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:
1. 50% – Lung
2. 15% – Breast
3. 10% – Gastrointestinal
4. 8% – Genitourinary
5. 6% – Miscellaneous
6. 11% – Unknown
The location in the brain of metastatic brain tumors follows the relevant blood flow and weight distribution in the brain:
1. 80% Cerebral hemispheres
2. 15% Cerebellum
3. 5% Brain stem
Treatment options available to treat metastatic brain tumors:
1. Surgery
2. Stereotactic radiosurgery
3. Whole brain radiation therapy(WBRT)
4. 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:
1. Patient age
2. Number of brain metastases
3. Controlled/uncontrolled primary disease
4. Extracranial metastases (metastases outside of the brain)
5. KPS (Karnofsky performance status)
6. (RPA) Recursive Partitioning Analysis
7. Histology
8. 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 surgery for metastatic brain tumor may be considered if:
1. Brain tumor is greater than 3.5 cm
2. Brain tumor is causing significant edema
3. Brain tumor is causing significant mass effect
4. Hemorrhage
5. Uncertain pathology
6. Single brain tumor in a surgically accessible area
Gamma Knife may be considered if:
1. Brain tumor does not meet surgical criteria
2. Patient has contraindications to surgery
3. Eloquent cortex
4. Salvage
5. 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:
1. Fatigue
2. Hair Loss
3. Urinary incontinence
4. Ataxia
5. 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. Some institutions administer Gamma Knife for the majority of the metastatic brain tumors treated. 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