of MRI as a screening tool are increasing their detection. Metastatic brain tumors are much more frequent than primary brain tumors and thus are the most common brain neoplasm.

Histology

Around 25% of all cancer patients develop brain metastases during the course of their illness. Primary lung cancer accounts for 30%-60% of all brain metastases. In patients with lung cancer 18-65% will develop brain metastases. More than 40% of patients with small cell lung cancer and adenocarcinoma of the lung will develop brain metastases. Breast cancer is the second most frequent occurring primary tumor causing brain metastases. Between 20-30% of breast cancer patients will develop brain metastases. Melanoma is the third most common cause of brain metastases. Of patients with brain metastases, between 5%-21% have melanoma as their primary tumor. Of note, melanoma has the highest propensity of all systemic malignant tumors to metastasis to the brain. Other primary malignancies causing brain metastases include: renal cell carcinoma (with 11% developing brain metastases), gastrointestinal cancer (with 1%-10% developing brain metastases), genitourinary cancers (including testicular cancer with an incidence ranging from 2%-21%), and gynecologic cancers (rarely causing metastases in 1%-10% of cases).

Diagnosis

Some primary tumors have a high enough tendency for brain metastases that screening MRI of the brain is often advocated, e.g. adenocarcinoma of the lung. In general, most lesions are detected when they become symptomatic. Symptoms include headache, seizure, weakness, and ataxia.

Imaging

MRI with gadolinium is the imaging modality of choice for detecting metastatic disease to the brain. Metastases will avidly contrast enhance.

T1 weighted Sagittal MRI with contrast showing a metastasis in the parietal lobe

Treatment Options

Treatment for metastases continues to evolve. Level 1 evidence supports surgical resection followed by whole brain radiation for solitary metastases to the brain. This has been shown to be superior to radiation alone. For multiple metastases, whole brain radiation has been advocated. Stereotactic radiosurgery is another treatment option that may be used for solitary, single or multiple metastases.

Surgical Resection

In two surgical series published by Patchell et al. (N Engl J Med. 1990 Feb 22;322(8):494-500, : JAMA. 1998 Nov 4;280(17):1485-9), Surgical resection followed by fractionated whole brain radiation has been shown to be superior to radiation alone.

Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) is a method of delivering a high dose of radiation (usually 18 - 20 Gy for tumors >2cm, and 22-25 Gy for tumors <2cm) to a metastasis. The high dose of radiation essentially renders histology irrelevant. This is important because some metastases are resistant to traditional types of fractionated radiation (e.g. melanoma, renal cell carcinoma, and sarcoma). One study has compared SRS alone to SRS plus WBRT. The results show no difference in survival, but intracranial relapse is more common when patients do not receive WBRT. (JAMA. 2006;295:2483-2491.)

Whole brain radiation

WBRT is commonly used for brain metastases, particularly patients with multiple metastases. It is often used after surgical resection, and level 1 evidence supports its use after resection or radiosurgery. Multiple reports support its use, particularly for controlling recurrent disease and minimizing the development of new metastases. However, there is a risk of neurocognitive decline after WBRT (e.g. short term memory loss). (Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1388-95)

Prognosis

Prognosis varies widely for metastatic brain disease and is dependent on numerous factors, including histology, age, Karnofsky performance score, and the status of systemic disease. One of the most widely used stratifications of survival is the Recursive Partitioning Analysis classfication. RPA Class I patients have the longest median survival (7.1 months), and include patients with KPS > or = 70, <65 years, with controlled primary and no extracranial metastases: Class 3 patients have KPS <70 and a median survival of 2.3 months, and Class 2 patients are all others with a median survival of 4.2 months. (Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51)

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