Metastatic Brain Tumors

Every year more than 1 million people are diagnosed with cancer in the United States. It is estimated that between 100,000 – 200,000 of these will develop single or multiple metastatic brain tumor(s). The most common cancers to metastasize to the brain include:

	Melanoma
	Lung – some studies suggest up to 40% of lung cancer patients will develop brain metastases
	Breast – up to 1/3 of breast cancer patients will develop metastases
	Kidney
	Colon

As highlighted by these statistics, metastatic brain tumors are a common and significant challenge in patients with systemic cancer. While some patients present with large lesions in the brain that have been causing symptoms, many metastatic brain tumors are smaller and are only found through screening studies. Studies indicate that 2/3 of patients presenting with metastatic brain tumors are experiencing symptoms. The most common symptoms of metastatic brain tumors include:

	33% present due to cognitive dysfunction, including memory loss or mood swings
	20-40% present due to focal neurologic dysfunction (hemiparesis is the most common)
	10-20% present with acute seizures
	5-10% present as a result of stroke (hemorrhage into the tumor)

Site of systemic cancer causing metastatic brain tumors:

	50% - Lung
	15% - Breast
	10% - Gastrointestinal
	8% - Genitourinary
	6% - Miscellaneous
	11% - Unknown

The location in the brain of metastatic brain tumors follows the relevant blood flow and weight distribution in the brain:

	80% Cerebral hemispheres
	15% Cerebellum
	5% Brain stem

Treatment options available to treat metastatic brain tumors:

	Surgery
	Stereotactic radiosurgery
	Whole brain radiation therapy (WBRT)
	Combination of above

Clinical trials have demonstrated that multi-modality approaches (combination therapy) to treating metastatic brain tumors have resulted in better quality of life and extended survival. Unfortunately the manner in which therapies are combined and how they are staged is a matter of much debate, and there does not appear to be one single prognostic factor in predicting outcome for the various therapeutic options. However, based upon clinical literature, the following should be taken into consideration in determining the best course of treatment for an individual with metastatic brain tumors:

	Patient age
	Number of brain metastases
	Controlled/uncontrolled primary disease
	Extracranial metastases (metastases outside of the brain)
	KPS (Karnofsky performance status)
	(RPA) Recursive Partitioning Analysis
	Histology
	Delay to first metastatic brain tumors from diagnosis of primary disease

Single Metastatic Brain Tumor

The treatment paradigm for a single metastatic brain tumor is much less debated than that for multiple metastatic brain tumors. The treatment options that most practitioners consider are conventional surgery and/or Gamma Knife stereotactic radiosurgery. One-third of metastatic brain tumors are single, and CINN recommends the following approach for a single metastatic brain tumor:

Surgery should be considered if:

	Brain tumor is greater than 3.5 cm
	Brain tumor is causing significant edema
	Brain tumor is causing significant mass effect
	Hemorrhage
	Uncertain pathology
	Single brain tumor in a surgically accessible area

Gamma Knife should be considered if:

	Brain tumor does not meet surgical criteria
	Patient has contraindications to surgery
	Eloquent cortex
	Salvage
	Multiple lesions

Multiple Metastatic Brain Tumors

Two-thirds of patients that present with metastatic brain tumors have multiple tumors. The main treatment options for these patients are surgery, Gamma Knife/stereotactic radiosurgery and whole brain radiation therapy (WBRT). Much information is available on outcomes, management morbidity, survival and quality of life.

Whole brain radiation therapy (WBRT) has been used for decades in the treatment of metastatic brain tumors and has shown to increase survival from 2 to 6 months from the time of brain tumor diagnosis. Different dose schemes and number of fractions have been evaluated with no significant differences in survival. Adverse effects of WBRT include:

	Fatigue
	Hair Loss
	Urinary incontinence
	Ataxia
	Dementia

These side effects worsen after six months post treatment. Therefore, patients with longer expected survival should be evaluated carefully and other options should be considered. Studies have shown a benefit from prophylactic cranial irradiation in patients with small cell lung cancer, but this practice should be avoided for most other tumor types.

Randomized studies have shown that WBRT following stereotactic radiosurgery is better than WBRT alone in controlling tumors, improving quality of life and prolonging survival in patients with fewer than four metastases. These patients should be considered for radiosurgery first, as WBRT remains an option after radiosurgery. In addition radiosurgery can be used recurringly to treat new tumors, due to the limited amount of brain tissue radiated during each procedure.

Given technological advancements and outcomes data for the use of Gamma Knife stereotactic radiosurgery in the treatment of multiple metastatic brain tumors, the use of conventional surgical resection in general is on the decline. Surgery is still advocated for single metastatic brain tumors meeting certain criteria as outlined in the “single metastatic brain tumor” section of this website, as well as in the case of failed Gamma Knife stereotactic radiosurgery. Studies have shown selected improvement in survival and no increase in surgical morbidity when conventional surgery is used after failed stereotactic radiosurgery.

An increasing number of patients are undergoing stereotactic radiosurgery. CINN utilizes the Gamma Knife for the majority of the metastatic brain tumors treated. In fact, CINN has used the Gamma Knife in nearly 550 cases for the treatment of metastatic brain tumors. Furthermore, as a percentage of the types of patients CINN treats with the Gamma Knife, metastatic brain tumor have increased from 20% of total cases (pre-2002) to nearly 30% of total cases. Current studies show that use of the Gamma Knife produces high local tumor control rates. In addition, treatment with the Gamma Knife yields fewer side effects than WBRT, including less depression, fatigue, and short-term and long-term memory loss.

In addition to fewer side effects, studies have shown that Gamma Knife stereotactic radiosurgery has higher local tumor control rates that WBRT. At the same time, radiosurgery minimizes the amount of brain that is radiated, even in patients with multiple tumors. Stereotactic radiosurgery is delivered in one session, thereby allowing the continuance or initiation of other systemic disease therapies.

Published tumor control rates and overall survival after treatment with the Gamma Knife include:

	Nonsmall cell and small cell lung cancer Tumor control rate - greater than 90% Overall median survival 14 – 18 months
	Breast cancer Tumor control rate - 86% - 94% Overall median survival 14.5 months

CINN has been selecting and treating patients with the Gamma Knife since May 1989. Many of our metastatic brain tumor patients have enjoyed longer survival and better quality of life due to their treatment choice. We strongly recommend that patients should consult an experienced and qualified neurosurgeon prior to receiving WBRT for metastatic brain tumor. Strong clinical evidence suggests that Gamma Knife stereotactic radiosurgery should be employed as the first line of defense in the treatment of patients with fewer than four metastatic brain tumors. While further data from clinical trials is necessary to make generalized conclusions on the staging of treatment for patients with more than four metastatic brain tumors, consultation with a neurosurgeon should take place so that the facts and circumstances of each individual patient can be discussed.

Weekly, CINN neurosurgeons meet with a team of experienced clinicians as part of the Gamma Knife conference. A radiation oncologist, clinical oncologist, physicist and nurse meet with the neurosurgeons as part of this process. Each patient being considered for treatment with the Gamma Knife is discussed. CINN’s experience of having treated over 2,000 patients since May 1989 is brought to bear on each new case. If you are interested in speaking with a neurosurgeon about treatment with the Gamma Knife, please call 1-800-446-1234.